Patent Publication Number: US-2022211790-A1

Title: Hemp extract for treatment of pain in animals

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Patent Application Ser. No. 62/655,170, filed Apr. 9, 2018, the entire disclosure of which is hereby incorporated herein by reference. 
    
    
     BACKGROUND 
     Routine nonsteroidal anti-inflammatory drug (NSAID) treatments, though efficacious, may not provide adequate relief of pain due to osteoarthritis (OA) and might have potential side effects that preclude its use, particularly in patients with certain comorbidities. In a systematic review of 35 canine models of OA and 29 clinical trials in dogs, treatment with NSAIDs caused adverse effects in 35 of the 64 (55%) studies, most common being gastro-intestinal signs. Although other pharmacological agents are advocated, there is little evidence regarding their efficacy in dogs with chronic or neuropathic pain related to OA. In the absence of an optimal treatment for these dogs, other potentially efficacious pharmacological agents, including cannabinoids, are often sought. 
     SUMMARY 
     The present disclosure is directed toward compositions comprising cannabidiol and their use for the treatment of pain in animals. In an aspect, provided herein is a pharmaceutical composition comprising hemp extract and a carrier, wherein the hemp extract comprises: 
     cannabidiol; 
     cannabidiolic acid; 
     cannabigerolic acid; 
     Δ9-tetrahydrocannabinol; and 
     cannabichromene; 
     wherein the ratio of cannabidiol to cannabidiolic acid is about 0.6:1 to about 1:0.6. 
     In an embodiment, the hemp extract further comprises four or more of the following: 
     α-pinene; 
     β-myrcene; 
     β-pinene; 
     δ-limonene; 
     linalool; 
     β-caryophyllene; 
     α-humulene; 
     nerolidol 2; 
     guaiol; 
     caryophyllene oxide; and 
     α-bisabolol. 
     In an embodiment, the concentration of Δ9-tetrahydrocannabinol is insufficient to produce a psychotropic effect. In an embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:25. In another embodiment, the concentration of Δ9 tetrahydrocannabinol is less than about 1 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.5 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.3 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.2 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.1 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is about 0 mg/mL. 
     In an embodiment, the ratio of cannabidiol to cannabidiolic acid is selected from the group consisting of about 1:100, about 1:50, about 1:10, and about 1:1. In another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 1:1. 
     In an embodiment, the hemp extract comprises: 
     about 1-10 mg/mL of cannabidiol; 
     about 1-10 mg/mL of cannabidiolic acid; 
     about 0.05-0.2 mg/mL cannabigerolic acid; 
     about 0.1-0.3 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.1-0.4 mg/mL cannabichromene. 
     In another embodiment, the hemp extract comprises: 
     about 5 mg/mL of cannabidiol; 
     about 5 mg/mL of cannabidiolic acid; 
     about 0.11 mg/mL cannabigerolic acid; 
     about 0.25 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.27 mg/mL cannabichromene. 
     In another embodiment, the hemp extract comprises: 
     about 0.09-0.13% α-pinene; 
     about 0.23-0.44% β-myrcene; 
     about 0.04-0.09% β-pinene; 
     about 0.05-0.09% δ-limonene; 
     about 0.03-0.06% linalool; 
     about 0.04-0.07% β-caryophyllene; 
     about 0.02-0.04% α-humulene; 
     about 0.04-0.07% nerolidol 2; 
     about 0.02-0.04% guaiol; 
     about 0.04-0.08% caryophyllene oxide; and 
     about 0.01-0.04% α-bisabolol. 
     In another embodiment, the hemp extract further comprises: 
     camphene; 
     β-ocimene; 
     eucalyptol; 
     isopulegol; and/or 
     nerolidol 1. 
     In another embodiment, the hemp extract comprises: 
     about 0.02% camphene; 
     about 0.02-0.03% β-ocimene; 
     about 0.02-0.05% eucalyptol; 
     about 0.02% isopulegol; and/or 
     about 0.02-0.04% nerolidol 1. 
     In an embodiment, the hemp extract comprises 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the composition is formulated in a carrier. In another embodiment, the carrier is selected from the group consisting of linseed oil, olive oil, fish oil, salmon oil, coconut oil, catnip oil, and grapeseed oil. In another embodiment, the carrier is grapeseed oil. In another embodiment, the carrier is catnip oil. In another embodiment, the composition comprises nepetalactone. In another embodiment, wherein the composition comprises taurine. 
     In an embodiment, the hemp extract comprises: 
     cannabidiol; 
     cannabidiolic acid; 
     cannabigerolic acid; 
     Δ9-tetrahydrocannabinol; and 
     cannabichromene; 
     wherein the carrier is grapeseed oil. 
     In an embodiment, the composition is formulated for administration using a nebulizer. In another embodiment, the composition is formulated for administration using a diffuser. In another embodiment, the composition is formulated for administration using a pet collar. In another embodiment, the composition is formulated as a pet food for oral administration. 
     In an embodiment, the composition is formulated as a chew for oral administration. In another embodiment, the weight of the chew is about 0.5-10 g. In another embodiment, the weight of the chew is about 4 g, about 6 g, about 9 g, or about 10 g. In another embodiment, the weight of the chew is about 4 g. 
     In another embodiment, the chew comprises: 
     about 7 mg of cannabidiol; 
     about 6 mg of cannabidiolic acid; 
     about 0.12 mg cannabigerolic acid; 
     about 0.32 mg Δ9-tetrahydrocannabinol; and 
     about 0.36 mg cannabichromene. 
     In an embodiment, a dosage form comprises: 
     cannabidiol; 
     cannabidiolic acid; 
     cannabigerolic acid; 
     Δ9-tetrahydrocannabinol; 
     cannabichromene; and 
     one or more pharmaceutically acceptable additives, flavoring agents, surfactants, and adjuvants. 
     In another embodiment, the dosage form comprises: 
     about 1-10 mg/mL of cannabidiol; 
     about 1-10 mg/mL of cannabidiolic acid; 
     about 0.05-0.2 mg/mL cannabigerolic acid; 
     about 0.1-0.3 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.1-0.4 mg/mL cannabichromene. 
     In another embodiment, the dosage form comprises: 
     about 5 mg/mL of cannabidiol; 
     about 5 mg/mL of cannabidiolic acid; 
     about 0.11 mg/mL cannabigerolic acid; 
     about 0.25 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.27 mg/mL cannabichromene. 
     In an embodiment, the dosage form comprises: 
     α-pinene; 
     β-myrcene; 
     β-pinene; 
     δ-limonene; 
     linalool; 
     β-caryophyllene; 
     α-humulene; 
     nerolidol 2; 
     guaiol; 
     caryophyllene oxide; and 
     α-bisabolol. 
     In another embodiment, the dosage form comprises: 
     about 0.09-0.13% α-pinene; 
     about 0.23-0.44% β-myrcene; 
     about 0.04-0.09% β-pinene; 
     about 0.05-0.09% δ-limonene; 
     about 0.03-0.06% linalool; 
     about 0.04-0.07% β-caryophyllene; 
     about 0.02-0.04% α-humulene; 
     about 0.04-0.07% nerolidol 2; 
     about 0.02-0.04% guaiol; 
     about 0.04-0.08% caryophyllene oxide; and 
     about 0.01-0.04% α-bisabolol. 
     In another embodiment, the dosage form further comprises: 
     camphene; 
     β-ocimene; 
     eucalyptol; 
     isopulegol; and/or 
     nerolidol 1. 
     In another embodiment, the dosage form comprises: 
     about 0.02% camphene; 
     about 0.02-0.03% β-ocimene; 
     about 0.02-0.05% eucalyptol; 
     about 0.02% isopulegol; and/or 
     about 0.02-0.04% nerolidol 1. 
     In another embodiment, the dosage form comprises 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises a flavoring agent selected from the group consisting of catnip oil, peppermint oil, mango extract, beef, poultry, and seafood. In an embodiment, the flavoring agent is catnip oil. In an embodiment, the flavoring agent is selected from the group consisting of catnip oil, chicken liver powder, poultry extract, maltodextrin, butter, and bacon. In an embodiment, the flavoring agent is chicken liver powder. 
     In an embodiment, the dosage form comprises nepetalactone. In an embodiment, the dosage form comprises taurine. 
     In an embodiment, the dosage form is formulated as a chew for oral administration. In an embodiment, the chew is produced using cold extrusion. In another embodiment, the dosage form is formulated as a sublingual spray. In another embodiment, the dosage form is formulated as a water or alcohol soluble solution, a gel, or a cream for transdermal application. In another embodiment, the dosage form is formulated as a gel for buccal or mucosal administration. In another embodiment, the dosage form is formulated as a powder. In another embodiment, the dosage form is formulated as a solution for subcutaneous injection. In another embodiment, the dosage form is formulated as a tablet. In another embodiment, the dosage form is formulated as a capsule. In another embodiment, the dosage form is formulated as a hard chewable. In another embodiment, the dosage form is formulated for inhalation. In another embodiment, the dosage form is formulated for administration using a nebulizer. In another embodiment, the dosage form is formulated for administration using a diffuser. In another embodiment, the dosage form is formulated for administration using a pet collar. 
     In an embodiment, the dosage form is formulated in a carrier for oral administration. In an embodiment, the carrier is selected from the group consisting of linseed oil, olive oil, fish oil, salmon oil, coconut oil, catnip oil, and grapeseed oil. In another embodiment, the carrier is grapeseed oil. In another embodiment, the carrier is catnip oil. 
     In an embodiment, a dosage form comprises: 
     glucosamine HCl; 
     chondroitin sulfate (76%); 
     brewer&#39;s yeast; 
     arabic gum; 
     guar gum; 
     a flavoring agent; 
     Verdilox; 
     Previon; 
     hemp extract; 
     glycerin; 
     sunflower lecithin; and 
     water. 
     In another embodiment, the dosage form comprises: 
     about 12-17% glucosamine HCl; 
     about 1-4% chondroitin sulfate (76%); 
     about 29-33% brewer&#39;s yeast; 
     about 3-6% arabic gum; 
     about 0.5-2% guar gum; 
     about 12-16% of a flavoring agent; 
     about 0.01-0.1% Verdilox; 
     about 0.5-1.5% Previon; 
     about 3-6% hemp extract; 
     about 13-17% glycerin; 
     about 3-7% sunflower lecithin; and 
     about 3-7% water. 
     In another embodiment, the dosage form comprises: 
     about 15.6% glucosamine HCl; 
     about 2.6% chondroitin sulfate (76%); 
     about 30% brewer&#39;s yeast; 
     about 4.7% arabic gum; 
     about 0.9% guar gum; 
     about 14.2% of a flavoring agent; 
     about 0.05% Verdilox; 
     about 0.9% Previon; 
     about 4.7% hemp extract; 
     about 15.1% glycerin; 
     about 5.7% sunflower lecithin; and 
     about 5.7% water. 
     In an embodiment, a dosage form comprises: 
     glucosamine HCl; 
     hyaluronic acid; 
     brewer&#39;s yeast; 
     arabic gum; 
     guar gum; 
     a flavoring agent; 
     Verdilox; 
     Previon; 
     hemp extract; 
     glycerin; 
     sunflower lecithin; and 
     water. 
     In another embodiment, the dosage form comprises: 
     about 12-17% glucosamine HCl; 
     about 0.01-1% hyaluronic acid; 
     about 29-33% brewer&#39;s yeast; 
     about 3-6% arabic gum; 
     about 0.5-2% guar gum; 
     about 12-16% of a flavoring agent; 
     about 0.01-0.1% Verdilox; 
     about 0.5-1.5% Previon; 
     about 3-6% hemp extract; 
     about 13-17% glycerin; 
     about 3-7% sunflower lecithin; and 
     about 3-7% water. 
     In another embodiment, the dosage form comprises: 
     about 16% glucosamine HCl; 
     about 0.1% hyaluronic acid; 
     about 30.6% brewer&#39;s yeast; 
     about 4.8% arabic gum; 
     about 0.97% guar gum; 
     about 14.5% of a flavoring agent; 
     about 0.05% Verdilox; 
     about 0.97% Previon; 
     about 4.8% hemp extract; 
     about 15.5% glycerin; 
     about 5.8% sunflower lecithin; and 
     about 5.8% water. 
     In an embodiment, a dosage form comprises: 
     hemp extract; 
     peanut butter; 
     rice bran; 
     glucosamine HCL; 
     sweet potato; 
     dry molasses; 
     sorbic acid 
     brewer&#39;s yeast; 
     sugar; 
     water; 
     glycerin; 
     potato starch; 
     dehydrated peanut butter; 
     rice starch; and 
     guar gum. 
     In another embodiment, the dosage form comprises: 
     about 5.0% hemp extract; 
     about 15.0% peanut butter; 
     about 12.5% rice bran; 
     about 12.75% glucosamine HCL; 
     about 5.5% sweet potato; 
     about 8.0% dry molasses; 
     about 1% sorbic acid; 
     about 5.0% brewer&#39;s yeast; 
     about 6.0% sugar; 
     about 9.25% water; 
     about 13.0 glycerin; 
     about 2.0% potato starch; 
     about 1.0% dehydrated peanut butter; 
     about 2.0% rice starch; and 
     about 2.0% guar gum. 
     In another embodiment, the dosage form comprises: 
     about 5.0% hemp extract; 
     about 15.0% peanut butter; 
     about 13.0% rice bran; 
     about 8.5% glucosamine HCL; 
     about 6.0% sweet potato; 
     about 9.0% dry molasses; 
     about 1% sorbic acid; 
     about 5.0% brewer&#39;s yeast; 
     about 6.0% sugar; 
     about 9.5% water; 
     about 13.0 glycerin; 
     about 4.0% potato starch; 
     about 1.0% dehydrated peanut butter; 
     about 2.0% rice starch; and 
     about 2.0% guar gum. 
     In another embodiment, the dosage form comprises: 
     about 3.0-10.0% hemp extract; 
     about 10.0-20.0% peanut butter; 
     about 10.0-15.0% rice bran; 
     about 5.0-15.0% glucosamine HCL; 
     about 4.0-10.0% sweet potato; 
     about 6.0-13.0% dry molasses; 
     about 0.5-5.0% sorbic acid; 
     about 2.0-8.0% brewer&#39;s yeast; 
     about 3.0-8.0% sugar; 
     about 5.0-15.0% water; 
     about 8.0-18.0% glycerin; 
     about 1.0-8.0% potato starch; 
     about 0.5-5.0% dehydrated peanut butter; 
     about 1.0-5.0% rice starch; and 
     about 1.0-5.0% guar gum. 
     In an aspect, provided herein is a method for treating or reducing pain in a veterinary subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compositions or a dosage forms described above. In an embodiment, the pain is associated with arthritis, post-operative pain, acute pain, dental pain, pain associated with gingivitis, or multi-joint pain. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1.0 mg/kg twice daily. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1.0 mg/kg three times daily. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2.0 mg/kg twice daily. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2.0 mg/kg three times daily. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.1-8.0 mg/kg. 
     In another embodiment, the pharmaceutical composition or dosage form is administered at twice the therapeutically effective dosage for one week, and then subsequently administered at a therapeutically effective dosage. In another embodiment, the therapeutically effective dosage is about 0.1-0.5 mg/kg. In another embodiment, the therapeutically effective dosage is about 2 mg/kg. In another embodiment, the therapeutically effective dosage is about 8 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1 mg/kg for one week, and then subsequently administered at a dosage of about 0.1-0.5 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 4 mg/kg for one week, and then subsequently administered at a dosage of about 2 mg/kg. 
     In an embodiment, the method results in a therapeutically effective median maximal serum concentration of cannabidiol. In an embodiment, the median maximal serum concentration of cannabidiol is about 102 ng/mL. In another embodiment, the median maximal serum concentration of cannabidiol is about 590 ng/mL. 
     In an aspect, provided herein is a method for treating or reducing pain associated with arthritis, post-operative pain, acute pain, dental pain, pain associated with gingivitis, or multi-joint pain in a veterinary subject in need thereof, comprising administering to the subject a therapeutically effective amount of hemp extract. 
     In an embodiment, the hemp extract is administered at a dosage of about 0.1-8.0 mg/kg. In another embodiment, the hemp extract is administered at twice the therapeutically effective dosage for one week, and then subsequently administered at a therapeutically effective dosage. In another embodiment, the therapeutically effective dosage is about 0.1-0.5 mg/kg. In another embodiment, the therapeutically effective dosage is about 1 mg/kg. In another embodiment, the therapeutically effective dosage is about 2 mg/kg. In another embodiment, the therapeutically effective dosage is about 8 mg/kg. 
     In an embodiment, the hemp extract is administered at a dosage of about 1 mg/kg for one week, and then subsequently administered at a dosage of about 0.1-0.5 mg/kg. In another embodiment, the hemp extract is administered at a dosage of about 4 mg/kg for one week, and then subsequently administered at a dosage of about 2 mg/kg. 
     In an embodiment, the method results in a therapeutically effective median maximal serum concentration of cannabidiol. In another embodiment, the median maximal serum concentration of cannabidiol is about 102 ng/mL. In another embodiment, the median maximal serum concentration of cannabidiol is about 590 ng/mL. 
     In an embodiment, the veterinary subject is canine, feline, bovine, porcine, or equine. In another embodiment, the veterinary subject is canine. In another embodiment, the veterinary subject is feline. 
     In an aspect, provided herein is a method of achieving an area under the curve from 0 time to 24 hours of between 42.4 and 3048 ng hr/ml for cannabidiol in a veterinary subject comprising administering to the subject an effective amount of hemp extract. In an embodiment, the subject is canine or feline. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1 : Box-and-whisker plot of serum alkaline phosphatase (ALP) activity at each time for treatment and placebo oils. Box represents the mean and 25th and 75th percentile and the whiskers represent the 99th and 1st percentiles. 
         FIG. 2 : Serum concentration (ng/mL) of 2 mg/kg and 8 mg/kg oral dosage of CBD oil in time (min) 
         FIG. 3A : Box-and-whisker plot of total CBPI score at each time for treatment and placebo oils. Box represents the mean and 25th and 75th percentile and the whiskers represent the 99th and 1st percentiles. 
         FIG. 3B : Box-and-whisker plot of total Hudson score at each time for treatment and placebo oils. Box represents the mean and 25th and 75th percentile and the whiskers represent the 99th and 1st percentiles. 
         FIG. 4 : Box-and-whisker plot of total vet pain assessment at each time for treatment and placebo oils. 
         FIGS. 5A-5F : Graphs showing trot stance % gait cycle symmetry ( FIG. 5A ), trot stance % gait cycle ( FIG. 5B ), trot step/stride ratio ( FIG. 5C ), walk stance % gait cycle symmetry ( FIG. 5D ), walk stance % gait cycle ( FIG. 5E ), and walk step/stride ratio ( FIG. 5F ) for five dogs treated with CBD. 
     
    
    
     DETAILED DESCRIPTION 
     The endocannabinoid receptor system is known to play a role in pain modulation and attenuation of inflammation. Cannabinoid receptors (CB 1  and CB 2 ) are widely distributed throughout the central and peripheral nervous system and are also present in the synovium. However, the psychotropic effects of certain cannabinoids prevent extensive research into their use as single agents for pain relief. The cannabinoids are a group of as many as 60 different compounds that may or may not act at CB receptors. One class of cannabinoids, cannabidiol (CBD), may actually be an antagonist of the CB receptors. In lower vertebrates, CBD can also have immunomodulatory, anti-hyperalgesic, antinociceptive, and anti-inflammatory actions, making it an attractive therapeutic option in dogs with OA. 
     The present disclosure is directed toward compositions comprising hemp extract and their use for the treatment of pain in animals. Also provided herein are methods for treatment of pain in veterinary subjects. The efficacy of these compositions and treatment methods has not previously been demonstrated. Clinical trial and pharmacokinetic data regarding dosing is also provided herein. 
     Definitions 
     Listed below are definitions of various terms used herein. These definitions apply to the terms as they are used throughout this specification and claims, unless otherwise limited in specific instances, either individually or as part of a larger group. 
     Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry, and peptide chemistry are those well-known and commonly employed in the art. 
     As used herein, the articles “a” and “an” refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. Furthermore, use of the term “including” as well as other forms, such as “include,” “includes,” and “included,” is not limiting. 
     As used herein, the term “about” will be understood by persons of ordinary skill in the art and will vary to some extent on the context in which it is used. As used herein when referring to a measurable value such as an amount, a temporal duration, and the like, the term “about” is meant to encompass variations of ±5%, from the specified value, as such variations are appropriate to perform the disclosed methods. 
     As used in the specification and in the claims, the term “comprising” may include the embodiments “consisting of” and “consisting essentially of.” The terms “comprise(s),” “include(s),” “having,” “has,” “may,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that require the presence of the named ingredients/steps and permit the presence of other ingredients/steps. However, such description should be construed as also describing compositions or processes as “consisting of” and “consisting essentially of” the enumerated compounds, which allows the presence of only the named compounds, along with any pharmaceutically acceptable carriers, and excludes other compounds. 
     All ranges disclosed herein are inclusive of the recited endpoint and independently combinable (for example, the range of “from 50 mg to 500 mg” is inclusive of the endpoints, 50 mg and 500 mg, and all the intermediate values). The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value; they are sufficiently imprecise to include values approximating these ranges and/or values. 
     As used herein, the term “treatment” or “treating,” is defined as the application or administration of a therapeutic agent, i.e., a compound provided herein (alone or in combination with another pharmaceutical agent), to a patient, or application or administration of a therapeutic agent to an isolated tissue or cell line from a patient (e.g., for diagnosis or ex vivo applications), with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect the symptoms of a disease, disorder, syndrome, or condition. Such treatments can be specifically tailored or modified, based on knowledge obtained from the field of pharmacogenomics. 
     In certain embodiments, the compositions described herein reduce pain in a subject. Pain can be measured using any metric known in the art. For example, pain can be measured using the canine brief pain inventory (CBPI), the Hudson activity scale, flexion and tension measurements and gait analysis. A reduction in any of these metrics shows a treatment of or reduction in pain. 
     As used herein, the term “prevent” or “prevention” means no disorder or disease development if none had occurred, or no further disorder or disease development if there had already been development of the disorder or disease. Also considered is the ability of one to prevent some or all of the symptoms associated with the disorder or disease. 
     As used herein, the term “use” includes any one or more of the following embodiments of the invention, respectively: the use in the treatment of pain the use for the manufacture of pharmaceutical compositions for use in the treatment of these diseases, e.g., in the manufacture of a medicament; methods of use of compounds of the invention in the treatment of these diseases; pharmaceutical preparations having compounds of the invention for the treatment of these diseases; and compounds of the invention for use in the treatment of these diseases; as appropriate and expedient, if not stated otherwise. 
     As used herein, the term “patient,” “individual,” or “subject” is intended to include organisms, e.g., prokaryotes and eukaryotes, which are capable of suffering from or afflicted with a disease, disorder or condition associated with the activity of a protein kinase. Examples of subjects include mammals, e.g., humans, dogs, cows, horses, pigs, sheep, goats, cats, mice, rabbits, rats, and transgenic non-human animals. In certain embodiments, the subject is a human, e.g., a human suffering from, at risk of suffering from, or potentially capable of suffering from, schizophrenia. In another embodiment, the subject is a cell. 
     When used with respect to methods of treatment/prevention and the use of the compounds and pharmaceutical compositions thereof described herein, an individual “in need thereof” may be an individual who has been diagnosed with or previously treated for the condition to be treated. With respect to prevention, the individual in need thereof may also be an individual who is at risk for a condition (e.g., a family history of the condition, life-style factors indicative of risk for the condition, etc.). Typically, when a step of administering a compound of the invention is disclosed herein, the invention further contemplates a step of identifying an individual or subject in need of the particular treatment to be administered or having the particular condition to be treated. 
     In some embodiments, the individual is a mammal, including, but not limited to, bovine, equine, feline, rabbit, canine, rodent, or primate. In some embodiments, the mammal is a primate. In some embodiments, the primate is a human. In some embodiments, the individual is human, including adults, children and premature infants. In some embodiments, the individual is a non-mammal. In some variations, the primate is a non-human primate such as chimpanzees and other apes and monkey species. The term “individual” does not denote a particular age or sex. 
     As used herein, the term “pharmaceutically acceptable” refers to a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively non-toxic, i.e., the material can be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. 
     As used herein, the term “pharmaceutically acceptable salt” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present invention include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington&#39;s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety. 
     As used herein, the term “composition” or “pharmaceutical composition” refers to a mixture of at least one compound useful within the invention with a pharmaceutically acceptable carrier. The pharmaceutical composition facilitates administration of the compound to a patient or subject. Multiple techniques of administering a compound exist in the art including, but not limited to, intravenous, oral, aerosol, parenteral, ophthalmic, pulmonary and topical administration. 
     As used herein, the term “pharmaceutically acceptable carrier” or “carrier” means a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, stabilizer, dispersing agent, suspending agent, diluent, excipient, thickening agent, solvent or encapsulating material, involved in carrying or transporting a compound useful within the invention within or to the patient such that it can perform its intended function. Typically, such constructs are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation, including the compound useful within the invention, and not injurious to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; surface active agents; alginic acid; pyrogen-free water; isotonic saline; Ringer&#39;s solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. As used herein, “pharmaceutically acceptable carrier” also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the compound useful within the invention, and are physiologically acceptable to the patient. Supplementary active compounds can also be incorporated into the compositions. The “pharmaceutically acceptable carrier” or “carrier” can further include a pharmaceutically acceptable salt of the compound useful within the invention. Other additional ingredients that can be included in the pharmaceutical compositions used in the practice of the invention are known in the art and described, for example in Remington&#39;s Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985, Easton, Pa.), which is incorporated herein by reference. 
     The term “stabilizer,” as used herein, refers to polymers capable of chemically inhibiting or preventing degradation. Stabilizers are added to formulations of compounds to improve chemical and physical stability of the compound. 
     As used herein, the term “adjuvant” may include, for example, preserving, wetting, suspending, sweetening, flavoring, perfuming, emulsifying, and dispensing agents. Prevention of the action of microorganisms is generally provided by various antibacterial and antifungal agents, such as, parabens, chlorobutanol, phenol, sorbic acid, and the like. Isotonic agents, such as sugars, sodium chloride, and the like, may also be included. Prolonged absorption of an injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin. The auxiliary agents also can include wetting agents, emulsifying agents, pH buffering agents, and antioxidants, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylated hydroxytoluene, and the like. 
     As used herein, the terms “effective amount,” “pharmaceutically effective amount,” and “therapeutically effective amount” refer to a nontoxic but sufficient amount of an agent to provide the desired biological result. That result may be reduction or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. An appropriate therapeutic amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation. 
     As used herein, the term “weight percent” is meant to refer to the quantity by weight of a compound and/or component in a composition as the quantity by weight of a constituent component of the composition as a percentage of the weight of the total composition. The weight percent can also be calculated by multiplying the mass fraction by 100. The “mass fraction” is the ratio of one substance of a mass m 1  to the mass of the total composition m T  such that weight percent=(m 1 /m T )*100. 
     “Aqueous buffer” refers to a water solution which resists change in hydronium ion and the hydroxide ion concentration (and consequent pH) upon addition of small amounts of acid or base, or upon dilution. Buffer solutions consist of a weak acid and its conjugate base (more common) or a weak base and its conjugate acid (less common). The buffer can be prepared by methods well known in the art with the appropriate buffering agents to give the desired pH value. Examples of the suitable buffering agents include hydrochloric acid, lactic acid, acetic acid, citric acid, malic acid, maleic acid, pyruvic acid, succinic acid, tris-hydroxymethylaminomethane, sodium hydroxide, sodium bicarbonate, phosphoric acid, sodium phosphate, and other biologically acceptable buffering agents. Aqueous buffers are readily available commercially and they can be used in preparation of the compositions of this invention without further treatment. 
     As used herein, the term “hemp extract” refers to a composition of cannabinoids and terpenes that are isolated from a hemp plant. The hemp extract can be obtained by any method known in the art. For example, the hemp extract can be obtained by supercritical (or subcritical) CO 2  extraction, which uses carbon dioxide under high pressure and low temperatures to isolate, preserve and maintain the purity of hemp extract. In an embodiment, the hemp extract is obtained from a supercritical CO 2  extraction. For example, supercritical CO 2  extraction may be performed as described in U.S. Pat. No. 8,895,078, which is incorporated herein by reference in its entirety. Alternatively, a solvent such as petroleum ether, ethanol, methanol, butanol, acetone, dry ice, or olive oil can be used, at room temperature (ambient temperature) with stirring, by passive extraction, heated to a temperature above room temperature, or under reflux, as known in the art to provide the hemp extract. In another embodiment, hemp extract from a butanol extraction is employed as starting material for methods disclosed herein. 
     As used herein, the term “flavoring agent” refers to an ingredient that is added to a composition to impart a particular flavor, smell, or other organoleptic property. 
     As used herein, the term “oil” refers to a nonpolar viscous liquid that is both hydrophobic and lipophilic. Oils may be isolated from animal, vegetable, or petrochemical products. 
     As used herein, the term “chew” refers to a product or a portion thereof that has rheological and other texture and organoleptic properties which tend to promote chewing upon the article by a target animal. Generally speaking, a chewable matrix will exhibit sufficient ductility that it is at least slightly malleable when bitten by the target animal and sufficient palatability that the target animal is not deterred by its taste from biting it multiple times. By contrast, “chewable” does not mean merely that an article can be chewed by an animal (i.e., it does not mean merely that some portion of the article will fit within an animal&#39;s mouth sufficiently to permit engagement of the animal&#39;s teeth against the portion). 
     The “maximal serum concentration level” of a substance, as used herein, refers to the maximal level of the substance found in a plasma sample following a single administration. 
     As used herein, the term “cold extrusion” refers to a process for producing edible food products comprising several unit operations including mixing, kneading, shearing, shaping, and forming, all of which are conducted at or near ambient temperature. 
     As used herein, the term “psychotropic effect” refers to a modification of brain function that results in an alteration of perception, mood, consciousness, or behavior. 
     Pharmaceutical Compositions 
     In an aspect, provided herein is a pharmaceutical composition comprising hemp extract and a carrier, wherein the hemp extract comprises: 
     cannabidiol; 
     cannabidiolic acid; 
     cannabigerolic acid; 
     Δ9-tetrahydrocannabinol; and 
     cannabichromene. 
     In another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is from about 1:50 to about 1:20. In an embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.1:1 to about 1:0.1. In another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.1:1, about 0.2:1, about 0.3:1, about 0.4:1, about 0.5:1, about 0.6:1, about 0.7:1, about 0.8:1, about 0.9:1, about 1:1, about 1:0.9, about 1:0.8, about 1:0.7, about 1:0.6, about 1:0.5, about 1:0.4, about 1:0.3, about 1:0.2, or about 1:0.1. In yet another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.6:1 to about 1:0.6. In still another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 1:1. 
     In an embodiment, the concentration of Δ9-tetrahydrocannabinol is insufficient to produce a psychotropic effect. In another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is from about 1:50 to about 1:20. In yet another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:50. In still another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:45. In an embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:40. In another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:35. In yet another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:30. In still another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:25. In an embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:20. 
     In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 2 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 1.5 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 1 mg/mL. In still another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.9 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.8 mg/mL. In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.7 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.6 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.5 mg/mL. In still another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.4 mg/mL. In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.3 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.2 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.1 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is about 0 mg/mL. 
     In an embodiment, the hemp extract comprises: 
     about 0.1-20 mg/mL of cannabidiol; 
     about 0.1-20 mg/mL of cannabidiolic acid; 
     about 0.01-0.5 mg/mL cannabigerolic acid; 
     about 0.01-0.5 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.01-0.5 mg/mL cannabichromene. 
     In another embodiment, the hemp extract comprises: 
     about 1-10 mg/mL of cannabidiol; 
     about 1-10 mg/mL of cannabidiolic acid; 
     about 0.05-0.2 mg/mL cannabigerolic acid; 
     about 0.1-0.3 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.1-0.4 mg/mL cannabichromene. 
     In yet another embodiment, the hemp extract comprises: 
     about 5 mg/mL of cannabidiol; 
     about 5 mg/mL of cannabidiolic acid; 
     about 0.11 mg/mL cannabigerolic acid; 
     about 0.25 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.27 mg/mL cannabichromene. 
     In an embodiment, provided herein is a pharmaceutical composition comprising hemp extract and a carrier, wherein the hemp extract comprises: 
     α-pinene; 
     β-myrcene; 
     β-pinene; 
     δ-limonene; 
     linalool; 
     β-caryophyllene; 
     α-humulene; 
     nerolidol 2; 
     guaiol; 
     caryophyllene oxide; and 
     α-bisabolol. 
     In another embodiment, the hemp extract comprises: 
     about 0.09-0.13% α-pinene; 
     about 0.23-0.44% β-myrcene; 
     about 0.04-0.09% β-pinene; 
     about 0.05-0.09% δ-limonene; 
     about 0.03-0.06% linalool; 
     about 0.04-0.07% β-caryophyllene; 
     about 0.02-0.04% α-humulene; 
     about 0.04-0.07% nerolidol 2; 
     about 0.02-0.04% guaiol; 
     about 0.04-0.08% caryophyllene oxide; and 
     about 0.01-0.04% α-bisabolol. 
     In another embodiment, the hemp extract comprises: 
     about 0.07-0.30% α-pinene; 
     about 0.10-0.60% β-myrcene; 
     about 0.02-0.20% β-pinene; 
     about 0.03-0.20% δ-limonene; 
     about 0.01-0.08% linalool; 
     about 0.03-0.09% β-caryophyllene; 
     about 0.01-0.06% α-humulene; 
     about 0.02-0.09% nerolidol 2; and 
     about 0.01-0.06% guaiol; 
     In another embodiment, the hemp extract comprises: 
     about 0.01-0.50% α-pinene; 
     about 0.01-0.90% β-myrcene; 
     about 0.01-0.50% β-pinene; 
     about 0.01-0.50% δ-limonene; 
     about 0.01-0.50% linalool; 
     about 0.01-0.50% β-caryophyllene; 
     about 0.01-0.50% α-humulene; 
     about 0.01-0.50% nerolidol 2; 
     about 0.01-0.50% guaiol; 
     about 0.01-0.50% caryophyllene oxide; and 
     about 0.01-0.50% α-bisabolol. 
     In another embodiment, the hemp extract further comprises: 
     camphene; 
     β-ocimene; 
     eucalyptol; 
     isopulegol; and/or 
     nerolidol 1. 
     In another embodiment, the hemp extract comprises: 
     about 0.02% camphene; 
     about 0.02-0.03% β-ocimene; 
     about 0.02-0.05% eucalyptol; 
     about 0.02% isopulegol; and/or 
     about 0.02-0.04% nerolidol 1. 
     In another embodiment, the hemp extract comprises: 
     about 0.01-0.04% camphene; 
     about 0.01-0.05% β-ocimene; 
     about 0.01-0.07% eucalyptol; 
     about 0.01-0.04% isopulegol; and/or 
     about 0.01-0.05% nerolidol 1. 
     In another embodiment, the hemp extract comprises: 
     about 0.01-0.50% camphene; 
     about 0.01-0.50% β-ocimene; 
     about 0.01-0.50% eucalyptol; 
     about 0.01-0.50% isopulegol; and/or 
     about 0.01-0.50% nerolidol 1. 
     In an embodiment, the hemp extract comprises 1 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 2 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 3 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 4 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 5 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 6 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 7 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 8 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 9 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 10 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 11 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 12 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 13 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 14 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 15 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the composition is formulated as an oil. In another embodiment, the carrier is selected from the group consisting of linseed oil, olive oil, fish oil, salmon oil, coconut oil, catnip oil and grapeseed oil. In yet another embodiment, the carrier is grapeseed oil. 
     In an embodiment, the dosage form comprises nepetalactone. 
     In an embodiment, the dosage form comprises taurine. 
     In an embodiment, the pharmaceutical composition is formulated as a sublingual spray. In still another embodiment, the pharmaceutical composition is formulated as a water or alcohol soluble solution, a gel, or a cream for transdermal application. In an embodiment, the dosage form is formulated as a gel for buccal or mucosal administration. In an embodiment, the pharmaceutical composition is formulated as a powder. In another embodiment, the pharmaceutical composition is formulated as a solution for subcutaneous injection. In yet another embodiment, the pharmaceutical composition is formulated as a tablet. In still another embodiment, the pharmaceutical composition is formulated as a capsule. In an embodiment, the pharmaceutical composition is formulated as a hard chewable. 
     In an embodiment, the composition is formulated as a chew for oral administration. In another embodiment, the chew is produced using cold extrusion. In another embodiment, the weight of the chew is about 0.5-10 g. In yet another embodiment, the weight of the chew is about 4 g, about 6 g, about 9 g, or about 10 g. In still another embodiment, the weight of the chew is about 0.5 g. In an embodiment, the weight of the chew is about 1 g. In another embodiment, the weight of the chew is about 1.5 g. In yet another embodiment, the weight of the chew is about 2 g. In still another embodiment, the weight of the chew is about 3 g. In an embodiment, the weight of the chew is about 4 g. In another embodiment, the weight of the chew is about 5 g. In yet another embodiment, the weight of the chew is about 6 g. In still another embodiment, the weight of the chew is about 7 g. In an embodiment, the weight of the chew is about 8 g. In another embodiment, the weight of the chew is about 9 g. In yet another embodiment, the weight of the chew is about 10 g. 
     In an embodiment, the 4 g chew comprises: 
     about 7 mg of cannabidiol; 
     about 6 mg of cannabidiolic acid; 
     about 0.12 mg cannabigerolic acid; 
     about 0.32 mg Δ9-tetrahydrocannabinol; and 
     about 0.36 mg cannabichromene. 
     The pharmaceutical compositions of the present disclosure may be manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, granulating, grinding, pulverizing, dragee-making, levigating, emulsifying, encapsulating, entrapping or by lyophilizing processes. 
     The compositions for use in accordance with the present disclosure thus may be formulated in conventional manner using one or more pharmaceutically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. 
     Dosage Forms 
     In an aspect, provided herein is a dosage form comprising: 
     cannabidiol; 
     cannabidiolic acid; 
     cannabigerolic acid; 
     Δ9-tetrahydrocannabinol; 
     cannabichromene; and 
     one or more pharmaceutically acceptable additives, flavoring agents, surfactants, and adjuvants. 
     In an embodiment, the ratio of cannabidiol to cannabidiolic acid is selected from the group consisting of about 1:100, about 1:50, about 1:10, and about 1:1. In an embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.1:1 to about 1:0.1. In another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.1:1, about 0.2:1, about 0.3:1, about 0.4:1, about 0.5:1, about 0.6:1, about 0.7:1, about 0.8:1, about 0.9:1, about 1:1, about 1:0.9, about 1:0.8, about 1:0.7, about 1:0.6, about 1:0.5, about 1:0.4, about 1:0.3, about 1:0.2, or about 1:0.1. In yet another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.6:1 to about 1:0.6. In still another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 1:1. 
     In an embodiment, the concentration of Δ9-tetrahydrocannabinol is insufficient to produce a psychotropic effect. In another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is from about 1:50 to about 1:20. In yet another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:50. In still another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:45. In an embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:40. In another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:35. In yet another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:30. In still another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:25. In an embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:20. 
     In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 2 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 1.5 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 1 mg/mL. In still another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.9 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.8 mg/mL. In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.7 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.6 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.5 mg/mL. In still another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.4 mg/mL. In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.3 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.2 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.1 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is about 0 mg/mL. 
     In an embodiment, the dosage form comprises: 
     about 0.1-20 mg/mL of cannabidiol; 
     about 0.1-20 mg/mL of cannabidiolic acid; 
     about 0.01-0.5 mg/mL cannabigerolic acid; 
     about 0.01-0.5 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.01-0.5 mg/mL cannabichromene. 
     In another embodiment, the dosage form comprises: 
     about 1-10 mg/mL of cannabidiol; 
     about 1-10 mg/mL of cannabidiolic acid; 
     about 0.05-0.2 mg/mL cannabigerolic acid; 
     about 0.1-0.3 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.1-0.4 mg/mL cannabichromene. 
     In yet another embodiment, the dosage form comprises: 
     about 5 mg/mL of cannabidiol; 
     about 5 mg/mL of cannabidiolic acid; 
     about 0.11 mg/mL cannabigerolic acid; 
     about 0.25 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.27 mg/mL cannabichromene. 
     In some embodiments, the dosage form comprises: 
     α-pinene; 
     β-myrcene; 
     β-pinene; 
     δ-limonene; 
     linalool; 
     β-caryophyllene; 
     α-humulene; 
     nerolidol 2; 
     guaiol; 
     caryophyllene oxide; and 
     α-bisabolol. 
     In another embodiment, the dosage form comprises: 
     about 0.09-0.13% α-pinene; 
     about 0.23-0.44% β-myrcene; 
     about 0.04-0.09% β-pinene; 
     about 0.05-0.09% δ-limonene; 
     about 0.03-0.06% linalool; 
     about 0.04-0.07% β-caryophyllene; 
     about 0.02-0.04% α-humulene; 
     about 0.04-0.07% nerolidol 2; 
     about 0.02-0.04% guaiol; 
     about 0.04-0.08% caryophyllene oxide; and 
     about 0.01-0.04% α-bisabolol. 
     In another embodiment, the dosage form comprises: 
     about 0.07-0.30% α-pinene; 
     about 0.10-0.60% β-myrcene; 
     about 0.02-0.20% β-pinene; 
     about 0.03-0.20% δ-limonene; 
     about 0.01-0.08% linalool; 
     about 0.03-0.09% β-caryophyllene; 
     about 0.01-0.06% α-humulene; 
     about 0.02-0.09% nerolidol 2; and 
     about 0.01-0.06% guaiol; 
     In another embodiment, the dosage form comprises: 
     about 0.01-0.50% α-pinene; 
     about 0.01-0.90% β-myrcene; 
     about 0.01-0.50% β-pinene; 
     about 0.01-0.50% δ-limonene; 
     about 0.01-0.50% linalool; 
     about 0.01-0.50% β-caryophyllene; 
     about 0.01-0.50% α-humulene; 
     about 0.01-0.50% nerolidol 2; 
     about 0.01-0.50% guaiol; 
     about 0.01-0.50% caryophyllene oxide; and 
     about 0.01-0.50% α-bisabolol. 
     In another embodiment, the dosage form further comprises: 
     camphene; 
     β-ocimene; 
     eucalyptol; 
     isopulegol; and/or 
     nerolidol 1. 
     In another embodiment, the dosage form comprises: 
     about 0.02% camphene; 
     about 0.02-0.03% β-ocimene; 
     about 0.02-0.05% eucalyptol; 
     about 0.02% isopulegol; and/or 
     about 0.02-0.04% nerolidol 1. 
     In another embodiment, the dosage form comprises: 
     about 0.01-0.04% camphene; 
     about 0.01-0.05% β-ocimene; 
     about 0.01-0.07% eucalyptol; 
     about 0.01-0.04% isopulegol; and/or 
     about 0.01-0.05% nerolidol 1. 
     In another embodiment, the dosage form comprises: 
     about 0.01-0.50% camphene; 
     about 0.01-0.50% β-ocimene; 
     about 0.01-0.50% eucalyptol; 
     about 0.01-0.50% isopulegol; and/or 
     about 0.01-0.50% nerolidol 1. 
     In an embodiment, the hemp extract comprises 1 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 2 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 3 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the hemp extract comprises 4 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 5 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 6 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 7 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 8 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 9 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 10 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 11 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 12 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, a-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 13 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 14 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises 15 or more of the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1. 
     In an embodiment, the dosage form comprises the following: α-pinene, β-myrcene, β-pinene, δ-limonene, linalool, β-caryophyllene, α-humulene, nerolidol 2, guaiol, caryophyllene oxide, α-bisabolol, camphene, β-ocimene, eucalyptol, isopulegol, and nerolidol 1 
     In an embodiment, the flavoring agent is selected from the group consisting of catnip oil, peppermint oil, mango extract, beef, poultry, and seafood. 
     In an embodiment, the dosage form is formulated as a sublingual spray. In still another embodiment, the dosage form is formulated as a water or alcohol soluble solution, a gel, or a cream for transdermal application. In an embodiment, the dosage form is formulated as a powder. In an embodiment, the dosage form is formulated as a gel for buccal or mucosal administration. In another embodiment, the dosage form is formulated as a solution for subcutaneous injection. In yet another embodiment, the dosage form is formulated as a tablet. In still another embodiment, the dosage form is formulated as a capsule. In an embodiment, the dosage form is formulated as a hard chewable. 
     In some embodiments, the invention includes infusing edible products with hemp extract. In another embodiment, the edible product is an extruded food product, baked food product, nut butter, spread, pelleted feed, or processed food. In another embodiment, the edible product is a pet food. In another embodiment the pet food is in a dry, shelf-stable form such as dried meals, dried fish, dried dairy products, fish meal, fish flour, cereals, flours, carbohydrates, dried fruits, etc. In another embodiment, the pet food is moist or semi-moist. In another embodiment, the pet food contains food additives or supplements such as vitamins, minerals, medicinals, etc., for example chemicals, enzymes, etc., capable of removing plaque or tartar from the animal&#39;s teeth, etc. 
     In an embodiment, the hemp extract is administered with catnip oil. In another embodiment, any of the dosage forms described can also include catnip. 
     In another embodiment, hemp extracts are administered using a nebulizer. In another embodiment, the nebulizer delivery device and system is capable of effectively and efficiently administering one or more nebulized drug to an animal. In another embodiment, the nebulizer system can easily be used on animals without removing them from their natural environment. In another embodiment, the nebulizer delivery device and system enables animals to be easily treated daily or multiple times a day without undue stress or the need for extensive resources. In another embodiment, the nebulizer delivery device and system can be used on animals having varying levels of training. 
     In one embodiment, hemp extract is administered using a diffuser. The diffuser can be any device which disperses hemp extract into the air. Hemp extract may be dispersed by any method, including by natural convection, by forced convection, by heating a wick or pad, for example, holding the hemp extract, by using pumps, or with fans. 
     In one embodiment, hemp extract is administered by a pet collar. The pet collar may comprise a belt with a buckle on one side, a free end on the other side and an attachment means, such as apertures disposed longitudinally within the central portion of the belt, or a quick release clasp mechanism, for securing the collar in a closed loop configuration. The pet collar may be made from a variety of materials including nylon, polyester leather or other suitable material. The belt material may be treated with a water-proofing compound. The nylon or polyester belt may be interwoven with reflective fibers to enhance the visibility of the pet collar during nighttime hours. In one embodiment, the collar is infused with hemp extract. 
     Chews 
     In an embodiment, the dosage form is formulated as a chew for oral administration. In another embodiment, the chew is produced using cold extrusion. In another embodiment, the weight of the chew is about 0.5-10 g. In yet another embodiment, the weight of the chew is about 4 g, about 6 g, about 9 g, or about 10 g. In still another embodiment, the weight of the chew is about 0.5 g. In an embodiment, the weight of the chew is about 1 g. In another embodiment, the weight of the chew is about 1.5 g. In yet another embodiment, the weight of the chew is about 2 g. In still another embodiment, the weight of the chew is about 3 g. In an embodiment, the weight of the chew is about 4 g. In another embodiment, the weight of the chew is about 5 g. In yet another embodiment, the weight of the chew is about 6 g. In still another embodiment, the weight of the chew is about 7 g. In an embodiment, the weight of the chew is about 8 g. In another embodiment, the weight of the chew is about 9 g. In yet another embodiment, the weight of the chew is about 10 g. 
     In one embodiment, the dosage form comprises: 
     glucosamine HCl; 
     chondroitin sulfate (76%); 
     brewer&#39;s yeast; 
     arabic gum; 
     guar gum; 
     a flavoring agent; 
     Verdilox; 
     Previon; 
     hemp extract; 
     glycerin; 
     sunflower lecithin; and 
     water. 
     In another embodiment, the dosage form comprises: 
     about 10-20% glucosamine HCl; 
     about 0.1-7% chondroitin sulfate (76%); 
     about 25-35% brewer&#39;s yeast; 
     about 1-10% arabic gum; 
     about 0.1-4% guar gum; 
     about 10-20% of a flavoring agent; 
     about 0.01-1% Verdilox; 
     about 0.1-2% Previon; 
     about 1-10% hemp extract; 
     about 10-20% glycerin; 
     about 1-10% sunflower lecithin; and 
     about 1-10% water. 
     In another embodiment, the dosage form comprises: 
     about 12-17% glucosamine HCl; 
     about 1-4% chondroitin sulfate (76%); 
     about 29-33% brewer&#39;s yeast; 
     about 3-6% arabic gum; 
     about 0.5-2% guar gum; 
     about 12-16% of a flavoring agent; 
     about 0.01-0.1% Verdilox; 
     about 0.5-1.5% Previon; 
     about 3-6% hemp extract; 
     about 13-17% glycerin; 
     about 3-7% sunflower lecithin; and 
     about 3-7% water. 
     In yet another embodiment, the dosage form comprises: 
     about 15.6% glucosamine HCl; 
     about 2.6% chondroitin sulfate (76%); 
     about 30% brewer&#39;s yeast; 
     about 4.7% arabic gum; 
     about 0.9% guar gum; 
     about 14.2% of a flavoring agent; 
     about 0.05% Verdilox; 
     about 0.9% Previon; 
     about 4.7% hemp extract; 
     about 15.1% glycerin; 
     about 5.7% sunflower lecithin; and 
     about 5.7% water. 
     In another embodiment, the dosage form comprises: 
     glucosamine HCl; 
     hyaluronic acid; 
     brewer&#39;s yeast; 
     arabic gum; 
     guar gum; 
     a flavoring agent; 
     Verdilox; 
     Previon; 
     hemp extract; 
     glycerin; 
     sunflower lecithin; and 
     water. 
     In another embodiment, the dosage form comprises: 
     about 10-20% glucosamine HCl; 
     about 0.01-3% hyaluronic acid; 
     about 25-35% brewer&#39;s yeast; 
     about 1-10% arabic gum; 
     about 0.1-5% guar gum; 
     about 10-20% of a flavoring agent; 
     about 0.01-1% Verdilox; 
     about 0.1-3% Previon; 
     about 1-10% hemp extract; 
     about 10-20% glycerin; 
     about 1-10% sunflower lecithin; and 
     about 1-10% water. 
     In another embodiment, the dosage form comprises: 
     about 12-17% glucosamine HCl; 
     about 0.01-1% hyaluronic acid; 
     about 29-33% brewer&#39;s yeast; 
     about 3-6% arabic gum; 
     about 0.5-2% guar gum; 
     about 12-16% of a flavoring agent; 
     about 0.01-0.1% Verdilox; 
     about 0.5-1.5% Previon; 
     about 3-6% hemp extract; 
     about 13-17% glycerin; 
     about 3-7% sunflower lecithin; and 
     about 3-7% water. 
     In yet another embodiment, the dosage form comprises: 
     about 16% glucosamine HCl; 
     about 0.1% hyaluronic acid; 
     about 30.6% brewer&#39;s yeast; 
     about 4.8% arabic gum; 
     about 0.97% guar gum; 
     about 14.5% of a flavoring agent; 
     about 0.05% Verdilox; 
     about 0.97% Previon; 
     about 4.8% hemp extract; 
     about 15.5% glycerin; 
     about 5.8% sunflower lecithin; and 
     about 5.8% water. 
     In yet another embodiment, the dosage form comprises: 
     hemp extract; 
     peanut butter; 
     rice bran; 
     glucosamine HCL; 
     sweet potato; 
     dry molasses; 
     sorbic acid 
     brewer&#39;s yeast; 
     sugar; 
     water; 
     glycerin; 
     potato starch; 
     dehydrated peanut butter; 
     rice starch; and 
     guar gum. 
     In yet another embodiment, the dosage form comprises: 
     about 5.0% hemp extract; 
     about 15.0% peanut butter; 
     about 12.5% rice bran; 
     about 12.75% glucosamine HCL; 
     about 5.5% sweet potato; 
     about 8.0% dry molasses; 
     about 1% sorbic acid; 
     about 5.0% brewer&#39;s yeast; 
     about 6.0% sugar; 
     about 9.25% water; 
     about 13.0 glycerin; 
     about 2.0% potato starch; 
     about 1.0% dehydrated peanut butter; 
     about 2.0% rice starch; and 
     about 2.0% guar gum. 
     In yet another embodiment, the dosage form comprises: 
     about 5.0% hemp extract; 
     about 15.0% peanut butter; 
     about 13.0% rice bran; 
     about 8.5% glucosamine HCL; 
     about 6.0% sweet potato; 
     about 9.0% dry molasses; 
     about 1% sorbic acid; 
     about 5.0% brewer&#39;s yeast; 
     about 6.0% sugar; 
     about 9.5% water; 
     about 13.0 glycerin; 
     about 4.0% potato starch; 
     about 1.0% dehydrated peanut butter; 
     about 2.0% rice starch; and 
     about 2.0% guar gum. 
     In yet another embodiment, the dosage form comprises: 
     about 3.0-10.0% hemp extract; 
     about 10.0-20.0% peanut butter; 
     about 10.0-15.0% rice bran; 
     about 5.0-15.0% glucosamine HCL; 
     about 4.0-10.0% sweet potato; 
     about 6.0-13.0% dry molasses; 
     about 0.5-5.0% sorbic acid; 
     about 2.0-8.0% brewer&#39;s yeast; 
     about 3.0-8.0% sugar; 
     about 5.0-15.0% water; 
     about 8.0-18.0% glycerin; 
     about 1.0-8.0% potato starch; 
     about 0.5-5.0% dehydrated peanut butter; 
     about 1.0-5.0% rice starch; and 
     about 1.0-5.0% guar gum. 
     In another embodiment, the dosage form comprises 2.0% hemp extract. In another embodiment, the dosage form comprises 3.0% hemp extract. In another embodiment, the dosage form comprises 4.0% hemp extract. In another embodiment, the dosage form comprises 5.0% hemp extract. In another embodiment, the dosage form comprises 6.0% hemp extract. In another embodiment, the dosage form comprises 7.0% hemp extract. In another embodiment, the dosage form comprises 8.0% hemp extract. In another embodiment, the dosage form comprises 9.0% hemp extract. In another embodiment, the dosage form comprises 10.0% hemp extract. 
     In an embodiment, the hemp extract comprises: 
     cannabidiol; 
     cannabidiolic acid; 
     cannabigerolic acid; 
     Δ9-tetrahydrocannabinol; and 
     cannabichromene. 
     In an embodiment, the ratio of cannabidiol to cannabidiolic acid is selected from the group consisting of about 1:100, about 1:50, about 1:10, and about 1:1. In an embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.1:1 to about 1:0.1. In another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.1:1, about 0.2:1, about 0.3:1, about 0.4:1, about 0.5:1, about 0.6:1, about 0.7:1, about 0.8:1, about 0.9:1, about 1:1, about 1:0.9, about 1:0.8, about 1:0.7, about 1:0.6, about 1:0.5, about 1:0.4, about 1:0.3, about 1:0.2, or about 1:0.1. In yet another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 0.6:1 to about 1:0.6. In still another embodiment, the ratio of cannabidiol to cannabidiolic acid is about 1:1. 
     In an embodiment, the concentration of Δ9-tetrahydrocannabinol is insufficient to produce a psychotropic effect. In another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is from about 1:50 to about 1:20. In yet another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:50. In still another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:45. In an embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:40. In another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:35. In yet another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:30. In still another embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:25. In an embodiment, the ratio of Δ9-tetrahydrocannabinol to the other cannabinoids is about 1:20. 
     In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 2 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 1.5 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 1 mg/mL. In still another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.9 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.8 mg/mL. In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.7 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.6 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.5 mg/mL. In still another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.4 mg/mL. In an embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.3 mg/mL. In another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.2 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is less than about 0.1 mg/mL. In yet another embodiment, the concentration of Δ9-tetrahydrocannabinol is about 0 mg/mL. 
     In an embodiment, the hemp extract comprises: 
     about 0.1-20 mg/mL of cannabidiol; 
     about 0.1-20 mg/mL of cannabidiolic acid; 
     about 0.01-0.5 mg/mL cannabigerolic acid; 
     about 0.01-0.5 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.01-0.5 mg/mL cannabichromene. 
     In another embodiment, the hemp extract comprises: 
     about 1-10 mg/mL of cannabidiol; 
     about 1-10 mg/mL of cannabidiolic acid; 
     about 0.05-0.2 mg/mL cannabigerolic acid; 
     about 0.1-0.3 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.1-0.4 mg/mL cannabichromene. 
     In yet another embodiment, the hemp extract comprises: 
     about 5 mg/mL of cannabidiol; 
     about 5 mg/mL of cannabidiolic acid; 
     about 0.11 mg/mL cannabigerolic acid; 
     about 0.25 mg/mL Δ9-tetrahydrocannabinol; and 
     about 0.27 mg/mL cannabichromene. 
     In an embodiment, the hemp extract comprises: 
     α-pinene; 
     β-myrcene; 
     β-pinene; 
     δ-limonene; 
     linalool; 
     β-caryophyllene; 
     α-humulene; 
     nerolidol 2; 
     guaiol; 
     caryophyllene oxide; and 
     α-bisabolol. 
     In another embodiment, the hemp extract comprises: 
     about 0.09-0.13% α-pinene; 
     about 0.23-0.44% β-myrcene; 
     about 0.04-0.09% β-pinene; 
     about 0.05-0.09% δ-limonene; 
     about 0.03-0.06% linalool; 
     about 0.04-0.07% β-caryophyllene; 
     about 0.02-0.04% α-humulene; 
     about 0.04-0.07% nerolidol 2; 
     about 0.02-0.04% guaiol; 
     about 0.04-0.08% caryophyllene oxide; and 
     about 0.01-0.04% α-bisabolol. 
     In another embodiment, the hemp extract comprises: 
     about 0.07-0.30% α-pinene; 
     about 0.10-0.60% β-myrcene; 
     about 0.02-0.20% β-pinene; 
     about 0.03-0.20% δ-limonene; 
     about 0.01-0.08% linalool; 
     about 0.03-0.09% β-caryophyllene; 
     about 0.01-0.06% α-humulene; 
     about 0.02-0.09% nerolidol 2; and 
     about 0.01-0.06% guaiol; 
     In another embodiment, the hemp extract comprises: 
     about 0.01-0.50% α-pinene; 
     about 0.01-0.90% β-myrcene; 
     about 0.01-0.50% β-pinene; 
     about 0.01-0.50% δ-limonene; 
     about 0.01-0.50% linalool; 
     about 0.01-0.50% β-caryophyllene; 
     about 0.01-0.50% α-humulene; 
     about 0.01-0.50% nerolidol 2; 
     about 0.01-0.50% guaiol; 
     about 0.01-0.50% caryophyllene oxide; and 
     about 0.01-0.50% α-bisabolol. 
     In another embodiment, the hemp extract further comprises: 
     camphene; 
     β-ocimene; 
     eucalyptol; 
     isopulegol; and/or 
     nerolidol 1. 
     In another embodiment, the hemp extract comprises: 
     about 0.02% camphene; 
     about 0.02-0.03% β-ocimene; 
     about 0.02-0.05% eucalyptol; 
     about 0.02% isopulegol; and/or 
     about 0.02-0.04% nerolidol 1. 
     In another embodiment, the hemp extract comprises: 
     about 0.01-0.04% camphene; 
     about 0.01-0.05% β-ocimene; 
     about 0.01-0.07% eucalyptol; 
     about 0.01-0.04% isopulegol; and/or 
     about 0.01-0.05% nerolidol 1. 
     In another embodiment, the hemp extract comprises: 
     about 0.01-0.50% camphene; 
     about 0.01-0.50% β-ocimene; 
     about 0.01-0.50% eucalyptol; 
     about 0.01-0.50% isopulegol; and/or 
     about 0.01-0.50% nerolidol 1. 
     In an embodiment, the composition is formulated as an oil. In another embodiment, the carrier is selected from the group consisting of linseed oil, olive oil, fish oil, salmon oil, coconut oil, catnip oil and grapeseed oil. In yet another embodiment, the carrier is grapeseed oil. 
     In an embodiment, the flavoring agent is selected from the group consisting of catnip oil, chicken liver powder, poultry extract, maltodextrin, butter, and bacon. In another embodiment, the flavoring agent is chicken liver powder. 
     In an embodiment, the composition is formulated as a chew for oral administration. In another embodiment, the chew is produced using cold extrusion. In another embodiment, the weight of the chew is about 0.5-10 g. In yet another embodiment, the weight of the chew is about 4 g, about 6 g, about 9 g, or about 10 g. In still another embodiment, the weight of the chew is about 0.5 g. In an embodiment, the weight of the chew is about 1 g. In another embodiment, the weight of the chew is about 1.5 g. In yet another embodiment, the weight of the chew is about 2 g. In still another embodiment, the weight of the chew is about 3 g. In an embodiment, the weight of the chew is about 4 g. In another embodiment, the weight of the chew is about 5 g. In yet another embodiment, the weight of the chew is about 6 g. In still another embodiment, the weight of the chew is about 7 g. In an embodiment, the weight of the chew is about 8 g. In another embodiment, the weight of the chew is about 9 g. In yet another embodiment, the weight of the chew is about 10 g. 
     In an embodiment, the 4 g chew comprises: 
     about 7 mg of cannabidiol; 
     about 6 mg of cannabidiolic acid; 
     about 0.12 mg cannabigerolic acid; 
     about 0.32 mg Δ9-tetrahydrocannabinol; and 
     about 0.36 mg cannabichromene. 
     Methods of Treatment 
     In an aspect, provided herein is a method for treating or reducing pain in a veterinary subject in need thereof, comprising administering to the subject a therapeutically effective amount of any of the compositions or dosage forms described above. 
     In an embodiment, the pain is associated with arthritis, post-operative pain, acute pain, dental pain, pain associated with gingivitis, or multi-joint pain. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.1-15.0 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.1-10.0 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.1 mg/kg. In still another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.2 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.3 mg/kg. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.4 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.5 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.6 mg/kg. In still another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.7 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.8 mg/kg. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 0.9 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1.5 mg/kg. In still another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2 mg/kg. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 3 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 4 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 5 mg/kg. In still another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 6 mg/kg. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 7 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 8 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 9 mg/kg. In still another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 10 mg/kg. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 11 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 12 mg/kg. In yet another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 13 mg/kg. In still another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 14 mg/kg. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 15 mg/kg. 
     In another embodiment, the pharmaceutical composition or dosage form is administered at twice the therapeutically effective dosage for one week, and then subsequently administered at a therapeutically effective dosage. In yet another embodiment, the therapeutically effective dosage is about 0.1-0.5 mg/kg. In still another embodiment, the therapeutically effective dosage is about 2 mg/kg. In an embodiment, the therapeutically effective dosage is about 8 mg/kg. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1 mg/kg for one week, and then subsequently administered at a dosage of about 0.1-0.5 mg/kg. In another embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 4 mg/kg for one week, and then subsequently administered at a dosage of about 2 mg/kg. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2 mg/kg every 12 hours for two weeks, then subsequently administered at a dosage of about 1 mg/kg every 12 hours for two weeks, and then subsequently administered at a dosage of about 2 mg/kg every 12 hours for four weeks. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 1.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 2.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 3.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 3.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 3.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 3.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 4.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 4.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 4.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 4.0 mg/kg four times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 5.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 5.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 5.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 5.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 6.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 6.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 6.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 6.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 7.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 7.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 7.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 7.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 8.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 8.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 8.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 8.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 9.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 9.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 9.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 9.0 mg/kg four times daily. 
     In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 10.0 mg/kg once daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 10.0 mg/kg twice daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 10.0 mg/kg three times daily. In an embodiment, the pharmaceutical composition or dosage form is administered at a dosage of about 10.0 mg/kg four times daily. 
     In an embodiment, the method results in a therapeutically effective median maximal serum concentration of cannabidiol. In another embodiment, the median maximal serum concentration of cannabidiol is about 90-310 ng/mL. In yet another embodiment, the median maximal serum concentration of cannabidiol is about 90 ng/mL. In still another embodiment, the median maximal serum concentration of cannabidiol is about 100 ng/mL. In still another embodiment, the median maximal serum concentration of cannabidiol is about 102 ng/mL. In an embodiment, the median maximal serum concentration of cannabidiol is about 200 ng/mL. In another embodiment, the median maximal serum concentration of cannabidiol is about 300 ng/mL. In yet another embodiment, the median maximal serum concentration of cannabidiol is about 400 ng/mL. In still another embodiment, the median maximal serum concentration of cannabidiol is about 500 ng/mL. In an embodiment, the median maximal serum concentration of cannabidiol is about 590 ng/mL. In another embodiment, the median maximal serum concentration of cannabidiol is about 600 ng/mL. 
     In an embodiment, the veterinary subject is canine, feline, bovine, porcine, or equine. In another embodiment, the veterinary subject is canine. In yet another embodiment, the veterinary subject is feline. 
     In an aspect, provided herein is a method for treating or reducing pain associated with arthritis, post-operative pain, acute pain, dental pain, pain associated with gingivitis, or multi-joint pain in a veterinary subject in need thereof, comprising administering to the subject a therapeutically effective amount of hemp extract. 
     In an embodiment, the hemp extract is administered ata dosage of about 0.1-15.0 mg/kg. In another embodiment, the hemp extract is administered at a dosage of about 0.1-10.0 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 0.1 mg/kg. In still another embodiment, the hemp extract is administered at a dosage of about 0.2 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 0.3 mg/kg. In an embodiment, the hemp extract is administered at a dosage of about 0.4 mg/kg. In another embodiment, the hemp extract is administered at a dosage of about 0.5 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 0.6 mg/kg. In still another embodiment, the hemp extract is administered at a dosage of about 0.7 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 0.8 mg/kg. In an embodiment, the hemp extract is administered at a dosage of about 0.9 mg/kg. In another embodiment, the hemp extract is administered at a dosage of about 1 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 1.5 mg/kg. In still another embodiment, the hemp extract is administered at a dosage of about 2 mg/kg. In an embodiment, the hemp extract is administered at a dosage of about 3 mg/kg. In another embodiment, the hemp extract is administered at a dosage of about 4 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 5 mg/kg. In still another embodiment, the hemp extract is administered at a dosage of about 6 mg/kg. In an embodiment, the hemp extract is administered at a dosage of about 7 mg/kg. In another embodiment, the hemp extract is administered at a dosage of about 8 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 9 mg/kg. In still another embodiment, the hemp extract is administered at a dosage of about 10 mg/kg. In an embodiment, the hemp extract is administered at a dosage of about 11 mg/kg. In another embodiment, the hemp extract is administered ata dosage of about 12 mg/kg. In yet another embodiment, the hemp extract is administered at a dosage of about 13 mg/kg. In still another embodiment, the hemp extract is administered at a dosage of about 14 mg/kg. In an embodiment, the hemp extract is administered at a dosage of about 15 mg/kg. 
     In another embodiment, the hemp extract is administered at twice the therapeutically effective dosage for one week, and then subsequently administered at a therapeutically effective dosage. In yet another embodiment, the therapeutically effective dosage is about 0.1-0.5 mg/kg. In still another embodiment, the therapeutically effective dosage is about 2 mg/kg. In an embodiment, the therapeutically effective dosage is about 8 mg/kg. 
     In an embodiment, the hemp extract is administered at a dosage of about 1 mg/kg for one week, and then subsequently administered at a dosage of about 0.1-0.5 mg/kg. In another embodiment, the hemp extract is administered at a dosage of about 4 mg/kg for one week, and then subsequently administered at a dosage of about 2 mg/kg. 
     In an embodiment, the method results in a therapeutically effective median maximal serum concentration of cannabidiol. In another embodiment, the median maximal serum concentration of cannabidiol is about 90-310 ng/mL. In yet another embodiment, the median maximal serum concentration of cannabidiol is about 90 ng/mL. In still another embodiment, the median maximal serum concentration of cannabidiol is about 100 ng/mL. In still another embodiment, the median maximal serum concentration of cannabidiol is about 102 ng/mL. In an embodiment, the median maximal serum concentration of cannabidiol is about 200 ng/mL. In another embodiment, the median maximal serum concentration of cannabidiol is about 300 ng/mL. In yet another embodiment, the median maximal serum concentration of cannabidiol is about 400 ng/mL. In still another embodiment, the median maximal serum concentration of cannabidiol is about 500 ng/mL. In an embodiment, the median maximal serum concentration of cannabidiol is about 590 ng/mL. In another embodiment, the median maximal serum concentration of cannabidiol is about 600 ng/mL. 
     In an embodiment, the veterinary subject is canine, feline, bovine, porcine, or equine. In another embodiment, the veterinary subject is canine. In yet another embodiment, the veterinary subject is feline. 
     The pharmaceutical compositions and dosage forms of the present disclosure may be administered by any convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with any other therapeutic agent. Administration can be systemic or local. 
     The therapeutic compositions of the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into formulations to provide improved transfer, delivery, tolerance, and the like. A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington&#39;s Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa. These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as LIPOFECTIN™), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax. See also Powell et al. “Compendium of excipients for parenteral formulations” PDA (1998) J Pharm Sci Technol 52:238-311. 
     The dose may vary depending upon the age and the weight of a subject to be administered, target disease, conditions, route of administration, and the like. Various delivery systems are known and can be used to administer the pharmaceutical composition of the invention, e.g., encapsulation in liposomes, microparticles, microcapsules, receptor mediated endocytosis (see, e.g., Wu et al. (1987) J. Biol. Chem. 262:4429-4432). Methods of introduction include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, transdermal, buccal, sublingual, subcutaneous, intranasal, epidural, and oral routes. The composition may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically active agents. Administration can be systemic or local. 
     Pharmacological preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carbomethylcellulose, and/or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. 
     Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. 
     The injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, local injection, drip infusions, etc. These injectable preparations may be prepared by methods publicly known. For example, the injectable preparations may be prepared, e.g., by dissolving, suspending or emulsifying the pharmaceutical composition or dosage form in a sterile aqueous medium or an oily medium conventionally used for injections. As the aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a nonionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated castor oil)], etc. As the oily medium, there are employed, e.g., sesame oil, soybean oil, etc., which may be used in combination with a solubilizing agent such as benzyl benzoate, benzyl alcohol, etc. The injection thus prepared can be filled in an appropriate ampoule. 
     Pharmaceutical compositions, which can be used orally, include push-fit capsules made of gelatin as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules may contain the active ingredients in admixture with filler such as lactose, binders such as starches, lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active components may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. 
     Alternatively, the composition may be in a powder form for constitution before use with a suitable vehicle, e.g., sterile, pyrogen-free water. The exact formulation, route of administration and dosage may be chosen by the physician familiar with the patient&#39;s condition. (See for example Fingl, et al., 1975, in “The Pharmacological Basis of Therapeutics”, Chapter I, p. 1). Depending on the severity and responsiveness of the condition treated, dosing can also be a single administration of a slow release composition, with course of treatment lasting from several days to several weeks or until cure is effected or diminution of the disease state is achieved. 
     Advantageously, the pharmaceutical compositions for oral or parenteral use described above are prepared into dosage forms in a unit dose suited to fit a dose of the active ingredients. Such dosage forms in a unit dose include, for example, tablets, pills, capsules, injections (ampoules), suppositories, chews, pet food, etc. In certain embodiments, for the dosages provided above, they are administered in one serving of pet food, e.g. 1 mg/kg of hemp extract provided in one serving of pet food. 
     In accordance with the methods disclosed herein, pharmaceutical formulations can be administered to the patient using any acceptable device or mechanism. For example, the administration can be accomplished using a syringe and needle or with a reusable pen and/or autoinjector delivery device. The methods of the present invention include the use of numerous reusable pen and/or autoinjector delivery devices to administer a pharmaceutical formulation. 
     In an embodiment for non-human animal administration, the term “pharmaceutical” as used herein may be replaced by “veterinary.” 
     EXAMPLES 
     Example 1 
     CBD Oil and Protocols Approval 
     The industrial hemp strain used in this study was a proprietary hemp strain utilizing ethanol and heat extraction with the final desiccated product reconstituted into an olive oil base containing approximately 10 mg/ml of CBD as an equal mix of CBD and carboxylic acid of CBD (CBDa), 0.24 mg/ml tetrahydrocannabinol (THC), 0.27 mg/ml cannabichromene (CBC), and 0.11 mg/ml cannabigerol (CBG) which is dehydrated; all other cannabinoids were less than 0.01 mg/ml. Analysis of 5 different production runs using a commercial analytical laboratory (MCR Laboratories, Framingham, Mass.) show less than a 9% difference across batches for each of the detected cannabinoids listed above. The study was performed after the Cornell University institutional animal care and use committee (IACUC) approved the study which follows the guidelines for animal use according to the IACUC. Client owned dogs were enrolled after informed consent in accordance with the Declaration of Helsinki. 
     Example 2 
     Terpene Profiles 
     Terpene profiles were examined for four separate oil extractions, prepared as described above. All oils contained 0.09-0.13% α-pinene, 0.23-0.44% β-myrcene, 0.04-0.09% β-pinene, 0.05-0.09% δ-limonene, 0.03-0.06% linalool, 0.04-0.07% β-caryophyllene, 0.02-0.04% α-humulene, 0.04-0.07% nerolidol 2, 0.02-0.04% guaiol, 0.04-0.08% caryophyllene oxide, and 0.01-0.04% α-bisabolol. In addition, some of the oils tested contained 0.02% camphene, 0.02-0.03% β-ocimene, 0.02-0.05% eucalyptol, 0.02% isopulegol, and/or 0.02-0.04% nerolidol 1. Total terpenes ranged from 0.73-1.10%, 
     Example 3 
     Pharmacokinetics 
     An initial investigation into single-dose oral pharmacokinetics was performed with 4 beagles (3.5-7 years, male castrated, 10.7-11.9 kg). Each dog received a 2 mg/kg and an 8 mg/kg oral dosage of CBD oil, with a 2-week washout period between each experiment. The dogs were fed two hours after dosing. Physical examination was performed at 0, 4, 8 and 24 hours after dosing. Attitude, behavior, proprioception, and gait were subjectively evaluated at each time point during free running/walking and navigation around standard traffic cones (weaving). Five ml of blood was collected at time 0, 0.5, 1, 2, 4, 8, 12 and 24 hours after oil administration. Blood samples were obtained via jugular venipuncture and transferred to a coagulation tube for 20 minutes. Samples were centrifuged (VWR, Clinical Centrifuge) at 3,600×g for 10 minutes; serum was removed and stored at −80° C. until analysis using liquid chromatography-mass spectrometry (LC-MS) at Colorado State University Core Mass Spectrometry facility. 
     Example 4 
     Extraction of CBD from Canine Serum and Mass Spectrometry Analysis 
     CBD was extracted from canine serum using a combination of protein precipitation and liquid-liquid extraction using n-hexane, with minor modifications for microflow ultra-high pressure liquid chromatography (UHPLC). Briefly, 0.05 ml of canine serum was subjected to protein precipitation in the presence of ice-cold acetonitrile (80% final concentration), spiked with deuterated CBD as the internal standard (0.06 mg/ml, CDB-d 3  Cerilliant, Round Rock, Tex., USA). 0.2 ml of water was added to each sample prior to the addition of 1.0 ml of hexane to enhance liquid-liquid phase separation. Hexane extract was removed and concentrated to dryness under laboratory nitrogen. Prior to LC-MS analysis, samples were resuspended in 0.06 mL of 100% acetonitrile. A standard curve using the CBD analytical standard was prepared in canine serum non-exposed to CBD and extracted as above. Cannabidiol concentration in serum was quantified using a chromatographically coupled triple-quadropole mass spectrometer (UHPLC-QQQ-MS). 
     Example 5 
     CBD Serum Concentration Data Analysis 
     From the UHPLC-QQQ-MS data, peak areas were extracted for CBD detected in biological samples and normalized to the peak area of the internal standard CBD-d 3 , in each sample using Skyline as well as an in-house R Script (www.r-project.org). CBD concentrations were calculated to nanograms per mL of serum as determined by the line of regression of the standard curve (r2=0.9994, 0-1000 ng/mL). For this assay, the limits of detection (LOD) and limits of quantification (LOQ) represent the lower limits of detection and quantification for each compound in the matrix of this study. Pharmacokinetic variables were estimated by means of non-compartmental analysis, utilizing a pharmacokinetic software package (PK Solution, version 2.0, Montrose, Colo., USA). 
     Example 6 
     Inclusion and Exclusion Criteria for Clinical Trial 
     The study population consisted of client-owned dogs presenting to Cornell University Hospital for Animals for evaluation and treatment of a lameness due to OA. Dogs were considered for inclusion in the study if they had radiographic evidence of OA, signs of pain according to assessment by their owners, detectable lameness on visual gait assessment and painful joint(s) on palpation. Each dog had an initial complete blood count ([CBC] Bayer Advia 120, Siemens Corp., New York, N.Y., USA) and serum chemistry analysis (Hitachi 911, Roche Diagnostics, Indianapolis, Ind., USA) performed to rule out any underlying disease that might preclude enrolment. Elevations in alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were allowed if prior hepatic ultrasound was deemed within normal limits except for potential non-progressive nodules (possible hepatic nodular hyperplasia). 
     All owners completed a brief questionnaire to define the affected limb(s), duration of lameness, and duration of analgesic or other medications taken. 
     All dogs underwent radiographic examination of affected joints and a radiologist confirmed the presence or absence of OA, and excluded the presence of concomitant disease that might preclude them from enrolment (i.e. lytic lesions). 
     During the trial, dogs were only allowed to receive NSAIDs, fish oil, and/or glucosamine/chondroitin sulphate without any change in these medications for 4 weeks prior to or during the 10-week study period as standard of care for the disease process. Other analgesic medications used, such as gabapentin and tramadol, were discontinued at least 2 weeks prior to enrollment. Dogs were excluded if they had evidence of renal, uncontrolled endocrine, neurologic, or neoplastic disease, or if they had a temperament not suited for gaiting on a lead or were undergoing physical therapy. Every dog was fed its regular diet with no change allowed during the trial. 
     Example 7 
     Clinical Trial 
     The study was a placebo-controlled, double-blind, cross-over clinical trial. Dogs received each of two treatments in random order (Randomizer iPhone Application): CBD, 2 mg/kg every 12 hours, or placebo (an equivalent volume of olive oil with 10 parts per thousands of anise oil and 5 parts per thousands of peppermint oil to provide a similar herbal smell) every 12 hours. Each treatment was administered for 4 weeks with a 2-week washout period in between treatments. Blood was collected to repeat complete blood counts and chemistry analysis at weeks 2 and 4 for each treatment. 
     At each visit, each dog was evaluated by a veterinarian based on a scoring system, as well as by its owner (canine brief pain inventory [CBPI], Hudson activity scale) before treatment initiation and at weeks 2 and 4 thereafter. 
     Example 8 
     Statistical Analysis 
     Initial power analysis was performed to assess number of dogs needed for this study as a cross over design with a power set 0.80 and alpha of 0.05 using prior data suggesting a baseline CBPI or Hudson score change of approximately 15 points (two tailed) with a standard deviation of 20. When calculated it was assumed that 14 dogs would be necessary to find significance. 
     Statistical analysis was performed with a commercially available software package (JMP 12.0, Cary, N.C., USA). All data was assessed utilizing a Shapiro-Wilks test for normality. Considering a majority of our blood, serum and scoring data was normally distributed a mixed model analysis of variance was used. Cross-over study variables included in the model were: fixed effects of treatment, time, sequence of oil, gender, age, NSAID usage, treatment x time; as well as random effects of observation period, period nested within dog, time point nested within period nested within dog. To control for difference and relative change in CBPI pain and activity interference assessments and Hudson scoring across dogs, the fixed effect of initial CPBI or Hudson Score was also included for these analyses. Dunnett&#39;s tests were performed post hoc on any significant effects of time x treatment to assess differences with week 0 of CBD oil or placebo oil as the baseline time point for comparison. A p value of less than 0.05 was determined to be significant for all analyses. 
     Example 9 
     Pharmacokinetic Results 
     Pharmacokinetics demonstrated that CBD half-life of elimination median was 4.2 hours (3.8-6.8 hours) with the 2 mg/kg dose, and 4.2 hours (3.8-4.8 hours) with the 8 mg/kg dose (Table 1). Median maximal concentration of CBD oil ( FIG. 2 ) was 102.3 mg/ml (60.7-132.0 ng/mL; 180 nM) and 590.8 ng/mL (389.5-904.5 ng/mL; 1.2 uM) and was reached after 1.5 hours and 2 hours, respectively, for 2 and 8 mg/kg doses. No obvious psychoactive properties were observed on evaluation at any time point during the 2 and 8 mg/kg doses over 24 hours. These results led to a practical dosing during the clinical trial of 2 mg/kg body weight every 12 hours. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Serum pharmacokinetic of 2 mg/kg and 8 mg/kg oral dosage of CBD oil 
               
               
                 medians and ranges after 2 mg/kg and 8 mg/kg single oral dosing 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                 T½ 
                   
                   
               
               
                   
                 Cmax 
                 Tmax 
                 clim 
                 AUC 0-t 
                 MRT 
               
               
                   
                 (ng/ml) 
                 (h) 
                 (h) 
                 (ng-hr/ml) 
                 (h) 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Dose 
                   
                   
                   
                   
                   
               
               
                 (2 mg/kg) 
               
               
                 Dog 1 
                 60.7 
                 1 
                 4.4 
                 183 
                 6 
               
               
                 Dog 2 
                 132 
                 1 
                 3.9 
                 351 
                 4.2 
               
               
                 Dog 3 
                 102.7 
                 2 
                 3.8 
                 382 
                 5.1 
               
               
                 Dog 4 
                 101.9 
                 2 
                 6.8 
                 437 
                 9.1 
               
               
                 Median 
                 102.3 
                 1.5 
                 4.2 
                 367.2 
                 5.6 
               
               
                 (Range) 
                 (60.7-132.0) 
                 (1.0-2.0) 
                 (3.8-6.8) 
                 (183.5-437.4) 
                 (4.2-9.1) 
               
               
                 Dose 
               
               
                 (8 mg/kg) 
               
               
                 Dog 1 
                 499 
                 2 
                 3.8 
                 2928 
                 5.7 
               
               
                 Dog 2 
                 389 
                 1 
                 4.8 
                 1753 
                 7 
               
               
                 Dog 3 
                 904 
                 2 
                 4.2 
                 3048 
                 5.1 
               
               
                 Dog 4 
                 682 
                 2 
                 4.1 
                 2389 
                 5.2 
               
               
                 Median 
                 590.8 
                 2.0 
                 4.2 
                 2658.6 
                 5.6 
               
               
                 (Range) 
                 (389.5-904.5) 
                 (1.0-2.0) 
                 (3.8-4.8) 
                 (17.53-3048.6) 
                 (5.1-7.0) 
               
               
                   
               
               
                 Legend: Cmax = maximum concentration; Tmax = time of maximum concentration; T1/2 el = half-life of elimination; AUC 0-t = area under the curve (time 0 to 24h); MRT = median residence time. 
               
            
           
         
       
     
     Example 10 
     Dogs Included in Clinical Trial 
     Twenty-two client-owned dogs with clinically and radiographically confirmed evidence of osteoarthritis were recruited. Sixteen of these dogs completed the trial and were included in the analyses; their breed, weight, age, sex, worse affected limb, radiographic findings, use of NSAIDs and sequence of treatments are summarized in Table 2. Dogs were removed due to osteosarcoma at the time of enrolment, gastric torsion (placebo), prior aggression issues (CBD oil), pyelonephritis/kidney insufficiency (CBD oil), recurrent pododermatitis (placebo oil), and diarrhea (placebo oil). 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Characteristics (breed, weight, age, sex, affected limbs, radiographic 
               
               
                 findings, concomitant utilization of NSAID and sequence of 
               
               
                 treatment) of the dogs included in this study. 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Radiographic 
                   
               
               
                   
                 Weight 
                 Age 
                   
                 Worse 
                 findings and OA 
                   
               
               
                 Breed 
                 (kg) 
                 (years) 
                 Sex 
                 limb 
                 localization 
                 NSAID 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Rottweiler 
                 
                   
                 
                 10 
                 FS 
                   
                 
                   
                 
                 
                   
                 
               
               
                 Mix 
                 
                   
                 
                 13 
                 MC 
                 RF 
                 
                   
                 
                 No 
               
               
                 Mix 
                 27.2 
                 9 
                 FS 
                 LF 
                 
                   
                 
                 No 
               
               
                 Mix 
                 30.5 
                 14 
                 MC 
                   
                 
                   
                 
                 No 
               
               
                 Mix 
                 23.5 
                 10 
                 FS 
                   
                 
                   
                 
                 
                   
                 
               
               
                 Mix 
                 25.1 
                 10 
                 FS 
                 LF 
                 
                   
                 
                 
                   
                 
               
               
                 English Bulldog 
                 25.2 
                 6 
                 MC 
                 LF 
                 
                   
                 
                 
                   
                 
               
               
                 German    
                 21.5 
                 14 
                 FS 
                 RH 
                 
                   
                 
                 
                   
                 
               
               
                 Labrador Retriever 
                 26.1 
                 
                   
                 
                 FS 
                   
                 
                   
                 
                 
                   
                 
               
               
                 Mix 
                 
                   
                 
                 13 
                 FS 
                 RF 
                 
                   
                 
                 
                   
                 
               
               
                 Mix 
                 22 
                 9 
                 FS 
                 RH 
                 
                   
                 
                 No 
               
               
                 
                   
                 
                 50 
                 3 
                 M 
                 RF 
                 
                   
                 
                 
                   
                 
               
               
                     Dog 
                   
                   
                   
                   
                 
                   
                 
                 No 
               
               
                 
                   
                 
                 26.1 
                 9 
                 FS 
                 RF 
                 
                   
                 
                 
                   
                 
               
               
                 Mix 
                 28.6 
                 13 
                 FS 
                   
                 
                   
                 
                 No 
               
               
                 Border Collie 
                 22 
                 14 
                 MC 
                   
                 
                   
                 
                 No 
               
               
                 Beagle 
                 17.6 
                 5 
                 MC 
                   
                 
                   
                 
                 No 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     Example 11 
     Clinical Trial Results 
     CBPI and Hudson scores ( FIG. 3A  and  FIG. 3B ) showed a significant decrease in pain and increase in activity (p&lt;0.01) at week 2 and 4 during CBD treatment when compared to baseline week 0, while placebo treatment showed no difference in CBPI and Hudson scoring from scores prior to initiation of treatments (Table 3). Lameness as assessed by veterinarians ( FIG. 4 ) showed an increase in lameness with age (p&lt;0.01), whereas NSAID use (p=0.03) results in significantly less lameness. Veterinary pain scores showed significantly less pain in dogs on NSAIDs (p&lt;0.01). CBD oil resulted in significantly less pain when compared to baseline on evaluation at both week 2 and week 4 (p&lt;0.03), while 24 placebo treatment showed no significant differences. No changes were observed in weight-bearing capacity when evaluated utilizing the veterinary lameness and pain scoring system (Table 3). 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Average and standard deviation for CBPI and Hudson; median and range for lameness, 
               
               
                 weight-bearing and pain scores at each time for treatment and placebo oils 
               
            
           
           
               
               
               
            
               
                   
                 Treatment A/CBD oil 
                 Treatment B placebo oil 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Week 0 
                 Week 2 
                 Week 4 
                 Week 0 
                 Week 2 
                 Week 4 
               
               
                   
               
               
                 CBPI Pain (0-40) 
                 21 ± 8  
                 14 ± 6*  
                 14 ± 8*  
                 17 ± 7  
                 19 ± 9  
                 19 ± 9  
               
               
                 CBPI Interference 
                 35 ± 15 
                 25 ± 15* 
                 26 ± 14* 
                 27 ± 15 
                 29 ± 15 
                 31 ± 16 
               
               
                 (0-60) 
                   
                   
                   
                   
                   
                   
               
               
                 Hudson (0-110) 
                 54 ± 13 
                 67 ± 15* 
                 67 ± 10* 
                 65 ± 14 
                 64 ± 16 
                 60 ± 19 
               
               
                 Veterinary lameness§ 
                 3 (1-4) 
                 3 (1-2) 
                 3 (1-4) 
                 3 (2-4) 
                  3(2-4) 
                 3 (1-4) 
               
               
                 Veterinary pain ∫ 
                 3 (3-4) 
                  3 (2-4)* 
                  3 (1-4)* 
                 3 (2-4) 
                 3 (2-4) 
                 3 (2-4) 
               
               
                 Veterinary 
                 2 (1-3) 
                 2 (1-3) 
                 2 (1-3) 
                 2 (1-3) 
                 2 (1-3) 
                 2 (1-3) 
               
               
                 weight-bearing    
               
               
                   
               
               
                 Legend: 
               
               
                 Asterisk (*) represents significant difference (p &lt; 0.05) from baseline week 0 of CBD treatment. 
               
               
                 §Lameness was scored as follows: 1 = no lameness observed/walks normally, 2 = slightly lame when walking, 3 = moderately lame when walking, 4 = severely lame when walking, 5 = reluctant to rise and will not walk more than 5 paces. 
               
               
                 ∫ Pain on palpation was scored as follows: 1 = none, 2 = mild signs, dog turns head in recognition, 3 = moderate signs, dog pulls limb away, 4 = severe signs, dog vocalizes or becomes aggressive, 5 = dog will not allow palpation. 
               
               
                     Weight-bearing was scored as follows: 1 = equal on all limbs standing and walking, 2 = normal standing, favors affected limb when walking, 3 = partial weight-bearing standing and walking, 4 = partial weight-bearing standing, non-weight-bearing walking, 5 = non-weight-bearing standing and walking. 
               
            
           
         
       
     
     Chemistry analysis and CBC were performed at each visit. No significant change in the measured CBC values was noted in either the CBD oil or placebo treated dogs (data not shown). Serum chemistry values were not different between placebo compared to CBD oil (Table 4), except for alkaline phosphatase (ALP) which significantly increased over time from baseline by week 4 of CBD oil treatment (p=0.005); with nine of the sixteen dogs showing increases over time ( FIG. 1 ). Glucose was increased in dogs receiving the placebo oil at each time point (p=0.04) and creatinine levels increased over time in both dogs receiving CBD oil and those receiving placebo oil (p&lt;0.01); though all values remained within reference ranges. Other notable significances in serum chemistry values were associated with primarily age or NSAID use. An increase in age was associated with significantly higher blood urea nitrogen (BUN; p&lt;0.001), calcium (p=0.014), phosphorus (p=0.001), alanine aminotransferase (ALT; p=0.028), ALP (p=0.012), gamma glutamyltransferase (GGT; p=0.018), globulin (p=0.021) and cholesterol (p=0.002) values. NSAID use was associated with significantly higher BUN (p=0.003), and creatinine (p=0.017), and significant decreases in total protein (p&lt;0.001) and serum globulin (p&lt;0.001). 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Mean ± SD values for serum chemistry data obtained 
               
               
                 at each time point for dogs receiving CBD and placebo oils 
               
            
           
           
               
               
               
            
               
                   
                 Treatment A/CBD oil 
                 Treatment B/placebo oil 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Reference 
                 Week 0 
                 Week 2 
                 Week 4 
                 Week 0 
                 Week 2 
                 Week 4 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Na 
                 145-153 
                 mEq/L 
                 149 ± 3  
                 149 ± 2  
                 149 ± 1  
                 149 ± 1  
                 149 ± 2  
                 149 ± 2  
               
               
                 K 
                 4.1-56 
                 mEq/L 
                 4.9 ± 0.3 
                 4.9 ± 0.5 
                 4.9 ± 0.3 
                 4.8 ± 0.4 
                 4.9 ± 0.4 
                 4.9 ± 0.3 
               
               
                 Cl 
                 105-116 
                 mEq/L 
                 110 ± 3  
                 109 ± 3  
                 100 ± 2  
                 110 ± 2  
                 110 ± 2  
                 110 ± 2  
               
               
                 BUN 
                 10-32 
                 mg/dL 
                 20 ± 9  
                 20 ± 7  
                 20 ± 6  
                 19 ± 6  
                 21 ± 7  
                 19 ± 6  
               
               
                 Creat 
                 0.6-1.4 
                 mg/dL 
                 1.0 ± 0.3 
                  1.1 ± 0.3* 
                  1.0 ± 0.3* 
                 0.9 ± 0.3 
                  1.0 ± 0.3* 
                  1.0 ± 0.3* 
               
               
                 Ca 
                 9.3-11.4 
                 mg/dL 
                 10.4 ± 0.5  
                 10.4 ± 0.4  
                 10.3 ± 0.4  
                 10.4 ± 0.6  
                 10.4 ± 0.4  
                 10.4 ± 0.4  
               
               
                 P 
                 2.9-5.2 
                 mg/dL 
                 3.8 ± 0.8 
                 3.9 ± 0.8 
                 3.9 ± 0.6 
                 4.0 ± 0.7 
                 3.9 ± 0.6 
                 4.0 ± 0.5 
               
               
                 Mg 
                 1.4-2.2 
                 mg/dL 
                 1.8 ± 0.2 
                 1.8 ± 0.2 
                 1.8 ± 0.2 
                 1.8 ± 0.1 
                 1.8 ± 0.1 
                 1.8 ± 0.1 
               
               
                 GLU 
                 63-118 
                 mg/dL 
                 92 ± 9  
                 89 ± 9  
                 92 ± 9  
                  97 ± 10* 
                 93 ± 8  
                  97 ± 10* 
               
               
                 ALT 
                 20-98 
                 U/L 
                 93 ± 86 
                 93 ± 88 
                 114 ± 119 
                 90 ± 98 
                 222 ± 606 
                 166 ± 284 
               
               
                 AST 
                 14-51 
                 U/L 
                 31 ± 8  
                 33 ± 13 
                 34 ± 16 
                 30 ± 8  
                 56 ± 99 
                 45 ± 34 
               
               
                 ALP 
                 17-111 
                 U/L 
                 160 ± 212 
                 238 ± 268 
                  323 ± 407* 
                 204 ± 287 
                 186 ± 287 
                 175 ± 248 
               
               
                 GGT 
                 0-6 
                 U/L 
                 4 ± 3 
                 3 ± 2 
                 3 ± 2 
                 3 ± 2 
                 4 ± 6 
                 5 ± 4 
               
               
                 TB 
                 0.0-0.2 
                 mg/dL 
                 0.1 ± 0.1 
                 0.0 ± 0.1 
                 0.1 ± 0.1 
                 0.0 ± 0.1 
                 0.0 ± 0.1 
                 0.0 ± 0.1 
               
               
                 TP 
                 5.3-7.0 
                 g/dL 
                 6.3 ± 0.4 
                 6.4 ± 0.5 
                 6.3 ± 0.4 
                 6.3 ± 0.1 
                 6.3 ± 0.4 
                 6.3 ± 0.4 
               
               
                 ALB 
                 3.1-4.2 
                 g/dL 
                 3.7 ± 0.2 
                 3.7 ± 0.2 
                 3.7 ± 0.2 
                 3..7 ± 0.2  
                 3.7 ± 0.2 
                 3.7 ± 0.2 
               
               
                 GLOB 
                 1.9-3.6 
                 g/dL 
                 2.6 ± 0.3 
                 2.6 ± 0.4 
                 2.6 ± 0.4 
                 2.6 ± 0.4 
                 2.6 ± 0.4 
                 2.6 ± 0.4 
               
               
                 CHOL 
                 138-332 
                 mg/dL 
                 291 ± 64  
                 301 ± 62  
                 302 ± 62  
                 295 ± 71  
                 300 ± 71  
                 308 ± 83  
               
               
                 CK 
                 48-260 
                 U/L 
                 148 ± 81  
                 147 ± 59  
                 134 ± 61  
                 139 ± 57  
                 158 ± 80  
                 168 ± 105 
               
               
                   
               
               
                 Legend: Asterisk (*) indicates significantly different (p &lt; 0.05) serum concentration from baseline week 0 CBD treatment. 
               
            
           
         
       
     
     Example 12 
     Canine Safety Study 
     A 12-week safety study was performed in canines to evaluate the safety of a soft chew containing CBD. 
     Animals and Study Design 
     Eight purebred beagle dogs, 11 months-5 years old, weighing 7.39-11.95 kg at study start were selected for the study, as shown in Table 5. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Animal information 
               
            
           
           
               
               
               
            
               
                 Dog ID 
                 Sex 
                 Date of Birth 
               
               
                   
               
            
           
           
               
               
               
            
               
                 13536 
                 F 
                 Dec. 24, 2013 
               
               
                 2753822 
                 F 
                 Jan. 4, 2015 
               
               
                 2808987 
                 F 
                 Mar. 8, 2015 
               
               
                 13644 
                 M 
                 Feb. 7, 2017 
               
               
                 2784123 
                 M 
                 Feb. 8, 2015 
               
               
                 2963028 
                 M 
                 Sep. 12, 2015 
               
               
                 13513 
                 F 
                 Jul. 31, 2013 
               
               
                 13490 
                 M 
                 Nov. 1, 2012 
               
               
                   
               
            
           
         
       
     
     Dogs were single housed in cages of a size in accordance with the Animal Welfare Act, with a 12-hour-light/12-hour-dark cycle and targeted conditions of 50° to 85° F. Cages and food bowls were cleaned daily and sanitized in accordance with the Animal Welfare Act. Fresh tap water, fit for human consumption, was available ad libitum by means of an automatic watering system. There were no known contaminants that were reasonably expected to be present in the dietary material that were known to be capable of interfering with the purpose or conduct of the study. 
     During the study, the control diet, Purina Dog Chow, was the sole source of food supplied to each animal once daily for approximately 1 hour. Dogs were fed according to ideal body condition and fasted for a minimum of 12 hours prior to blood collections. CBD was administered by a soft chew offered twice daily at the approximate dosage of 2 mg/kg. Dosing is shown in Table 6. 
     
       
         
           
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 Quantity of chews offered per week 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Dog ID 
                 Sex 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
               
               
                   
               
               
                 13536 
                 F 
                 2 small 
                 1 large, 1 small 
                 1 large, 1 small 
                 1 large, 1 small 
                 1 large, 1 small 
                 1 large, 1 small 
               
               
                 2753822 
                 F 
                 1 large 
                 1 large 
                 1 large 
                 1 large 
                 1 large 
                 1 large 
               
               
                 2808987 
                 F 
                 2 small 
                 2 small 
                 2 small 
                 2 small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 13644 
                 M 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 2784123 
                 M 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 2963028 
                 M 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 13513 
                 F 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 13490 
                 M 
                 2 small 
                 2 small 
                 2 small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Dog ID 
                 Sex 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
               
               
                   
               
               
                 13536 
                 F 
                 1 large, 1 small 
                 1 large, 1 small 
                 1 large, 1 small 
                 1 large, 1 small 
                 1 large, 1 small 
                 1 large, 1 small 
               
               
                 2753822 
                 F 
                 1 large 
                 1 large 
                 1 large 
                 1 large 
                 1 large 
                 1 large 
               
               
                 2808987 
                 F 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 13644 
                 M 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 2784123 
                 M 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 2963028 
                 M 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 13513 
                 F 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
               
               
                 13490 
                 M 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 1 large, ½ small 
                 2 small 
               
               
                   
               
            
           
         
       
     
     CBC and Serum Chemistry 
     Prior to study initiation, 5 milliliters of blood was collected for each dog and was used to determine eligibility for the study. During the study, 5 milliliters of blood was collected weekly (±2 days). Blood was collected via jugular venipuncture in sterile syringes. Samples were split into two tubes: a red-top serum separator tube and a lavender-top EDTA tube. Red-top tubes were spun in a refrigerated centrifuge for 15 minutes at 3000 RPM after being allowed to clot. Lavender-top tubes were placed on a rocker to allow the blood to adequately mix with the anticoagulant. Blood samples were packaged and sent by priority-overnight to Antech Diagnostics for analysis. 
     Pharmacokinetic (PK) Blood Collection 
     On the first day of dosing, blood was collected for a PK analysis from 6 of the 8 dogs. The most cooperative dogs were selected for the PK analysis. Approximately 6 milliliters of blood was collected via jugular venipuncture in sterile syringes at 0 min, 30 min, 60 min, 2 hrs, 4 hrs, 8 hrs, 12 hrs, and 24 hrs after treatment. Samples were placed into red top clotting tubes with no serum separator. Serum was harvested by centrifuging the tubes at 3000 RPM for 15 minutes. The harvested serum was placed in cyrovials and stored at −70° C. Each tube was labeled with the dog id, date of collection, and collection time point. 
     Samples were shipped overnight on dry ice to the Proteomics &amp; Metabolomics Facility at the Colorado State University. 
     Clinical Observations 
     A veterinarian performed a complete physical examination of all dogs prior to the initiation of the study and at study completion. Each dog was evaluated as to general health, body and hair coat condition. Qualified personnel performed clinical observations twice daily in accordance with Summit Ridge Farms&#39; Program of Veterinary Care and SOP VC-003 (Rounds Observations). All animals were evaluated twice daily with reference to SOP VC-016 (Recognizing Pain, Stress and/or Distress). Clinical laboratory diagnostic procedures were performed as needed. Veterinary care was given as appropriate to each individual animal in accordance with the Program of Veterinary Care. 
     Blood Analysis 
     Blood was analyzed for white blood cell count, red blood cell count, hemoglobin, hematocrit, MCV, MCHC, MCH, and platelet count along with a complete differential. In addition, a 22-test chemistry screen was performed consisting of Glucose, Urea Nitrogen, Creatinine, Total Protein, Albumin, Total Bilirubin, Alkaline Phosphatase, ALT, AST, CPK, Cholesterol, Calcium, Phosphorus, Sodium, Potassium, Chloride, A/G Ratio, BUN/Creatinine Ratio, Globulin, Triglycerides, GGTP and Magnesium. Measurements were taken prior to the start of the study and then weekly during the course of the study. 
     PK Analysis 
     Analysis of the blood level values and pharmacokinetics of the test article were performed. 
     Results 
     Body Weight 
     The mean average weight change for dogs during the 12 weeks of the study was −0.04 kg (−0.43%). Weight data is presented in Tables 7 and 8. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Weekly body weights (weeks 1-6) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Dog ID 
                 Sex 
                 Base 
                 1 
                 2 
                 3 
                 4 
                   
                 6 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 13536 
                 F 
                 11.95 
                 12.34 
                 11.95 
                 12.10 
                 12.05 
                 12.08 
                 12.04 
               
               
                 2753822 
                 F 
                 7.39 
                 7.24 
                 7.18 
                 7.16 
                 7.03 
                 6.99 
                 7.03 
               
               
                 2808987 
                 F 
                 10.40 
                 10.40 
                 10.36 
                 10.23 
                 10.16 
                 10.21 
                 10.20 
               
               
                 13644 
                 M 
                 8.92 
                 9.25 
                 9.56 
                 9.65 
                 9.63 
                 9.50 
                 9.64 
               
               
                 2784123 
                 M 
                 9.21 
                 8.93 
                 9.07 
                 9.27 
                 9.18 
                 9.13 
                 9.33 
               
               
                 2963028 
                 M 
                 9.28 
                 9.15 
                 9.13 
                 8.98 
                 9.07 
                 9.32 
                 9.28 
               
               
                 13513 
                 F 
                 9.67 
                 9.58 
                 9.52 
                 9.16 
                 9.10 
                 9.14 
                 8.78 
               
               
                 13490 
                 M 
                 10.58 
                 10.64 
                 10.45 
                 10.39 
                 10.27 
                 10.39 
                 10.28 
               
               
                   
                 Mean: 
                 9.68 
                 9.69 
                 9.65 
                 9.62 
                 9.56 
                 9.60 
                 9.57 
               
               
                   
                 SD: 
                 1.346 
                 1.488 
                 1.371 
                 1.410 
                 1.418 
                 1.438 
                 1.425 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Weekly body weights (weeks 7-12) 
               
            
           
           
               
               
               
            
               
                   
                 Week 
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Dog ID 
                 Sex 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
                 Chg. 
                 % Chg. 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 13536 
                 F 
                 12.09 
                 11.99 
                 12.04 
                 12.09 
                 12.10 
                 11.97 
                 0.02 
                 0.17 
               
               
                 2753822 
                 F 
                 7.17 
                 7.04 
                 7.23 
                 7.41 
                 7.28 
                 7.34 
                 −0.05 
                 −0.68 
               
               
                 2808987 
                 F 
                 10.32 
                 9.98 
                 9.90 
                 9.98 
                 9.95 
                 10.15 
                 −0.25 
                 −2.40 
               
               
                 13644 
                 M 
                 9.53 
                 9.49 
                 9.28 
                 9.42 
                 9.28 
                 9.12 
                 0.20 
                 2.24 
               
               
                 2784123 
                 M 
                 9.46 
                 9.58 
                 9.47 
                 9.67 
                 9.39 
                 9.18 
                 −0.03 
                 −0.33 
               
               
                 2963028 
                 M 
                 9.32 
                 9.26 
                 9.23 
                 9.51 
                 9.66 
                 9.55 
                 0.27 
                 2.91 
               
               
                 13513 
                 F 
                 9.09 
                 9.58 
                 9.15 
                 8.88 
                 8.81 
                 8.89 
                 −0.78 
                 −8.07 
               
               
                 13490 
                 M 
                 10.42 
                 11.06 
                 10.98 
                 10.90 
                 11.06 
                 10.87 
                 0.29 
                 2.74 
               
               
                   
                 Mean: 
                 9.68 
                 9.75 
                 9.66 
                 9.73 
                 9.69 
                 9.63 
                 −0.04 
                 −0.43 
               
               
                   
                 SD: 
                 1.395 
                 1.439 
                 1.414 
                 1.376 
                 1.444 
                 1.391 
                 0.350 
                 3.605 
               
               
                   
               
            
           
         
       
     
     Food Consumption 
     The mean daily food consumption per week for dogs during the study was 204 g. Food consumption data is presented in Tables 9 and 10. 
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Average daily food consumption per week (weeks 1-6) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Dog ID 
                 Sex 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 13536 
                 F 
                 250 
                 207 
                 200 
                 200 
                 200 
                 177 
               
               
                 2753822 
                 F 
                 144 
                 162 
                 176 
                 157 
                 154 
                 186 
               
               
                 2808987 
                 F 
                 203 
                 223 
                 212 
                 184 
                 209 
                 235 
               
               
                 13644 
                 M 
                 285 
                 300 
                 275 
                 350 
                 229 
                 225 
               
               
                 2784123 
                 M 
                 300 
                 300 
                 300 
                 300 
                 300 
                 300 
               
               
                 2963028 
                 M 
                 137 
                 150 
                 150 
                 192 
                 173 
                 160 
               
               
                 13513 
                 F 
                 149 
                 128 
                 146 
                 157 
                 145 
                 127 
               
               
                 13490 
                 M 
                 190 
                 246 
                 253 
                 143 
                 144 
                 166 
               
               
                   
                 Mean: 
                 207 
                 215 
                 214 
                 198 
                 194 
                 197 
               
               
                   
                 SD: 
                 64.5 
                 65.6 
                 57.4 
                 53.1 
                 52.9 
                 54.1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Average daily food consumption per week (weeks 7-12) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Dog ID 
                 Sex 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
                 Avg 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 13536 
                 F 
                 200 
                 200 
                 200 
                 200 
                 200 
                 182 
                 201 
               
               
                 2753822 
                 F 
                 208 
                 145 
                 160 
                 207 
                 202 
                 242 
                 179 
               
               
                 2808987 
                 F 
                 231 
                 197 
                 203 
                 222 
                 194 
                 217 
                 211 
               
               
                 13644 
                 M 
                 200 
                 200 
                 200 
                 200 
                 190 
                 190 
                 229 
               
               
                 2784123 
                 M 
                 300 
                 300 
                 275 
                 275 
                 165 
                 165 
                 273 
               
               
                 2963028 
                 M 
                 200 
                 190 
                 179 
                 199 
                 226 
                 185 
                 179 
               
               
                 13513 
                 F 
                 205 
                 280 
                 143 
                 104 
                 168 
                 191 
                 162 
               
               
                 13490 
                 M 
                 191 
                 266 
                 193 
                 214 
                 215 
                 210 
                 203 
               
               
                   
                 Mean: 
                 217 
                 222 
                 194 
                 203 
                 195 
                 198 
                 204 
               
               
                   
                 SD: 
                 35.5 
                 53.3 
                 39.1 
                 47.1 
                 20.9 
                 24.0 
                 34.9 
               
               
                   
               
            
           
         
       
     
     Test Article Consumption 
     Five of the eight dogs had 100% acceptance of the chews. Three dogs had to be dosed on occasion during the study: Dog ID #13644 (dosed 6.5% of the time), Dog ID #13513 (dosed 2.4% of the time) and Dog ID #2784123 (dosed 17.3% of the time). 
     Hematology and Serum Chemistry 
     Beginning in Week 1, there was a slight increase mean alkaline phosphatase (ALP) value for the group. This value remained stable until Week 7 when the group mean ALP value became increasingly elevated. The highest group mean value was observed during the final week of the study, but did not exceed the normal reference range, shown in Table 11. The cause of the group mean value elevations appeared to be due to three dogs (13536, 2753822 and 2808987). By the end of the study 13536 and 2753822 were above 100 U/L, but did not exceed the normal high of 131U/L. Thus, their levels remained within the normal reference range. The observed elevations in only a few animals in the group may indicate individual sensitivity to the product. All other blood parameters remained within normal limits and no apparent trends were noted. Hematology and serum chemistry results are presented in Tables 12-19. 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Hematology and serum chemistry normal reference ranges 
               
            
           
           
               
               
               
            
               
                   
                 Parameter 
                 Normal Reference Ranges 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Total Protein (g/dL): 
                 5.0-7.4 
                 g/dL 
               
               
                   
                 Albumin (g/dL): 
                 2.7-4.4 
                 g/dL 
               
               
                   
                 Globulin (g/dL): 
                 1.6-3.6 
                 g/dL 
               
               
                   
                 A/G Ratio: 
                 0.8-2.0 
                 Ratio 
               
               
                   
                 AST (U/L): 
                 15-66 
                 U/L 
               
               
                   
                 ALT (U/L): 
                 12-118 
                 U/L 
               
               
                   
                 Alkaline Phosphatase (U/L): 
                 5-131 
                 U/L 
               
               
                   
                 GGTP (U/L): 
                 1-12 
                 U/L 
               
               
                   
                 Total Bilirubin (mg/dL): 
                 0.1-0.3 
                 mg/dL 
               
               
                   
                 Urea Nitrogen (mg/dL): 
                 6-31 
                 mg/dL 
               
               
                   
                 Creatine (mg/dL): 
                 0.5-1.6 
                 mg/dL 
               
               
                   
                 BUN/Creatinine Ratio: 
                 4-27 
                 Ratio 
               
               
                   
                 Phosphorus (mg/dL): 
                 2.5-6.6 
                 mg/dL 
               
               
                   
                 Glucose (mg/dL): 
                 70-138 
                 mg/dL 
               
               
                   
                 Calcium (mg/dL): 
                 8.9-11.4 
                 mg/dL 
               
               
                   
                 Magnesium (mEq/L): 
                 1.5-2.5 
                 mEq/L 
               
               
                   
                 Sodium (mEq/L): 
                 139-154 
                 mEq/L 
               
               
                   
                 Potassium (mEq/L): 
                 3.6-5.5 
                 mEq/L 
               
               
                   
                 Chloride (mEq/L): 
                 102-120 
                 mEq/L 
               
               
                   
                 Cholesterol (mg/dL): 
                 92-324 
                 mg/dL 
               
               
                   
                 Triglycerides (mg/dL) 
                 29-291 
                 mg/dL 
               
               
                   
                 CPK (U/L) 
                 59-895 
                 U/L 
               
            
           
           
               
               
               
            
               
                   
                 WBC(10{circumflex over ( )}3/mm3): 
                         4.0-15.3 10{circumflex over ( )}3/mm3 
               
               
                   
                 RBC(10{circumflex over ( )}6/mm3): 
                       4.8-9.3 10{circumflex over ( )}6/mm3 
               
            
           
           
               
               
               
               
            
               
                   
                 Hemoglobin (g/dL): 
                 12.1-20.3 
                 g/dL 
               
            
           
           
               
               
               
            
               
                   
                 Hematocrit (%): 
                 36-60%     
               
            
           
           
               
               
               
               
            
               
                   
                 MCV (um{circumflex over ( )}3): 
                 58-79 
                 um{circumflex over ( )}3 
               
               
                   
                 MCH (uug): 
                 19-28 
                 uug 
               
               
                   
                 MCHC (g/dL): 
                 30-38 
                 g/dL 
               
            
           
           
               
               
               
            
               
                   
                 Platelets (10{circumflex over ( )}3/mm3): 
                       170-400 10{circumflex over ( )}3/mm3 
               
               
                   
                 Absolute Polys: 
                 2060-10600  
               
               
                   
                 Absolute Bands: 
                 0-300 
               
               
                   
                 Absolute Lymphs: 
                 690-4500  
               
               
                   
                 Absolute Monos: 
                 0-840 
               
               
                   
                 Absolute Eos: 
                  0-1200 
               
               
                   
                 Absolute Bases: 
                 0-150 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 0-5) - Part 1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 Total 
                 Urea 
                   
               
               
                   
                 Protein 
                 Albumin 
                   
                 A/G 
                 AST 
                 ALT 
                 Alkaline 
                 GGIP 
                 Bilirubin 
                 Nitrogen 
                 Creatinine 
               
               
                   
                 (g/dL) 
                 (g/dL) 
                 Globulin 
                 Ratio 
                 (U/L) 
                 (U/L) 
                 (U/L) 
                 (U/L) 
                 (mg/dL) 
                 (mg/dL) 
                 (mg/dL) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.1 
                 3.5 
                 2.6 
                 1.4 
                 27 
                 34 
                 39 
                 4 
                 0.1 
                 11 
                 0.5 
               
               
                 SD: 
                 0.30 
                 0.22 
                 0.33 
                 0.21 
                 6.9 
                 7.6 
                 16.1 
                 0.5 
                 0.04 
                 2.1 
                 0.07 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.2 
                 3.5 
                 2.7 
                 1.3 
                 26 
                 29 
                 46 
                 4 
                 0.1 
                 11 
                 0.5 
               
               
                 SD: 
                 0.34 
                 0.25 
                 0.43 
                 0.24 
                 5.7 
                 5.8 
                 26.7 
                 1.3 
                 0.00 
                 2.4 
                 0.09 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.0 
                 3.5 
                 2.5 
                 1.4 
                 26 
                 30 
                 49 
                 3 
                 0.1 
                 10 
                 0.5 
               
               
                 SD: 
                 0.49 
                 0.24 
                 0.48 
                 0.29 
                 5.9 
                 5.7 
                 23.8 
                 0.5 
                 0.00 
                 1.6 
                 0.06 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.2 
                 3.4 
                 2.7 
                 1.3 
                 25 
                 28 
                 48 
                 3 
                 0.1 
                 10 
                 0.5 
               
               
                 SD: 
                 0.43 
                 0.23 
                 0.40 
                 0.18 
                 6.0 
                 5.4 
                 19.6 
                 0.5 
                 0.00 
                 1.8 
                 0.06 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5.9 
                 3.5 
                 2.5 
                 1.5 
                 25 
                 27 
                 46 
                 3 
                 0.3 
                 10 
                 0.5 
               
               
                 SD: 
                 0.45 
                 0.23 
                 0.40 
                 0.24 
                 7.0 
                 5.9 
                 21.0 
                 0.9 
                 0.00 
                 1.6 
                 0.05 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 5 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.2 
                 3.5 
                 2.8 
                 1.3 
                 25 
                 29 
                 48 
                 4 
                 0.1 
                 10 
                 0.6 
               
               
                 SD: 
                 0.42 
                 0.24 
                 0.42 
                 0.21 
                 5.7 
                 6.3 
                 22.0 
                 0.6 
                 0.04 
                 1.9 
                 0.09 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 6-10) - Part 1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Total 
                   
                   
                   
                   
                   
                 Alkaline 
                   
                 Total 
                 Urea 
                   
               
               
                   
                 Protein 
                 Albumin 
                 Globulin 
                 A/G 
                 AST 
                 ALT 
                 Phosphatase 
                 GGTP 
                 Bilirubin 
                 Nitrogen 
                 Creatinine 
               
               
                   
                 (g/dL) 
                 (g/dL) 
                 (g/dL) 
                 Ratio 
                 (U/L) 
                 (U/L) 
                 (U/L) 
                 (U/L) 
                 (mg/dL) 
                 (mg/dL) 
                 (mg/dL) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.0 
                 3.4 
                 2.6 
                 1.4 
                 24 
                 29 
                 47 
                 4 
                 0.1 
                 10 
                 0.5 
               
               
                 SD: 
                 0.41 
                 0.24 
                 0.42 
                 0.25 
                 5.8 
                 6.4 
                 23.0 
                 0.4 
                 0.00 
                 1.5 
                 0.07 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 7 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.4 
                 3.6 
                 2.8 
                 1.3 
                 25 
                 32 
                 54 
                 4 
                 0.1 
                 10 
                 0.6 
               
               
                 SD: 
                 0.41 
                 0.32 
                 0.35 
                 0.21 
                 6.2 
                 8.3 
                 25.6 
                 0.7 
                 0.00 
                 1.5 
                 0.11 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.3 
                 3.5 
                 2.9 
                 1.2 
                 23 
                 35 
                 56 
                 4 
                 0.1 
                 11 
                 0.5 
               
               
                 SD: 
                 0.45 
                 0.28 
                 0.41 
                 0.18 
                 4.5 
                 28.2 
                 23.3 
                 0.5 
                 0.00 
                 2.8 
                 0.08 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 9 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.2 
                 3.6 
                 2.6 
                 1.4 
                 25 
                 31 
                 55 
                 5 
                 0.2 
                 11 
                 0.6 
               
               
                 SD: 
                 0.39 
                 0.20 
                 0.41 
                 0.22 
                 4.2 
                 8.8 
                 29.2 
                 0.8 
                 0.05 
                 1.8 
                 0.10 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.1 
                 3.5 
                 2.6 
                 1.4 
                 24 
                 29 
                 56 
                 4 
                 0.1 
                 11 
                 0.5 
               
               
                 SD: 
                 0.42 
                 0.22 
                 0.43 
                 0.26 
                 5.0 
                 7.0 
                 32.7 
                 0.6 
                 0.00 
                 1.7 
                 0.08 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.0 
                 3.4 
                 2.6 
                 1.4 
                 25 
                 28 
                 61 
                 4 
                 0.1 
                 11 
                 0.5 
               
               
                 SD: 
                 0.47 
                 0.23 
                 0.46 
                 0.26 
                 4.2 
                 7.3 
                 35.7 
                 1.1 
                 0.05 
                 1.1 
                 0.11 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 0-5) - Part 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 BUN/ 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Creatinine 
                 Phosphorus 
                 Glucose 
                 Calcium 
                 Magnesium 
                 Sodium 
                 Potassium 
                 Chloride 
                 Cholesterol 
                 Triglycerides 
               
               
                   
                 Ratio 
                 (mg/dL) 
                 (mg/dL) 
                 (mg/dL) 
                 (mEq/L) 
                 (mEq/L) 
                 (mEq/L) 
                 (mEq/L) 
                 (mg/dL) 
                 (mg/dL) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 21 
                 4.3 
                 97 
                 10.4 
                 1.6 
                 148 
                 4.3 
                 113 
                 182 
                 48 
               
               
                 SD: 
                 2.7 
                 0.62 
                 0.4 
                 0.33 
                 0.13 
                 1.2 
                 0.35 
                 0.9 
                 36.5 
                 11.1 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 21 
                 4.2 
                 95 
                 10.5 
                 1.6 
                 147 
                 4.4 
                 112 
                 188 
                 45 
               
               
                 SD: 
                 3.0 
                 0.89 
                 6.6 
                 0.31 
                 0.08 
                 0.6 
                 0.25 
                 1.6 
                 45.8 
                 10.8 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 20 
                 4.0 
                 93 
                 10.4 
                 1.5 
                 147 
                 4.5 
                 111 
                 191 
                 47 
               
               
                 SD: 
                 2.7 
                 0.78 
                 6.4 
                 0.28 
                 0.13 
                 1.6 
                 0.33 
                 1.6 
                 43.8 
                 12.8 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 20 
                 4.2 
                 102 
                 10.5 
                 1.6 
                 150 
                 4.0 
                 113 
                 200 
                 43 
               
               
                 SD: 
                 4.1 
                 0.79 
                 6.0 
                 0.39 
                 0.09 
                 1.8 
                 0.26 
                 2.2 
                 11.4 
                 9.1 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 20 
                 4.1 
                 92 
                 10.0 
                 1.6 
                 148 
                 4.4 
                 113 
                 203 
                 44 
               
               
                 SD: 
                 2.0 
                 0.64 
                 6.5 
                 0.32 
                 0.08 
                 1.1 
                 0.37 
                 1.5 
                 33.4 
                 10.7 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 5 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 18 
                 3.9 
                 96 
                 10.3 
                 1.5 
                 148 
                 4.4 
                 112 
                 206 
                 43 
               
               
                 SD: 
                 2.1 
                 0.54 
                 7.7 
                 0.25 
                 0.07 
                 1.4 
                 0.27 
                 1.6 
                 30.8 
                 12.2 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 6-10) - Part 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 BUN/ 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Creatinine 
                 Phosphorus 
                 Glucose 
                 Calcium 
                 Magnesium 
                 Sodium 
                 Potassium 
                 Chloride 
                 Cholesterol 
                 Triglycerides 
               
               
                   
                 Ratio 
                 (mg/dL) 
                 (mg/dL) 
                 (mg/dL) 
                 (mEq/L) 
                 (mEq/L) 
                 (mEq/L) 
                 (mEq/L) 
                 (mg/dL) 
                 (mg/dL) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 20 
                 3.9 
                 91 
                 10.0 
                 1.5 
                 147 
                 4.4 
                 112 
                 191 
                 44 
               
               
                 SD: 
                 1.8 
                 0.48 
                 6.3 
                 0.27 
                 0.09 
                 0.7 
                 0.10 
                 2.6 
                 31.5 
                 13.1 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 7 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 18 
                 4.1 
                 96 
                 10.0 
                 1.6 
                 149 
                 4.4 
                 112 
                 197 
                 48 
               
               
                 SD: 
                 2.9 
                 0.50 
                 8.0 
                 0.38 
                 0.12 
                 2.0 
                 0.27 
                 1.2 
                 31.3 
                 12.3 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 22 
                 4.2 
                 102 
                 10.2 
                 1.6 
                 146 
                 4.3 
                 111 
                 211 
                 43 
               
               
                 SD: 
                 6.9 
                 0.92 
                 7.9 
                 0.35 
                 0.10 
                 2.2 
                 0.21 
                 1.6 
                 33.7 
                 12.9 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 9 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 20 
                 3.8 
                 100 
                 10.3 
                 1.5 
                 149 
                 4.5 
                 114 
                 204 
                 44 
               
               
                 SD: 
                 3.5 
                 0.71 
                 8.5 
                 0.33 
                 0.12 
                 1.2 
                 0.29 
                 1.5 
                 34.1 
                 11.5 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 22 
                 4.3 
                 94 
                 10.3 
                 1.6 
                 149 
                 4.4 
                 113 
                 206 
                 46 
               
               
                 SD: 
                 2.8 
                 0.81 
                 9.2 
                 0.25 
                 0.11 
                 0.5 
                 0.26 
                 1.9 
                 41.3 
                 12.4 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 2.2 
                 4.0 
                 99 
                 10.1 
                 1.6 
                 148 
                 4.2 
                 113 
                 212 
                 46 
               
               
                 SD: 
                 3.9 
                 0.68 
                 6.4 
                 0.34 
                 0.12 
                 1.2 
                 0.14 
                 3.0 
                 49.2 
                 15.8 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 0-5) - Part 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 CPK 
                 WBC 
                 RBC 
                 Hemoglobin 
                 Hematocrit 
                 MCV 
                 MCH 
                 MCHC 
                 Platelets 
               
               
                   
                 (U/L) 
                 (10{circumflex over ( )}3/mm3) 
                 (10{circumflex over ( )}6/mm3) 
                 (g/dL) 
                 (%) 
                 (um{circumflex over ( )}3) 
                 (uug) 
                 (g/dl) 
                 (10{circumflex over ( )}3/mm3) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 130 
                 8.4 
                 7.5 
                 17.5 
                 54 
                 72 
                 23.5 
                 33 
                 318 
               
               
                 SD: 
                 45.2 
                 2.06 
                 0.72 
                 1.67 
                 4.1 
                 2.4 
                 0.80 
                 1.0 
                 50.7 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 95 
                 9.8 
                 7.1 
                 16.6 
                 52 
                 73 
                 23.3 
                 32 
                 312 
               
               
                 SD: 
                 12.6 
                 2.39 
                 0.37 
                 0.86 
                 2.5 
                 2.1 
                 0.58 
                 0.4 
                 54.6 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 96 
                 8.5 
                 7.5 
                 17.0 
                 54 
                 72 
                 22.8 
                 31 
                 318 
               
               
                 SD: 
                 23.5 
                 1.63 
                 0.37 
                 0.60 
                 2.1 
                 1.9 
                 0.59 
                 0.7 
                 59.8 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 81 
                 8.7 
                 7.4 
                 16.8 
                 53 
                 72 
                 22.7 
                 32 
                 306 
               
               
                 SD: 
                 20.5 
                 1.57 
                 0.43 
                 0.82 
                 2.9 
                 2.4 
                 0.72 
                 1.4 
                 43.3 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 142 
                 7.7 
                 7.3 
                 17.1 
                 53 
                 72 
                 23.4 
                 33 
                 311 
               
               
                 SD: 
                 122.3 
                 1.26 
                 0.57 
                 1.29 
                 3.0 
                 3.5 
                 0.43 
                 1.2 
                 43.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 5 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 109 
                 8.6 
                 7.3 
                 17.2 
                 54 
                 73 
                 23.5 
                 32 
                 314 
               
               
                 SD: 
                 29.5 
                 1.38 
                 0.51 
                 1.08 
                 3.2 
                 2.1 
                 0.63 
                 0.4 
                 27.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 6-10) - Part 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 CPK 
                 WBC 
                 RBC 
                 Hemoglobin 
                 Hematocrit 
                 MCV 
                 MCH 
                 MCHC 
                 Platelets 
               
               
                   
                 (U/L) 
                 (10{circumflex over ( )}3/mm3) 
                 (10{circumflex over ( )}6/mm3) 
                 (g/dL) 
                 (%) 
                 (um{circumflex over ( )}3) 
                 (uug) 
                 (g/dl) 
                 (10{circumflex over ( )}3/mm3) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 89 
                 8.9 
                 7.4 
                 17.2 
                 50 
                 68 
                 23.4 
                 34 
                 348 
               
               
                 SD: 
                 30.6 
                 2.23 
                 0.44 
                 1.04 
                 2.6 
                 1.9 
                 0.63 
                 0.5 
                 40.3 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 7 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 110 
                 7.4 
                 7.9 
                 17.9 
                 58 
                 74 
                 22.8 
                 31 
                 313 
               
               
                 SD: 
                 44.8 
                 1.27 
                 0.50 
                 1.21 
                 3.4 
                 1.8 
                 0.70 
                 0.6 
                 47.3 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 83 
                 7.3 
                 7.9 
                 17.9 
                 57 
                 73 
                 22.7 
                 32 
                 304 
               
               
                 SD: 
                 14.4 
                 2.56 
                 0.36 
                 0.56 
                 2.2 
                 1.7 
                 0.76 
                 0.5 
                 30.6 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 9 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 83 
                 8.4 
                 7.8 
                 18.1 
                 54 
                 70 
                 23.2 
                 33 
                 321 
               
               
                 SD: 
                 16.6 
                 2.52 
                 0.36 
                 0.84 
                 3.0 
                 2.8 
                 1.00 
                 2.1 
                 20.9 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 102 
                 7.8 
                 7.6 
                 17.9 
                 56 
                 74 
                 23.6 
                 32 
                 325 
               
               
                 SD: 
                 22.2 
                 1.94 
                 0.31 
                 0.79 
                 2.4 
                 1.9 
                 0.64 
                 0.0 
                 41.9 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 97 
                 7.7 
                 7.5 
                 17.8 
                 51 
                 69 
                 23.7 
                 35 
                 347 
               
               
                 SD: 
                 14.5 
                 1.91 
                 0.39 
                 0.82 
                 2.1 
                 1.9 
                 0.71 
                 0.5 
                 54.3 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 0-5) - Part 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
               
               
                   
                 Polys 
                 Polys 
                 Bands 
                 Bands 
                 Lymphs 
                 Lymphs 
                 Monos 
                 Monos 
                 Eos 
                 Eos 
                 Basos 
                 Basos 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5508 
                 65 
                 0 
                 0 
                 2346 
                 28 
                 361 
                 5 
                 197 
                 2 
                 0 
                 0 
               
               
                 SD: 
                 1065.1 
                 5.3 
                 0.0 
                 0.0 
                 476.4 
                 4.0 
                 159.1 
                 2.4 
                 87.1 
                 0.9 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6602 
                 67 
                 0 
                 0 
                 2219 
                 24 
                 615 
                 6 
                 326 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 2065.4 
                 6.2 
                 0.0 
                 0.0 
                 323.3 
                 6.0 
                 411.8 
                 3.2 
                 230.6 
                 2.4 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5562 
                 65 
                 0 
                 0 
                 2223 
                 27 
                 370 
                 4 
                 308 
                 4 
                 0 
                 0 
               
               
                 SD: 
                 1270.4 
                 4.2 
                 0.0 
                 0.0 
                 354.4 
                 4.0 
                 113.0 
                 1.1 
                 108.5 
                 0.9 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5877 
                 67 
                 0 
                 0 
                 2166 
                 25 
                 440 
                 5 
                 255 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 1235.5 
                 3.7 
                 0.0 
                 0.0 
                 450.1 
                 3.3 
                 92.9 
                 1.1 
                 82.2 
                 1.2 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 523.6 
                 68 
                 6 
                 0 
                 1912 
                 25 
                 297 
                 4 
                 238 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 1098.9 
                 3.7 
                 0.0 
                 0.0 
                 185.4 
                 3.7 
                 102.8 
                 1.2 
                 103.1 
                 1.2 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 5 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5864 
                 68 
                 0 
                 0 
                 2061 
                 24 
                 402 
                 5 
                 261 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 1124.4 
                 4.0 
                 0.0 
                 0.0 
                 410.2 
                 5.0 
                 178.4 
                 1.8 
                 112.2 
                 1.1 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 19 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results (weeks 6-10) - Part 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
                 Abs 
                 % 
               
               
                   
                 Polys 
                 Polys 
                 Bands 
                 Bands 
                 Lymphs 
                 Lymphs 
                 Monos 
                 Monos 
                 Eos 
                 Eos 
                 Basos 
                 Basos 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5961 
                 66 
                 0 
                 0 
                 2281 
                 27 
                 400 
                 5 
                 296 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 1852.8 
                 4.9 
                 0.0 
                 0.0 
                 289.4 
                 4.8 
                 121.8 
                 1.9 
                 204.1 
                 1.5 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 7 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 4944 
                 67 
                 0 
                 0 
                 1918 
                 26 
                 329 
                 5 
                 209 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 1030.3 
                 1.9 
                 0.0 
                 0.0 
                 374.2 
                 4.1 
                 115.0 
                 1.4 
                 40.6 
                 0.6 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 4889 
                 65 
                 0 
                 0 
                 1960 
                 28 
                 335 
                 5 
                 154 
                 2 
                 0 
                 0 
               
               
                 SD: 
                 2096.3 
                 5.6 
                 0.0 
                 0.0 
                 371.7 
                 4.5 
                 186.2 
                 1.3 
                 65.9 
                 1.5 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 9 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5705 
                 67 
                 0 
                 0 
                 2056 
                 26 
                 366 
                 4 
                 249 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 1967.2 
                 4.1 
                 0.0 
                 0.0 
                 364.1 
                 4.1 
                 155.1 
                 1.1 
                 222.5 
                 1.6 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5188 
                 66 
                 0 
                 0 
                 1997 
                 26 
                 375 
                 5 
                 190 
                 3 
                 0 
                 0 
               
               
                 SD: 
                 1507.5 
                 3.7 
                 0.0 
                 0.0 
                 386.8 
                 3.5 
                 95.1 
                 0.8 
                 68.9 
                 0.8 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 5221 
                 67 
                 0 
                 0 
                 1940 
                 26 
                 359 
                 5 
                 181 
                 2 
                 0 
                 0 
               
               
                 SD: 
                 1658.6 
                 5.0 
                 5.9 
                 0.0 
                 0.0 
                 453.8 
                 7.0 
                 197.9 
                 2.4 
                 0.5 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     Clinical Observations 
     During the study, occasional instances of loose stool and emesis were recorded. Dog ID #13536 was observed having five instances of food or bile emesis and six instances of loose stool. Dog ID #13513 was observed having two instances of loose stool. Dog ID #27583822 was observed having two instances of food emesis and eight instances of loose stool. Dog ID #13644 was observed having 12 instances of loose stool. Dog ID #13490 was observed having two instances of loose stool. Dog ID #2808987 was observed having four instances of loose stool. Dog ID #2963028 was observed having six instances of loose stool. Dog ID #2784123 was observed having six instances of loose stool. Occasional episodes of loose stool and bile emesis are not unusual in the dog colony and were not considered to be related to the test article. Clinical observations are listed in Table 20. 
     
       
         
           
               
             
               
                 TABLE 20 
               
             
            
               
                   
               
               
                 Clinical observations 
               
            
           
           
               
               
               
            
               
                 Dog ID 
                 Date 
                 Observation 
               
               
                   
               
            
           
           
               
               
               
            
               
                 13490 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 13490 
                 Feb. 4, 2018 
                 Loose stool 
               
               
                 13313 
                 Jan. 16, 2018 
                 Small amount loose stool 
               
               
                 13513 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 13513 
                 Jan. 19, 2018 
                 Afraid and shaking head 
               
               
                 13513 
                 Jan. 25, 2018 
                 Shaking head 
               
               
                 13536 
                 Jan. 14, 2018 
                 Food and chew vomit 
               
               
                 13536 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 13536 
                 Jan. 22, 2018 
                 Food vomit prior to dosing 
               
               
                 13536 
                 Jan. 26, 2018 
                 Food vomit prior to dosing 
               
               
                 13536 
                 Jan. 29, 2018 
                 Bile vomit 
               
               
                 13536 
                 Feb. 4, 2018 
                 Bile vomit with blood 
               
               
                 13536 
                 Feb. 12, 2018 
                 Loose stool with mucus 
               
               
                 13536 
                 Feb. 15, 2018 
                 Loose stool 
               
               
                 13536 
                 Feb. 16, 2018 
                 Loose stool 
               
               
                 13536 
                 Mar. 21, 2018 
                 Loose stool 
               
               
                 13536 
                 Mar. 24, 2018 
                 Loose stool 
               
               
                 13644 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 13644 
                 Feb. 2, 2018 
                 Loose stool with mucus 
               
               
                 13644 
                 Feb. 4, 2018 
                 Loose stool 
               
               
                 13644 
                 Feb. 3, 2018 
                 Loose stool with mucus 
               
               
                 13644 
                 Feb. 6, 2018 
                 Loose stool 
               
               
                 13644 
                 Feb. 7, 2018 
                 Loose stool 
               
               
                 13644 
                 Feb. 10, 2018 
                 Loose stool 
               
               
                 13644 
                 Feb. 11, 2018 
                 Loose stool 
               
               
                 13644 
                 Feb. 15, 2018 
                 Loose stool 
               
               
                 13644 
                 Mar. 15, 2018 
                 Loose stool 
               
               
                 13644 
                 Mar. 17, 2018 
                 Loose stool 
               
               
                 13644 
                 Mar. 20, 2018 
                 Loose stool with mucus 
               
               
                 2753822 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 2753822 
                 Jan. 21, 2018 
                 Food vomit 
               
               
                 2753822 
                 Feb. 10, 2018 
                 Loose stool 
               
               
                 2753822 
                 Mar. 15, 2018 
                 Loose stool with blood 
               
               
                 2753822 
                 Mar. 18, 2018 
                 Loose stool 
               
               
                 2753822 
                 Mar. 20, 2018 
                 Loose stool 
               
               
                 2753822 
                 Mar. 24, 2018 
                 Two instances of loose stool 
               
               
                 2753822 
                 Mar. 29, 2018 
                 Loose stool 
               
               
                 2753822 
                 Mar. 31, 2018 
                 Food vomit 
               
               
                 2784123 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 2784123 
                 Mar. 18, 2018 
                 Loose stool 
               
               
                 2784123 
                 Mar. 21, 2018 
                 Loose stool 
               
               
                 2784123 
                 Mar. 24, 2018 
                 Two instances of loose stool 
               
               
                 2784123 
                 Mar. 29, 2018 
                 Loose stool 
               
               
                 2808987 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 2808987 
                 Feb. 5, 2018 
                 Loose stool 
               
               
                 2808987 
                 Feb. 10, 2018 
                 Loose stool 
               
               
                 2803987 
                 Mar. 20, 2018 
                 Loose stool 
               
               
                 2963028 
                 Jan. 18, 2018 
                 Loose stool 
               
               
                 2963028 
                 Feb. 10, 2018 
                 Loose stool 
               
               
                 2963028 
                 Mar. 20, 2018 
                 Loose stool 
               
               
                 2963028 
                 Mar. 22, 2018 
                 Loose stool 
               
               
                 2963028 
                 Mar. 24, 2018 
                 Loose stool 
               
               
                 2963028 
                 Mar. 25, 2018 
                 Loose stool 
               
               
                   
               
            
           
         
       
     
     Conclusions 
     There were no adverse effects on body weights or food consumption. Group mean alkaline phosphatase values exhibited mild elevations during the study without exceeding the normal reference range. The remaining hematology and serum chemistry results remained within normal limits throughout the study and apparent trends were not observed over time. No clinical observations that were considered to be related to the administration of the test article were observed for any of the dogs during the course of the study. Overall acceptance of the treat was 96.7% with 5 out of 8 consuming the treat 100% of the time for the duration of the study. 
     Example 13 
     Canine Pilot Study 
     A pilot study was conducted to assess the effectiveness of ElleVet Mobility Oil on the treatment of osteoarthritis in canines. 
     Methods 
     Five dogs suffering from end stage osteoarthritis, joint pain, and geriatric pain were selected for the study, as shown in Tables 21 and 22. 
     Per manufacturer&#39;s instructions, dogs were given a loading dose of 2 mg/kg every 12 hours for the first 2 weeks then reduced to 1 mg/kg every 12 hours for 2 weeks. Dogs were then returned to doses of 2 mg/kg every 12 hours for the final four weeks of the study. 
     On days 0, 14, 30, and 60, dogs were evaluated by flexion and extension measurements, muscle musculature measurements, a canine brief pain inventory survey, and a gait analysis using a pressure sensing walkway. 
     
       
         
           
               
             
               
                 TABLE 21 
               
             
            
               
                   
               
               
                 Animal Information 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 OA 
                 Body 
                   
               
               
                 Patient 
                   
                   
                   
                   
                 Weight 
                 Score 
                 Condition 
               
               
                 Number 
                 Name 
                 Age 
                 Sex 
                 Breed 
                 (#) 
                 (0-3) 
                 (1-9) 
                 Medications 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 3496 
                 Gipper 
                 12 yrs 
                 FS 
                 Golden 
                 64.9 
                 R: 3 
                 6 
                 Rimadyl, apoquel, 
               
               
                   
                 Hatch 
                 6 mo 
                   
                 Retriever 
                   
                 L: 2 
                   
                 dasuquin advanced 
               
               
                 21652 
                 Rocoo 
                 15 yrs 
                 MN 
                 Mixed 
                 67.7 
                 B: 2 
                 5 
                 Keppra, Galliprant 
               
               
                   
                 Payne 
                 4 mo 
                   
                 Breed 
               
               
                 13750 
                 Bubba 
                 14 yrs 
                 MN 
                 Labrador 
                 65.6 
                 R: 2 
                 4 
                 Galliprant, 
               
               
                   
                 Schlimm 
                 8 mo 
                   
                 Retriever 
                   
                 L: 1 
                   
                 Gabapentin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 Theophyline 
               
               
                 24478 
                 Aiden 
                 7 yrs 
                 MN 
                 German 
                 86 
                 B: 2-3 
                 5-5 
                 Gabapentin, rimadyl 
               
               
                   
                 Langhans- 
                 2 mo 
                   
                 Shepherd 
                   
                   
                   
                 as needed 
               
               
                   
                 Lindstadt 
               
               
                 19821 
                 Moose 
                 11 yrs 
                 MN 
                 Mixed 
                 65 
                 L: 3/3 
                 5 
                 Tramadol as needed 
               
               
                   
                 Baker 
                 7 mo 
                   
                 Breed 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 22 
               
             
            
               
                   
               
               
                 Animal history 
               
            
           
           
               
               
               
               
            
               
                 Patient 
                   
                   
                   
               
               
                 Number 
                 Name 
                 Enrollment Date 
                 History Notes 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 3496 
                 Gipper 
                 Wed, Jun. 11, 2014 
                 Bilateral medial shoulder syndrome (Subscapular tendinopathy); 
               
               
                   
                 Hatch 
                   
                 Bilateral chronic supraspinatus insertionopathy - Bilateral shoulder 
               
               
                   
                   
                   
                 arthroscopy and radio-frequency treatment; Hobbles application, 
               
               
                   
                   
                   
                 Bilateral elbow arthroscopy (2011); ADPC/PRP injections - bilateral 
               
               
                   
                   
                   
                 supraspinatus, Intra-articular injections ADPC/ACS - bilateral 
               
               
                   
                   
                   
                 shoulders (2011, 2012); ADPC/PRP injection -Bilateral biceps, Left 
               
               
                   
                   
                   
                 teres (2014); ADPC/PRP injection - right shoulder, elbow, biceps 
               
               
                   
                   
                   
                 (2016); PRP injection - right elbow (2016); OsteoBioScaff injection - 
               
               
                   
                   
                   
                 right elbow (2017). 
               
               
                 21652 
                 Rocoo 
                 Fri, Jun. 13, 2014 
                 Elbow arthritis, history of seizure activity, history of elevated liver 
               
               
                   
                 Payne 
                   
                 enzymes 
               
               
                 13750 
                 Bubba 
                 Tue, Jun. 17, 2014 
                 Bilateral elbow OA, hind limb weakness 
               
               
                   
                 Schlimm 
               
               
                 24478 
                 Aiden 
                 Tue, Jul. 1, 2014 
                 Bilateral Hip Dysplasia 
               
               
                   
                 Langhans- 
               
               
                   
                 Lindstadt 
               
               
                 19821 
                 Moose 
                 Fri, Jul. 18, 2014 
                 Left medial shoulder syndrome, bilateral surpaspinatus 
               
               
                   
                 Baker 
                   
                 tendinopathies (R &gt; L), L FCP −&gt; L elbow scope &amp; L RF tx performed 
               
               
                   
                   
                   
                 (May 2016); L elbow OA 
               
               
                   
               
            
           
         
       
     
     Results 
     Three out of five owners (60%) reported a significant improvement in pain severity score and pain interference score. Gait analysis revealed that total pressure index (TPI%), step/stride ratio, and stance percentage did not significantly improve or decline throughout the length of the study, as shown in Tables 23-34 and  FIGS. 5A-5F . Flexion improved in 3 out of 5 dogs and declined by &gt;5 degrees in 2 out of 5 dogs. Extension improved in 2 out of 5 dogs and declined in 1 out of 5 dogs. Following completion of the study, 3 out of 4 owners that respond to a questionnaire indicated that they would like to continue using the supplements. Improvements observed by owners included improved function and comfort laying down, rising, resting, walking, energy, playing, and overall health. 
     
       
         
           
               
             
               
                 TABLE 23 
               
             
            
               
                   
               
               
                 Total pressure index (TPI) 
               
            
           
           
               
               
               
               
            
               
                 Patient 
                   
                 Average TPI (%) Walk 
                 Average TPI (%) Trot 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Number 
                 Name 
                 Date 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Day 0 
                 26.3 
                 26.9 
                 21.0 
                 25.8 
                 25.8 
                 26.2 
                 22.5 
                 25.5 
               
               
                   
                 Hatch 
                 Day 14 
                 26.5 
                 26.4 
                 21.9 
                 25.2 
                 24.8 
                 26.3 
                 24.0 
                 25.0 
               
               
                   
                   
                 Day 30 
                 25.7 
                 25.7 
                 24.1 
                 24.3 
                 26.8 
                 26.2 
                 24.5 
                 22.4 
               
               
                   
                   
                 Day 60 
                 26 
                 26.4 
                 21.5 
                 26 
               
               
                 2 
                 Rocco 
                 Day 0 
                 26.4 
                 28.8 
                 21.8 
                 23 
                 26.1 
                 29.3 
                 21.4 
                 23.4 
               
               
                   
                 Payne 
                 Day 14 
                 27 
                 30.3 
                 21.3 
                 21.5 
                 27.4 
                 27.8 
                 21.1 
                 24 
               
               
                   
                   
                 Day 30 
                 28 
                 30.3 
                 19.3 
                 22.6 
                 28 
                 29.1 
                 21.5 
                 21.6 
               
               
                   
                   
                 Day 60 
                 27.4 
                 28.9 
                 21.6 
                 21.9 
                 25.9 
                 28.7 
                 21.4 
                 24.2 
               
               
                 3 
                 Bubba 
                 Day 0* 
                 31.6 
                 31 
                 18.7 
                 18.6 
                 28.8 
                 30.9 
                 18.7 
                 21.5 
               
               
                   
                 Schlimm 
                 Day 0 
                 30.8 
                 31.7 
                 19.2 
                 18.2 
                 28.8 
                 32.5 
                 19.9 
                 18.9 
               
               
                   
                   
                 Day 14 
                 31.8 
                 31.2 
                 18.9 
                 18 
                 29.4 
                 31.9 
                 19.7 
                 19 
               
               
                   
                   
                 Day 30 
                 31.4 
                 30.7 
                 19.3 
                 18.5 
                 29.7 
                 32 
                 19.8 
                 18.7 
               
               
                   
                   
                 Day 60 
                 31.4 
                 31.3 
                 18.5 
                 18.8 
                 31.2 
                 33.4 
                 17.1 
                 18.1 
               
               
                 4 
                 Aiden 
                 Day 0 
                 31 
                 32 
                 18.4 
                 18.5 
                 31.8 
                 29.1 
                 19.4 
                 19.6 
               
               
                   
                 Langhans- 
                 Day 14 
                 32.6 
                 30.3 
                 18.4 
                 18.8 
                 31.2 
                 31.7 
                 18.3 
                 18.9 
               
               
                   
                 Lindstadt 
                 Day 30 
                 31.9 
                 32.2 
                 18 
                 18 
                 31.4 
                 29.1 
                 19.3 
                 20.2 
               
               
                   
                   
                 Day 60 
                 32.1 
                 30.7 
                 18.2 
                 18.9 
                 31.2 
                 29.8 
                 19.4 
                 19.5 
               
               
                 5 
                 Moose 
                 Day 0 
                 25.1 
                 34.4 
                 20.9 
                 19.5 
                 23.3 
                 35.6 
                 20.8 
                 20.1 
               
               
                   
                 Baker 
                 Day 14 
                 25.1 
                 35 
                 21.1 
                 18.8 
                 23.1 
                 36.2 
                 20.1 
                 20.4 
               
               
                   
                   
                 Day 30 
                 24.5 
                 35.6 
                 19.5 
                 20.4 
                 22.1 
                 37.2 
                 20.3 
                 20.3 
               
               
                   
                   
                 Day 60 
                 25.1 
                 34.5 
                 19.5 
                 20.8 
                 23.7 
                 36.2 
                 19.9 
                 20.1 
               
               
                   
               
               
                 *= removed from study 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 24 
               
             
            
               
                   
               
               
                 Exam notes 
               
            
           
           
               
               
               
               
            
               
                 Patient 
                   
                   
                   
               
               
                 Number 
                 Name 
                 Date 
                 Exam Notes 
               
               
                   
               
               
                 1 
                 Gipper Hatch 
                 Day 0 
                 Mild mid lumbar pain - reaction to palpation; 
               
               
                   
                   
                   
                 right elbow thick/crepitus; left elbow swollen - 
               
               
                   
                   
                   
                 moderate medial 
               
               
                   
                   
                 Day 14 
                 Moderate left elbow effusion (medial) 
               
               
                   
                   
                 Day 30 
               
               
                   
                   
                 Day 60 
                 P was scuffing at a trot, cannot currently be 
               
               
                   
                   
                   
                 processed. O does not think that he saw 
               
               
                   
                   
                   
                 any effect during the study and actually 
               
               
                   
                   
                   
                 think that P&#39;s mood dropped while receiving 
               
               
                   
                   
                   
                 the higher dose. O also was upset that the 
               
               
                   
                   
                   
                 gel capsules he received were not large 
               
               
                   
                   
                   
                 enough to hold even a half dose. 
               
               
                 2 
                 Rocco Payne 
                 Day 0 
                 Mild −&gt; Moderate discomfort from L5 to LS; 
               
               
                   
                   
                   
                 Discomfort for hip extension &amp; ilio palpation 
               
               
                   
                   
                   
                 bilaterally 
               
               
                   
                   
                 Day 14 
                 bilat ilio discomfort &amp; discomfort for hip 
               
               
                   
                   
                   
                 extension L &gt; R, significant discomfort for 
               
               
                   
                   
                   
                 elbow flexion bilat, mod effusion bilat elbow 
               
               
                   
                   
                   
                 medially, no back discomfort noted 
               
               
                   
                   
                 Day 30 
               
               
                   
                   
                 Day 60 
               
               
                 3 
                 Bubba 
                 Day 0* 
                 **P had to be removed during the first week 
               
               
                   
                 Schlimm 
                   
                 of the study due to impacted/infected anal 
               
               
                   
                   
                   
                 glad. P had to go onto IV antibiotic restarted 
               
               
                   
                   
                   
                 study once P was back to normal. 
               
               
                   
                   
                 Day 0 
                 Bilat elbow discomfort for flexion (L &gt; R) 
               
               
                   
                   
                 Day 14 
               
               
                   
                   
                 Day 30 
                 O notes that P has been much more feisty 
               
               
                   
                   
                   
                 and playful 
               
               
                   
                   
                 Day 60 
               
               
                 4 
                 Aiden 
                 Day 0 
               
               
                   
                 Langhans- 
                 Day 14 
               
               
                   
                 Lindstadt 
                 Day 30 
               
               
                   
                   
                 Day 60 
               
               
                 5 
                 Moose Baker 
                 Day 0 
                 Discomfort for R shoulder extension - 
               
               
                   
                   
                   
                 mineralization in area of R supraspinatus 
               
               
                   
                   
                   
                 tendon 
               
               
                   
                   
                 Day 14 
               
               
                   
                   
                 Day 30 
               
               
                   
                   
                   
                 O stated that they did not see an 
               
               
                   
                   
                   
                 improvement during the study. Hip 
               
               
                   
                   
                   
                 radiographs were taken after the final 
               
               
                   
                   
                   
                 recheck. It was discovered that P also has 
               
               
                   
               
               
                 *= removed from study 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 25 
               
             
            
               
                   
               
               
                   
                   
                   
                   
                 Subjective 
                 Humeral Musculature 
               
               
                 Patient 
                   
                   
                   
                 Lameness 
                 Circumference (cm) 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Number 
                 Name 
                 OA 
                 Date 
                 Score (0-6) 
                 Left 
                 Right 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Bilateral 
                 Day 0 
                 3 
                 33 
                 33 
               
               
                   
                 Hatch 
                 Elbows 
                 Day 14 
                 3 
                 34 
                 34 
               
               
                   
                   
                   
                 Day 30 
                 3 
                 32 
                 32 
               
               
                   
                   
                   
                 Day 60 
                 3 
                 33 
                 33 
               
               
                 2 
                 Rocco 
                 Bilateral 
                 Day 0 
                 4 
                 35 
                 35 
               
               
                   
                 Payne 
                 Elbows 
                 Day 14 
                 4 
                 36.5 
                 36 
               
               
                   
                   
                   
                 Day 30 
                 4 
                 36 
                 36 
               
               
                   
                   
                   
                 Day 60 
                 3 
                 36 
                 35 
               
               
                 3 
                 Bubba 
                 Bilateral 
                 Day 0* 
                 3 
                 37 
                 37 
               
               
                   
                 Schlimm 
                 Elbows 
                 Day 0 
                 3 
                 36 
                 37 
               
               
                   
                   
                   
                 Day 14 
                 3 
                 36 
                 36 
               
               
                   
                   
                   
                 Day 30 
                 2 
                 36 
                 37 
               
               
                   
                   
                   
                 Day 60 
                 2 
                 36 
                 36 
               
               
                 4 
                 Aiden 
                 Bilateral 
                 Day 0 
                 2 
                 47 
                 47 
               
               
                   
                 Langhans- 
                 Hips 
                 Day 14 
                 2 
                 46 
                 47.5 
               
               
                   
                 Lindstadt 
                   
                 Day 30 
                 1 
                 47 
                 47 
               
               
                   
                   
                   
                 Day 60 
                 1 
                 37 
                 37 
               
               
                 5 
                 Moose 
                 Left 
                 Day 0 
                 3 
                 34 
                 34.5 
               
               
                   
                 Baker 
                 Elbow 
                 Day 14 
                 2 
                 33.5 
                 34 
               
               
                   
                   
                   
                 Day 30 
                 3 
                 34 
                 35.5 
               
               
                   
                   
                   
                 Day 60 
                 3 
                 34 
                 35 
               
               
                   
               
               
                 *= removed from study 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 26 
               
             
            
               
                   
               
               
                 Measurements - Part 2 
               
            
           
           
               
               
               
            
               
                   
                   
                 Discomfort on Palpation (N—None, 
               
               
                   
                 Goniometry Measurements (°) 
                 Y—Yes, M—Mild) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Patient 
                   
                 Left 
                 Right 
                 Left 
                 Right 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Number 
                 Name 
                 OA 
                 Date 
                 Extension 
                 Flexion 
                 Extension 
                 Flexion 
                 Extension 
                 Flexion 
                 Extension 
                 Flexion 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Bilateral 
                 Day 0 
                 160 
                 30 
                 160 
                 39 
                 N 
                 Y 
                 N 
                 Y 
               
               
                   
                 Hatch 
                 Elbows 
                 Day 14 
                 160 
                 35 
                 165 
                 40 
                 N 
                 Y 
                 Y 
                 Y 
               
               
                   
                   
                   
                 Day 30 
                 164 
                 38 
                 158 
                 42 
                 Y 
                 Y 
                 Y 
                 Y 
               
               
                   
                   
                   
                 Day 60 
                 165 
                 41 
                 162 
                 44 
                 N 
                 Y 
                 Y 
                 N 
               
               
                 2 
                 Rocco 
                 Bilateral 
                 Day 0 
                 152 
                 52 
                 164 
                 60 
                 Y 
                 Y 
                 Y 
                 Y 
               
               
                   
                 Payne 
                 Elbows 
                 Day 14 
                 162 
                 69 
                 164 
                 55 
                 N 
                 Y 
                 N 
                 Y 
               
               
                   
                   
                   
                 Day 30 
                 158 
                 69 
                 163 
                 63 
                 N 
                 Y 
                 N 
                 Y 
               
               
                   
                   
                   
                 Day 60 
                 164 
                 70 
                 162 
                 68 
                 N 
                 Y 
                 N 
                 Y 
               
               
                 3 
                 Bubba 
                 Bilateral 
                 Day 0* 
                 158 
                 42 
                 163 
                 50 
                 N 
                 Y 
                 N 
                 Y 
               
               
                   
                 Schlimm 
                 Elbows 
                 Day 0 
                 165 
                 45 
                 162 
                 52 
                 N 
                 Y 
                 N 
                 Y 
               
               
                   
                   
                   
                 Day 14 
                 170 
                 44 
                 174 
                 42 
                 N 
                 Y 
                 N 
                 Y 
               
               
                   
                   
                   
                 Day 30 
                 170 
                 38 
                 165 
                 46 
                 N 
                 Y 
                 N 
                 Y 
               
               
                   
                   
                   
                 Day 60 
                 161 
                 42 
                 168 
                 46 
                 N 
                 Y 
                 N 
                 Y 
               
               
                 4 
                 Aiden 
                 Bilateral 
                 Day 0 
                 150 
                 48 
                 156 
                 52 
                 Y 
                 N 
                 Y 
                 N 
               
               
                   
                 Langhans- 
                 Hips 
                 Day 14 
                 140 
                 50 
                 148 
                 47 
                 Y 
                 N 
                 Y 
                 N 
               
               
                   
                 Lindstadt 
                   
                 Day 30 
                 149 
                 60 
                 145 
                 49 
                 Y 
                 N 
                 Y 
                 N 
               
               
                   
                   
                   
                 Day 60 
                 145 
                 50 
                 142 
                 52 
                 Y 
                 N 
                 Y 
                 N 
               
               
                 5 
                 Moose 
                 Left 
                 Day 0 
                 157 
                 69 
                 162 
                 28 
                 Y 
                 Y 
                 Y 
                 N 
               
               
                   
                 Baker 
                 Elbow 
                 Day 14 
                 160 
                 64 
                 170 
                 31 
                 Y 
                 Y 
                 N 
                 N 
               
               
                   
                   
                   
                 Day 30 
                 152 
                 60 
                 172 
                 28 
                 Y 
                 Y 
                 N 
                 N 
               
               
                   
                   
                   
                 Day 60 
                 162 
                 64 
                 172 
                 28 
                 N 
                 Y 
                 Y 
                 N 
               
               
                   
               
               
                 *= removed from study 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 27 
               
             
            
               
                   
               
               
                 Schedule 
               
            
           
           
               
               
               
               
            
               
                 Patient 
                   
                   
                   
               
               
                 Number 
                 Name 
                 Day 
                 Date 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 Gipper Hatch 
                 Day 0 
                 Tue, Jun. 12, 2018 
                   
               
               
                 2 
                 Rocco Payne 
                 Day 0 
                 Thu, Jun. 14, 2018 
               
               
                 3 
                 Bubba Schlimm 
                 Day 0* 
                 Mon, Jun. 18, 2018 
                 **P had to be removed during the first week of 
               
               
                   
                   
                   
                   
                 the study due to impacted/infected anal glad. P 
               
               
                   
                   
                   
                   
                 had to go onto IV antibiotic restarted study once 
               
               
                   
                   
                   
                   
                 P was back to normal. 
               
               
                   
                   
                 Day 0 
                 Mon, Jul. 9, 2018 
               
               
                 4 
                 Aiden Langhans- 
                 Day 0 
                 Mon, Jul. 2, 2018 
               
               
                   
                 Lindstadt 
               
               
                 5 
                 Moose Baker 
                 Day 0 
                 Thu, Jul. 19, 2018 
               
               
                   
               
               
                 *= removed from study 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 28 
               
             
            
               
                   
               
               
                 Canine brief pain index - description of pain 
               
            
           
           
               
               
               
               
            
               
                   
                 Description of Pain: No Pain (0) → Extreme 
                   
                   
               
               
                   
                 Pain (10) 
                   
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                 Pain at 
                 Pain at 
                 Pain at 
                   
                   
                   
               
               
                   
                   
                   
                 worst in 
                 least in 
                 average 
                 Pain 
                 Pain 
                   
               
               
                 Patient 
                   
                   
                 last 7 
                 last 7 
                 in last 7 
                 right 
                 Severity 
                   
               
               
                 Number 
                 Name 
                 Date 
                 days 
                 days 
                 days 
                 now 
                 Mean 
                 Comments 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Day 0 
                 8 
                 5 
                 6 
                 5 
                 6 
                   
               
               
                   
                 Hatch 
                 Day 14 
                 8 
                 5 
                 7 
                 6 
                 7 
                   
               
               
                   
                   
                 Day 30 
                 8 
                 6 
                 6 
                 6 
                 7 
                   
               
               
                   
                   
                 Day 60 
                 8 
                 6 
                 7 
                 6 
                 7 
                   
               
               
                 2 
                 Rocco 
                 Day 0 
                 6 
                 6 
                 5 
                 6 
                 6 
                   
               
               
                   
                 Payne 
                 Day 14 
                 9 
                 9 
                 9 
                 9 
                 9 
                   
               
               
                   
                   
                 Day 30 
                 7 
                 5 
                 6 
                 6 
                 6 
                   
               
               
                   
                   
                 Day 60 
                 5 
                 3 
                 4 
                 3 
                 4 
                   
               
               
                 3 
                 Bubba 
                 Day 0* 
                 6 
                 4 
                 5 
                 5 
                 5 
                 **P had to be 
               
               
                   
                 Schlimm 
                   
                   
                   
                   
                   
                   
                 removed during the 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 first week of the 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 study due to 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 impacted/infected 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 anal glad. P had to 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 go onto IV antibiotic 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 restarted study once 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 P was back to 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 normal. 
               
               
                   
                   
                 Day 0 
                 5 
                 4 
                 4 
                 4 
                 4 
                   
               
               
                   
                   
                 Day 14 
                 4 
                 3 
                 3 
                 3 
                 3 
                   
               
               
                   
                   
                 Day 30 
                 5 
                 3 
                 4 
                 5 
                 4 
                   
               
               
                   
                   
                 Day 60 
                 3 
                 2 
                 2 
                 2 
                 2 
                   
               
               
                 4 
                 Aiden 
                 Day 0 
                 9 
                 5 
                 7 
                 9 
                 8 
                   
               
               
                   
                 Langhans- 
                 Day 14 
                 7 
                 4 
                 5 
                 3 
                 5 
                   
               
               
                   
                 Lindstadt 
                 Day 30 
                 7 
                 4 
                 5 
                 4 
                 5 
                   
               
               
                   
                   
                 Day 60 
                 8 
                 3 
                 4 
                 3 
                 5 
                   
               
               
                 5 
                 Moose 
                 Day 0 
                 7 
                 3 
                 6 
                 6 
                 6 
                   
               
               
                   
                 Baker 
                 Day 14 
                 7 
                 4 
                 5 
                 5 
                 5 
                   
               
               
                   
                   
                 Day 30 
                 7 
                 3 
                 5 
                 4 
                 5 
                   
               
               
                   
                   
                 Day 60 
                 5 
                 4 
                 5 
                 5 
                 5 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 29 
               
             
            
               
                   
               
               
                 Canine brief pain index - description of function 
               
            
           
           
               
               
               
               
            
               
                   
                 Description of Function: Does Not Interfere (0) → Completely Interferes (10) 
                   
                 Quality of 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Pain has 
                   
                   
                 Pain has 
                   
                 Life in the 
               
               
                   
                   
                   
                   
                   
                 interfered 
                   
                   
                 interfered 
                   
                 last 7 days 
               
               
                   
                   
                   
                 Pain has 
                 Pain has 
                 with ability 
                 Pain has 
                 Pain has 
                 with ability 
                   
                 (Poor → 
               
               
                   
                   
                   
                 interfered 
                 interfered 
                 to rise to 
                 interfered 
                 interfered 
                 to climb up 
                 Pain 
                 Fair → 
               
               
                   
                   
                   
                 with general 
                 with enjoyment 
                 standing from 
                 with ability 
                 with ability 
                 (stairs, 
                 Inter- 
                 Good → 
               
               
                 Patient 
                   
                   
                 activity in 
                 of life in 
                 lying down in 
                 to walk in 
                 to run in 
                 curbs, etc) in 
                 ference 
                 Very Good → 
               
               
                 Number 
                 Name 
                 Date 
                 last 7 days 
                 last 7 days 
                 last 7 days 
                 last 7 days 
                 last 7 days 
                 last 7 days 
                 Mean 
                 Excellent) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Day 0 
                 7 
                 7 
                 8 
                 6 
                 9 
                 7 
                 7 
                 Good 
               
               
                   
                 Hatch 
                 Day 14 
                 6 
                 5 
                 8 
                 6 
                 9 
                 7 
                 7 
                 Good 
               
               
                   
                   
                 Day 30 
                 7 
                 6 
                 8 
                 6 
                 8 
                 8 
                 7 
                 Good 
               
               
                   
                   
                 Day 60 
                 7 
                 6 
                 8 
                 6 
                 9 
                 6 
                 7 
                 Good 
               
               
                 2 
                 Rocco 
                 Day 0 
                 6 
                 6 
                 8 
                 8 
                 10 
                 10 
                 8 
                 Very Good 
               
               
                   
                 Payne 
                 Day 14 
                 8 
                 8 
                 7 
                 7 
                 10 
                 10 
                 8 
                 Fair 
               
               
                   
                   
                 Day 30 
                 6 
                 5 
                 6 
                 4 
                 5 
                 10 
                 6 
                 Very Good 
               
               
                   
                   
                 Day 60 
                 3 
                 2 
                 3 
                 2 
                 7 
                 10 
                 5 
                 Very Good 
               
               
                 3 
                 Bubba 
                 Day 0* 
                 6 
                 3 
                 0 
                 5 
                 9 
                 6 
                 5 
                 Good 
               
               
                   
                 Schlimm 
                 Day 0 
                 3 
                 3 
                 3 
                 5 
                 7 
                 5 
                 4 
                 Good 
               
               
                   
                   
                 Day 14 
                 3 
                 3 
                 3 
                 3 
                 7 
                 6 
                 4 
                 Very Good 
               
               
                   
                   
                 Day 30 
                 5 
                 4 
                 4 
                 4 
                 7 
                 4 
                 5 
                 Good 
               
               
                   
                   
                 Day 60 
                 2 
                 1 
                 1 
                 2 
                 3 
                 1 
                 2 
                 Very Good 
               
               
                 4 
                 Aiden 
                 Day 0 
                 7 
                 8 
                 7 
                 8 
                 9 
                 8 
                 8 
                 Fair 
               
               
                   
                 Langhans- 
                 Day 14 
                 4 
                 5 
                 5 
                 4 
                 4 
                 5 
                 5 
                 Good 
               
               
                   
                 Lindstadt 
                 Day 30 
                 4 
                 5 
                 4 
                 5 
                 6 
                 5 
                 5 
                 Good 
               
               
                   
                   
                 Day 60 
                 2 
                 4 
                 4 
                 3 
                 3 
                 5 
                 4 
                 Good 
               
               
                 5 
                 Moose 
                 Day 0 
                 2 
                 2 
                 2 
                 2 
                 3 
                 4 
                 3 
                 Very Good 
               
               
                   
                 Baker 
                 Day 14 
                 5 
                 3 
                 4 
                 4 
                 6 
                 5 
                 5 
                 Good 
               
               
                   
                   
                 Day 30 
                 4 
                 2 
                 5 
                 4 
                 5 
                 5 
                 4 
                 Very Good 
               
               
                   
                   
                 Day 60 
                 4 
                 3 
                 6 
                 3 
                 5 
                 4 
                 4 
                 Good 
               
               
                   
               
               
                 *= removed from study 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 30 
               
             
            
               
                   
               
               
                 Full gait data - walks Part 1 
               
            
           
           
               
               
               
               
               
            
               
                 Patient 
                   
                 Average TPI (%) Walk 
                 Step Length 
                 Stride Length 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Number 
                 Name 
                 Date 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Day 0 
                 26.3 
                 26.9 
                 21.0 
                 25.8 
                 32.585 
                 30.600 
                 31.650 
                 31.235 
                 63.350 
                 63.050 
                 62.950 
                 62.950 
               
               
                   
                 Hatch 
                 Day 14 
                 26.5 
                 26.4 
                 21.9 
                 25.2 
                 29.596 
                 30.057 
                 27.966 
                 31.446 
                 59.852 
                 59.750 
                 59.552 
                 59.470 
               
               
                   
                   
                 Day 30 
                 25.7 
                 25.7 
                 24.1 
                 24.3 
                 30.842 
                 30.824 
                 30.386 
                 31.619 
                 61.683 
                 61.683 
                 62.036 
                 61.930 
               
               
                   
                   
                 Day 60 
                 26.0 
                 26.4 
                 21.5 
                 26.0 
                 31.083 
                 31.844 
                 31.821 
                 31.232 
                 62.904 
                 63.020 
                 63.043 
                 63.107 
               
               
                 2 
                 Rocco 
                 Day 0 
                 26.4 
                 28.8 
                 21.8 
                 23.0 
                 37.714 
                 40.795 
                 37.246 
                 40.751 
                 78.778 
                 78.553 
                 78.040 
                 78.148 
               
               
                   
                 Payne 
                 Day 14 
                 27.0 
                 30.3 
                 21.3 
                 21.5 
                 34.911 
                 39.238 
                 34.514 
                 39.132 
                 74.154 
                 74.204 
                 73.615 
                 73.637 
               
               
                   
                   
                 Day 30 
                 28.0 
                 30.3 
                 19.3 
                 22.6 
                 32.567 
                 37.123 
                 34.396 
                 34.979 
                 69.572 
                 69.809 
                 69.420 
                 69.578 
               
               
                   
                   
                 Day 60 
                 27.4 
                 28.9 
                 21.6 
                 21.9 
                 37.370 
                 40.368 
                 38.088 
                 39.272 
                 78.098 
                 77.798 
                 77.221 
                 77.432 
               
               
                 3 
                 Bubba 
                 Day 0 
                 30.8 
                 31.7 
                 19.2 
                 18.2 
                 44.450 
                 43.688 
                 42.005 
                 46.344 
                 88.530 
                 88.159 
                 88.635 
                 88.424 
               
               
                   
                 Schlimm 
                 Day 14 
                 31.8 
                 31.2 
                 18.9 
                 18.0 
                 41.677 
                 42.757 
                 40.654 
                 43.858 
                 84.416 
                 84.561 
                 84.801 
                 84.501 
               
               
                   
                   
                 Day 30 
                 31.4 
                 30.7 
                 19.3 
                 18.5 
                 40.255 
                 41.444 
                 38.424 
                 43.342 
                 82.028 
                 81.598 
                 81.936 
                 81.936 
               
               
                   
                   
                 Day 60 
                 31.4 
                 31.3 
                 18.5 
                 18.8 
                 43.487 
                 45.702 
                 42.958 
                 46.337 
                 89.517 
                 88.918 
                 89.235 
                 89.535 
               
               
                 4 
                 Aiden 
                 Day 0 
                 31.0 
                 32.0 
                 18.4 
                 18.5 
                 57.309 
                 56.180 
                 58.120 
                 56.198 
                 113.453 
                 113.665 
                 114.794 
                 114.865 
               
               
                   
                 Langhans- 
                 Day 14 
                 32.6 
                 30.3 
                 18.4 
                 18.8 
                 49.939 
                 48.789 
                 49.346 
                 49.054 
                 99.272 
                 98.407 
                 98.460 
                 98.037 
               
               
                   
                 Lindstadt 
                 Day 30 
                 31.9 
                 32.2 
                 18.0 
                 18.0 
                 51.946 
                 50.571 
                 52.106 
                 50.747 
                 102.376 
                 103.434 
                 102.729 
                 103.152 
               
               
                   
                   
                 Day 60 
                 32.1 
                 30.7 
                 18.2 
                 18.9 
                 50.800 
                 50.504 
                 51.806 
                 50.490 
                 101.441 
                 101.424 
                 102.235 
                 102.252 
               
               
                 5 
                 Moose 
                 Day 0 
                 25.1 
                 34.4 
                 20.9 
                 19.5 
                 35.285 
                 36.647 
                 39.741 
                 33.669 
                 71.522 
                 72.390 
                 73.152 
                 73.766 
               
               
                   
                 Baker 
                 Day 14 
                 25.1 
                 35.0 
                 21.1 
                 18.8 
                 35.656 
                 35.097 
                 39.580 
                 32.569 
                 70.594 
                 71.271 
                 71.773 
                 72.632 
               
               
                   
                   
                 Day 30 
                 24.5 
                 35.6 
                 19.5 
                 20.4 
                 35.963 
                 36.233 
                 39.960 
                 32.299 
                 72.284 
                 72.408 
                 72.231 
                 72.496 
               
               
                   
                   
                 Day 60 
                 25.1 
                 34.4 
                 19.5 
                 20.8 
                 34.491 
                 35.909 
                 39.317 
                 32.427 
                 70.242 
                 70.792 
                 71.671 
                 71.893 
               
               
                   
               
               
                     = removed from study 
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 31 
               
             
            
               
                   
               
               
                 Full gait data - walks Part 2 
               
            
           
           
               
               
               
               
               
            
               
                 Patient 
                   
                 Stance % 
                 Stance Time 
                 Stride/Step 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Number 
                 Name 
                 Date 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Day 0 
                 64.0 
                 68.6 
                 57.4 
                 60.7 
                 0.430 
                 0.460 
                 0.385 
                 0.405 
                 51.4 
                 48.5 
                 50.3 
                 49.6 
               
               
                   
                 Hatch 
                 Day 14 
                 68.2 
                 70.1 
                 59.6 
                 61.2 
                 0.449 
                 0.460 
                 0.392 
                 0.400 
                 49.4 
                 50.3 
                 47.0 
                 52.9 
               
               
                   
                   
                 Day 30 
                 66.9 
                 67.9 
                 59.7 
                 59.9 
                 0.458 
                 0.463 
                 0.408 
                 0.410 
                 50.0 
                 50.0 
                 49.0 
                 51.1 
               
               
                   
                   
                 Day 60 
                 67.3 
                 68.4 
                 58.7 
                 60.1 
                 0.443 
                 0.450 
                 0.387 
                 0.395 
                 49.4 
                 50.5 
                 50.5 
                 49.5 
               
               
                 2 
                 Rocco 
                 Day 0 
                 64.8 
                 64.3 
                 56.1 
                 59.5 
                 0.534 
                 0.525 
                 0.458 
                 0.491 
                 47.9 
                 51.9 
                 47.7 
                 52.1 
               
               
                   
                 Payne 
                 Day 14 
                 66.2 
                 65.8 
                 57.6 
                 61.2 
                 0.573 
                 0.568 
                 0.488 
                 0.518 
                 47.1 
                 52.9 
                 46.9 
                 53.1 
               
               
                   
                   
                 Day 30 
                 69.3 
                 66.4 
                 59.0 
                 63.5 
                 0.682 
                 0.653 
                 0.579 
                 0.628 
                 46.8 
                 53.2 
                 49.5 
                 50.3 
               
               
                   
                   
                 Day 60 
                 62.3 
                 63.1 
                 55.2 
                 57.2 
                 0.447 
                 0.453 
                 0.389 
                 0.404 
                 47.9 
                 51.9 
                 49.3 
                 50.7 
               
               
                 3 
                 Bubba 
                 Day 0 
                 60.3 
                 61.0 
                 57.5 
                 57.5 
                 0.494 
                 0.494 
                 0.475 
                 0.474 
                 50.2 
                 49.6 
                 47.4 
                 52.4 
               
               
                   
                 Schlimm 
                 Day 14 
                 60.4 
                 60.2 
                 56.4 
                 55.0 
                 0.453 
                 0.451 
                 0.421 
                 0.411 
                 49.4 
                 50.6 
                 47.9 
                 51.9 
               
               
                   
                   
                 Day 30 
                 62.6 
                 62.6 
                 58.9 
                 58.4 
                 0.534 
                 0.535 
                 0.501 
                 0.500 
                 49.1 
                 50.8 
                 46.9 
                 52.9 
               
               
                   
                   
                 Day 60 
                 60.1 
                 60.8 
                 57.0 
                 57.1 
                 0.474 
                 0.480 
                 0.453 
                 0.451 
                 48.6 
                 51.4 
                 48.1 
                 51.8 
               
               
                 4 
                 Aiden 
                 Day 0 
                 53.9 
                 53.7 
                 48.4 
                 48.5 
                 0.330 
                 0.331 
                 0.297 
                 0.296 
                 50.5 
                 49.4 
                 50.6 
                 48.9 
               
               
                   
                 Langhans- 
                 Day 14 
                 60.6 
                 59.9 
                 56.6 
                 55.2 
                 0.446 
                 0.445 
                 0.417 
                 0.410 
                 50.3 
                 49.6 
                 50.1 
                 50.0 
               
               
                   
                 Lindstadt 
                 Day 30 
                 56.6 
                 57.9 
                 50.9 
                 53.0 
                 0.379 
                 0.391 
                 0.342 
                 0.352 
                 50.7 
                 48.9 
                 50.7 
                 49.2 
               
               
                   
                   
                 Day 60 
                 57.7 
                 58.5 
                 53.6 
                 53.2 
                 0.413 
                 0.421 
                 0.387 
                 0.385 
                 50.1 
                 49.8 
                 50.7 
                 49.4 
               
               
                 5 
                 Moose 
                 Day 0 
                 60.1 
                 61.4 
                 57.7 
                 57.7 
                 0.405 
                 0.413 
                 0.388 
                 0.384 
                 49.3 
                 50.6 
                 54.3 
                 45.6 
               
               
                   
                 Baker 
                 Day 14 
                 63.2 
                 66.9 
                 58.0 
                 58.1 
                 0.429 
                 0.455 
                 0.393 
                 0.394 
                 50.5 
                 49.2 
                 55.1 
                 44.8 
               
               
                   
                   
                 Day 30 
                 61.6 
                 59.9 
                 56.8 
                 57.6 
                 0.394 
                 0.381 
                 0.361 
                 0.364 
                 49.8 
                 50.0 
                 55.3 
                 44.6 
               
               
                   
                   
                 Day 60 
                 61.0 
                 66.8 
                 57.7 
                 57.7 
                 0.407 
                 0.446 
                 0.388 
                 0.385 
                 49.1 
                 50.7 
                 54.9 
                 45.1 
               
               
                   
               
               
                     = removed from study 
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 32 
               
             
            
               
                   
               
               
                 Full gait data - trots Part 1 
               
            
           
           
               
               
               
               
               
            
               
                 Patient 
                   
                 Average TPI (%) Trot 
                 Step Length 
                 Stride Length 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Number 
                 Name 
                 Date 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Gipper 
                 Day 0 
                 25.8 
                 26.2 
                 22.5 
                 25.5 
                 36.830 
                 35.510 
                 37.285 
                 35.720 
                 72.850 
                 72.200 
                 73.650 
                 72.650 
               
               
                   
                 Hatch 
                 Day 14 
                 24.8 
                 26.3 
                 24.0 
                 25.0 
                 28.776 
                 40.279 
                 40.868 
                 31.082 
                 69.208 
                 69.918 
                 72.262 
                 70.561 
               
               
                   
                   
                 Day 30 
                 27.4 
                 26.9 
                 23.0 
                 23.6 
                 37.412 
                 37.465 
                 36.293 
                 39.123 
                 74.789 
                 75.141 
                 75.071 
                 75.635 
               
               
                   
                   
                 Day 60 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 2 
                 Rocco 
                 Day 0 
                 26.1 
                 29.3 
                 21.4 
                 23.4 
                 41.118 
                 45.579 
                 40.697 
                 45.649 
                 86.766 
                 87.014 
                 86.638 
                 86.353 
               
               
                   
                 Payne 
                 Day 14 
                 27.4 
                 27.8 
                 21.1 
                 24.0 
                 43.480 
                 45.385 
                 41.875 
                 47.308 
                 89.041 
                 88.759 
                 89.676 
                 88.970 
               
               
                   
                   
                 Day 30 
                 28.0 
                 29.1 
                 21.5 
                 21.6 
                 40.030 
                 45.014 
                 40.993 
                 44.715 
                 84.861 
                 84.861 
                 86.078 
                 85.707 
               
               
                   
                   
                 Day 60 
                 25.9 
                 28.7 
                 21.4 
                 24.2 
                 43.621 
                 45.861 
                 43.603 
                 46.214 
                 89.450 
                 90.226 
                 89.803 
                 90.283 
               
               
                 3 
                 Bubba 
                 Day 0 
                 28.8 
                 32.5 
                 19.9 
                 18.9 
                 47.096 
                 47.766 
                 47.413 
                 47.272 
                 94.474 
                 95.391 
                 94.827 
                 94.827 
               
               
                   
                 Schlimm 
                 Day 14 
                 29.4 
                 31.9 
                 19.7 
                 19.0 
                 45.741 
                 47.149 
                 45.314 
                 47.879 
                 92.498 
                 93.271 
                 93.049 
                 92.932 
               
               
                   
                   
                 Day 30 
                 29.7 
                 32.0 
                 19.8 
                 18.7 
                 42.189 
                 40.756 
                 41.871 
                 42.302 
                 82.867 
                 83.167 
                 84.720 
                 83.820 
               
               
                   
                   
                 Day 60 
                 31.2 
                 33.4 
                 17.1 
                 18.1 
                 46.270 
                 44.549 
                 45.286 
                 46.210 
                 91.034 
                 91.264 
                 91.352 
                 91.951 
               
               
                 4 
                 Aiden 
                 Day 0 
                 31.8 
                 29.1 
                 19.4 
                 19.6 
                 65.740 
                 65.511 
                 65.846 
                 64.805 
                 130.739 
                 131.798 
                 130.245 
                 131.727 
               
               
                   
                 Langhans- 
                 Day 14 
                 31.2 
                 31.7 
                 18.3 
                 18.9 
                 64.682 
                 61.817 
                 63.465 
                 61.860 
                 126.824 
                 127.035 
                 126.048 
                 125.042 
               
               
                   
                 Lindstadt 
                 Day 30 
                 31.4 
                 29.1 
                 19.3 
                 20.2 
                 63.698 
                 62.389 
                 63.302 
                 61.701 
                 126.418 
                 126.453 
                 125.448 
                 125.360 
               
               
                   
                   
                 Day 60 
                 31.2 
                 29.8 
                 19.4 
                 19.5 
                 63.236 
                 64.929 
                 64.950 
                 63.712 
                 128.605 
                 127.970 
                 128.958 
                 128.993 
               
               
                 5 
                 Moose 
                 Day 0 
                 23.3 
                 35.6 
                 20.8 
                 20.1 
                 45.942 
                 46.842 
                 45.612 
                 46.574 
                 92.696 
                 92.915 
                 91.962 
                 92.304 
               
               
                   
                 Baker 
                 Day 14 
                 23.1 
                 36.2 
                 20.1 
                 20.4 
                 46.119 
                 48.122 
                 44.898 
                 48.609 
                 94.636 
                 94.414 
                 94.181 
                 93.229 
               
               
                   
                   
                 Day 30 
                 22.1 
                 37.2 
                 20.3 
                 20.3 
                 43.110 
                 45.164 
                 42.968 
                 
                   
                 
                 
                   
                 
                 
                   
                 
                 
                   
                 
                 88.554 
               
               
                   
                   
                 Day 60 
                 23.7 
                 36.2 
                 19.9 
                 20.1 
                 43.808 
                 47.159 
                 43.102 
                 47.773 
                 91.250 
                 91.017 
                 91.006 
                 91.027 
               
               
                   
               
               
                     = removed from study 
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 33 
               
             
            
               
                   
               
               
                 Full gait data - trots Part 2 
               
            
           
           
               
               
               
               
               
            
               
                 Patient 
                   
                 Stance % 
                 Stance Time 
                 Step/Stride Ratio 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Number 
                 Name 
                 Date 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
                 LF 
                 RF 
                 LH 
                 RH 
               
               
                   
               
               
                 1 
                 Gipper 
                 Day 0 
                 60.4 
                 62.6 
                 51.0 
                 53.2 
                 0.330 
                 0.345 
                 0.280 
                 0.295 
                 50.6 
                 49.2 
                 50.6 
                 49.2 
               
               
                   
                 Hatch 
                 Day 14 
                 55.3 
                 61.6 
                 55.1 
                 51.7 
                 0.265 
                 0.286 
                 0.245 
                 0.241 
                 41.6 
                 57.6 
                 56.6 
                 44.1 
               
               
                   
                   
                 Day 30 
                 60.0 
                 61.4 
                 49.4 
                 50.4 
                 0.334 
                 0.341 
                 0.276 
                 0.282 
                 50.0 
                 49.9 
                 48.3 
                 51.7 
               
               
                   
                   
                 Day 60 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 2 
                 Rocco 
                 Day 0 
                 58.3 
                 57.5 
                 47.8 
                 50.1 
                 0.371 
                 0.370 
                 0.306 
                 0.319 
                 47.4 
                 52.4 
                 47.0 
                 52.9 
               
               
                   
                 Payne 
                 Day 14 
                 55.8 
                 55.8 
                 43.3 
                 45.3 
                 0.350 
                 0.352 
                 0.279 
                 0.284 
                 48.8 
                 51.1 
                 46.7 
                 53.2 
               
               
                   
                   
                 Day 30 
                 59.4 
                 57.4 
                 47.9 
                 50.0 
                 0.382 
                 0.376 
                 0.314 
                 0.332 
                 47.2 
                 53.0 
                 47.6 
                 52.2 
               
               
                   
                   
                 Day 60 
                 53.3 
                 52.3 
                 41.7 
                 44.2 
                 0.301 
                 0.296 
                 0.243 
                 0.255 
                 48.8 
                 50.8 
                 48.6 
                 51.2 
               
               
                 3 
                 Bubba 
                 Day 0 
                 50.5 
                 49.4 
                 44.0 
                 43.3 
                 0.295 
                 0.286 
                 0.269 
                 0.261 
                 49.9 
                 50.1 
                 50.0 
                 49.9 
               
               
                   
                 Schlimm 
                 Day 14 
                 50.9 
                 50.4 
                 42.3 
                 42.1 
                 0.290 
                 0.285 
                 0.245 
                 0.243 
                 49.5 
                 50.6 
                 48.7 
                 51.5 
               
               
                   
                   
                 Day 30 
                 53.6 
                 55.1 
                 48.5 
                 50.1 
                 0.337 
                 0.350 
                 0.315 
                 0.327 
                 50.9 
                 49.0 
                 49.4 
                 50.5 
               
               
                   
                   
                 Day 60 
                 53.7 
                 54.9 
                 49.9 
                 48.3 
                 0.333 
                 0.341 
                 0.314 
                 0.302 
                 50.8 
                 48.8 
                 49.6 
                 50.3 
               
               
                 4 
                 Aiden 
                 Day 0 
                 45.0 
                 44.0 
                 40.1 
                 39.0 
                 0.241 
                 0.235 
                 0.215 
                 0.208 
                 50.3 
                 49.7 
                 50.6 
                 49.2 
               
               
                   
                 Langhans- 
                 Day 14 
                 44.5 
                 43.8 
                 38.5 
                 38.5 
                 0.228 
                 0.226 
                 0.199 
                 0.199 
                 51.0 
                 48.7 
                 50.3 
                 49.5 
               
               
                   
                 Lindstadt 
                 Day 30 
                 46.4 
                 46.0 
                 39.0 
                 38.8 
                 0.259 
                 0.255 
                 0.213 
                 0.210 
                 50.4 
                 49.3 
                 50.5 
                 49.2 
               
               
                   
                   
                 Day 60 
                 44.4 
                 45.1 
                 37.7 
                 38.1 
                 0.241 
                 0.249 
                 0.203 
                 0.207 
                 49.2 
                 50.7 
                 50.4 
                 49.4 
               
               
                 5 
                 Moose 
                 Day 0 
                 44.7 
                 48.2 
                 42.9 
                 42.5 
                 0.214 
                 0.232 
                 0.205 
                 0.203 
                 49.6 
                 50.4 
                 49.6 
                 50.5 
               
               
                   
                 Baker 
                 Day 14 
                 43.5 
                 47.8 
                 43.3 
                 42.9 
                 0.203 
                 0.221 
                 0.203 
                 0.197 
                 48.7 
                 51.0 
                 47.7 
                 52.1 
               
               
                   
                   
                 Day 30 
                 47.5 
                 50.5 
                 44.7 
                 45.5 
                 0.228 
                 0.245 
                 0.215 
                 0.220 
                 48.6 
                 51.1 
                 48.6 
                 51.1 
               
               
                   
                   
                 Day 60 
                 46.3 
                 49.8 
                 42.7 
                 45.2 
                 0.223 
                 0.243 
                 0.204 
                 0.217 
                 48.0 
                 51.8 
                 47.4 
                 52.5 
               
               
                   
               
               
                     = removed from study 
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 34 
               
             
            
               
                   
               
               
                 Gait analysis summary 
               
            
           
           
               
               
               
               
               
            
               
                 Dog 1 
                 Dog 2 
                 Dog 3 
                 Dog 4 
                 Dog 5 
               
               
                   
               
               
                 Walk 
                 Walk 
                 Walk 
                 Walk 
                 Walk 
               
               
                 Step/Stride - 
                 Step/Stride - 
                 Step/Stride - 
                 Step/Stride - 
                 Step/Stride - 
               
               
                 declined Day 14, 
                 improves day 30 &amp; 
                 Declined day 60 
                 Unchanged 
                 Unchanged 
               
               
                 improved day 60 
                 60 
                 Stance % - 
                 Stance % - 
                 Stance % - 
               
               
                 Stance % - 
                 Stance % - 
                 unchanged 
                 slightly declined day 
                 decline day 14, 60 
               
               
                 improved day 14, 30, 
                 declined day 30, 
                   
                 14, 30 
               
               
                 and 60 
                 improved day 60 
                 Trot 
                 Trot 
                 Trot 
               
               
                 Trot 
                 Trot 
                 Step/Stride - 
                   
                 Step/Stride - 
               
               
                   
                   
                 Unchanged, (slightly 
                 Step/Stride - 
                 slightly declined at 
               
               
                 Step/Stride - 
                 Step/Stride - 
                 declined) 
                 Unchanged 
                 each recheck 
               
               
                 declined day 14 (no 
                 slowly improved at 
               
               
                 day 60 data) 
                 each recheck 
                 Stance % - 
                 Stance % - 
                 Stance % - 
               
               
                   
                   
                 slightly declined day 
                 slightly improved 
                 forelimbs slight 
               
               
                 Stance % - 
                 Stance % - 
                 30, 60 
                 day 14, 30, 60 
                 improve day 30 but 
               
               
                 Declined day 14, 
                 declined day 30 
                   
                   
                 hindlimb declined, 
               
               
                 slightly improved 
                   
                   
                   
                 declined day 60 
               
               
                 day 30 (no day 60 
               
               
                 data) 
               
               
                   
               
            
           
         
       
     
     Example 14 
     Feline Safety Study 
     A 12-week safety study was performed in felines to evaluate the safety of an oil containing CBD. 
     Animals and Study Design 
     Eight cats, 2-6 years old, weighing 3.33-5.17 kg at study start were selected for the study, as shown in Table 35. 
                     TABLE 35                  Animal information                                 Cat ID   Sex   Date of Birth                       15EGA5   FS   Apr. 8, 2015           13IRD3   FS   Oct. 5, 2013           15KGA2   FS   Apr. 7, 2015           13CNL3   MC   May 20, 2013           13CCL1   MC   Feb. 11, 2013           GJY3   MC   Jul. 17, 2011           15KGC3   MC   Apr. 8, 2015           13CPJ7   FS   Oct. 25, 2013                        
Cats were single housed in cages of a size in accordance with the Animal Welfare Act, with a 12-hour-light/12-hour-dark cycle and targeted conditions of 50° to 85° F. Cages, food bowls, water bowls and litter boxes were cleaned daily and sanitized in accordance with the Animal Welfare Act. Fresh tap water, fit for human consumption, was available ad libitum by means of stainless steel bowls. There were no known contaminants that were reasonably expected to be present in the dietary material that were known to be capable of interfering with the purpose or conduct of the study
 
     During the study, the control diet, Purina Cat Chow, was the sole source of food supplied to each animal once daily for approximately 4 hours. Cats were fed according to ideal body condition and were fasted for a minimum of 12 hours prior to blood collections. CBD oil was orally administered twice a day using a 1 ml syringe at a dosage of 2 mg/kg. The total dose per 24 hour period was 4 mg/kg. Dosing is shown in Tables 36 and 37. 
     
       
         
           
               
             
               
                 TABLE 36 
               
             
            
               
                   
               
               
                 Dosage per week (mL) (weeks 1-6) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Cat ID 
                 Sex 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 15EGA5 
                 FS 
                 0.14 
                 0.14 
                 0.14 
                 0.15 
                 0.14 
                 0.14 
               
               
                 13IRD3 
                 FS 
                 0.13 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
               
               
                 15KGA2 
                 FS 
                 0.13 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
               
               
                 13CNL3 
                 MC 
                 0.19 
                 0.19 
                 0.19 
                 0.19 
                 0.19 
                 0.19 
               
               
                 13CCL1 
                 MC 
                 0.20 
                 0.20 
                 0.20 
                 0.20 
                 0.21 
                 0.20 
               
               
                 GJY3 
                 MC 
                 0.21 
                 0.22 
                 0.22 
                 0.22 
                 0.23 
                 0.23 
               
               
                 15KGC3 
                 MC 
                 0.19 
                 0.20 
                 0.21 
                 0.21 
                 0.21 
                 0.21 
               
               
                 13CPJ7 
                 FS 
                 0.15 
                 0.15 
                 0.15 
                 0.15 
                 0.16 
                 0.16 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 37 
               
             
            
               
                   
               
               
                 Dosage per week (mL) (weeks 7-12) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Cat ID 
                 Sex 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 15EGA5 
                 FS 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
                 0.13 
               
               
                 13IRD3 
                 FS 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
                 0.13 
                 0.13 
               
               
                 15KGA2 
                 FS 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
                 0.14 
                 0.13 
               
               
                 13CNL3 
                 MC 
                 0.19 
                 0.19 
                 0.19 
                 0.19 
                 0.19 
                 0.19 
               
               
                 13CCL1 
                 MC 
                 0.21 
                 0.20 
                 0.20 
                 0.20 
                 0.19 
                 0.19 
               
               
                 GJY3 
                 MC 
                 0.23 
                 0.23 
                 0.23 
                 0.23 
                 0.23 
                 0.22 
               
               
                 15KGC3 
                 MC 
                 0.21 
                 0.21 
                 0.21 
                 0.21 
                 0.21 
                 0.21 
               
               
                 13CPJ7 
                 FS 
                 0.16 
                 0.15 
                 0.15 
                 0.15 
                 0.15 
                 0.15 
               
               
                   
               
            
           
         
       
     
     CBC and Serum Chemistry 
     Prior to study initiation, 5 milliliters of blood was collected for each cat and was used to determine eligibility for the study. During the study, 5 milliliters of blood was collected weekly (±2 days). Blood was collected via jugular venipuncture in sterile syringes. Samples were split into two tubes: a red-top serum separator tube and a lavender-top EDTA tube. Redtop tubes were spun in a refrigerated centrifuge for 15 minutes at 3000 RPM after being allowed to clot. Lavender-top tubes were placed on a rocker to allow the blood to adequately mix with the anticoagulant. Blood samples were packaged and sent by priority-overnight to Antech Diagnostics for analysis. 
     Pharmacokinetic (PK) Blood Collection 
     On the first day of dosing, blood was collected for a PK analysis from 6 of the 8 cats. The most cooperative cats were selected for the PK analysis. Approximately 4 milliliters of blood was collected via jugular venipuncture in sterile syringes at one day prior to treatment (timepoint 0) and then 1, 4, 8 and 24 hours after treatment. Samples were placed into a red top clotting tube with no serum separator. Serum was harvested by centrifuging the tubes at 3000 RPM for 15 minutes. The harvested serum was placed in cyrovials stored at −70° C. Each tube was labeled with the cat id, date of collection and collection time point. Samples were shipped overnight on dry ice to the Proteomics &amp; Metabolomics Facility at Colorado State University. 
     Clinical Observations 
     A veterinarian performed a complete physical examination to all cats prior to the initiation of the study and at study completion. Each cat was evaluated as to general health, body and hair coat condition. Qualified personnel performed clinical observations twice daily in accordance with Summit Ridge Farms&#39; Program of Veterinary Care and SOP VC-003 (Rounds Observations). All animals were evaluated twice daily with reference to SOP VC-016 (Recognizing Pain, Stress and/or Distress). Clinical laboratory diagnostic procedures were performed as needed. Veterinary care was given as appropriate to each individual animal in accordance with the Program of Veterinary Care. 
     Blood Analysis 
     Blood was analyzed for white blood cell count, red blood cell count, hemoglobin, hematocrit, MCV, MCHC, MCH, and platelet count along with a complete differential. In addition, a 22-test chemistry screen was performed consisting of Glucose, Urea Nitrogen, Creatinine, Total Protein, Albumin, Total Bilirubin, Alkaline Phosphatase, ALT, AST, CPK, Cholesterol, Calcium, Phosphorus, Sodium, Potassium, Chloride, NG Ratio, BUN/Creatinine Ratio, Globulin, Triglycerides, GGTP and Magnesium. Measurements were taken prior to the start of the study and then weekly during the course of the study. 
     PK Analysis 
     Extraction of Cannabidiol from Feline serum for LC-MS 
     Aliquots of feline serum were delivered to the facility on dry ice and stored at −80° C. upon receipt. For cannabidiol (CBD) extraction, serum was thawed on ice and 50 μL of each sample was placed into a 2.0 ml glass extraction vial (VWR ROBO Unassembled Autosampler Vial) kept on chilled on ice. 200 μL of cold (−20 C) 100% Acetonitrile (spiked with 60 ng/mL of d3-CBD) was added to each sample and vortexed at room temperature for 5 minutes. 200 μL of water was added and vortexed for an additional 5 minutes. 1 ml of 100% hexane was then added to each sample and vortexed for a final 5 minutes. Phase separation was enhanced under centrifugation at 3000 rpm for 15 minutes at 4 C. The upper hexane layer was transferred to new-labeled glass vials (˜900 uL per sample), carefully avoiding the middle and lower layers. Samples were concentrated to dryness under N2 and resuspended in 60 μL of 100% acetonitrile. 
     Standard Curve 
     An 8 point standard curve of CBD was generated in matrix background using a blank serum. Concentrations ranged from 0 ng/mL 1000 ng/mL (3.2× dilution series). 50 uL of each spiked serum sample was extracted as above. 
     LC-MS/MS Analysis 
     LC-MS/MS was performed on a Waters Acquity M-Class UPLC coupled to a Waters Xevo TQ-S triple quadrupole mass spectrometer. Chromatographic separations were carried out on a Waters BEH C18 iKey Separation Device (150 μm×50 mm, 1.7 μM). Mobile phases were 99.9% acetonitrile, 0.1% formic acid (B) and water with 0.1% formic acid (A). The analytical gradient was as follows: time=0 min, 70% B; time=1.0 min, 70% B; time=6 min, 100% B; time 7.0 min, 100% B; time 7.5 min, 70% B. Total run time was 10 minutes. Flow rate was 3.0 μL/min and injection volume was 2.0 μL. Samples were held at 6° C. in the autosampler, and the column was operated at 70° C. The MS was operated in selected reaction monitoring (SRM) mode, where a parent ion is selected by the first quadrupole, fragmented in the collision cell, then a fragment ion selected for by the third quadrupole. Product ions, collision energies, and cone voltages were optimized for each analyte by direct injection of individual synthetic standards. Inter-channel delay was set to 3 ms. The MS was operated in positive ionization mode with the capillary voltage set to 3.6 kV. Source temperature was 120° C. and desolvation temperature 992° C. Desolvation gas flow was 1 L/hr, cone gas flow was 150 L/hr, and collision gas flow was 0.2 mL/min. Nebulizer pressure (nitrogen) was set to 7 Bar. Argon was used as the collision gas. 
     Data Analysis and Statistics 
     All Raw data files were imported into the Skyline open source software package. Each target analyte was visually inspected for retention time and peak area integration. Peak areas were extracted for target compounds detected in biological samples and normalized to the peak area of the appropriate internal standard in each sample using in-house R Script (TQS-tools). CBD concentrations were calculated in nanograms per milliliter of extract (0.06 mL) and then back calculated to nanograms per mL of serum (0.05 mL of serum). 
     Calculation of Variance using QC Pool 
     50 uL of all serum samples (feline and canine) were pooled into a single Quality Control sample and 50 uL was extracted as described above. The QC pool was injected every 10 samples and CBD concentrations were used to measure the technical variance over the course of data acquisition. 
     Limits of Detection (LOD) and Limits of Quantification (LOQ) 
     The LOD and LOQ represent the lower limits of detection and quantification for each compound in the matrix of this study. LOD are calculated based on the standard deviation of the response (Sy) of the 0 point calibration standard (i.e. 0 ng/mL CBD as an estimate on noise) and the slope of the calibration curve (S) at levels approximating the LOD according to the formula: LOD=3*(Sy/S). LOQ=10*(Sy/S). The Sy of y is the standard deviation used for LOD and LOQ calculation. 
     Results 
     Body Weight 
     The mean average weight change for cats during the 12 weeks of the study was 0.06 kg (1.04%). Weight data is presented in Tables 38 and 39. 
     
       
         
           
               
             
               
                 TABLE 38 
               
             
            
               
                   
               
               
                 Weekly body weights (weeks 1-6) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Cat ID 
                 Sex 
                 Base 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 15EGA5 
                 FS 
                 3.43 
                 3.60 
                 3.62 
                 3.76 
                 3.62 
                 3.60 
                 3.62 
               
               
                 13IRD3 
                 FS 
                 3.34 
                 3.48 
                 3.61 
                 3.61 
                 3.48 
                 3.51 
                 3.52 
               
               
                 15KGA2 
                 FS 
                 3.33 
                 3.42 
                 3.48 
                 3.51 
                 3.53 
                 3.53 
                 3.49 
               
               
                 13CNL3 
                 MC 
                 4.66 
                 4.63 
                 4.70 
                 4.81 
                 4.82 
                 4.81 
                 4.78 
               
               
                 13CCL1 
                 MC 
                 5.03 
                 5.01 
                 5.00 
                 5.11 
                 5.14 
                 5.07 
                 5.19 
               
               
                 GJY3 
                 MC 
                 5.17 
                 5.53 
                 5.55 
                 5.57 
                 5.63 
                 5.64 
                 5.67 
               
               
                 15KGC3 
                 MC 
                 4.82 
                 5.11 
                 5.21 
                 5.18 
                 5.27 
                 5.26 
                 5.31 
               
               
                 13CPJ7 
                 FS 
                 3.72 
                 3.73 
                 3.86 
                 3.87 
                 3.93 
                 3.92 
                 3.92 
               
               
                   
                 Mean: 
                 4.19 
                 4.31 
                 4.38 
                 4.43 
                 4.43 
                 4.42 
                 4.44 
               
               
                   
                 SD: 
                 0.806 
                 0.849 
                 0.828 
                 0.824 
                 0.880 
                 0.871 
                 0.898 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 39 
               
             
            
               
                   
               
               
                 Weekly body weights (weeks 7-12) 
               
            
           
           
               
               
               
            
               
                   
                 Week 
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Cat ID 
                 Sex 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
                 Chg. 
                 % Chg. 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 15EGA5 
                 FS 
                 3.50 
                 3.51 
                 3.49 
                 3.38 
                 3.37 
                 3.33 
                 −0.10 
                 −2.92 
               
               
                 13IRD3 
                 FS 
                 3.46 
                 3.42 
                 3.38 
                 3.36 
                 3.27 
                 3.25 
                 −0.09 
                 −2.69 
               
               
                 15KGA2 
                 FS 
                 3.43 
                 3.43 
                 3.40 
                 3.39 
                 3.34 
                 3.37 
                 0.04 
                 1.20 
               
               
                 13CNL3 
                 MC 
                 4.78 
                 4.82 
                 4.82 
                 4.84 
                 4.80 
                 4.83 
                 0.17 
                 3.65 
               
               
                 13CCL1 
                 MC 
                 4.99 
                 4.96 
                 4.96 
                 4.87 
                 4.85 
                 4.74 
                 −0.29 
                 −5.77 
               
               
                 GJY3 
                 MC 
                 5.67 
                 5.67 
                 5.69 
                 5.71 
                 5.55 
                 5.50 
                 0.33 
                 6.38 
               
               
                 15KGC3 
                 MC 
                 5.35 
                 5.33 
                 5.29 
                 5.21 
                 5.15 
                 5.11 
                 0.29 
                 6.02 
               
               
                 13CPJ7 
                 FS 
                 3.87 
                 3.86 
                 3.82 
                 3.81 
                 3.80 
                 3.81 
                 0.09 
                 2.42 
               
               
                   
                 Mean: 
                 4.38 
                 4.38 
                 4.36 
                 4.32 
                 4.27 
                 4.24 
                 0.06 
                 1.04 
               
               
                   
                 SD: 
                 0.920 
                 0.922 
                 0.936 
                 0.943 
                 0.920 
                 0.902 
                 0.210 
                 4.439 
               
               
                   
               
            
           
         
       
     
     Food Consumption 
     The Mean Daily Food Consumption Per Week for Cats During the Study was 62g. Food Consumption Data Is Presented in Tables 40 and 41. 
     
       
         
           
               
             
               
                 TABLE 40 
               
             
            
               
                   
               
               
                 Average daily food consumption per week (weeks 1-6) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Cat ID 
                 Sex 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 15EGA5 
                 FS 
                 70 
                 70 
                 65 
                 56 
                 55 
                 55 
               
               
                 13IRD3 
                 FS 
                 70 
                 70 
                 60 
                 51 
                 50 
                 50 
               
               
                 15KGA2 
                 FS 
                 70 
                 70 
                 65 
                 61 
                 55 
                 50 
               
               
                 13CNL3 
                 MC 
                 62 
                 59 
                 65 
                 65 
                 64 
                 64 
               
               
                 13CCL1 
                 MC 
                 75 
                 70 
                 87 
                 54 
                 64 
                 69 
               
               
                 GJY3 
                 MC 
                 100 
                 100 
                 95 
                 86 
                 80 
                 75 
               
               
                 15KGC3 
                 MC 
                 100 
                 98 
                 92 
                 93 
                 89 
                 82 
               
               
                 13CPJ7 
                 FS 
                 70 
                 70 
                 68 
                 66 
                 60 
                 55 
               
               
                   
                 Mean: 
                 77 
                 76 
                 75 
                 67 
                 64 
                 63 
               
               
                   
                 SD: 
                 14.6 
                 14.8 
                 14.2 
                 15.3 
                 13.3 
                 12.0 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 41 
               
             
            
               
                   
               
               
                 Average daily food consumption per week (weeks 6-12) 
               
            
           
           
               
               
            
               
                   
                 Week 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Cat ID 
                 Sex 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
                 Average 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 15EGA5 
                 FS 
                 51 
                 50 
                 50 
                 50 
                 50 
                 50 
                 56 
               
               
                 13IRD3 
                 FS 
                 46 
                 45 
                 45 
                 45 
                 45 
                 45 
                 52 
               
               
                 15KGA2 
                 FS 
                 50 
                 50 
                 50 
                 50 
                 50 
                 50 
                 56 
               
               
                 13CNL3 
                 MC 
                 64 
                 65 
                 62 
                 64 
                 61 
                 61 
                 63 
               
               
                 13CCL1 
                 MC 
                 63 
                 54 
                 75 
                 61 
                 42 
                 54 
                 64 
               
               
                 GJY3 
                 MC 
                 71 
                 66 
                 65 
                 55 
                 45 
                 45 
                 74 
               
               
                 15KGC3 
                 MC 
                 76 
                 66 
                 64 
                 60 
                 60 
                 60 
                 78 
               
               
                 13CPJ7 
                 FS 
                 51 
                 50 
                 50 
                 50 
                 49 
                 50 
                 57 
               
               
                   
                 Mean: 
                 59 
                 56 
                 58 
                 54 
                 50 
                 52 
                 62 
               
               
                   
                 SD: 
                 11.2 
                 8.5 
                 10.3 
                 6.7 
                 6.8 
                 6.2 
                 9.3 
               
               
                   
               
            
           
         
       
     
     Test Article Acceptance 
     Overall all cats exhibited behaviors of licking, salivating, pacing, head shaking, chomping, dose resentment (uncooperative behavior), etc. at various intervals throughout the study that were indicative of dislike of the test article. Results are shown in Tables 42-69. 
     
       
         
           
               
             
               
                 TABLE 42 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 1-3) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 1 
                 Day 2 
                 Day 3 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 chomping, white 
                 licking 
                 licking 
                 licking 
                 licking, 
                 licking 
               
               
                   
                 foamy mouth 
                   
                   
                   
                 chomping 
                   
               
               
                 13IRD3 
                 chomping, 
                 licking, head 
                 head shake, 
                 chomping 
                 licking, 
                 head shake 
               
               
                   
                 salivating 
                 shake, drooling 
                 licking 
                   
                 chomping 
                   
               
               
                 15KGA2 
                 chomping, 
                 licking 
                 licking 
                 licking 
                 licking, 
                 licking 
               
               
                   
                 salivating 
                   
                   
                   
                 chomping 
                   
               
               
                 13CNL3 
                 licking 
                 licking, head 
                 heads shake, 
                 — 
                 head shake, 
                 head shake 
               
               
                   
                   
                 shake, foaming 
                 licking 
                   
                 licking 
                   
               
               
                 13CCL1 
                 chomping, head 
                 licking, chomping 
                 licking 
                 chomping, 
                 chomping, 
                 — 
               
               
                   
                 shake, salivating 
                   
                   
                 salivating 
                 salivating 
                   
               
               
                   
                 chomping 
                 licking, chomping 
                 head shake, 
                 licking 
                 licking 
                 head shake 
               
               
                   
                   
                   
                 licking 
                   
                   
                   
               
               
                 15KGC3 
                 chomping 
                 licking 
                 licking 
                 licking 
                 head shake, 
                 licking 
               
               
                   
                   
                   
                   
                   
                 grimace 
                   
               
               
                 13CP17 
                 chomping, pacing 
                 pacing, chomping, 
                 licking, 
                 licking, pacing 
                 pacing 
                 pacing 
               
               
                   
                   
                 licking 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 43 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 4-6) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 4 
                 Day 5 
                 Day 6 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 AM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 drooling 
                 licking 
                 licking 
                 head shake 
                 head shake 
                 — 
               
               
                 13IRD3 
                 — 
                 chomping 
                 — 
                 — 
                 licking 
                 chewing 
               
               
                 15KGA2 
                 very 
                 chomping 
                 — 
                 licking 
                 licking 
                 — 
               
               
                   
                 relaxed 
                   
                   
                   
                   
                   
               
               
                 13CNL3 
                 pacing 
                 — 
                 — 
                 — 
                 — 
                 little 
               
               
                   
                   
                   
                   
                   
                   
                 head shake 
               
               
                 13CCL1 
                 head shake 
                 chomping 
                 — 
                 chomping 
                 chomping 
                 — 
               
               
                 GJY3 
                 licking 
                 licking 
                 licking 
                 — 
                 licking 
                 licking 
               
               
                 15KGC3 
                 — 
                 licking 
                 chomping 
                 licking 
                 — 
                 — 
               
               
                 13CP17 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 44 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 7-9) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 7 
                 Day 8 
                 Day 9 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 head shake 
                 head shake 
                 head shake 
                 head shake 
                 licking 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 — 
                 head shake 
                 — 
               
               
                 15KGA2 
                 — 
                 chewing 
                 — 
                 licking 
                 chomping 
                 — 
               
               
                 13CNL3 
                 — 
                 — 
                 — 
                 head shake 
                 — 
                 — 
               
               
                 13CCL1 
                 head shake 
                 head shake 
                 licking 
                 — 
                 — 
                 chomping 
               
               
                 GJY3 
                 licking 
                 licking 
                 — 
                 — 
                 — 
                 licking 
               
               
                 15KGC3 
                 licking 
                 licking/head shake 
                 licking 
                 — 
                 head shake 
                 — 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 45 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 10-12) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 10 
                 Day 11 
                 Day 12 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 — 
                 licking 
                 — 
                 head shake 
                 chomping 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 — 
                 — 
                 — 
                 head shake 
                 licking 
                 — 
               
               
                 13CNL3 
                 licking 
                 licking 
                 — 
                 licking 
                 — 
                 — 
               
               
                 13CCL1 
                 — 
                 — 
                 head shake 
                 — 
                 head shake 
                 head shake 
               
               
                 GJY3 
                 — 
                 — 
                 — 
                 licking 
                 — 
                 — 
               
               
                 15KGC3 
                 head shake 
                 licking 
                 — 
                 — 
                 licking 
                 licking 
               
               
                 13CP17 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 46 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 13-15) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 13 
                 Day 14 
                 Day 15 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 — 
                 — 
                 head shake 
                 licking 
                 chomping 
                 licking 
               
               
                 13IRD3 
                 licking 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 licking 
                 licking 
                 chomping 
                 — 
                 chomping 
                 licking 
               
               
                 13CNL3 
                 — 
                 — 
                 — 
                 chomping 
                 — 
                 — 
               
               
                 13CCL1 
                 — 
                 — 
                 food vomit 
                 — 
                 — 
                 — 
               
               
                   
                   
                   
                 before dosing 
               
               
                 GJY3 
                 licking 
                 — 
                 hairball vomit 
                 licking 
                 — 
                 — 
               
               
                   
                   
                   
                 before dosing 
               
               
                 15KGC3 
                 licking 
                 head shake 
                 — 
                 — 
                 — 
                 — 
               
               
                 13CPJ7 
                 licking 
                 pacing 
                 pacing 
                 — 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 47 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 16-18) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 16 
                 Day 17 
                 Day 18 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 chomping 
                 — 
                 head shake 
                 licking 
                 licking 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 licking 
                 — 
                 salivating 
                 — 
               
               
                   
                   
                   
                   
                   
                 before dosing 
               
               
                 15KGA2 
                 licking 
                 licking 
                 head shake, licking 
                 — 
                 — 
                 — 
               
               
                 13CNL3 
                 — 
                 — 
                 — 
                 licking 
                 hairball vomit 
                 — 
               
               
                   
                   
                   
                   
                   
                 before dosing 
               
               
                 13CCL1 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 GJY3 
                 licking 
                 licking 
                 — 
                 — 
                 — 
                 licking 
               
               
                 15KGC3 
                 — 
                 — 
                 head shake 
                 head shake 
                 head shake 
                 — 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 chomping 
                 licking 
                 — 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 48 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 19-21) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 19 
                 Day 20 
                 Day 21 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 — 
                 — 
                 head shake 
                 licking 
                 head shake 
                 head shake 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 — 
                 chomping 
                 chomping 
                 chomping 
                 licking 
                 licking 
               
               
                 13CNL3 
                 — 
                 — 
                 — 
                 — 
                 licking 
                 — 
               
               
                 13CCL1 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 GJY3 
                 — 
                 licking 
                 licking 
                 — 
                 licking 
                 licking 
               
               
                 15KGC3 
                 head shake 
                 head shake 
                 licking 
                 head shake 
                 head shake 
                 head shake 
               
               
                 13CP17 
                 — 
                 pacing 
                 head shake 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 49 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 22-24) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 22 
                 Day 23 
                 Day 24 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 — 
                 licking 
                 — 
                 licking 
                 head shake 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 — 
                 licking 
                 head shake 
                 — 
                 head shake 
                 licking 
               
               
                 13CNL3 
                 — 
                 — 
                 head shake 
                 head shake 
                 head shake 
                 — 
               
               
                 13CCL1 
                 licking, head shake 
                 — 
                 — 
                 chomping 
                 — 
                 uncooperative, l;icking 
               
               
                 GJY3 
                 — 
                 head shake 
                 licking 
                 licking 
                 — 
                 — 
               
               
                 15KGC3 
                 head shake 
                 head shake 
                 licking 
                 — 
                 licking 
                 — 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 head shake 
                 — 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 50 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 25-27) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 25 
                 Day 26 
                 Day 27 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 — 
                 licking 
                 — 
                 head shake 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 head shake 
                 licking 
                 — 
                 head shake 
               
               
                 15KGA2 
                 licking 
                 licking 
                 — 
                 licking 
                 — 
                 licking 
               
               
                 13CNL3 
                 licking 
                 licking 
                 licking 
                 — 
                 licking 
                 — 
               
               
                 13CCL1 
                 head shake 
                 heading 
                 — 
                 chomping 
                 head shake 
                 — 
               
               
                 GJY3 
                 — 
                 — 
                 licking 
                 licking 
                 licking, head shaking 
                 licking 
               
               
                 15KGC3 
                 — 
                 — 
                 head shake, licking 
                 head shake 
                 licking 
                 head shake, licking 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 51 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 28-30) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 28 
                 Day 29 
                 Day 30 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 — 
                 — 
                 — 
                 licking, head shake 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 head shake 
                 — 
                 head shake 
               
               
                 15KGA2 
                 — 
                 head shake 
                 — 
                 licking 
                 — 
                 licking 
               
               
                 13CNL3 
                 — 
                 — 
                 head shake 
                 head shake 
                 licking 
                 — 
               
               
                 13CCL1 
                 licking 
                 head shake, licking 
                 licking 
                 — 
                 — 
                 — 
               
               
                 GJY3 
                 licking 
                 — 
                 licking 
                 licking, head shake 
                 — 
                 licking 
               
               
                 15KGC3 
                 — 
                 licking, head shake 
                 head shake, licking 
                 licking 
                 licking 
                 head shake 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 head shake, pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 52 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 31-33) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 31 
                 Day 32 
                 Day 33 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 head shake 
                 licking 
                 head shake 
                 head shake 
                 head shake, licking 
                 licking 
               
               
                 13IRD3 
                 head shake 
                 — 
                 — 
                 licking 
                 — 
                 head shake 
               
               
                 15KGA2 
                 — 
                 — 
                 chomping, licking 
                 — 
                 chomping 
                 licking 
               
               
                 13CNL3 
                 licking 
                 head shake 
                 licking 
                 licking 
                 — 
                 — 
               
               
                 13CCL1 
                 — 
                 licking 
                 — 
                 — 
                 — 
                 head shake 
               
               
                 GJY3 
                 licking 
                 licking 
                 — 
                 licking 
                 licking 
                 — 
               
               
                 15KGC3 
                 licking, chomping 
                 head shake 
                 head shake 
                 head shake, likcing 
                 — 
                 head shake 
               
               
                 13CPJ7 
                 head shake 
                 pacing 
                 head shake 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 53 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 79-81) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 34 
                 Day 35 
                 Day 36 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 licking 
                 licking 
                 — 
                 — 
                 chomping 
               
               
                 13IRD3 
                 — 
                 — 
                 head shake 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 chomping, licking 
                 licking 
                 — 
                 chomping 
                 chomping, licking 
                 — 
               
               
                 13CNL3 
                 — 
                 — 
                 — 
                 — 
                 head shake 
                 — 
               
               
                 13CCL1 
                 — 
                 — 
                 licking 
                 licking 
                 — 
                 —n 
               
               
                 GJY3 
                 — 
                 licking 
                 — 
                 licking 
                 — 
                 — 
               
               
                 15KGC3 
                 licking 
                 licking 
                 — 
                 licking 
                 — 
                 licking 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 licking 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 54 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 37-39) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 37 
                 Day 38 
                 Day 39 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 chomping 
                 head shake 
                 licking 
                 licking 
                 licking 
                 head shake, licking 
               
               
                 13IRD3 
                 — 
                 — 
                 head shake 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 licking 
                 licking 
                 — 
                 licking, head shake 
                 — 
                 licking 
               
               
                 13CNL3 
                 uncooperative 
                 head shake 
                 jumping, licking 
                 — 
                 jumping, licking 
                 licking 
               
               
                 13CCL1 
                 uncooperative 
                 — 
                 — 
                 drooling, head shake 
                 — 
                 head shake, licking 
               
               
                 GJY3 
                 — 
                 licking 
                 — 
                 — 
                 — 
                 jumping 
               
               
                 15KGC3 
                 uncooperative 
                 licking 
                 head shake, licking 
                 head shake 
                 head shake, licking 
                 head shake, licking 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 55 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 40-42) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 40 
                 Day 41 
                 Day 42 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 head shake, licking 
                 chomping, licking 
                 — 
                 licking 
                 — 
                 — 
               
               
                 13IRD3 
                 — 
                 — 
                 head shake 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 licking 
                 licking 
                 — 
                 licking, head shake 
                 — 
                 licking 
               
               
                 13CNL3 
                 uncooperative 
                 head shake 
                 jumping, licking 
                 — 
                 jumping, licking 
                 licking 
               
               
                 13CCL1 
                 uncooperative 
                 — 
                 — 
                 drooling, head shake 
                 — 
                 head shake, licking 
               
               
                 GJY3 
                 — 
                 licking 
                 — 
                 — 
                 — 
                 jumping 
               
               
                 15KGC3 
                 uncooperative 
                 licking 
                 head shake, licking 
                 head shake 
                 head shake, licking 
                 head shake, licking 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 56 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 43-45) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 43 
                 Day 44 
                 Day 45 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 chomping, licking 
                 chomping, licking 
                 head shake, licking 
                 licking 
                 chewing 
                 chewing 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 head shake, licking 
                 head shake 
                 licking 
                 head shake, chomping 
                 head shake, chewing 
                 — 
               
               
                 13CNL3 
                 — 
                 — 
                 — 
                 — 
                 head shake 
                 head shake 
               
               
                 13CCL1 
                 — 
                 gagging 
                 food vomit 
                 — 
                 head shake 
                 head shake 
               
               
                   
                   
                   
                 before dosing 
               
               
                 GJY3 
                 licking 
                 licking 
                 — 
                 — 
                 licking 
                 a little chewing 
               
               
                 15KGC3 
                 head shake, licking, 
                 licking 
                 head shake, licking 
                 head shake 
                 licking 
                 head shake 
               
               
                   
                 chomping 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 57 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 46-48) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 46 
                 Day 47 
                 Day 48 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking, chomping 
                 — 
                 licking, head shake 
                 licking 
                 licking 
                 head shake, licking 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 — 
                 — 
                 drooling 
               
               
                 15KGA2 
                 licking 
                 licking 
                 head shake, chomping 
                 chomping 
                 chewing, head shake 
                 licking 
               
               
                 13CNL3 
                 — 
                 — 
                 licking 
                 — 
                 licking 
                 — 
               
               
                 13CCL1 
                 head shake 
                 licking, chewing 
                 — 
                 — 
                 head shake 
                 — 
               
               
                 GJY3 
                 licking 
                 head shake 
                 — 
                 licking 
                 — 
                 licking 
               
               
                 15KGC3 
                 head shake, licking 
                 — 
                 head shake 
                 — 
                 licking 
                 licking 
               
               
                 13CPJ7 
                 pacing, head shake 
                 pacing 
                 pacing 
                 pacing 
                 head shake, pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                 Observations following test article administration (days 49-51) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 49 
                 Day 50 
                 Day 51 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 — 
                 licking, head shake 
                 licking, head shake 
                 head shake, chomping 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 — 
                 head shake 
                 — 
               
               
                 15KGA2 
                 licking 
                 licking 
                 licking 
                 — 
                 head shake 
                 licking 
               
               
                 13CNL3 
                 licking 
                 head shake 
                 — 
                 head shake 
                 — 
                 licking 
               
               
                 13CCL1 
                 licking 
                 head shake 
                 salivating 
                 — 
                 — 
                 gagging 
               
               
                 GJY3 
                 head shake 
                 licking 
                 head shake 
                 — 
                 licking 
                 head shake, licking 
               
               
                 15KGC3 
                 licking, head shake 
                 head shake, licking 
                 licking, head shake 
                 licking, head shake 
                 head shake, chomping 
                 licking 
               
               
                 13CPJ7 
                 head shake, pacing 
                 licking, head shake 
                 head shake 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 59 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 52-54) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 52 
                 Day 53 
                 Day 54 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 — 
                 Chomping 
                 licking 
                 head shake, licking 
                 — 
               
               
                 13IRD3 
                 — 
                 head shake 
                 — 
                 head shake 
                 — 
                 — 
               
               
                 15KGA2 
                 — 
                 licking 
                 head shake, chomping 
                 licking 
                 head shake, licking 
                 head shake, licking 
               
               
                 13CNL3 
                 head shake 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 13CCL1 
                 licking 
                 — 
                 gagging, chomping 
                 — 
                 head shake 
                 gagging, head shake 
               
               
                 GJY3 
                 licking 
                 licking 
                 — 
                 — 
                 — 
                 — 
               
               
                 15KGC3 
                 head shake, licking 
                 head shake 
                 chomping 
                 head shake, licking 
                 chomping, head shake 
                 head shake, licking 
               
               
                 13CPJ7 
                 head shaking, pacing 
                 pacing 
                 pacing 
                 pacing 
                 paring 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 60 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 55-57) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 55 
                 Day 56 
                 Day 57 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 chomping, drooling 
                 licking 
                 chomping, licking 
                 licking 
                 head shake, chomping, 
                 chomping, licking 
               
               
                   
                   
                   
                   
                   
                 drooling 
               
               
                 13IRD3 
                 head shake 
                 — 
                 — 
                 head shake 
                 — 
                 — 
               
               
                 15KGA2 
                 chomping 
                 — 
                 chomping 
                 head shake, licking 
                 — 
                 licking 
               
               
                 13CNL3 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 13CCL1 
                 gagging 
                 gagging 
                 — 
                 head shake 
                 — 
                 gagging 
               
               
                 GJY3 
                 — 
                 licking 
                 — 
                 licking 
                 licking 
                 licking 
               
               
                 15KGC3 
                 head shake, chomping 
                 head shake 
                 head shake, chomping 
                 head shake, chomping 
                 licking 
                 chomping, licking 
               
               
                 13CP17 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 61 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 58-60) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 58 
                 Day 59 
                 Day 60 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 — 
                 head shake 
                 — 
                 — 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 — 
                 licking 
                 — 
                 — 
               
               
                 15KGA2 
                 licking 
                 — 
                 licking 
                 — 
                 licking 
                 licking 
               
               
                 13CNL3 
                 — 
                 head shake 
                 head shake 
                 licking 
                 head shake 
                 head shake 
               
               
                 13CCL1 
                 gagging 
                 licking 
                 — 
                 head shake, licking 
                 licking 
                 licking 
               
               
                 GJY3 
                 licking 
                 licking 
                 licking 
                 head shake 
                 licking, head shake 
                 licking 
               
               
                 15KGC3 
                 head shake, chomping 
                 head shake, licking 
                 head shake 
                 violent head shake 
                 licking 
                 head shake 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing, licking 
                 pacing, head shake 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 62 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 61-63) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 61 
                 Day 62 
                 Day 63 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 — 
                 — 
                 licking 
                 chomping, licking 
                 head shake 
                 licking 
               
               
                 13IRD3 
                 head shake 
                 licking 
                 head shake 
                 licking 
                 head shake 
                 — 
               
               
                 15KGA2 
                 — 
                 head shake 
                 head shake, licking 
                 licking, head shake 
                 head shake, licking 
                 head shake, licking 
               
               
                 13CNL3 
                 licking 
                 — 
                 — 
                 — 
                 — 
                 head shake 
               
               
                 13CCL1 
                 gagging 
                 head shake 
                 — 
                 gagging 
                 gagging 
                 gagging 
               
               
                 GJY3 
                 — 
                 — 
                 licking 
                 head shake 
                 — 
                 — 
               
               
                 15KGC3 
                 head shake, licking 
                 head shake 
                 chomping, licking 
                 — 
                 head shake, licking 
                 head shake, licking 
               
               
                 13CPJ7 
                 pacing 
                 uncooperative, pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 63 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 64-66) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 64 
                 Day 65 
                 Day 66 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 head shake, licking 
                 licking 
                 licking 
                 licking, head shake 
                 chomping 
                 head shake, licking 
               
               
                 13IRD3 
                 head shake 
                 — 
                 licking 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 pacing, licking 
                 pacing 
                 head shake 
                 head shake, licking 
                 head shake 
                 head shake, licking 
               
               
                 13CNL3 
                 — 
                 — 
                 licking 
                 — 
                 — 
                 head shake, licking 
               
               
                 13CCL1 
                 head shake, licking 
                 licking 
                 — 
                 gagging 
                 licking 
                 — 
               
               
                 GJY3 
                 licking 
                 licking, head shake 
                 — 
                 licking 
                 licking 
                 licking 
               
               
                 15KGC3 
                 head shake, licking 
                 licking 
                 head shake, licking 
                 — 
                 head shake, licking 
                 head shake 
               
               
                 13CP17 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing, head shake 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 64 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 67-69) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 67 
                 Day 68 
                 Day 69 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 — 
                 licking 
                 head, shake 
                 licking 
                 licking 
                 head shake, licking 
               
               
                 13IRD3 
                 head shake 
                 — 
                 head shake 
                 head shake 
                 head shake 
                 — 
               
               
                 15KGA2 
                 licking 
                 — 
                 head shake 
                 licking 
                 — 
                 licking 
               
               
                 13CNL3 
                 head shake 
                 — 
                 — 
                 — 
                 licking 
                 — 
               
               
                 13CCL1 
                 — 
                 — 
                 gagging 
                 gagging 
                 head shake, licking 
                 head shake 
               
               
                 GJY3 
                 licking 
                 licking 
                 licking 
                 licking, head shake 
                 licking 
                 licking 
               
               
                 15KGC3 
                 head shake 
                 head shake, licking 
                 head shake, chomping 
                 head shake, licking 
                 head shake 
                 head shake 
               
               
                 13CPJ7 
                 licking 
                 pacing, licking 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 65 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 70-72) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 79 
                 Day 71 
                 Day 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking 
                 head shake 
                 licking 
                 head shake, licking 
                 head shake, licking 
                 licking 
               
               
                 13IRD3 
                 — 
                 — 
                 head shake 
                 head shake 
                 — 
                 — 
               
               
                 15KGA2 
                 licking 
                 — 
                 chomping, licking 
                 licking 
                 head shake, licking 
                 — 
               
               
                 13CNL3 
                 licking, head shake 
                 head shake, licking 
                 licking 
                 licking 
                 ha 
                 — 
               
               
                 13CCL1 
                 head shake 
                 likcing 
                 gagging 
                 gagging 
                 head shake 
                 gagging, drooling 
               
               
                 GJY3 
                 licking 
                 licking 
                 licking 
                 licking, head shake 
                 licking 
                 head shake, licking 
               
               
                 15KGC3 
                 licking 
                 head shake 
                 head shake, licking 
                 head shake, licking 
                 head shake, licking 
                 — 
               
               
                 13CPJ7 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 66 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 73-75) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 73 
                 Day 74 
                 Day 75 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 — 
                 head shake 
                 chomping, licking, head 
                 licking 
                 licking, head shake 
                 head shake 
               
               
                   
                   
                   
                 shake 
               
               
                 13IRD3 
                 — 
                 — 
                 head shake 
                 head shake 
                 head shake 
                 — 
               
               
                 15KGA2 
                 — 
                 licking 
                 licking 
                 — 
                 head shake, pacing 
                 head shake, licking 
               
               
                 13CNL3 
                 licking 
                 head shake 
                 — 
                 — 
                 head shake, licking 
                 — 
               
               
                 13CCL1 
                 gagging 
                 gagging, licking 
                 head shake, licking 
                 gagging, drooling 
                 — 
                 — 
               
               
                 GJY3 
                 licking 
                 licking 
                 licking 
                 — 
                 licking 
                 licking 
               
               
                 15KGC3 
                 licking, chewing 
                 licking, head shake 
                 head shake, licking 
                 head shake, licking 
                 chomping 
                 head shake, licking 
               
               
                 13CPJ7 
                 head shake 
                 head shake 
                 pacing 
                 pacing 
                 pacing 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 67 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 76-78) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 76 
                 Day 77 
                 Day 78 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking, chomping 
                 head shake, licking 
                 chomping, licking 
                 — 
                 head shake 
                 licking 
               
               
                 13IRD3 
                 — 
                 head shake 
                 — 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 licking 
                 head shake, licking 
                 licking 
                 head shake 
                 — 
                 licking 
               
               
                 13CNL3 
                 head shake 
                 — 
                 licking 
                 head shake 
                 head shake 
                 licking, head shake 
               
               
                 13CCL1 
                 gagging, licking 
                 gagging 
                 head shake 
                 gagging, head shake 
                 gagging 
                 licking 
               
               
                 GJY3 
                 licking 
                 licking 
                 licking 
                 licking 
                 licking 
                 — 
               
               
                 15KGC3 
                 head shake, licking 
                 head shake, chomping 
                 licking, head shake 
                 licking 
                 head shake, licking 
                 licking 
               
               
                 13CPJ7 
                 head shake, pacing 
                 pacing 
                 head shake 
                 pacing 
                 pacing 
                 head shake, pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 68 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 79-81) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 79 
                 Day 80 
                 Day 81 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking, head shake 
                 licking 
                 head shake, licking 
                 — 
                 head shake, licking 
                 licking 
               
               
                 13IRD3 
                 head shake 
                 head shake 
                 — 
                 head shake 
                 licking 
                 head shake, licking 
               
               
                 15KGA2 
                 licking 
                 — 
                 — 
                 head shake, licking 
                 licking 
                 licking, head shake 
               
               
                 13CNL3 
                 head shake 
                 licking 
                 licking 
                 licking 
                 licking 
                 — 
               
               
                 13CCL1 
                 licking 
                 gagging, grimace 
                 — 
                 gagging 
                 licking 
                 drooling 
               
               
                 GJY3 
                 licking 
                 licking 
                 head shake, licking 
                 licking 
                 licking 
                 licking 
               
               
                 15KGC3 
                 head shake 
                 head shake, licking 
                 head shake, licking 
                 head shake 
                 head shake 
                 head shake, licking 
               
               
                 13CPJ7 
                 pacing 
                 head shake, pacing 
                 pacing, licking 
                 pacing, head shake 
                 pacing, head shake 
                 pacing 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 69 
               
             
            
               
                   
               
               
                 Observations following test article administration (days 82-84) 
               
            
           
           
               
               
               
               
            
               
                   
                 Day 82 
                 Day 83 
                 Day 84 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cat Id 
                 AM 
                 PM 
                 AM 
                 PM 
                 AM 
                 PM 
               
               
                   
               
               
                 15EGA5 
                 licking, head shake 
                 licking 
                 licking 
                 licking 
                 licking 
                 licking 
               
               
                 13IRD3 
                 — 
                 head shake 
                 head shake 
                 — 
                 — 
                 — 
               
               
                 15KGA2 
                 head shake 
                 licking 
                 — 
                 — 
                 — 
                 licking 
               
               
                 13CNL3 
                 licking 
                 head shake 
                 licking 
                 head shake 
                 head shake 
                 head shake 
               
               
                 13CCL1 
                 gagging 
                 head shake, licking 
                 licking 
                 licking, head shake 
                 grimace, head shake 
                 licking, grimace 
               
               
                 GJY3 
                 licking 
                 licking 
                 licking, grimace 
                 licking, head shake 
                 licking 
                 licking 
               
               
                 15KGC3 
                 licking, head shake 
                 licking 
                 head shake 
                 licking 
                 head shake, licking 
                 head shake, licking 
               
               
                 13CPJ7 
                 pacing 
                 licking 
                 head shake 
                 licking, pacing 
                 head shake, pacing 
                 head shake, licking 
               
               
                   
               
               
                 — denotes no reaction recorded 
               
            
           
         
       
     
     Hematology and Serum Chemistry 
     Beginning in Week 2, there was an increase in the mean alanine aminotransferase (ALT) value for the group. This value remained increased from baseline until the end of the study. Mild increases in individual ALT levels were observed in the majority of the cats throughout the study. The cat with the greatest increase in ALT (above the normal reference range of 100 U/L), with a concurrent increase in aspartate aminotransferase (AST), was 13CNL3. Beginning in Week 4, this cat&#39;s ALT and AST levels began to decrease, but remained elevated from baseline. ALT levels remained above the normal reference range, shown in Table 70, for the duration of the study. Also during Week 2, the ALT levels of cats 13IRD3 and 13CPJ7 increased by 23 to 31 U/L, respectively, from baseline values. The ALT levels of cat 13CPJ7 returned to baseline by Week 10. At Week 4, the ALT of cat 13CCL1 was elevated from baseline by 32 U/L. Levels returned to baseline by Week 10. The test article appeared to cause mild ALT changes in the majority of cats with one cat maintaining elevated ALT levels above normal limits throughout the study. The group mean values of all other blood parameters remained within normal limits and no apparent trends were noted. Hematology and serum chemistry results are presented in Tables 71-74. 
     
       
         
           
               
             
               
                 TABLE 70 
               
             
            
               
                   
               
               
                 Hematology and serum chemistry normal reference ranges 
               
            
           
           
               
               
               
            
               
                   
                 Parameter 
                 Normal Reference Ranges 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Total Protein (g/dL): 
                 5.2-8.8 
                 g/dL 
               
               
                   
                 Albumin (g/dL): 
                 2.5-3.9 
                 g/dL 
               
               
                   
                 Globulin (g/dL): 
                 2.3-5.3 
                 g/dL 
               
               
                   
                 A/G Ratio: 
                 0.4-1.5 
                 Ratio 
               
               
                   
                 AST (IU/L): 
                 10-100 
                 IU/L 
               
               
                   
                 ALT (IU/L): 
                 10-100 
                 IU/L 
               
               
                   
                 Alkaline Phosphatase (IU/L): 
                 6-102 
                 IU/L 
               
               
                   
                 GGTP (IU/L): 
                 1-10 
                 IU/L 
               
               
                   
                 Total Bilirubin (mg/dL): 
                 0.1-0.4 
                 mg/dL 
               
               
                   
                 Urea Nitrogen (mg/dL): 
                 14-36 
                 mg/dL 
               
               
                   
                 Creatinine (mg/dL): 
                 0.6-2.4 
                 mg/dL 
               
               
                   
                 BUN/Creatinine Ratio: 
                 4-33 
                 Ratio 
               
               
                   
                 Phosphorus (mg/dL ): 
                 2.4-8.2 
                 mg/dL 
               
               
                   
                 Glucose (mg/dL): 
                 64-170 
                 mg/dL 
               
               
                   
                 Calcium (mg/dL): 
                 8.2-10.8 
                 mg/dL 
               
               
                   
                 Magnesium (mEq/L): 
                 1.5-2.5 
                 mEq/L 
               
               
                   
                 Sodium (mEq/L): 
                 145-158 
                 mEq/L 
               
               
                   
                 Potassium (mEq/L): 
                 3.4-5.6 
                 mEq/L 
               
               
                   
                 Chloride (mEq/L): 
                 104-128 
                 mEq/L 
               
               
                   
                 Cholesterol (mg/dL): 
                 75-220 
                 mg/dL 
               
               
                   
                 Triglycerides (mg/dL): 
                 25-160 
                 mg/dL 
               
               
                   
                 CPK (U/L): 
                 56-529 
                 IU/L 
               
            
           
           
               
               
               
            
               
                   
                 WBC(10 3 /L): 
                 3.5-16.0 10 3 /L 
               
               
                   
                 RBC (10 6 / L): 
                 5.9-9.9 10 6 /L  
               
            
           
           
               
               
               
               
            
               
                   
                 Hemoglobin (g/dL): 
                 9.3-15.9 
                 g/dL 
               
            
           
           
               
               
               
            
               
                   
                 Hematocrit (%): 
                 29-48%       
               
            
           
           
               
               
               
               
            
               
                   
                 MCV (fL): 
                 37-61 
                 fL 
               
               
                   
                 MCH (pg): 
                 11-21 
                 pg 
               
               
                   
                 MCHC (g/dL): 
                 30-38 
                 g/dL 
               
            
           
           
               
               
               
            
               
                   
                 Platelets (10 3 /μL): 
                 200-500 10 3 /μL 
               
            
           
           
               
               
               
               
            
               
                   
                 Absolute Polys (μL): 
                 2500-8500 
                 μL 
               
               
                   
                 Absolute Bands (μL): 
                 0 
                 μL 
               
               
                   
                 Absolute Lymphs (μL): 
                 1200-8000 
                 μL 
               
               
                   
                 Absolute Monos (μL): 
                 0-000 
                 μL 
               
               
                   
                 Absolute Eos (μL): 
                 0-1000 
                 μL 
               
               
                   
                 Absolute Bases (μL): 
                 0-150 
                 μL 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 71 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results - Part 1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Total 
                   
                   
                   
                   
                   
                 Alkaline 
                   
                 Total 
                 Urea 
                   
               
               
                   
                 Protein 
                 Albumin 
                 Globulin 
                 A/G 
                 AST 
                 ALT 
                 Phospahte 
                 GGTP 
                 Bilirubin 
                 Nitrogen 
                 Creatinine 
               
               
                   
                 (g/dL) 
                 (g/dL) 
                 (g/dL) 
                 Ratio 
                 (U/L) 
                 (U/L) 
                 (U/L) 
                 (U/L) 
                 (mg/dL) 
                 (mg/dL) 
                 (mg/dL 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7.2 
                 3.2 
                 4.0 
                 0.8 
                 21 
                 51 
                 30 
                 2 
                 0.1 
                 25 
                 1.3 
               
               
                 SD: 
                 0.46 
                 0.27 
                 0.60 
                 0.18 
                 4.8 
                 15.2 
                 15.4 
                 0.8 
                 0.00 
                 2.6 
                 0.19 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7.1 
                 3.2 
                 3.9 
                 0.9 
                 27 
                 104 
                 33 
                 2 
                 0.1 
                 23 
                 1.1 
               
               
                 SD: 
                 0.51 
                 0.30 
                 0.70 
                 0.20 
                 19.5 
                 117.7 
                 16.7 
                 1.0 
                 0.04 
                 3.1 
                 0.18 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.7 
                 3.2 
                 3.5 
                 0.9 
                 24 
                 90 
                 30 
                 1 
                 0.1 
                 22 
                 1.2 
               
               
                 SD: 
                 0.48 
                 0.30 
                 0.67 
                 0.21 
                 11.6 
                 85.2 
                 16.1 
                 0.0 
                 0.00 
                 2.9 
                 0.13 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6.5 
                 3.3 
                 3.2 
                 1.1 
                 25 
                 80 
                 32 
                 1 
                 0.1 
                 20 
                 1.1 
               
               
                 SD: 
                 0.41 
                 0.31 
                 0.63 
                 0.26 
                 13.1 
                 48.1 
                 17.0 
                 0.4 
                 0.04 
                 3.5 
                 0.11 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7.1 
                 3.4 
                 3.8 
                 0.9 
                 25 
                 76 
                 29 
                 2 
                 0.2 
                 20 
                 1.3 
               
               
                 SD: 
                 0.49 
                 0.36 
                 0.63 
                 0.19 
                 10.8 
                 46.8 
                 15.3 
                 0.9 
                 0.00 
                 2.4 
                 0.16 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7.0 
                 3.3 
                 3.8 
                 0.9 
                 24 
                 67 
                 30 
                 1 
                 0.1 
                 23 
                 1.3 
               
               
                 SD: 
                 0.48 
                 0.31 
                 0.61 
                 0.20 
                 7.7 
                 30.2 
                 17.6 
                 0.4 
                 0.00 
                 2.7 
                 0.11 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7.0 
                 3.2 
                 3.9 
                 0.9 
                 24 
                 75 
                 28 
                 1 
                 0.1 
                 19 
                 1.3 
               
               
                 SD: 
                 0.55 
                 0.31 
                 0.73 
                 0.20 
                 9.4 
                 42.2 
                 15.9 
                 0.4 
                 0.00 
                 1.6 
                 0.20 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 72 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results - Part 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 BUN/Creatinine 
                 Phosphorus 
                 Glucose 
                 Calcium 
                 Magnesium 
                 Sodium 
                 Potassium 
                 Chloride 
                 Cholesterol 
                 Triglycerides 
               
               
                   
                 Ratio 
                 (mg/dL) 
                 (mg/dL) 
                 (mg/dL) 
                 (mEq/L) 
                 (mEq/L) 
                 (mEq/L) 
                 (mEq/L) 
                 (mg/dL) 
                 (mg/dL) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 18 
                 4.5 
                 90 
                 9.6 
                 1.9 
                 151 
                 4.7 
                 119 
                 139 
                 32 
               
               
                 SD: 
                 3.3 
                 1.08 
                 7.2 
                 0.41 
                 0.16 
                 2.3 
                 0.60 
                 2.8 
                 24.7 
                 4.4 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 22 
                 4.9 
                 84 
                 9.4 
                 2.0 
                 153 
                 5.2 
                 122 
                 126 
                 37 
               
               
                 SD: 
                 2.5 
                 1.10 
                 11.0 
                 0.31 
                 0.12 
                 1.6 
                 0.48 
                 1.9 
                 13.5 
                 12.5 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 19 
                 4.6 
                 8.5 
                 9.0 
                 1.8 
                 153 
                 4.7 
                 121 
                 123 
                 28 
               
               
                 SD: 
                 2.7 
                 0.97 
                 6.9 
                 0.37 
                 0.10 
                 1.6 
                 0.41 
                 1.8 
                 17.6 
                 5.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 18 
                 4.8 
                 79 
                 9.3 
                 1.9 
                 153 
                 5.2 
                 121 
                 125 
                 29 
               
               
                 SD: 
                 2.4 
                 0.96 
                 5.4 
                 0.35 
                 0.12 
                 1.5 
                 0.28 
                 1.3 
                 17.1 
                 7.3 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 16 
                 4.3 
                 87 
                 9.5 
                 1.8 
                 154 
                 4.7 
                 122 
                 128 
                 26 
               
               
                 SD: 
                 1.4 
                 0.92 
                 8.3 
                 0.42 
                 0.11 
                 3.4 
                 0.77 
                 2.4 
                 15.6 
                 4.2 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 17 
                 4.1 
                 85 
                 9.2 
                 1.8 
                 152 
                 4.5 
                 120 
                 123 
                 22 
               
               
                 SD: 
                 1.5 
                 0.90 
                 0.4 
                 0.39 
                 0.10 
                 1.7 
                 0.43 
                 1.6 
                 19.5 
                 3.9 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 15 
                 4.1 
                 86 
                 9.3 
                 1.8 
                 152 
                 4.5 
                 120 
                 123 
                 25 
               
               
                 SD: 
                 2.0 
                 0.68 
                 10.2 
                 0.31 
                 0.13 
                 1.5 
                 0.30 
                 1.5 
                 19.4 
                 4.5 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 73 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results - Part 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 CPK 
                 WBC 
                 RBC 
                 Hemoglobin 
                 Hematocrit 
                 MCV 
                 MCH 
                 MCHC 
                 Platelets 
               
               
                   
                 (U/L) 
                 (10{circumflex over ( )}3/mm3) 
                 (10{circumflex over ( )}6/mm3) 
                 (g/dL) 
                 (%) 
                 (um{circumflex over ( )}3) 
                 (uug) 
                 (G/dl) 
                 (10{circumflex over ( )}3/mm3) 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 197 
                 14.0 
                 8.8 
                 11.4 
                 39 
                 44 
                 13.0 
                 30 
                 308 
               
               
                 SD: 
                 89.3 
                 4.45 
                 0.73 
                 1.09 
                 4.1 
                 2.5 
                 0.35 
                 2.1 
                 138.2 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 153 
                 12.1 
                 8.3 
                 11.1 
                 36 
                 44 
                 13.4 
                 31 
                 375 
               
               
                 SD: 
                 88.2 
                 3.91 
                 0.77 
                 0.95 
                 3.0 
                 3.1 
                 0.42 
                 1.6 
                 106.2 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 114 
                 13.6 
                 8.0 
                 10.7 
                 34 
                 42 
                 13.4 
                 32 
                 374 
               
               
                 SD: 
                 40.7 
                 4.10 
                 0.96 
                 1.31 
                 3.9 
                 1.0 
                 0.32 
                 0.5 
                 84.8 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 135 
                 12.3 
                 8.8 
                 11.7 
                 39 
                 44 
                 13.3 
                 30 
                 362 
               
               
                 SD: 
                 66.2 
                 4.14 
                 0.79 
                 0.97 
                 3.4 
                 1.8 
                 0.80 
                 1.4 
                 99.6 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 106 
                 12.9 
                 9.0 
                 12.4 
                 40 
                 44 
                 13.7 
                 31 
                 361 
               
               
                 SD: 
                 32.4 
                 375 
                 0.73 
                 1.06 
                 3.7 
                 1.7 
                 0.46 
                 1.0 
                 57.9 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 137 
                 10.9 
                 8.8 
                 11.6 
                 40 
                 45 
                 13.3 
                 29 
                 329 
               
               
                 SD: 
                 76.9 
                 3.82 
                 0.89 
                 1.45 
                 4.5 
                 1.9 
                 0.43 
                 1.2 
                 63.7 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 126 
                 12.5 
                 9.0 
                 11.8 
                 39 
                 43 
                 13.3 
                 31 
                 289 
               
               
                 SD: 
                 40.0 
                 4.56 
                 1.11 
                 1.46 
                 5.6 
                 2.6 
                 0.64 
                 1.4 
                 54.5 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 74 
               
             
            
               
                   
               
               
                 Summary of hematology and serum chemistry results - Part 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Abs 
                   
                 Abs 
                   
                 Abs 
                   
                 Abs 
                   
                 Abs 
                   
                 Abs 
                   
               
               
                   
                 Polys 
                 % Polys 
                 Bands 
                 % Bands 
                 Lymphs 
                 % Lymphs 
                 Monos 
                 % Monos 
                 Eos 
                 % Eos 
                 Basos 
                 % Basos 
               
               
                   
                   
               
            
           
           
               
               
            
               
                   
                 Initial Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7980 
                 56 
                 0 
                 0 
                 4481 
                 32 
                 428 
                 3 
                 1149 
                 9 
                 0 
                 0 
               
               
                 SD: 
                 3059.8 
                 9.0 
                 0.0 
                 0.0 
                 1466.5 
                 7.0 
                 138.0 
                 1.0 
                 417.8 
                 3.4 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7762 
                 64 
                 0 
                 0 
                 2988 
                 26 
                 495 
                 4 
                 817 
                 7 
                 0 
                 0 
               
               
                 SD: 
                 2917.9 
                 7.0 
                 0.0 
                 0.0 
                 902.2 
                 7.0 
                 255.7 
                 1.4 
                 392.0 
                 2.1 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 4 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 8993 
                 65 
                 0 
                 0 
                 3315 
                 25 
                 417 
                 3 
                 876 
                 7 
                 0 
                 0 
               
               
                 SD: 
                 3181.7 
                 4.0 
                 0.0 
                 0.0 
                 781.7 
                 5.3 
                 187.0 
                 0.8 
                 395.3 
                 2.7 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 6 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7032 
                 57 
                 0 
                 0 
                 4264 
                 35 
                 440 
                 3 
                 539 
                 5 
                 0 
                 0 
               
               
                 SD: 
                 2704.4 
                 7.4 
                 0.0 
                 0.0 
                 1366.9 
                 3.6 
                 296.7 
                 1.2 
                 539.6 
                 5.1 
                 0.0 
                 0.0 
               
               
                 N 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 8 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7394 
                 56 
                 0 
                 0 
                 3856 
                 31 
                 545 
                 4 
                 1026 
                 8 
                 30 
                 0 
               
               
                 SD: 
                 3061.4 
                 7.0 
                 0.0 
                 0.0 
                 802.9 
                 8.3 
                 388.9 
                 2.1 
                 601.2 
                 3.2 
                 54.9 
                 0.5 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Week 10 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 6159 
                 57 
                 0 
                 0 
                 3732 
                 34 
                 355 
                 4 
                 603 
                 5 
                 0 
                 0 
               
               
                 SD: 
                 2300.3 
                 7.2 
                 0.0 
                 0.0 
                 1464.7 
                 8.1 
                 108.3 
                 1.1 
                 451.0 
                 2.2 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
            
           
           
               
               
            
               
                   
                 Final Results 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Mean: 
                 7847 
                 61 
                 0 
                 0 
                 3614 
                 31 
                 364 
                 3 
                 650 
                 6 
                 0 
                 0 
               
               
                 SD: 
                 3819.8 
                 9.8 
                 0.0 
                 0.0 
                 1051.7 
                 9.3 
                 207.7 
                 0.7 
                 258.2 
                 2.9 
                 0.0 
                 0.0 
               
               
                 N: 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
                 8 
               
               
                   
               
            
           
         
       
     
     Clinical Observations 
     During the study, occasional instances of loose stool and emesis were recorded, as shown in Table 75. Cat ID #13CCL1 was observed having five instances of food emesis. Cat ID #13CNL3 was observed having one instance of hairball emesis and one instance of hair and bile emesis. Cat ID #131RD3 was observed having one instance of food emesis. Cat ID #15EGA5 was observed having three instances of food vomit and one instance of hair and bile emesis. Cat ID #GJY3 was observed having two instances of hairball emesis and one instance of food emesis. Occasional episodes of hairball and food emesis are not unusual in the cat colony and were not considered to be related to the test article. 
     
       
         
           
               
             
               
                 TABLE 75 
               
             
            
               
                   
               
               
                 Clinical observations 
               
            
           
           
               
               
               
            
               
                 Cat Id 
                 Date 
                 Observation 
               
               
                   
               
               
                 13CCL1 
                 Jan. 19, 2018 
                 Very calm, relaxed prior to dosing in am and pm 
               
               
                 13CCL1 
                 Jan. 21, 2018 
                 Very calm, relaxed prior to dosing in pm 
               
               
                 13CCL1 
                 Jan. 25, 2018 
                 Food vomit 
               
               
                 13CCL1 
                 Jan. 31, 2018 
                 Food vomit 
               
               
                 13CCL1 
                 Feb. 9, 2018 
                 Food vomit 
               
               
                 13CCL1 
                 Mar. 2, 2018 
                 Food vomit 
               
               
                 13CCL1 
                 Apr. 8, 2018 
                 Food vomit 
               
               
                 13CNL3 
                 Jan. 19, 2018 
                 Very calm, relaxed prior to dosing in pm 
               
               
                 13CNL3 
                 Jan. 21, 2018 
                 Very calm, relaxed prior to dosing in pm 
               
               
                 13CNL3 
                 Jan. 22, 2018 
                 Very relaxed 
               
               
                 13CNL3 
                 Feb. 4, 2018 
                 Hairball vomit 
               
               
                 13CNL3 
                 Mar. 6, 2018 
                 Bile vomit and hairball vomit 
               
               
                 13IRD3 
                 Feb. 8, 2018 
                 Semi digested food vomit 
               
               
                 15EGA5 
                 Jan. 26, 2018 
                 Food vomit 
               
               
                 15EGA5 
                 Feb. 8, 2018 
                 Semi digested food vomit 
               
               
                 15EGA5 
                 Mar. 9, 2018 
                 Bile vomit and hairball vomit 
               
               
                 15EGA5 
                 Mar. 19, 2018 
                 Digested food vomit 
               
               
                 15KGA2 
                 Jan. 19, 2018 
                 Very calm, relaxed prior to dosing in am and pm 
               
               
                 15KGA2 
                 Jan. 21, 2018 
                 Very calm, relaxed prior to dosing in am and pm 
               
               
                 15KGA2 
                 Jan. 22, 2018 
                 Very relaxed 
               
               
                 GJY3 
                 Jan. 31, 2018 
                 Hairball vomit 
               
               
                 GJY3 
                 Feb. 18, 2018 
                 Digested food vomit 
               
               
                 GJY3 
                 Mar. 19, 2018 
                 Hairball vomit 
               
               
                   
               
            
           
         
       
     
     PK Data 
     Table 76 shows the quantification of cannabidiol in feline serum and Table 77 shows cat cannabadiol pharmacokinetics. 
     
       
         
           
               
             
               
                 TABLE 76 
               
             
            
               
                   
               
               
                 Cannabidiol quantification in feline serum. 
               
            
           
           
               
               
               
               
               
               
            
               
                 PMF 
                   
                   
                   
                 Replicate 
                 ppb in 
               
               
                 No. 
                 Animal ID 
                 Species 
                 Time Point 
                 (A or B) 
                 Serum 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 53 
                 13CCL1 
                 Feline 
                 1 day prior 
                 A 
                 ND 
               
               
                 53 
                   
                   
                 1 day prior 
                 B 
                 ND 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 59 
                   
                   
                 60 
                 min 
                 B 
                 32.85 
               
               
                 59 
                   
                   
                 60 
                 min 
                 A 
                 34.26 
               
               
                 65 
                   
                   
                 4 
                 hr 
                 B 
                 1.69** 
               
               
                 65 
                   
                   
                 4 
                 hr 
                 A 
                 1.82** 
               
               
                 71 
                   
                   
                 8 
                 hr 
                 B 
                 65.42 
               
               
                 71 
                   
                   
                 8 
                 hr 
                 A 
                 79.30 
               
               
                 77 
                   
                   
                 24 
                 hr 
                 B 
                 42.76 
               
               
                 77 
                   
                   
                 24 
                 hr 
                 A 
                 44.88 
               
            
           
           
               
               
               
               
               
               
            
               
                 52 
                 13CNL3 
                 Feline 
                 1 day prior 
                 A 
                 ND 
               
               
                 52 
                   
                   
                 1 day prior 
                 B 
                 ND 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 58 
                   
                   
                 60 
                 min 
                 B 
                 24.44 
               
               
                 58 
                   
                   
                 60 
                 min 
                 A 
                 26.32 
               
               
                 64 
                   
                   
                 4 
                 hr 
                 A 
                 ND 
               
               
                 64 
                   
                   
                 4 
                 hr 
                 B 
                 ND 
               
               
                 70 
                   
                   
                 8 
                 hr 
                 B 
                 1.82** 
               
               
                 70 
                   
                   
                 8 
                 hr 
                 A 
                 2.22* 
               
               
                 76 
                   
                   
                 24 
                 hr 
                 A 
                 141.92 
               
               
                 76 
                   
                   
                 24 
                 hr 
                 B 
                 147.74 
               
            
           
           
               
               
               
               
               
               
            
               
                 50 
                 13IRD3 
                 Feline 
                 1 day prior 
                 A 
                 ND 
               
               
                 50 
                   
                   
                 1 day prior 
                 B 
                 ND 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 56 
                   
                   
                 60 
                 min 
                 B 
                 44.14 
               
               
                 56 
                   
                   
                 60 
                 min 
                 A 
                 45.40 
               
               
                 62 
                   
                   
                 4 
                 hr 
                 B 
                 1.53** 
               
               
                 62 
                   
                   
                 4 
                 hr 
                 A 
                 ND 
               
               
                 68 
                   
                   
                 8 
                 hr 
                 A 
                 ND 
               
               
                 68 
                   
                   
                 8 
                 hr 
                 B 
                 ND 
               
               
                 74 
                   
                   
                 24 
                 hr 
                 A 
                 10.28 
               
               
                 74 
                   
                   
                 24 
                 hr 
                 B 
                 10.31 
               
            
           
           
               
               
               
               
               
               
            
               
                 49 
                 15EGA5 
                 Feline 
                 1 day prior 
                 A 
                 ND 
               
               
                 49 
                   
                   
                 1 day prior 
                 B 
                 ND 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 55 
                   
                   
                 60 
                 min 
                 B 
                 28.10 
               
               
                 55 
                   
                   
                 60 
                 min 
                 A 
                 31.02 
               
               
                 61 
                   
                   
                 4 
                 hr 
                 A 
                 ND 
               
               
                 61 
                   
                   
                 4 
                 hr 
                 B 
                 ND 
               
               
                 67 
                   
                   
                 8 
                 hr 
                 A 
                 44.23 
               
               
                 67 
                   
                   
                 8 
                 hr 
                 B 
                 46.05 
               
               
                 73 
                   
                   
                 24 
                 hr 
                 A 
                 13.95 
               
               
                 73 
                   
                   
                 24 
                 hr 
                 B 
                 17.17 
               
            
           
           
               
               
               
               
               
               
            
               
                 51 
                 15KGA2 
                 Feline 
                 1 day prior 
                 A 
                 ND 
               
               
                 51 
                   
                   
                 1 day prior 
                 B 
                 ND 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 57 
                   
                   
                 60 
                 min 
                 A 
                 ND 
               
               
                 57 
                   
                   
                 60 
                 min 
                 B 
                 ND 
               
               
                 63 
                   
                   
                 4 
                 hr 
                 A 
                 ND 
               
               
                 63 
                   
                   
                 4 
                 hr 
                 B 
                 ND 
               
               
                 69 
                   
                   
                 8 
                 hr 
                 B 
                 365.18 
               
               
                 69 
                   
                   
                 8 
                 hr 
                 A 
                 376.28 
               
               
                 75 
                   
                   
                 24 
                 hr 
                 B 
                 0.18** 
               
               
                 75 
                   
                   
                 24 
                 hr 
                 A 
                 0.36** 
               
            
           
           
               
               
               
               
               
               
            
               
                 54 
                 GJY3 
                 Feline 
                 1 day prior 
                 A 
                 ND 
               
               
                 54 
                   
                   
                 1 day prior 
                 B 
                 ND 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 60 
                   
                   
                 60 
                 min 
                 A 
                 378.59 
               
               
                 60 
                   
                   
                 60 
                 min 
                 B 
                 535.08 
               
               
                 66 
                   
                   
                 4 
                 hr 
                 A 
                 51.48 
               
               
                 66 
                   
                   
                 4 
                 hr 
                 B 
                 68.31 
               
               
                 72 
                   
                   
                 8 
                 hr 
                 A 
                 71.64 
               
               
                 72 
                   
                   
                 8 
                 hr 
                 B 
                 79.59 
               
               
                 78 
                   
                   
                 24 
                 hr 
                 B 
                 33.12 
               
               
                 78 
                   
                   
                 24 
                 hr 
                 A 
                 35.88 
               
               
                   
               
               
                 Cannabidiol quantification in Feline Serum is reported as ng/mL (ppb). 
               
               
                 ND = Not Detected (no quantifiable value). 
               
               
                 *= values below calculated Limit of Quantification (6.2 ppb). 
               
               
                 **= values below calculated Limit of Detection (1.9 ppb). 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 77 
               
             
            
               
                   
               
               
                 Cat cannabadiol pharmacokinetics 
               
            
           
           
               
               
               
               
               
               
            
               
                 Cat # 
                 Cmax 
                 Tmax 
                 T½ el 
                 AUC 0 −&gt; t 
                 MRT 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 15EGA5 
                 75.3 
                 1 
                 1.2 
                 212.2 
                 2.1 
               
               
                 13IRD3 
                 40.5 
                 1 
                 1.3 
                 125.0 
                 2.4 
               
               
                 15KGA2 
                 53.3 
                 1 
                 1.7 
                 194.1 
                 2.9 
               
               
                 13CNL3 
                 21.2 
                 4 
                 1.7 
                 134.2 
                 5.4 
               
               
                 13CCL1 
                 20.4 
                 1 
                 1.7 
                 60.2 
                 2.7 
               
               
                 GJY3 
                 47.6 
                 4 
                 1.2 
                 265.0 
                 5.7 
               
               
                 15KGC3 
                 8.8 
                 1 
                 2.3 
                 54.2 
                 3.8 
               
               
                 13CPJ7 
                 12.1 
                 1 
                 2.3 
                 42.4 
                 2.4 
               
               
                   
               
               
                 Oral administration of 2/mg/kg cannabidiol in capsule form 
               
               
                 Cmax = Maximum concentration (ng/ml) 
               
               
                 Tmax = Time of maximum concentration (hr) 
               
               
                 T½ el = Half-life of elimination (hr) 
               
               
                 AUC 0-t = Area under the curve (0 time to time of last collection [24 hr]) (ng-hr/ml) 
               
               
                 MRT = Mean residence time (hr) 
               
            
           
         
       
     
     The LOD for CBD in feline serum was calculated to be 1.9 ng/mL (ppb in serum). The LOQ for CBD in feline serum was calculated to be 6.2 ng/mL (ppb in serum). 
     Conclusions 
     There were no adverse effects on body weights or food consumption. Group mean alanine aminotransferase values exhibited elevations during the study that peaked at Week 2. Levels decreased during the following weeks, but did not return to baseline levels. ALT levels of one cat (13CNL3) remained significantly elevated throughout the study, exceeding normal reference ranges for the duration of the treatment period. The remaining group mean hematology and serum chemistry values remained within normal reference limits throughout the study and apparent trends were not observed over time. No adverse clinical observations that were considered to be related to the administration of the test article were observed for any of the cats during the course of the study. However, acceptance of the test article was considered to be poor. 
     The disclosed subject matter is not to be limited in scope by the specific embodiments and examples described herein. Indeed, various modifications of the disclosure in addition to those described will become apparent to those skilled in the art from the foregoing description and accompanying figures. Such modifications are intended to fall within the scope of the appended claims. 
     All references (e.g., publications or patents or patent applications) cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual reference (e.g., publication or patent or patent application) was specifically and individually indicated to be incorporated by reference in its entirety for all purposes. Other embodiments are within the following claims.