Endourage Complete Spectrum Oral Mucosal Drops (OMD) in Adults Desiring a Reduction in Ethanol Use

Study Overview
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Brief Summary
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This is the first clinical trial of Endourage OMD 1200 for persons desiring to reduce their alcohol consumption.

Detailed Description
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CBD is the second most abundant component of the cannabis plant after tetrahydrocannabinol (THC). Unlike THC, CBD does not get users high, but there is some evidence suggesting that it might have anti-anxiety, anticonvulsant, anti-inflammatory and immune boosting, antioxidant effects. Currently, the only CBD product approved by the Food and Drug Administration is a prescription oil called Epidiolex (Greenwich Biosciences, Inc. 2018). It is approved to treat two types of epilepsy. Aside from Epidiolex, state laws on the use of CBD vary. While CBD is being studied as a treatment for a wide range of conditions, including Parkinson's disease, schizophrenia, diabetes, multiple sclerosis and anxiety, and addiction, research supporting the drug's benefits is still limited. CBD use carries some risks. Though it is often well-tolerated, CBD can cause side effects, such as dry mouth, diarrhea, reduced appetite, drowsiness, and fatigue. CBD can also interact with other medications you are taking, such as blood thinners. Another cause for concern is the unreliability of the purity and dosage of CBD in products. A recent study of 84 CBD products bought online showed that more than a quarter of the products contained less CBD than labeled. In addition, THC was found in 18 products. If you plan to use products containing CBD, talk to your primary health care provider. People take cannabidiol by mouth for anxiety, bipolar disorder, a muscle disorder called dystonia, seizures, multiple sclerosis, Parkinson's disease, and schizophrenia. Cannabidiol is possibly safe when taken by mouth and appropriately in adults. Cannabidiol doses of up to 300 mg daily have been used safely for up to 6 months. Higher doses of 1200-1500 mg daily have been used safely for up to 4 weeks. Cannabidiol sprays used under the tongue have been used in doses of 2.5 mg for up to 2 weeks.

Official Title
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A Post Marketing Study to Evaluate the Safety and Efficacy of Endourage Complete Spectrum Oral Mucosal Drops (OMD) in Adults Desiring a Reduction in Ethanol Use

Conditions
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Alcohol Drinking, Alcohol Use, Unspecified, Alcohol Abstinence, Alcohol-Related Disorders

Intervention / Treatment
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* Dietary Supplement: Endourage 1200 mg OMD ™ Oral Mucosal Drops
* Dietary Supplement: Isolate
* Other: Placebo
* Dietary Supplement: Peppermint Oil, masking flavor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years of age or older who can provide informed consent Ability to read and write in the English language and follow study-related procedures Ability to have mail/ study drug delivered to an address and/or P.O. Box in the recipient's name. If a woman of childbearing age, willing to use a dual method of contraception (barrier and/or hormonal) Exclusion Criteria: Active illicit or non-prescribed drug use Concomitant use of benzodiazepines Concomitant use of Antabuse Documented history and active treatment for seizure disorder Transaminase elevation Hepatitis C infection (currently on therapy and/or any transaminitis elevation) Hepatitis B infection (currently on therapy and/or any transaminitis elevation) Any form of mental impairment that will/could hinder safe participation in the study Pregnancy or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a 112-day, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of Endourage 1200 mg Complete Spectrum Oral Mucosal Drops (OMD ™). A total of 32 study participants will be enrolled. Placebo (Hemp seed oil and peppermint flavoring) Isolate (CBD no terpenes Hemp seed oil [slightly lower concentration of CBD ratio]) Endourage OMD (Full flower extract with a 1:1 ratio of cannabis terpenes, Hemp seed oil and peppermint flavoring)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1 Placebo<br>Placebo Isolate Placebo (Hemp seed oil and peppermint flavoring) | Dietary Supplement: Isolate<br>* The isolate formulation contains 0% cannabinoids (CBD 0.00%; CBDa 0.00%; detla 9 THC 0.00%; THCa 0.00%).<br>Other: Placebo<br>* Total CBD = CBD + (CBD-A * 0.877). Total THC = THCA-A * 0.877 + Delta 9 THC, ND = <LOQ, T-Caryophyllene = Trans-Caryophyllene, <LOQ = Less Than Limit of Quantitation, QNS = Quantity Not Sufficient. (%) = Percent, (ppm) = Parts per Million, (ppb) = Parts per Billion, (μg/Kg) = Microgram per Kilogram, (mg/g) = Milligram per Gram, ppm = (μg/g), ppb = (μg/kg),<br>Dietary Supplement: Peppermint Oil, masking flavor<br>* Mentha piperita Leaf /Stem Oil; Physical state: Liquid. Color: Colorless to pale yellow; Characteristic peppermint odor; Not dangerous goods.<br>* Other names: Peppermint Oil, Natural;|
| Active Comparator: Group 2 Isolate Comparator<br>Isolate Placebo Isolate (CBD no terpenes Hemp seed oil [slightly lower concentration of CBD ratio]) | Dietary Supplement: Isolate<br>* The isolate formulation contains 0% cannabinoids (CBD 0.00%; CBDa 0.00%; detla 9 THC 0.00%; THCa 0.00%).<br>Other: Placebo<br>* Total CBD = CBD + (CBD-A * 0.877). Total THC = THCA-A * 0.877 + Delta 9 THC, ND = <LOQ, T-Caryophyllene = Trans-Caryophyllene, <LOQ = Less Than Limit of Quantitation, QNS = Quantity Not Sufficient. (%) = Percent, (ppm) = Parts per Million, (ppb) = Parts per Billion, (μg/Kg) = Microgram per Kilogram, (mg/g) = Milligram per Gram, ppm = (μg/g), ppb = (μg/kg),<br>Dietary Supplement: Peppermint Oil, masking flavor<br>* Mentha piperita Leaf /Stem Oil; Physical state: Liquid. Color: Colorless to pale yellow; Characteristic peppermint odor; Not dangerous goods.<br>* Other names: Peppermint Oil, Natural;|
| Placebo Comparator: Group 3 Placebo Comparator<br>Placebo OMD Endourage OMD (Full flower extract with a 1:1 ratio of cannabis terpenes, Hemp seed oil and peppermint flavoring) | Dietary Supplement: Endourage 1200 mg OMD ™ Oral Mucosal Drops<br>* The CBD/THC ratio of OMD 1200 is 14:1 and the CBD/Terpene ratio is 1:1. Each ¼ dropper contains 10.2 mg of CBD and 0.7 mg of THC. The total % THC is 0.28%. These ratios indicate that the product will not cause euphoria.<br>* Other names: Endourage OMD 1200;Other: Placebo<br>* Total CBD = CBD + (CBD-A * 0.877). Total THC = THCA-A * 0.877 + Delta 9 THC, ND = <LOQ, T-Caryophyllene = Trans-Caryophyllene, <LOQ = Less Than Limit of Quantitation, QNS = Quantity Not Sufficient. (%) = Percent, (ppm) = Parts per Million, (ppb) = Parts per Billion, (μg/Kg) = Microgram per Kilogram, (mg/g) = Milligram per Gram, ppm = (μg/g), ppb = (μg/kg),<br>Dietary Supplement: Peppermint Oil, masking flavor<br>* Mentha piperita Leaf /Stem Oil; Physical state: Liquid. Color: Colorless to pale yellow; Characteristic peppermint odor; Not dangerous goods.<br>* Other names: Peppermint Oil, Natural;|
| Experimental: Group 4 Experimental Placebo<br>OMD Placebo Endourage OMD (Full flower extract with a 1:1 ratio of cannabis terpenes, Hemp seed oil and peppermint flavoring) | Dietary Supplement: Endourage 1200 mg OMD ™ Oral Mucosal Drops<br>* The CBD/THC ratio of OMD 1200 is 14:1 and the CBD/Terpene ratio is 1:1. Each ¼ dropper contains 10.2 mg of CBD and 0.7 mg of THC. The total % THC is 0.28%. These ratios indicate that the product will not cause euphoria.<br>* Other names: Endourage OMD 1200;Other: Placebo<br>* Total CBD = CBD + (CBD-A * 0.877). Total THC = THCA-A * 0.877 + Delta 9 THC, ND = <LOQ, T-Caryophyllene = Trans-Caryophyllene, <LOQ = Less Than Limit of Quantitation, QNS = Quantity Not Sufficient. (%) = Percent, (ppm) = Parts per Million, (ppb) = Parts per Billion, (μg/Kg) = Microgram per Kilogram, (mg/g) = Milligram per Gram, ppm = (μg/g), ppb = (μg/kg),<br>Dietary Supplement: Peppermint Oil, masking flavor<br>* Mentha piperita Leaf /Stem Oil; Physical state: Liquid. Color: Colorless to pale yellow; Characteristic peppermint odor; Not dangerous goods.<br>* Other names: Peppermint Oil, Natural;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety scores | Generalized Anxiety Disorder (GAD-7), measure for anxiety. Baseline scores will be compared to scores at end of study across arms. Change in anxiety scores from baseline to end of study will be measured. Range from 0-4 for minimal; 5-9 mild; 10-14 moderate; 15-21 severe. Changes will be compared across arms. Increased scores will indicate that study product was not effective in decreasing symptoms measured (anxiety). | 112 days (4-months) | 
| Depression scores | Patient Health Questionnaire (PHQ-9), measure for depression. Change in depression scores from baseline to end of study. Total Score for Depression Severity will be compared across arms from baseline to end of study at 112-days. Score ranges from: 1-4 Minimal depression; 5-9 Mild depression; 10-14 Moderate depression; 15-19 Moderately severe depression; 20-27 Severe depression. Increased scores indicate that study product is not effective in decreasing symptoms measured (depression). | 112 days (4-months) | 
| Alcohol craving scores | The Alcohol Craving Questionnaire Short Form (ACQ-SF-R) will be compared from baseline to end of study. Changes in craving score will be measured in each arm of study. Scores from 1-7 (strongly disagree to strongly agree) is measured across 12 items and 4 sub-scales ([1] compulsivity, [2] expectancy, [3] purposefulness, and [4] emotionality). The sum of the raw scores for each factor will be calculated and compared from baseline to the end of study across arms. Increased scores indicate that study product is not effective in reducing cravings for alcohol. | 112 days (4-months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine CBDs impact on anxiety, depression, and alcohol craving that trigger desires to consume alcohol versus abstain. | Daily diary of symptom(s), dose(s) of study product and alcohol use will be kept by participants. Diary entries of symptoms, daily dose of study product and daily alcohol use will be measured and compared across study arms from baseline to end of study. | 112 days (4-months) |