CBD Cannabis Extract: Pharmacokinetic Studies

Study Overview
=================
Brief Summary
-----------------
The initial goal is to ascertain the pharmacokinetic (PK) profile of CBD (cannabidiol) after a single dose of CBDE (cannabidiol extract), although the plan is to extend these studies to multiple dose administrations in the future, since it is likely that (cannabidiol) and/or its metabolites will show some accumulation. These studies will provide detailed information that will inform the continuation and expansion of CBDE in other research projects.

Detailed Description
-----------------
The objective is to determine the PK profile of CBD(cannabidiol) , its metabolites, and minor phytocannabinoids after single dose administration of CBDE (at 2.5 mg/kg CBD). Attainment of this goal will provide essential information on phytocannabinoid disposition and dosing regimen optimization. To accomplish this objective, the working hypothesis that complex phytochemical mixtures present in full spectrum hemp extracts (FSHEs), as exemplified by CBDE, differ from purified CBD-containing products with regard to PK, will be tested. The approach to testing this working hypothesis will be to use liquid chromatography-mass spectrometry (LC/MS) to both characterize the phytocannabinoid concentration-time profiles following CBDE administration (single and multiple dosing).

Official Title
-----------------
CBD Cannabis Extract: Pharmacokinetic Studies

Conditions
-----------------
Epilepsy

Intervention / Treatment
-----------------
* Drug: cannabidiol extract


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Normal, healthy adults aged 21 to 55 years Exclusion Criteria: Allergy to sesame oil/products Obese: BMI is 35 or higher Smoker (tobacco & marijuana use [smoking or use of oral hemp/CBD products]) Currently any taking prescriptions medication(s) [with exception of oral contraceptives] or over-the-counter medications/supplements Consuming botanical/non-botanical dietary supplements (3 days prior to study) Known history of cardiac, liver, kidney or hematological disease, diabetes Autoimmune disorders Known history of Neurologic/Psychiatric disorders Report of an active infection Subject is pregnant or breast-feeding, or is expecting to conceive during the study Subjects of child bearing potential will use (or is currently using) during the study, one of the following acceptable methods of contraception: Male sterilization (vasectomy) Female sterilization (tubal ligation, hysterectomy) Intrauterine service intrauterine device (IUD) or other implant Oral contraceptive, injectable contraceptive Contraceptive patch/ring Diaphragm Male condom Sponge/spermicide

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: This study is a single center, prospective, Phase I PK trial. A total of 10 healthy subjects will be enrolled into the study. This study will evaluate the pharmacokinetics of CBDE. The PK of CBD, 9-tetrahydrocannabinol (THC) and their principal metabolites will be determined after a single CBDE dose delivering 2.5 mg/kg CBD. ). CBDE will be provided in liquid concentration of 50mg/ml in sesame seed oil (SSO).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol extract<br>10 healthy subjects (5 female, 5 male), will be enrolled into the study. Each subject will receive a single CBDE dose delivering 2.5 mg/kg CBD, after consumption of a standardized meal. Nine (9mL) of blood for PK analysis, at each of the following timepoints: 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours and 72 hours after the study drug administration. Urine will be collected at the following timepoints: Predose, 0-4 hrs, 4-8 hrs, 8-12 hrs, 12-24 hrs, 24-36 hrs, 36-48 hrs, and 48-72 hrs for PK analysis | Drug: cannabidiol extract<br>* The test article CBD Cannabis Extract Oral Solution will be manufactured by the University of Mississippi National Center for Natural Products Research (NCNPR) at the Coy Waller Laboratory under FDA Current Good Manufacturing Practices. The drug product, derived from hemp and containing less than 0.3% of Δ9-tetrahydrocannabinol, is no longer a Drug Enforcement Agency (DEA) controlled substance. DEA registrations are not required for the manufacturing, handling or dispensing of these clinical test materials<br>* Other names: cannabidiol, CBD;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of minor phytocannabinoids, and metabolites following single dose administration of Cannabis extract (CBDE) (at 2.5 mg/kg cannabidiol (CBD). | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers | 0- 72 hours | 
| Urine concentration of minor phytocannabinoids, and metabolites following single dose administration of Cannabis extract (CBDE) (at 2.5 mg/kg cannabidiol (CBD). | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers | 0- 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area-under-the-concentration-time profiles (AUC), and area-under-the moment curve (AUMC), for CBD (cannabidiol) , up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers | 0-72 hours | 
| Clearance (Cl/F) up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers | 0-72 hours | 
| Volume of distribution (Vd),up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers | 0-72 hours | 
| Volume of distribution at steady state (Vdss),up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers. | 0-72 hours | 
| Terminal elimination rate constant (ke), half-life (t1/2), up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers. | 0-72 hours | 
| Mean residence time (MRT), up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers. | 0-72 hours | 
| Maximum serum concentration (Cmax), up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers. | 0-72 hours | 
| Time to reach Cmax (Tmax), up to 72 hours after Cannabis extract administration. | This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers. | 0-72 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CBD, cannabidiol extract, cannabidiol, CBDE, pharmacokinetics