CBD Cannabis Extract: Pharmacokinetic Studies

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 2020

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).

Interventions

  • Drug: cannabidiol extract
    • 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

Arms, Groups and Cohorts

  • Experimental: Cannabidiol extract
    • 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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • 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.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers
  • Clearance (Cl/F) up to 72 hours after Cannabis extract administration.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers
  • Volume of distribution (Vd),up to 72 hours after Cannabis extract administration.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers
  • Volume of distribution at steady state (Vdss),up to 72 hours after Cannabis extract administration.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.
  • Terminal elimination rate constant (ke), half-life (t1/2), up to 72 hours after Cannabis extract administration.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.
  • Mean residence time (MRT), up to 72 hours after Cannabis extract administration.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.
  • Maximum serum concentration (Cmax), up to 72 hours after Cannabis extract administration.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.
  • Time to reach Cmax (Tmax), up to 72 hours after Cannabis extract administration.
    • Time Frame: 0-72 hours
    • This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Mississippi, Oxford
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Bill Gurley, Ph. D., Principal Investigator, Principal Scientist, National Center for Natural Products Research
  • Overall Contact(s)
    • Bill Gurley, Ph. D., 662-915-7130, bjgurley@olemiss.edu

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