CBD Cannabis Extract: Pharmacokinetic Studies

NCT ID: NCT04280289

Last Updated: 2024-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-01

Study Completion Date

2021-12-01

Brief Summary

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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

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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).

Conditions

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Epilepsy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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).
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

cannabidiol extract

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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cannabidiol, CBD

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Mississippi, Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bill Gurley, Ph. D.

Role: PRINCIPAL_INVESTIGATOR

Principal Scientist, National Center for Natural Products Research

Locations

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University of Mississippi

University, Mississippi, United States

Site Status

Countries

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United States

References

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Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 2017 Nov 7;318(17):1708-1709. doi: 10.1001/jama.2017.11909.

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Borchardt D. Hemp cannabis product sales projected to hit $1 billion in 3 years. Forbes 2017, August, 23.

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Carvalho RK, Andersen ML, Mazaro-Costa R. The effects of cannabidiol on male reproductive system: A literature review. J Appl Toxicol. 2020 Jan;40(1):132-150. doi: 10.1002/jat.3831. Epub 2019 Jul 17.

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Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, Greenwood S, Morrison G, Sommerville K; GWPCARE1 Part A Study Group. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018 Apr 3;90(14):e1204-e1211. doi: 10.1212/WNL.0000000000005254. Epub 2018 Mar 14.

Reference Type RESULT
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Ewing LE, Skinner CM, Quick CM, Kennon-McGill S, McGill MR, Walker LA, ElSohly MA, Gurley BJ, Koturbash I. Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. Molecules. 2019 Apr 30;24(9):1694. doi: 10.3390/molecules24091694.

Reference Type RESULT
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Ewing LE, McGill MR, Yee EU, Quick CM, Skinner CM, Kennon-McGill S, Clemens M, Vazquez JH, McCullough SS, Williams DK, Kutanzi KR, Walker LA, ElSohly MA, James LP, Gurley BJ, Koturbash I. Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration. Molecules. 2019 Jun 17;24(12):2256. doi: 10.3390/molecules24122256.

Reference Type RESULT
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Foster BC, Abramovici H, Harris CS. Cannabis and Cannabinoids: Kinetics and Interactions. Am J Med. 2019 Nov;132(11):1266-1270. doi: 10.1016/j.amjmed.2019.05.017. Epub 2019 May 30.

Reference Type RESULT
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Reference Type RESULT
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(Harvey et al; Ujvary and Hanus; Jiang et al; Huestis, etc.1999): CBD is a potent inhibitor of CYP450 isozymes, primarily CYP2C and CYP3A isoforms, in in vitro and animal models

Reference Type RESULT

Huestis MA, Solimini R, Pichini S, Pacifici R, Carlier J, Busardo FP. Cannabidiol Adverse Effects and Toxicity. Curr Neuropharmacol. 2019;17(10):974-989. doi: 10.2174/1570159X17666190603171901.

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H.R.2 - Agriculture Improvement Act of 2018, Public Law No: 115-334, Dec. 20, 2018.

Reference Type RESULT

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Morrison G, Crockett J, Blakey G, Sommerville K. A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects. Clin Pharmacol Drug Dev. 2019 Nov;8(8):1009-1031. doi: 10.1002/cpdd.665. Epub 2019 Feb 21.

Reference Type RESULT
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Reference Type RESULT
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Personal statement from principal investigator, Dr. John Ingram, Dept. of Pediatrics, University of Mississippi Medical Center on his experience with "Cannabidiol (CBD) Cannabis Extract Oral Solution for Drug Resistant Pediatric Epilepsy (Compassionate Use)," April 18, 2018.

Reference Type RESULT

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Reference Type RESULT
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Tzadok M, Uliel-Siboni S, Linder I, Kramer U, Epstein O, Menascu S, Nissenkorn A, Yosef OB, Hyman E, Granot D, Dor M, Lerman-Sagie T, Ben-Zeev B. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure. 2016 Feb;35:41-4. doi: 10.1016/j.seizure.2016.01.004. Epub 2016 Jan 6.

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Wang YH, Avula B, ElSohly MA, Radwan MM, Wang M, Wanas AS, Mehmedic Z, Khan IA. Quantitative Determination of Delta9-THC, CBG, CBD, Their Acid Precursors and Five Other Neutral Cannabinoids by UHPLC-UV-MS. Planta Med. 2018 Mar;84(4):260-266. doi: 10.1055/s-0043-124873. Epub 2017 Dec 20.

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Related Links

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https://www.fda.gov/media/128592/download

US FDA Hearing on Cannabis-Derived Compounds and Products

Other Identifiers

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CBD Study 1

Identifier Type: -

Identifier Source: org_study_id

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