Back to results

CBD Cannabis Extract: Pharmacokinetic Studies

Primary Purpose

Epilepsy

Status

Unknown status

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

cannabidiol extract

About this trial

This is an interventional basic science trial for Epilepsy focused on measuring CBD, cannabidiol extract, cannabidiol, CBDE, pharmacokinetics

Eligibility Criteria

21 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University of Mississippi

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cannabidiol extract

Arm Description

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

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome 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.

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.

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.

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.

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.

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.

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.

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.

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.

Full Information

NCT ID

NCT04280289

First Posted

February 7, 2020

Last Updated

October 14, 2020

Sponsor

University of Mississippi, Oxford

1. Study Identification

Unique Protocol Identification Number

NCT04280289

Brief Title

CBD Cannabis Extract: Pharmacokinetic Studies

Official Title

CBD Cannabis Extract: Pharmacokinetic Studies

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Unknown status

Study Start Date

December 1, 2020 (Anticipated)

Primary Completion Date

December 2021 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Mississippi, Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy

Keywords

CBD, cannabidiol extract, cannabidiol, CBDE, pharmacokinetics

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cannabidiol extract

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

cannabidiol extract

Other Intervention Name(s)

cannabidiol, CBD

Intervention Description

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

Primary Outcome Measure Information:

Title

Plasma concentration of minor phytocannabinoids, and metabolites following single dose administration of Cannabis extract (CBDE) (at 2.5 mg/kg cannabidiol (CBD).

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers

Time Frame

0- 72 hours

Title

Urine concentration of minor phytocannabinoids, and metabolites following single dose administration of Cannabis extract (CBDE) (at 2.5 mg/kg cannabidiol (CBD).

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers

Time Frame

0- 72 hours

Secondary Outcome Measure Information:

Title

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.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers

Time Frame

0-72 hours

Title

Clearance (Cl/F) up to 72 hours after Cannabis extract administration.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers

Time Frame

0-72 hours

Title

Volume of distribution (Vd),up to 72 hours after Cannabis extract administration.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers

Time Frame

0-72 hours

Title

Volume of distribution at steady state (Vdss),up to 72 hours after Cannabis extract administration.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.

Time Frame

0-72 hours

Title

Terminal elimination rate constant (ke), half-life (t1/2), up to 72 hours after Cannabis extract administration.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.

Time Frame

0-72 hours

Title

Mean residence time (MRT), up to 72 hours after Cannabis extract administration.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.

Time Frame

0-72 hours

Title

Maximum serum concentration (Cmax), up to 72 hours after Cannabis extract administration.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.

Time Frame

0-72 hours

Title

Time to reach Cmax (Tmax), up to 72 hours after Cannabis extract administration.

Description

This study would provide information on differential pharmacokinetics and metabolism of Cannabis extract in normal human volunteers.

Time Frame

0-72 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Bill Gurley, Ph. D.

Phone

662-915-7130

bjgurley@olemiss.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Kerri Harrison

Phone

662-915-2103

kaharri6@olemiss.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bill Gurley, Ph. D.

Organizational Affiliation

Principal Scientist, National Center for Natural Products Research

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Mississippi

City

University

State/Province

Mississippi

ZIP/Postal Code

38677

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

28237318

Citation

Wolff V, Jouanjus E. Strokes are possible complications of cannabinoids use. Epilepsy Behav. 2017 May;70(Pt B):355-363. doi: 10.1016/j.yebeh.2017.01.031. Epub 2017 Feb 23.

Results Reference

background

PubMed Identifier

29114823

Citation

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.

Results Reference

result

Citation

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

Results Reference

result

PubMed Identifier

31313338

Citation

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.

Results Reference

result

PubMed Identifier

26724101

Citation

Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, Cilio MR. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8. doi: 10.1016/S1474-4422(15)00379-8. Epub 2015 Dec 24. Erratum In: Lancet Neurol. 2016 Apr;15(4):352.

Results Reference

result

PubMed Identifier

28538134

Citation

Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S; Cannabidiol in Dravet Syndrome Study Group. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.

Results Reference

result

PubMed Identifier

29540584

Citation

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.

Results Reference

result

PubMed Identifier

31052254

Citation

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.

Results Reference

result

PubMed Identifier

31212965

Citation

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.

Results Reference

result

PubMed Identifier

31152723

Citation

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.

Results Reference

result

PubMed Identifier

29701252

Citation

Grof CPL. Cannabis, from plant to pill. Br J Clin Pharmacol. 2018 Nov;84(11):2463-2467. doi: 10.1111/bcp.13618. Epub 2018 May 24.

Results Reference

result

Citation

(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

Results Reference

result

PubMed Identifier

31161980

Citation

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.

Results Reference

result

Citation

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

Results Reference

result

PubMed Identifier

30250864

Citation

McCoy B, Wang L, Zak M, Al-Mehmadi S, Kabir N, Alhadid K, McDonald K, Zhang G, Sharma R, Whitney R, Sinopoli K, Snead OC 3rd. A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome. Ann Clin Transl Neurol. 2018 Aug 1;5(9):1077-1088. doi: 10.1002/acn3.621. eCollection 2018 Sep.

Results Reference

result

PubMed Identifier

30791225

Citation

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.

Results Reference

result

PubMed Identifier

30687209

Citation

Pamplona FA, da Silva LR, Coan AC. Corrigendum: Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. Front Neurol. 2019 Jan 10;9:1050. doi: 10.3389/fneur.2018.01050. eCollection 2018.

Results Reference

result

Citation

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.

Results Reference

result

PubMed Identifier

20204561

Citation

Purohit V, Rapaka R, Shurtleff D. Role of cannabinoids in the development of fatty liver (steatosis). AAPS J. 2010 Jun;12(2):233-7. doi: 10.1208/s12248-010-9178-0. Epub 2010 Mar 5.

Results Reference

result

PubMed Identifier

27179600

Citation

Russo EB. Beyond Cannabis: Plants and the Endocannabinoid System. Trends Pharmacol Sci. 2016 Jul;37(7):594-605. doi: 10.1016/j.tips.2016.04.005. Epub 2016 May 11.

Results Reference

result

PubMed Identifier

21749363

Citation

Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011 Aug;163(7):1344-64. doi: 10.1111/j.1476-5381.2011.01238.x.

Results Reference

result

PubMed Identifier

30100226

Citation

Szaflarski JP, Bebin EM, Cutter G, DeWolfe J, Dure LS, Gaston TE, Kankirawatana P, Liu Y, Singh R, Standaert DG, Thomas AE, Ver Hoef LW; UAB CBD Program. Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. Epilepsy Behav. 2018 Oct;87:131-136. doi: 10.1016/j.yebeh.2018.07.020. Epub 2018 Aug 9.

Results Reference

result

PubMed Identifier

30374683

Citation

Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects. CNS Drugs. 2018 Nov;32(11):1053-1067. doi: 10.1007/s40263-018-0578-5. Erratum In: CNS Drugs. 2019 Apr;33(4):397.

Results Reference

result

PubMed Identifier

30921490

Citation

Taylor L, Crockett J, Tayo B, Morrison G. A Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment. J Clin Pharmacol. 2019 Aug;59(8):1110-1119. doi: 10.1002/jcph.1412. Epub 2019 Mar 28.

Results Reference

result

PubMed Identifier

26800377

Citation

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.

Results Reference

result

PubMed Identifier

29262425

Citation

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.

Results Reference

result

Links:

URL

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

Description

US FDA Hearing on Cannabis-Derived Compounds and Products

Learn more about this trial

CBD Cannabis Extract: Pharmacokinetic Studies

We'll reach out to this number within 24 hrs