CBD Cannabis Extract: Pharmacokinetic Studies

NCT04280289 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: CBD Study 1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy

Keywords

CBD; cannabidiol extract; cannabidiol; CBDE; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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.

  0-72 hours

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

  0-72 hours

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

  0-72 hours

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

  0-72 hours

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

  0-72 hours

Study Arms (1)

Cannabidiol extract

EXPERIMENTAL

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

Interventions

cannabidiol extract 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

Also known as: cannabidiol, CBD

Cannabidiol extract

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normal, healthy adults aged 21 to 55 years

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Mississippi, Oxford: lead

Study Sites (1)

University of Mississippi

University, Mississippi, 38677, United States

Location

Related Publications (26)

• 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.

  PMID: 28237318 BACKGROUND

• 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.

  PMID: 29114823 RESULT

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

  RESULT

• 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.

  PMID: 31313338 RESULT

• 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. doi: 10.1016/S1474-4422(16)00061-2.

  PMID: 26724101 RESULT

• 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.

  PMID: 28538134 RESULT

• 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.

  PMID: 29540584 RESULT

• 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.

  PMID: 31052254 RESULT

• 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.

  PMID: 31212965 RESULT

• 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.

  PMID: 31152723 RESULT

• 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.

  PMID: 29701252 RESULT

• (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

  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.

  PMID: 31161980 RESULT

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

  RESULT

• 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.

  PMID: 30250864 RESULT

• 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.

  PMID: 30791225 RESULT

• 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.

  PMID: 30687209 RESULT

• 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.

  RESULT

• 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.

  PMID: 20204561 RESULT

• 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.

  PMID: 27179600 RESULT

• 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.

  PMID: 21749363 RESULT

• 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.

  PMID: 30100226 RESULT

• 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.

  PMID: 30374683 RESULT

• 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.

  PMID: 30921490 RESULT

• 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.

  PMID: 26800377 RESULT

• 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.

  PMID: 29262425 RESULT

Related Links

• US FDA Hearing on Cannabis-Derived Compounds and Products

MeSH Terms

Conditions

Epilepsy

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Bill Gurley, Ph. D.

  Principal Scientist, National Center for Natural Products Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 21, 2020
• Study Start: February 1, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)