CBD Cannabis Extract: Pharmacokinetic Studies

Epilepsy Clinical Trial

Official title:

CBD Cannabis Extract: Pharmacokinetic Studies

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04280289
• Other study ID #: CBD Study 1
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: December 1, 2020
• Est. completion date: December 2021

Study information

• Verified date: October 2020
• Source: University of Mississippi, Oxford
• Contact: Bill Gurley, Ph. D.
• Phone: 662-915-7130
• Email: bjgurley[@]olemiss.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy

Intervention

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 ?9-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

Locations

Country	Name	City	State
United States	University of Mississippi	University	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
University of Mississippi, Oxford

Country where clinical trial is conducted

United States, 

References & Publications (26)

(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

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. — View Citation

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

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. Review. — View 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. — View 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 w — View 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: 1 — View 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 — View 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). pii: E1694. doi: 10.3390/molecules24091694. — View 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. Review. — View 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. Review. — View Citation

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

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

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. Review. — View 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. Review. — View 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. Review. — View 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 a — View 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: — View 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 Health — View 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. 20 — View Citation

Wang YH, Avula B, ElSohly MA, Radwan MM, Wang M, Wanas AS, Mehmedic Z, Khan IA. Quantitative Determination of ?9-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-00 — View 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. Review. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   US FDA Hearing on Cannabis-Derived Compounds and Products