Cannabidiol and CES1 Interactions in Healthy Subjects

NCT ID: NCT04603391

Last Updated: 2024-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-25
• Study Completion Date: 2021-12-31

Brief Summary

The proposed study will assess the drug interaction potential between oral cannabidiol (Epidiolex®) and the carboxylesterase 1 (CES1) substrate methylphenidate (Ritalin®) in 12 healthy research subjects

Detailed Description

Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as an OTC supplement, a component of medical cannabis, and a prescriptive treatment of childhood epilepsies. In vitro studies suggest CBD may inhibit a number of drug-metabolizing enzymes, including carboxylesterase 1 (CES1). The aim of this study was to evaluate effect of CBD on the disposition of the CES1 substrate methylphenidate (MPH). This was a randomized, placebo-controlled, crossover study involving 12 healthy subjects. Each subject ingested 750 mg of CBD solution, or alternatively, a placebo solution twice daily for a 3-day run-in period followed by an additional CBD dose (or placebo) and a single 10 mg dose of MPH and completed serial blood sampling for pharmacokinetic analysis. MPH and CBD concentrations were measured by liquid chromatography with tandem mass spectrometry.

Conditions

Drug Interaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

CBD, then placebo

Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution [100 mg/ml]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg (administered as as 7.5 mL of Epidiolex® solution [100 mg/ml]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).

After a minimum washout period of five days, subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).

Group Type: EXPERIMENTAL

dl-Methylphenidate plus Cannabidiol

Intervention Type: DRUG

Subjects will be administered one 10 mg tablet of dl-methylphenidate (Ritalin®) plus 7.5 mL Epidiolex® solution

dl-Methylphenidate plus Cannabidiol Placebo solution

Intervention Type: DRUG

Subjects will be administered one 10 mg tablet of dl-methylphenidate (Ritalin®) plus 7.5 mL of Epidiolex® placebo solution

Placebo, then CBD

Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).

After a minimum washout period of five days, subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution [100 mg/ml]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg (administered as as 7.5 mL of Epidiolex® solution [100 mg/ml]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).

Group Type: EXPERIMENTAL

dl-Methylphenidate plus Cannabidiol

Intervention Type: DRUG

Subjects will be administered one 10 mg tablet of dl-methylphenidate (Ritalin®) plus 7.5 mL Epidiolex® solution

dl-Methylphenidate plus Cannabidiol Placebo solution

Intervention Type: DRUG

Subjects will be administered one 10 mg tablet of dl-methylphenidate (Ritalin®) plus 7.5 mL of Epidiolex® placebo solution

Interventions

dl-Methylphenidate plus Cannabidiol

Subjects will be administered one 10 mg tablet of dl-methylphenidate (Ritalin®) plus 7.5 mL Epidiolex® solution

Intervention Type: DRUG

dl-Methylphenidate plus Cannabidiol Placebo solution

Subjects will be administered one 10 mg tablet of dl-methylphenidate (Ritalin®) plus 7.5 mL of Epidiolex® placebo solution

Intervention Type: DRUG

Other Intervention Names

Ritalin®; Epidiolex®; Ritalin®; Epidiolex®

Eligibility Criteria

Inclusion Criteria

• Signed Informed Consent
• Age: 21-45 years
• Gender: males and females (50:50)
• Race or ethnicity: no restrictions
• Body Mass Index (BMI) between 18.5 to 28 kg/m2 (inclusive)
• Satisfactory completion of the screening medical history, physical exam, and laboratory evaluations.
• Females of child-bearing potential must have a negative urine pregnancy test prior to enrollment and avoid pregnancy during study participation.
• With the exception of oral contraceptives, subjects must not be taking prescription or OTC medication for the duration of study participation
• Subjects must have no ongoing use of any botanical/nutritional supplement, vitamin, or energy drink for the duration of study participation

Exclusion Criteria

• The presence of a known allergy, hypersensitivity, or adverse reaction to CBD or cannabis, or sesame seed oil
• The presence of a known allergy, hypersensitivity, or adverse reaction to methylphenidate or dexmethylphenidate (Focalin®)
• A history (within the past year) or presence of clinically significant cardiovascular, cerebrovascular, renal, hepatic, gastrointestinal, pulmonary, immunological, hematological, endocrine, or neurologic disease will render subjects ineligible for the study.
• The presence of any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion including;

1. Gastric bezoar

2. Swallowing disorders

3. Strictures

4. Fistulas

5. GI obstruction

6. Severe dsyphasgia

7. Crohn's disease

8. Diverticulitis

9. A positive urine pregnancy test.

10. A positive Urine Drug Screen

11. Any concomitant prescription medication, OTC medication, herbal or other dietary supplement or vitamins during the study period.

All subjects must be medication-free from 7 Days before initiation of the first active study day, through the duration of the study. This exclusion the use of vitamins, herbal preparations and OTC supplements.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Consortium for Medical Marijuana Clinical Outcomes Research

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Markowitz, Pharm.D

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

OCR39758

Identifier Type: OTHER

Identifier Source: secondary_id

IRB202002547-A

Identifier Type: -

Identifier Source: org_study_id