Cannabidiol and CES1 Interactions in Healthy Subjects

An Assessment of the Drug Interaction Potential Between Oral Cannabidiol (Epidiolex®) and the CES1 Substrate Methylphenidate in Healthy Volunteers

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

Study Overview

• Status: Completed
• Conditions: Drug Interaction
• Intervention / Treatment: Drug: di-Methylphenidate plus Cannabidiol; Drug: di-Methylphenidate plus Cannabidiol Placebo solution

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exposure A; Subjects will be administered one (1) 10 mg tablet of dl-methylphenidate (Ritalin®) CBD 750 mg (administered as 7.5 ml of Epidiolex® solution [100 mg/ml] of CBD)	Drug: di-Methylphenidate plus Cannabidiol; Subjects will be administered one (1) 10 mg tablet of dl-methylphenidate (Ritalin®) plus CBD 750 mg (administered as 7.5 ml of Epidiolex® solution [100 mg/ml] of CBD); Other Names: Epidiolex®; Ritalin®
Active Comparator: Exposure B; Subjects will be administered one (1) 10 mg tablet of dl-methylphenidate (Ritalin®) 7.5 ml of Epidiolex® placebo solution containing no CBD.	Drug: di-Methylphenidate plus Cannabidiol Placebo solution; Subjects will be administered one (1) 10 mg tablet of dl-methylphenidate (Ritalin®) 7.5 ml of Epidiolex® placebo solution containing no CBD.; Other Names: Epidiolex®; Ritalin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Differences in the geometric mean ratios (GMR) of the pharmacokinetic parameters will be compared between the two exposure conditions; i.e. methylphenidate + CBD vs methylphenidate + placebo.	8 hours for each exposure condition for pharmacokinetic assessments

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: State of Florida Consortium for Medical Marijuana Clinical Outcomes Research
• Investigators: Principal Investigator: John Markowitz, Pharm.D, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2021
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Anticonvulsants; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate; Cannabidiol
• Other Study ID Numbers: IRB202002547-A; OCR39758 (Other Identifier: UF OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes