Cannabidiol and CES1 Interactions in Healthy Subjects

University of Florida

Status and phase: Completed; Phase 4

Conditions: Drug Interaction

Treatments: Drug: dl-Methylphenidate plus Cannabidiol; Drug: dl-Methylphenidate plus Cannabidiol Placebo solution

Study type: Interventional

Funder types: Other

Identifiers

NCT04603391

OCR39758 (Other Identifier)

IRB202002547-A

Details and patient eligibility

About

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

Full 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.

Enrollment: 14 patients

Sex: All

Ages: 21 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

---

14 participants in 2 patient groups

CBD, then placebo

Experimental group

Description:

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).

Treatment:

Drug: dl-Methylphenidate plus Cannabidiol Placebo solution

Drug: dl-Methylphenidate plus Cannabidiol

Placebo, then CBD

Experimental group

Description:

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).

Treatment:

Drug: dl-Methylphenidate plus Cannabidiol Placebo solution

Drug: dl-Methylphenidate plus Cannabidiol