Cannabidiol and CES1 Interactions in Healthy Subjects

Study Overview
=================
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

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

Conditions
-----------------
Drug Interaction

Intervention / Treatment
-----------------
* Drug: di-Methylphenidate plus Cannabidiol
* Drug: di-Methylphenidate plus Cannabidiol Placebo solution


Participation Criteria
=================
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; Gastric bezoar Swallowing disorders Strictures Fistulas GI obstruction Severe dsyphasgia Crohn's disease Diverticulitis A positive urine pregnancy test. A positive Urine Drug Screen 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.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: An open-label, randomized crossover design is proposed wherein healthy volunteer subjects (n=12) would receive a single dose of immediate-release dl-methylphenidate (Ritalin®) concomitantly with orally administered CBD (Epidiolex®) solution or an equal volume of Epidiolex® placebo solution (i.e vehicle with no CBD) which have been dosed to plasma steady-state conditions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exposure A<br>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<br>* 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)<br>* Other names: Epidiolex®;|
| Active Comparator: Exposure B<br>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<br>* Subjects will be administered one (1) 10 mg tablet of dl-methylphenidate (Ritalin®) 7.5 ml of Epidiolex® placebo solution containing no CBD.<br>* Other names: Epidiolex®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |