The Pharmacokinetic and Pharmacodynamic Effects of Oral Cannabidiol (CBD) Under Acute and Chronic Exposure Conditions

Study Overview
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Brief Summary
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This study will evaluate the pharmacokinetic and pharmacodynamic effects of oral Cannabidiol (with or without low levels of THC), under acute and chronic dosing conditions.

Detailed Description
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Participants (N=60), will be randomized to 1 of 3 oral dosing conditions that include: 100mg CBD/3.7mg THC (0.39% THC), 100mg CBD/2.8mg THC (0.3% THC), or 100mg CBD/0mg THC (0.0% THC). Participants will first complete an 8-hour drug administration session and after this initial session, participants will take participants' assigned study drug for the next 14 days at home, twice daily (participants will visit the lab on days 2, 7, and 14). Participants will return on day 21 (after 1 week washout) for a final visit. During the 8-hour session and visits occurring during the following 21 days, participants will provide biospecimens (urine, blood, oral fluid, hair) which will be tested for cannabinoid concentrations. Pharmacodynamic assessments (subjective and cognitive effects) will also be assessed during these visits.

Official Title
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The Pharmacokinetic and Pharmacodynamic Effects of Oral Cannabidiol (CBD) Under Acute and Chronic Exposure Conditions

Conditions
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Cannabis, Drug Effects

Intervention / Treatment
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* Drug: CBD
* Drug: THC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have provided written informed consent Be between the ages of 18 and 55 Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests Test negative for recent cannabis use in urine at the screening visit and again upon admission for each experimental session Test negative for other drugs of abuse, including alcohol at the screening visit and upon arrival for each experimental session Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at clinic admission. Have a body mass index (BMI) in the range of 19 to 36 kg/m2 Have head hair that is at least 4 cm (approximately one and a half inches) in length on the back of the head. Blood pressure at Screening Visit does not exceed a systolic blood pressure (SBP) of 150 mmHg or a diastolic blood pressure (DBP) of 90 mmHg Report prior experience using cannabis or CBD. Have not donated blood in the prior 30 days. Have a smartphone capable of downloading/operating the Redcap mobile application. Exclusion Criteria: Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine in the month prior to the screening visit. History of or current evidence of significant medical or psychiatric illness judged by the investigator to put the participant at greater risk of experiencing an adverse event due to exposure or completion of other study procedures. Use of an over-the-counter (OTC), systemic or topical drug(s), herbal supplement(s), or vitamin(s) within 14 days of study entry; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject. Use of a prescription medication (with the exception of birth control prescriptions) within 14 days of study entry; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject. This includes any medication metabolized via CYP2D6, CYP2C9, CYP2B10, or which induce/inhibit CYP3A4 enzymes. Use of hemp seeds or hemp oil in any form in the past 3 months. Use of dronabinol (Marinol) within the past 6 months. History of xerostomia (dry mouth), or the presence of mucositis, gum infection or bleeding, or other significant oral cavity disease or disorder that in the investigator's opinion may affect the collection of oral fluid samples. History of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina). Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing. Epilepsy or a history of seizures. Individuals who have a recent history of traumatic brain injury diagnosed by CT/MRI and have current sequela from prior brain injury, as determined by the study physician Individuals with anemia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants (N=60), will be randomized to 1 of 3 oral dosing conditions that include: 100mg CBD/3.7mg THC (0.39% THC), 100mg CBD/2.8mg THC (0.3% THC), or 100mg CBD/0mg THC (0.0% THC).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD without THC<br>oral formulation containing 100mg CBD and 0mg THC | Drug: CBD<br>* CBD will be orally ingested<br>|
| Experimental: CBD with 3.7 mg THC<br>oral formulation containing 100mg CBD and 3.7mg THC | Drug: CBD<br>* CBD will be orally ingested<br>Drug: THC<br>* THC will be orally ingested<br>|
| Experimental: CBD with 2.8 mg THC<br>oral formulation containing 100mg CBD and 2.8 mg THC | Drug: CBD<br>* CBD will be orally ingested<br>Drug: THC<br>* THC will be orally ingested<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine cannabinoids | Concentration of cannabinoids will be measured in urine (unit of measurement: nanograms/mL) | Day 1, 2, 7, 14, and 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective drug effects as assessed by the Drug Effect Questionnaire | Subjective drug effect ratings (0-100) will be collected with the Drug Effect Questionnaire, with 0 being no effect and 100 being maximum effect. | Day 1 | 
| Subjective drug effects as assessed by the Drug Effect Questionnaire | Subjective drug effect ratings (0-100) will be collected with the Drug Effect Questionnaire, with 0 being no effect and 100 being maximum effect. | Day 2 | 
| Subjective drug effects as assessed by the Drug Effect Questionnaire | Subjective drug effect ratings (0-100) will be collected with the Drug Effect Questionnaire, with 0 being no effect and 100 being maximum effect. | Day 7 | 
| Subjective drug effects as assessed by the Drug Effect Questionnaire | Subjective drug effect ratings (0-100) will be collected with the Drug Effect Questionnaire, with 0 being no effect and 100 being maximum effect. | Day 14 | 
| Subjective drug effects as assessed by the Drug Effect Questionnaire | Subjective drug effect ratings (0-100) will be collected with the Drug Effect Questionnaire, with 0 being no effect and 100 being maximum effect. | Day 21 | 
| Blood cannabinoids | Concentration of cannabinoids will be measured in blood (unit of measurement: nanograms/mL) | Day 1, 2, 7, 14, and 21 | 
| Oral Fluid cannabinoids | Concentration of cannabinoids will be measured in oral fluid (unit of measurement: nanograms/mL) | Day 1, 2, 7, 14, and 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabidiol