Clinical trial NCT06099379: Modulation of THC Effects by CBD: a Dose-ranging Study
Official title: Modulation of ∆9-tetrahydrocannabinol Acute Psychoactive Effects by Ranging Doses of Cannabidiol in Healthy, Occasional Cannabis Users: a Controlled, Triple Blind, Randomized, Cross-over Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cannabis
THC
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
First posted: 2023-10-25
Enrollment: 100
Sex: ALL
Minimum age (years): 21
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: In this crossover design, participants will be administered all phytocannabinoid doses contained in the four CBD:THC products and the control product (THC only) during participation in the study. Participant will be randomly assigned to one of the predetermined sequences with a CBD:THC product or control product at 5 dosages (CBD:THC of 0:20 mg, 20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg). Participants will be randomized based on a balanced 5 by 5 Latin square.
Primary purpose: OTHER

Brief summary: The purposes of this study are 1) to determine if CBD modulates THC-induced acute psychoactive effects at different CBD:THC ratios, compared with the control product (0:20, 20:20, 40:20, 80:20, 120:20) and 2) to determine if different doses of CBD modulate other THC induced behavioral effects, compared with the control product and 3)To explore qualitatively whether CBD modulates THC effects by mechanisms that are not detected with standard clinical research tools.

Detailed description: Despite more than 40 years of research on the active compounds present in the cannabis plant, the influence of CBD consumption on the metabolism, pharmacology, and behavioral effects of THC remains fragmentary and scarcely documented in vivo in humans. Cannabis users are currently encouraged to choose products containing CBD, but evidence is lacking regarding its potential benefits when consumed jointly with THC across different ratios. Given the recent cannabis legalization in Canada and the widespread use of inhalation as the preferred mode of administration for non-therapeutic cannabis, closing this knowledge gap will help ensure public safety and allow regulatory bodies and public health authorities to elaborate more refined cannabis use guidelines and harm reduction strategies. It will also empower people who use cannabis to make more informed purchasing decisions and will drive the incubation of future research endeavors in the fields of medical and social sciences. The aim of this study is to improve our understanding of the (acute) behavioral and pharmacological effects of different doses of CBD administered concomitantly with THC via inhalation in individuals who engage in occasional cannabis use, taking into consideration multiple factors that can modulate such effects. This study will put to the test conceptions surrounding the interaction between specific cannabinoids by evaluating the role of CBD on the modulation of THC's effects pertaining to cognition, behavior, subjective experience, and physiological parameters.

Eligibility criteria: Inclusion Criteria:

1. Between 21 and 49 years of age, inclusively;
2. Have used cannabis at least once in their lifetime and have used cannabis three days or less in the 30 days prior to enrollment;
3. Be able to provide a signed informed consent;
4. Willing to comply with study procedures and requirements as per protocol;
5. Have a forced expiratory volume in first second (FEV) less than or equal to 90 %;
6. Able to communicate and understand English or French language;
7. For female participants:

   a. No childbearing potential, defined as: i. postmenopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age); or ii. Documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or b. For female of childbearing potential: i. Must have negative pregnancy test result at screening and at subsequent visits.

ii. AND have no pregnancy plan while on the study iii. AND must agree to use a medically accepted method of birth control throughout the study.

Exclusion criteria

Participants will be excluded if any of the following criteria are met:

1. Any disabling medical condition, as assessed by medical history, physical exam, vital signs and/or laboratory assessments that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent;
2. Severe psychiatric condition (history of schizophrenia, schizoaffective disorder or bipolar disorder; current acute psychosis, mania or current suicidality based on the Mini International Neuropsychiatric Interview);
3. Any other disabling, unstable or acute mental condition that, in the opinion of the study physician, precludes safe participation in the study or ability to provide fully informed consent;
4. Known chronic liver disease or aspartate transaminase/alanine transaminase (AST/ALT) two times higher than upper limit of normal values at screening visit;
5. Blood pressure higher than 130/80 mmHg;
6. Kidney disorders;
7. Bleeding disorders;
8. Current moderate or severe DSM-5 substance use disorder (except nicotine) according to SCID-V;
9. Currently pregnant, breastfeeding or planning to become pregnant either at screening or while enrolled in the study;
10. Pending legal action or other reason that, in the opinion of the study physician, might prevent study completion;
11. Use of medication within 7 days of experimental sessions; which, in the opinion of the Investigator, may interact with cannabis.
12. Participation in clinical studies or undergoing other investigational procedure involving cannabis or cannabinoids administration within 30 days prior to randomization.
13. Resting heart rate over 100 beats per minute.
14. Current body mass index (BMI) over 29.9 kg/m2.
15. Any clinically significant electrocardiogram abnormalities at screening visit.

Primary outcomes:
measure: Objective and subjective measures of cannabinoids effect
timeFrame: Prior to the Product administration ,10 minutes and 80 minutes after inhalation
Secondary outcomes:
measure: Positive and Negative Affect
timeFrame: Prior to the Product administration , 10 minutes and 80 minutes post inhalation
measure: Neural oscillations
timeFrame: Prior to the Product administration, 80 minutes post inhalation and at the end of the study visit, approximatively 140 minutes after inhalation
measure: Anxiety Symptoms
timeFrame: Prior to the Product administration, 10 minutes and 80 minutes after inhalation
measure: Subjective Drug Effects
timeFrame: 10 minutes and 80 minutes after inhalation
measure: Experience with Study Products
timeFrame: 140 minutes after inhalation
measure: Social Exposition Challenge
timeFrame: 70 minutes after inhalation
measure: Change on cognition
timeFrame: Prior to the Product administration (only at Visite 1) and 10 minutes after inhalation at each visit
measure: Success of Blinding Questionnaire
timeFrame: 10 minutes and 140 minutes after inhalation
measure: Inhalation Adherence
timeFrame: During inhalation procedure
measure: Change in Safety
timeFrame: Baseline,10 minutes, 80 minutes and 140 minutes after inhalation
measure: Visit Intoxication Assessment
timeFrame: Through study visit completion, approximatively 140 minutes after product inhalation
Other outcomes:
measure: Change in plasma concentrations of CBD
timeFrame: Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration
measure: Change in plasma concentrations of THC
timeFrame: Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration
measure: Change in plasma concentrations of Anandamide (AEA)
timeFrame: Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration
measure: Change in plasma concentrations of 2-Arachidonoylglycerol (2-AG)
timeFrame: Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration
measure: Genetic markers
timeFrame: Baseline, Prior to the Product administration (only at visite 1)
Locations:
city: Montréal
country: Canada
facility: Centre de recherche du Centre Hospitalier Universitaire de Montréal
state: Quebec
Study officials:
affiliation: CRCHUM
name: Didier Jutras-Aswad, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: