None listed
Conditions
Brief summary
Concomitant use of the anxiolytic drugs diazepam and cannabidiol (CBD) is expected to increase in the community. However, findings from a recent investigation by Lambert Initiative scientists suggest that CBD, via inhibition of the CYP2C19 and CYP3A4 enzymes, could reduce the rate at which diazepam is metabolised. Higher plasma diazepam concentrations (or concentrations that remain elevated for an extended period of time) have the potential to increase the risk of unwanted side effects and to exacerbate or prolong diazepam-induced sedation and impairment. This could have significant implications for individuals performing safety sensitive tasks such as driving. Thus, the overall objective of this study is to determine whether CBD alters the pharmacokinetics and pharmacodynamics of diazepam. Participants will complete two 7-day treatment periods: one involving the administration of a placebo, and the other, CBD (600 mg per day). Individuals will receive a single dose of diazepam (10 mg) along with their existing treatment at a test session on the morning of Day 7. Blood will be drawn, and simulated driving and cognitive performance measured, at regular intervals over the following 24 hours. We hypothesise that CBD will: (1) increase diazepam exposure; that is, the area under the plasma diazepam concentration–time curve; and (2) exacerbate diazepam-induced sedation and impairment.
Interventions
The intervention (‘perpetrator drug’) will be cannabidiol (CBD).
The specific IP will be a soft-gel capsule containing 200 mg CBD in medium chain triglyceride oil.
Participants will consume 400 mg CBD (or placebo) in the morning (i.e., between 6 AM – 12 PM), preferably with food, and 200 mg CBD (or placebo) in the evening (i.e., between 6 PM – 12 AM), preferably with food for seven consecutive days. The second-last dose (i.e., 400 mg CBD or placebo) will be taken with 10 mg diazepam (the 'vict
The intervention (‘perpetrator drug’) will be cannabidiol (CBD). The specific IP will be a soft-gel capsule containing 200 mg CBD in medium chain triglyceride oil. Participants will consume 400 mg CBD (or placebo) in the morning (i.e., between 6 AM – 12 PM), preferably with food, and 200 mg CBD (or placebo) in the evening (i.e., between 6 PM – 12 AM), preferably with food for seven consecutive days. The second-last dose (i.e., 400 mg CBD or placebo) will be taken with 10 mg diazepam (the 'victim drug') at a Test Session beginning on the morning of Day 7. Each 7-day Treatment Period will be separated by a washout period of at least 14-days. Treatment compliance will be measured using a ‘daily diary’ and a ‘pill count’.
Sponsors
The University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
21 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
a) Between 21–35 years of age. b) Holds (and has held for at least 1 year) a full (unrestricted) driver’s licence. c) Proficient in English (i.e., able to provide informed consent).
Exclusion criteria
a) An ‘active’ (i.e., uncontrolled, symptomatic) physical or mental health condition. b) Self-reported use of cannabinoids or benzodiazepines within the last 3 months or a positive point-of-care urine drug screen for cannabinoids or benzodiazepines. c) A self-reported history of allergic reaction (e.g., rhinitis, urticaria, contact dermatitis, anaphylaxis) to cannabinoid- or benzodiazepine-containing products. d) A self-reported history of liver disease, renal disease, respiratory disease (including sleep apnoea), or drug/alcohol dependence (excluding nicotine dependence). e) A suspected drug/alcohol dependence (excluding nicotine dependence). f) A self-reported neurological disorder or intellectual disability. g) Self-reported or suspected suicidal ideation. h) A body weight <50 kg or body mass index >30 kg/m2. i) Regular (i.e., weekly, or more often) use of medications or herbal remedies that induce or inhibit the cytochrome P450 (CYP) enzyme system or are metabolised by CYP enzymes that are inhibited by CBD (e.g., CYP2C19, CYP3A4). j) Carrying one or more non-functional CYP2C19 alleles (i.e., *2 or *3). k) Frequent (i.e., more than thrice weekly) use of psychoactive substances (excluding caffeine). l) Unwilling or unable to adhere to trial procedures. m) Pregnant, lactating or trying to conceive a child.
Outcome results
None listed