Purpose: To examine the neurological effects of cannabis on stress reactivity and inhibition in healthy adults using recreational cannabis weekly and drinking heavily. This is a phase I/pilot healthy subjects trial.~Primary Hypotheses:~The intervention will be feasible to implement~Cannabis oil will attenuate stress, measured via biological and self-report data, including salivary molecules, functional Magnetic Resonance Imaging, and standardized psychosocial assessments.~Justification: Current cannabis research focuses on medical uses for cannabis, clinical populations and/or non-commercially available products. There remains limited experimental research on the effects of commercial products in non-clinical regular users of cannabis. Further, most drug use research excludes polysubstance users. Given the high number of people using cannabis to cope with stress, biological evidence is needed to determine the validity of this claim. Stress is known to negatively impact daily functioning and has been linked to poorer mental and physical health outcomes. The effects of cannabinoids on cognitive functioning also have implications for daily functioning.~Objectives: Determine a causal link between commercially available cannabinoid products and mechanisms involved with stress response in polysubstance users, specifically weekly cannabis users with heavy drinking (males: minimum 5 drinks, females: minimum 4 drinks on at least one occasional per month for the past 12 months). Examine the short-term effects of cannabinoids on sleep quality in this population.~Study Design: The study is a Phase I non-therapeutic pilot trial and will utilize a double-blind, placebo-controlled, within-subjects design. The acute effects of the investigational products (IPs) will be examined. Each participant will undergo an initial phone screen and 5 sessions, with sessions 2-4 involving drug administration. There will be three investigational product arms for the drug administration sessions: cannabis oil with a high ratio of THC to CBD, cannabis oil with a high ratio of CBD to THC, and placebo. Each participant will be exposed to all three arms, one per drug administration session. The order of arm will be randomized. Each drug administration session will be a minimum of10 days apart to ensure a sufficient washout period.
The purpose of this Phase I non-therapeutic trial is to examine the neurological effects of cannabis on stress reactivity and inhibition in healthy cannabis and heavy alcohol co-users. We expect differences between high ratio CBD:THC cannabis oil, low ratio CBD:THC cannabis oil, and/or placebo on outcome measures.