Cannabis Use Disorder, Severe

Cannabis is the most commonly used psychoactive substance in Canada. A sub-group of cannabis users develop Cannabis Use Disorder (CUD). CUD is a pattern of cannabis use that results in impairment in functioning, symptoms of tolerance, withdrawal, and distress. Several pharmacological and psychosocial interventions have been evaluated for their efficacy in treating CUD, however they lack high success rates. GLP-1RA's have shown promising results in reducing food and alcohol cravings and intake. Tirzepatide acts as both a GLP-1RA and a glucose-dependent insulinotropic polypeptide receptor agonist. Tirzepatide has been reported to reduce alcohol consumption, and therefore may have promising effects as a treatment for CUD. This study aims to evaluate the feasibility and tolerability of weekly injections of Tirzepatide combined with Motivational Enhancement Therapy in adults with CUD. This trial will be the first to examine the potential therapeutic effects of Tirzepatide in CUD.

The goal of this study is to test a causal neural mechanism of cannabis use-related problem recognition in individuals with severe cannabis use disorder using a non-invasive form of neuromodulation called transcranial magnetic stimulation (TMS). The main question it aims to answer is: -Does manipulating neural activity in the medial orbitofrontal cortex of the brain affect cannabis use-related problem recognition? Researchers will compare three forms of theta burst stimulation (TBS; sham, intermittent, and continuous) in each participant to see if manipulations in neural activity lead to changes in cannabis use-related problem recognition. Participants will complete a screening interview about their mental health and substance use history and complete four in-person laboratory sessions, which involve questionnaires, four brief magnetic resonance imaging (MRI) scans, three TBS sessions, and three electroencephalogram (EEG) sessions. Participants will also be asked to provide urine samples and take saliva and/or breathalyzer tests at some of the lab visits.

This research study evaluates the effects of an FDA-approved medication Gabapentin in individuals with Bipolar Disorder who smoke marijuana. Participants in the study will will be assigned to take either Gabapentin or a matched placebo. Study medication will be taken for 17 days. There will be 5 study visits, with 2 MRI brain imaging scans completed. Questionnaires and clinical interview measures will be completed at study visits along with consistent assessment of potential side effects from study medication.

Cannabis is the most commonly used psychoactive substance in Canada (Lowry \& Corsi, 2020). A sub-group of cannabis users develop a condition known as Cannabis Use Disorder (CUD), which is defined as a regular pattern of cannabis use that causes performance difficulty at work, school and relationships (Hasin et al., 2013). A review of current treatments available for CUD indicate the lack of a pharmacological and psychological treatment with high success rates, which highlights the importance of exploring potential psychosocial interventions for the treatment of CUD. Given the evidence of psilocybin's therapeutic potential in the treatment of substance use disorders (de Veen et al., 2017), we aim to conduct a study using psilocybin-assisted-psychotherapy in the treatment of CUD. The study aims to evaluate the feasibility, safety, tolerability and potential therapeutic effect of 2 doses \[25 mg\] of psilocybin administered as part of an 8-week Motivational Enhancement Therapy (MET) and supportive therapy. This trial will be the first to evaluate the potential treatment effects of psilocybin on symptoms of CUD.