Cognitive impairment is well established in people with psychosis and is associated with cannabis use. The current study will investigate the neurobiological basis of cognitive change associated with 28-days of cannabis abstinence in people with psychosis and non-psychiatric controls with cannabis use. Participants will be randomized to a cannabis abstinent group or a non-abstinent control group and will undergo magnetic resonance imaging at baseline and following 28-days of abstinence. This study will help characterize the neuropathophysiological processes underlying cognitive dysfunction associated with cannabis use and its recovery which may guide the development of novel interventions for problematic cannabis use.

Background/Importance: Cognitive impairment is well established in people with psychosis and is associated with cannabis use. Despite high rates of cannabis use among people with psychosis and the general population, cannabis' effects on cognition and the brain and their recovery remain unclear. Therefore, this study will investigate the neurobiological basis of changes in cognitive processes associated with cannabis abstinence in people with psychosis and non-psychiatric controls.

Aims: To examine the effects of 28-days of cannabis abstinence in psychosis patients with cannabis use and non-psychiatric controls with cannabis use on (i) brain activity (paired with a memory task); (ii) brain morphology; (iii) to determine if changes in memory following 28-days of abstinence correlate with changes in brain activity and/or morphology and (iv) to determine if baseline brain function and morphology can predict successful abstinence.

Methods: Seventy-four psychosis patients with cannabis use and 60 non-psychiatric controls with cannabis use will be randomized to: (1) contingency reinforcement where biochemically verified abstinence at day 28 will be rewarded; or (2) a non-abstinent control group. The investigators will also recruit a group of healthy non-psychiatric controls (n=40) to determine if neural outcomes in cannabis-using participants do indeed normalize ("recover") following abstinence. Participants will undergo structural and functional magnetic resonance imaging while completing a memory task at baseline (pre-abstinence) and following 28-days of abstinence. Urine samples will be collected twice weekly for abstinence verification.

Relevance: This study will help to characterize the neuropathophysiological processes underlying cognitive dysfunction associated with cannabis use in people with psychosis and non-psychiatric controls which may help to guide the development of novel neurobiologically-informed interventions to treat problematic cannabis use.

Inclusion Criteria:

• Able to provide informed consent in English or French
• Heavy cannabis use (defined as weekly cannabis use for at six months) and/or DSM-5 diagnosis of CUD
• Have a Full-Scale IQ ≥ 75
• Meet DSM-5 criteria for a psychotic disorder (psychosis patient arm only)
• Be an outpatient receiving a stable dose of medication(s) for at least two months (psychosis patient arm only)
• Clinically stable (as measured by the PANSS-6, total score <30) (psychosis patient arm only)

Exclusion Criteria:

• current SUD (other than CUD)
• MRI contraindications
• Positive urine screen for psychoactive substances other than cannabis, nicotine, or caffeine
• Current suicidal or homicidal ideation
• Head injury requiring hospitalization or loss of consciousness > 5 minutes
• Current medical diseases that requires hospitalization or regular monitoring
• Being pregnant
• DSM-5 Axis 1 diagnosis (other than CUD) (non-psychiatric controls only)
• Taking psychotropic medication

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Research Assistant