Genetics of Cannabis Use Disorder and Cannabinoid Response in Humans

Cannabis is widely used worldwide and is associated with negative outcomes including cannabis use disorder (CanUD), psychosis, and cognitive impairment amongst others. Given the legalization of "recreational" and "medical" cannabis globally, the increasing availability of cannabis, the higher potency of cannabis, the availability of highly potent cannabinoid products, the commercialization of cannabis, and the rising rates of cannabis use, it is critical to understand how genetic factors influence 1) an individual's vulnerability for addiction and psychosis, 2) the response to cannabinoids, 3) the response to novel treatments for CanUD. CanUD is strongly genetically influenced; the investigators published the first CanUD genomewide association study (GWAS) with genomewide-significant results; however, the precise nature of the contribution of genetic factors in the development of CanUD is still not clear. Cannabis exposure has also been linked to a number of psychosis outcomes including schizophrenia (SCZ). SCZ is highly heritable and population-based and genetics studies both support a bidirectional genetic relationship between SCZ and CanUD. However, the precise contribution of genetic factors in the development of psychosis outcomes related to cannabis are not clear.

Control: small amount of alcohol administered intravenously (quarter teaspoon), with no delta-9-THC, over 20 minutes.

Control: Small amount of sterile 190 proof USP ethanol (1-2 mLs), with no THC, administered intravenously over 20 minutes.

Measured at baseline, 20 mins, 45 mins, 90 mins, 140 mins, 165 mins, 210 mins, 270 mins, and 360 mins after the start of the initial THC/placebo drug infusion.

The Positive and Negative Syndrome Scale is a 30-item scale to assess both the positive and negative symptom symptoms of schizophrenia. The range total score is 30-210. An improvement in symptoms is reflected by a lower score.

Measured at baseline, 45 mins, 90 mins, 165 mins, 210 mins, and 360 mins after the start of the initial THC/placebo drug infusion.

Perceptual alterations will be measured using scales such as the Clinician Administered Dissociative Symptoms Scale (CADSS), a scale consisting of 19 self-report items and 8 clinician-rated items (0 = not at all, 4 = extremely) that we have shown to be sensitive to THC effects. The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment.

Measured at baseline, 45 mins, 90 mins, 165 mins, 210 mins, and 360 mins after the start of the initial THC/placebo drug infusion.

Measured at baseline, 45 mins, and 165 mins after the start of the initial THC/placebo drug infusion.

Inclusion Criteria: -Ages 18-60 years old Exclusion Criteria: Major or unstable medical conditions based on history, the Structured Clinical Interview for DSM-5, collateral information, physical and laboratory examinations, ECG, and vital signs. Cannabis naïve individuals Positive pregnancy test