208. Predictors of Cannabis-Induced Psychosis

Abstract

Abstract Background: The endocannabinoid system (ECS) has been implicated in the pathophysiology of psychosis and epidemiological studies demonstrate an association between exposure to exogenous cannabinoids and acute as well as delayed psychosis outcomes. Family history of psychosis represents a nonmodifiable risk factor for psychosis, while cannabis exposure is a modifiable one. Individuals with a family history of psychosis (FHP) are at a greater risk for a psychotic disorder such as schizophrenia, psychosis associated with cannabis use, and enhanced sensitivity to the acute psychotomimetic effects of THC. In fact, it has been suggested that enhanced sensitivity to cannabis’ psychotomimetic effects may be a marker of familial risk for psychosis. Methods: Data will be presented from ongoing studies systematically examining the ECS in FHP individuals compared to those without a family history of psychosis (FHN) using a multidimensional approach. Cannabinoid 1 receptor (CB1R) availability was measured using the reversible ligand [11C]OMAR and High Resolution Research Tomography PET. The acute response to delta-9-tetrahydrocannabinol (THC) was measured in randomized, placebo-controlled, double-blind, acute pharmacological challenge study designed to examine the effects of intravenous THC on a wide range of subjective, cognitive, and electrophysiological biomarkers of psychosis. FHP and FHN subjects were matched on a number of relevant variables such as age, education, BMI, cannabis use histories, other substance exposure, and so on. Results: Data will be presented demonstrating that compared to FHN, FHP have (A) ↓ CB1R availability ([11C]OMAR VT)), (B) ↑ THC-induced psychotomimetic effects (Positive And Negative Syndrome Scale [PANSS] positive subscale), and (C) ↑ THC-induced cortical noise (Lempel-Ziev complexity scores) compared to FHN. Conclusion: These data are the very first to examine the confluence of the endocannabinoid and exogenous cannabinoid hypotheses in the risk for psychosis. Preliminary data suggest that a family history of psychosis is associated with lower CB1R availability and altered response to THC, a pattern of effects similar to that observed in individuals with a psychotic disorder. Future studies should aim to develop a stratification of the risk of exposure to cannabinoids in individuals with a family history of psychosis and inform public health policies. This is particularly important given that cannabis exposure is the main modifiable risk factor for psychosis.