A Cannabinoid Hypothesis of Schizophrenia Pathways to Psychosis.
Observations regarding psychostimulant and psychedelic drug-induced psychotic states led to the dopamine, serotonin, and glutamate hypotheses of schizophrenia. Expanding knowledge about the endocannabinoid system and the impact of exogenous cannabinoids on the brain and behavior have elucidated several putative pathways to cannabis-induced psychosis. The purpose of the present article was to describe these pathways and propose a cannabinoid hypothesis of schizophrenia. The endocannabinoid system was reviewed. Evidence regarding the effect of delta 9-tetrahydrocannabinol (THC) on the brain was described. A connection between cannabis use and first-episode psychosis was elucidated. Understanding the putative pathways to cannabis-induced psychosis might lead to targeted therapeutic interventions and prevention of schizophrenia in susceptible individuals.