Cannabinoids, monoamines, COMT and schizophrenia: Pathobiological mechanisms in psychosis

Chronic cannabis use is associated with increased risk for developing a psychotic disorder, with risk to develop psychosis highest among individuals who use cannabis during adolescence. The majority of cannabis users, however, do not develop a diagnosable psychiatric disorder. Individuals genetically predisposed to the development of psychosis seem at increased risk to the effects of cannabis. Contemporary models of psychosis posit that genetic predisposition and/or disruption at critical developmental periods is a substrate on which act various biological and psychosocial adversities, resulting in early functional impairments and later emergence of diagnostic symptoms. Recent years has seen the generation of experimental models of psychosis based on the interaction of genetic mutations and environmental factors (e.g. exposure to drugs of abuse). An emerging human and animal literature has shown showing that variation in the genes implicated in dopamine neurotransmission (COMT, AKT1, D2R) moderates the psychotomimetic effects of cannabis exposure. Further studies are required to clarify the molecular underpinnings of dopamine system involvement in cannabis-induced psychosis.