Cannabis use is associated with an increased risk of developing psychotic disorders among people already at clinical high risk for psychosis. In a prospective study of this population, cannabis use was linked to a higher incidence of psychotic disorders and to more persistent psychotic symptoms, as well as poorer functional outcomes. The findings strengthen evidence that cannabis acts as a risk factor for psychosis, though the direction of causality remains debated.
No licensed pharmacological treatments exist to prevent the onset of psychosis in people at clinical high risk. This chapter reviews four preclinical models that inform the development of such treatments: neonatal hippocampal lesion, prenatal immune activation, and administration of PCP or methylazoxymethanol acetate (MAM). The neonatal hippocampal model lacks construct validity, evidence linking prenatal immune activation to psychosis is limited, and the chronic PCP model lacks a neurodevelopmental component. The MAM model best reproduces neural and behavioral changes resembling human psychosis onset. Together, these models have advanced understanding of mechanisms underlying psychotic disorders and provide a rationale for novel preventative interventions.