The constraints that CB1 activity imposes on NMDAR function may underlie both neuroprotection and the negative effects of cannabinoids, and thus smoked cannabis abuse may lead to psychosis and circumstantially precipitate or intensify symptoms of schizophrenia (Degenhardt et al., 2003; Fernandez-Espejo et al., 2009), albeit mostly in subjects bearing a previous vulnerability (Cannon and Clarke, 2005;Harrison and Weinberger, 2005). The gene discussed is CNR1; the disease is psychotic disorder.