Cannabinoid ‘model’ psychosis, dopamine–cannabinoid interactions and implications for schizophrenia

Abstract

Hypotheses relating to the association between cannabis and psychosis may be divided into two groups. The exogenous hypothesis, which has received far greater attention, suggests that the consumption of cannabinoid compounds produces psychotic disorders by mechanisms that are extrinsic to the pathophysiology of naturally occurring psychoses. As discussed elsewhere in this book, converging evidence from epidemiological, genetic, neurochemical, pharmacological and postmortem studies have provided support for an association between ‘cannabis and madness’ (see Chapters 3, 6, 8 and 9). These data also suggest a second, relatively nascent endogenous hypothesis, according to which cannabinoid (CB 1 ) receptor dysfunction may contribute to the pathophysiology of psychosis and/or schizophrenia, and further, that the putative CB 1 receptor dysfunction may be unrelated to the consumption of cannabinoid compounds. This chapter addresses the exogenous hypothesis of cannabis consumption and psychosis. First, we review studies from a number of sources, supporting an association between cannabis consumption and the manifestation of psychotic symptoms in humans (the interested reader is referred to Chapters 3 and 5 for a more detailed exposition). We then detail a recent pharmacological study that assessed the effects of exposure to the principal psychoactive constituent of cannabis, Δ 9 - tetrahydrocannabinol (Δ 9 -THC) in patients with schizophrenia and normal controls. We conclude by suggesting possible mechanisms by which cannabis may induce psychosis and articulate the implications of these findings for a potential endocannabinoid contribution to the pathophysiology of schizophrenia.