58. Focusing on the Significance of, and the Mechanisms Underlying, Cannabis-Induced Psychosis

Abstract

Overall Abstract: Dr Marta Di Forti Cannabis use across Europe and its interaction with the polygenic risk score for schizophrenia. Dr Di Forti examined the pattern of cannabis use across 16 European sites as part of the EU-GEI study. She will show striking differences in incidence of psychosis (high in North and low in South), and how differences in pattern of cannabis use result in differences in the proportion of new cases of psychosis attributable to cannabis use across Europe (highest in London and Amsterdam). Dr Di Forti will examine the effects of cannabis use on incidence of psychosis, and show how cannabis use interacts with the Schizophrenia Polygenic Risk Score (in 1200 cases and similar number of controls). Dr David Lewis Adolescent Cannabis Use, Cortical Circuitry and Schizophrenia Dr Lewis studied both adolescent monkeys and boys. In adolescent monkeys, repeated exposure to Δ9-tetrahydrocannabinol (THC) blunted the trajectory of accuracy improvements in spatial working memory. These effects were more marked and more persistent in male than in female monkeys. In a longitudinal human study, 1006 boys were followed regularly through their adolescence. For each year that they engaged in regular marijuana use, their expected odds of experiencing subsequent subclinical paranoia or hallucinations rose by 133% and 92%, respectively. Dr Steve Laviolette The Molecular and Neuronal Effects of Adolescent THC Exposure in Mesocorticolimbic Circuitry. Dr Laviolette has discovered that neurodevelopmental exposure to THC dramatically dysregulates dopamine transmission in the mesocorticolimbic circuit, inducing a hyper-DAergic phenotype into adulthood; schizophrenia-like abnormalities are found in affective and cognitive processes and schizophrenia-like molecular adaptations in the prefrontal cortex (PFC) and nucleus accumbens involving the GSK-3 pathway. Developmental THC exposure leads to deficits in GABAergic inhibitory substrates within the PFC and a loss of control over subcortical DAergic activity states. Dr Anissa Abi Dargham Chronic cannabis use is associated with abnormal dopaminergic function. Dr Abi Dargham measured amphetamine induced dopamine release with PET and D2 radiotracers in striatal subdivisions in multiple cohorts of patients with schizophrenia, patients with schizophrenia and comorbid substance use disorders, in patients with cannabis use, and in controls matched to each cohort. Her studies show that substance use disorders, and cannabis use, result in blunting of dopamine release. In addition, patients with schizophrenia exposed to chronic substance use show excess responsivity of the D2 system associated with psychosis, despite low presynaptic storage capacity. These findings will be discussed and compared to address the contribution of cannabis use to the dopaminergic dysfunction in schizophrenia.