with Chrm3 playing an inhibitory role in dopamine release24. In animal models, oxotremorine can reverse methamphetamine-, ketamine-, and cocaine-induced hyperlocomotion26. Blockade of cholinergic receptors, particularly muscarinic receptors, causes a psychosis characterized by hallucinations and cognitive impairment in normal human subjects and exacerbates symptoms in schizophrenic patients26. This is consistent with the assumption that cannabis use is an environmental risk factor in the etiology of schizophrenia, as THC may directly affect T-type calcium channels in the THAL by increasing the excitability of THAL neurons27. In our study, the risk rs115455482*T allele is most significantly associated with lower expression of CHRM3 in THAL, suggesting potential excitatory-to-inhibitory imbalance in the THAL may predispose to cannabis-induced psychosis or schizophrenia.
