Thought insertion in schizophrenia may arise from altered Bayesian inference within the predictive coding framework. Early 20th-century phenomenological accounts by the Heidelberg School described thought insertion as a self-disturbance involving disrupted inner connectedness of thoughts, which become sensory and feel inserted. Mescaline was used as a model psychosis to explore these mechanisms. The authors propose that reduced precision of context-dependent predictions, relative to sensory precision, increases prediction-error signals for internal events like thoughts. This aberrant salience, analogous to that proposed for external events, leads individuals to interpret thoughts as inserted by an alien agent, similar to delusion formation from aberrant sensory salience.
Cannabis use at age 16 is associated with psychotic-like experiences (PLEs) even after accounting for genetic risk for schizophrenia, according to an analysis of 1740 European adolescents from the IMAGEN cohort and replicated in 1223 individuals from a Dutch cohort. Polygenic risk scores for schizophrenia predicted both cannabis use and PLEs, and cannabis use remained a significant predictor of PLEs in models including genetic risk. However, no evidence was found that genetic risk mediates or moderates the cannabis–psychosis link. The findings suggest cannabis use is a risk factor for PLEs independent of genetic vulnerability to schizophrenia.
CB1 receptor antagonists rimonabant and AM251 reversed deficits in sensorimotor gating caused by phencyclidine in rats, an effect comparable to the atypical antipsychotic clozapine. Rimonabant also attenuated gating disruptions from dizocilpine and apomorphine. No augmentation was seen when rimonabant and clozapine were given together. The findings suggest that blocking CB1 receptors may help restore disrupted interactions between the endocannabinoid and glutamate systems implicated in schizophrenia.