Pre-treatment with 600 mg of cannabidiol (CBD) reduced the likelihood of clinically significant psychotic symptoms and paranoia caused by intravenous delta-9-tetrahydrocannabinol (THC, 1.5 mg) in healthy volunteers. Participants who received CBD before THC had lower scores on the State Social Paranoia Scale and smaller declines in episodic memory compared with those who received placebo before THC. The odds of experiencing a clinically significant increase in positive psychotic symptoms were about 78% lower in the CBD group. These results support the view that cannabis products high in THC and low in CBD pose greater mental health risks.
Schizophrenia is best understood as a syndrome rather than a single disease, with high heritability and multiple genetic and environmental factors pushing individuals over a threshold into clinical expression. Evidence that certain drugs can induce schizophrenia-like psychosis has been neglected as an environmental factor. Over the past 60 years, understanding the link between drug abuse and psychosis has shaped the modern view that liability to psychosis, including schizophrenia, is distributed continuously through the general population, similar to hypertension and diabetes. This review examines hypotheses arising from the association between common psychotomimetic drugs (LSD, amphetamines, cannabis, phencyclidine) and schizophrenia.
THC impairs subjective time perception and reduces the rate of button pressing in healthy volunteers, but the change in button pressing rate is more closely related to impaired concentration and intoxication than to time perception. The disruption of self-timed actions from THC may arise from a different mechanism than alterations in time perception.
Cannabis use is considered a contributory cause of schizophrenia and psychotic illness, but only a small proportion of users develop psychosis. The amount, duration, and strength of cannabis consumption, as well as age at first exposure, partly explain this. Genetic factors likely play a role in both short- and long-term effects on psychosis. This review discusses studies using genetic, epidemiological, experimental, and observational techniques to investigate gene-environment correlation and interaction within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction underlie the link, with multiple genetic variations and other environmental factors (e.g., stress) interacting with cannabis to increase psychosis risk. Further research on higher-order interactions is needed.