Intravenous delta-9-tetrahydrocannabinol (THC) can produce a temporary psychotic reaction in healthy people. In a double-blind, placebo-controlled experiment with 22 participants, a single 2.5 mg dose of THC significantly increased both self-reported and observer-rated positive psychotic symptoms, which were closely linked (correlation of 0.62). The symptoms involved a disrupted sense of self-agency and heightened paranoia. Participants also reported more negative symptoms, which were not due to sedation, and their working memory and executive function were consistently impaired. The findings suggest THC recreates symptoms across three major dimensions of schizophrenia without clouding consciousness. Preliminary evidence indicates that cannabidiol (CBD) may inhibit THC-induced positive symptoms.
Cannabis legalization and commercialization are increasing worldwide, with rising tetrahydrocannabinol potency linked to greater risks of dependence and psychosis. Dependence risk has risen from 9% to near 30% as potency increased. Daily use of high-potency cannabis raises psychosis risk up to 9-fold, comparable to the lung cancer risk from smoking 30 cigarettes daily. Evidence from prospective studies shows a causal relationship between cannabis use and later schizophrenia-like psychosis, not explained by confounding factors or reverse causation. Adolescents and those with a family history of psychosis are especially vulnerable. The cannabis industry's marketing and lobbying echo tactics used by the tobacco industry to downplay health harms.
Heavy use of high-potency cannabis that is high in THC and low in CBD increases the risk of psychotic disorders, with greater risk for early use and use of synthetic cannabinoids. Frequent cannabis use also raises the risk for mania and suicide, but the effect on depression is less clear and findings on anxiety are contradictory. Depression and anxiety may lead to greater cannabis consumption in some studies. THC interacts with genetic predisposition and other environmental factors, while CBD may reduce the psychotogenic effects of THC but is absent from many high-potency varieties. The evidence is strong enough to merit public health education about psychosis risk.