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Background and Hypothesis Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs. Study Design We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African ancestry; 42% female; 74% meeting lifetime criteria for an AUD). Study Results Cannabis use disorder (CUD) was prevalent in this analytic sample (70%), with 40% classified as mild, 25% as moderate, and 35% as severe. Polygenic risk for schizophrenia was positively associated with cannabis-related paranoia, feeling depressed or anhedonia, social withdrawal, and cognitive difficulties, even when controlling for duration of daily cannabis use, CUD, and age at first cannabis use. The schizophrenia PRS was most robustly associated with cannabis-related cognitive difficulties (β = 0.22, SE = 0.04, P = 5.2e−7). In an independent replication sample (N = 1446), associations between the schizophrenia PRS and cannabis-related experiences were in the expected direction and not statistically different in magnitude from those in the COGA sample. Conclusions Among individuals who regularly use cannabis, genetic liability for schizophrenia—even in those without clinical features—may increase the likelihood of reporting unusual experiences related to cannabis use. [ABSTRACT FROM AUTHOR]

Cannabis is the most commonly used illicit drug worldwide, with ∼5 million daily users worldwide. Emerging evidence supports a number of associations between cannabis and psychosis/psychotic disorders, including schizophrenia. These associations-based on case-studies, surveys, epidemiological studies, and experimental studies indicate that cannabinoids can produce acute, transient effects; acute, persistent effects; and delayed, persistent effects that recapitulate the psychopathology and psychophysiology seen in schizophrenia. Acute exposure to both cannabis and synthetic cannabinoids (Spice/K2) can produce a full range of transient psychotomimetic symptoms, cognitive deficits, and psychophysiological abnormalities that bear a striking resemblance to symptoms of schizophrenia. In individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Several factors appear to moderate these associations, including family history, genetic factors, history of childhood abuse, and the age at onset of cannabis use. Exposure to cannabinoids in adolescence confers a higher risk for psychosis outcomes in later life and the risk is dose-related. Individuals with polymorphisms of COMT and AKT1 genes may be at increased risk for psychotic disorders in association with cannabinoids, as are individuals with a family history of psychotic disorders or a history of childhood trauma. The relationship between cannabis and schizophrenia fulfills many but not all of the standard criteria for causality, including temporality, biological gradient, biological plausibility, experimental evidence, consistency, and coherence. At the present time, the evidence indicates that cannabis may be a component cause in the emergence of psychosis, and this warrants serious consideration from the point of view of public health policy. [ABSTRACT FROM AUTHOR]

Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis. Delta-9-Tetrahydrocannabinol (Δ-9-THC) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals. Whether people who frequently use cannabis are either protected from or are tolerant to these effects of Δ-9-THC has not been established. In a 3-day, double-blind, randomized, placebo-controlled study, the dose-related effects of 0, 2.5, and 5 mg intravenous Δ-9-THC were studied in 30 frequent users of cannabis and compared to 22 healthy controls. Δ-9-THC (1) produced transient psychotomimetic effects and perceptual alterations; (2) impaired memory and attention; (3) increased subjective effects of ‘high’; (4) produced tachycardia; and (5) increased serum cortisol in both groups. However, relative to controls, frequent users showed blunted responses to the psychotomimetic, perceptual altering, cognitive impairing, anxiogenic, and cortisol increasing effects of Δ-9-THC but not to its euphoric effects. Frequent users also had lower prolactin levels. These data suggest that frequent users of cannabis are either inherently blunted in their response to, and/or develop tolerance to the psychotomimetic, perceptual altering, amnestic, endocrine, and other effects of cannabinoids.Neuropsychopharmacology (2008) 33, 2505–2516; doi:10.1038/sj.npp.1301643; published online 9 January 2008 [ABSTRACT FROM AUTHOR]

Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (Δ-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. Δ-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that Δ-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders. [ABSTRACT FROM AUTHOR]