Cannabis and psychosis/schizophrenia: human studies

Abstract

The association between cannabis use and psychosis has long been recognized. Recent advances in knowledge about cannabinoid receptor function have renewed interest in this association. Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative, and cognitive symptoms in some healthy individuals. Also clear is that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. The mechanisms by which cannabinoids produce transient psychotic symptoms, while unclear may involve dopamine, GABA, and glutamate neurotransmission. However, only a very small proportion of the general population exposed to cannabinoids develop a psychotic illness. It is likely that cannabis exposure is a "component cause" that interacts with other factors to "cause" schizophrenia or a psychotic disorder, but is neither necessary nor sufficient to do so alone. Nevertheless, in the absence of known causes of schizophrenia, the role of component causes remains important and warrants further study. Dose, duration of exposure, and the age of first exposure to cannabinoids may be important factors, and genetic factors that interact with cannabinoid exposure to moderate or amplify the risk of a psychotic disorder are beginning to be elucidated. The mechanisms by which exposure to cannabinoids increase the risk for developing a psychotic disorder are unknown. However, novel hypotheses including the role of cannabinoids on neurodevelopmental processes relevant to psychotic disorders are being studied.

Fig. 1

Δ⁹-THC induces transient psychotomimetic effects in healthy individuals. Effects of Δ⁹-THC on the seven-item positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) (left panel) and the clinician rated subscale of the clinician administered dissociative symptoms scale (CADSS) (right panel). The PANSS is used to measure the symptoms associated with schizophrenia. Scores for each item range from 0 (absent) to 7 (extremely). The range of scores on the PANSS positive subscale is 0–49. The CADSS is used to measure perceptual alterations. Scores for each item range from 0 (absent) to 4 (extremely). The range of scores on the CADSS clinician-rated subscale is 0–32. Green circles placebo (vehicle); blue squares 2.5 mg Δ⁹-THC; red triangle 5 mg Δ⁹-THC

Fig. 2

Δ⁹-THC induces memory impairments. Effects of Δ⁹-THC on learning, immediate free recall, delayed free recall, delayed cued and recognition recall measured by a 12-word learning task (Hopkins verbal learning test). Green circles placebo (vehicle); blue squares 2.5 mg Δ⁹-THC; red triangle 5 mg Δ⁹-THC; solid line schizophrenia; dotted line controls

Fig. 3

Enhanced sensitivity to the psychotomimetic effects of Δ⁹-THC in schizophrenia. Peak increase in positive symptoms measured by the positive symptoms subscale of the positive and negative symptoms scale (PANSS) (group means 1 SD). Clinically significant increase = 3 point or greater increase in PANSS positive symptom subscale score. Yellow symbols placebo; green symbols 2.5 mg Δ⁹-THC; red symbols 5 mg Δ⁹-THC; circles control; triangle schizophrenia