Psychosis-relevant effects of intravenous delta-9-tetrahydrocannabinol - A mega analysis of individual participant-data from human laboratory studies.

INTRODUCTION: There is increasing interest in the relationship between cannabinoids and psychosis. While individual human laboratory studies have been critical in demonstrating that cannabinoids (e.g., delta-9-tetrahydrocannabinol [THC]) can induce acute transient psychosis-like effects in healthy human volunteers, combining data from multiple studies offers a fine-grained view of these effects. METHODS: THC-induced psychosis-relevant effects were examined using a data-repository of 10 double-blind, randomized, placebo-controlled, crossover studies with 400 intravenous THC infusions in healthy human volunteers. The Positive and Negative Syndrome scale (PANSS) was used to measure psychotomimetic effects. The profile of symptoms, frequency of a response, its relationship to THC dose and substance use, latent structure in PANSS response, and the relationships between psychotomimetic and perceptual alteration symptoms were evaluated. RESULTS: Clinically meaningful increases in positive symptoms were noted in 44.75% infusions; conceptual disorganization, hallucinations, blunted affect, somatic concern, motor retardation and poor attention were the most frequently items altered by THC. The increase in PANSS positive symptoms was positively associated with THC dose and (beta = 11.13, SE = 4.94, Wald χ2 = 19.88, p < 0.001) and negatively associated with frequent cannabis use (beta = -0.575, SE = 0.14, Wald χ2 = 18.13, p < 0.001). Furthermore, positive symptoms were strongly correlated with CADSS perceptual alterations score (rs = 0.514, p<0.001). CONCLUSION: Intravenous administration of THC consistently induces psychotomimetic effects that include symptoms across PANSS domains. Moreover, healthy subjects who frequently use cannabis, have a blunted psychotomimetic response.