The association between cannabis use and paranoia: Meta-analysis of experimental and observational studies

Paranoia is common and has negative implications at clinical and societal levels. Cannabis may cause paranoia, although conflicting evidence exists. We reviewed studies on the association between cannabinoid use and paranoid symptoms. PubMed was searched from inception to July 2023, seeking experimental and observational studies that measured paranoid symptoms with specific assessments. Data of 13 studies (n = 13.559 participants) were pooled using Bayesian Model-Averaged Meta-Analysis, hierarchical Bayesian meta-analyses and Robust Bayesian Meta-Analysis. Effect size measures were Standardized Mean Difference (SMD) or Odds Ratio (OR). Five experimental studies showed that participants receiving cannabinoids developed more severe paranoid symptoms than those receiving placebo (SMD = 0.47; 95 % CI, 0.13 - 0.48, Posterior Probability of Inclusion, PPI: 94 %). Studies using TCH-prevalent cannabinoids detected higher effects than those administering mixed THC-CBD or CBD- prevalent cannabinoids. In four cross-sectional studies from the general population, the odds of displaying paranoid symptoms in cannabinoid users was higher than in non-users (OR: 1.75, 95 % CI, 1.43-2.07, PPI: 99 %), with effects increasing with the percentage of males in the sample. The pooled effect was not significant in studies recruiting patients with psychiatric disorders. Results of three prospective studies also suggest that cannabis is associated with the subsequent onset of paranoid symptoms. In conclusion, converging evidence from experimental and observational studies suggest that cannabinoids are associated with, and may cause paranoid symptoms. Preventive and therapeutical actions may be warranted, considering the implications of paranoia, and the dramatic increase in cannabis use worldwide.