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Background: The impact of cannabis uses on blood levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) remains uncertain, with conflicting findings reported in the literature. BDNF and NGF both are essential proteins for neuron's growth, and their dysregulation is seen in various mental disorders. This study aims to evaluate the relationship between cannabis usage and BDNF and NGF levels due to their potential implications for mental health., Methods: A comprehensive search of electronic databases was performed using appropriate MeSH terms and keywords. Inclusion criteria comprised human studies investigating the relationship between cannabis use and BDNF and NGF levels., Results: A total of 11 studies met the inclusion criteria and were included. The pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of BDNF (random-effects model, standardized mean differences [SMD] = .26, 95% CI -.34 to .76, p = .40). The results of our subgroup analysis based on BDNF source showed a nonsignificant between-group difference. For NGF levels, four studies were included, the pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of NGF (random-effects model, SMD = -.60, 95% CI -1.43 to -.23, p = .16). In both analyses, high heterogeneity was observed among the included studies which is a notable limitation to current meta-analysis., Conclusion: This systematic review highlights the need for further research to elucidate the relationship between cannabis use and these neurotrophic factors. A better understanding of these associations can contribute to our knowledge of the neurobiological effects of cannabis and inform potential implications for mental health, cognitive function, and neurodegenerative disorders., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)