Molecular brain differences and cannabis involvement: A systematic review of positron emission tomography studies

Background: An increasing number of studies have used positron emission tomography (PET) to investigate molecular neurobiological differences in individuals who use cannabis. This study aimed to systematically review PET imaging research in individuals who use cannabis or have cannabis use disorder (CUD). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, a comprehensive systematic review was undertaken using the PubMed, Scopus, PsycINFO and Web of Science databases.Results: In total, 20 studies were identified and grouped into three themes: (1) studies of the dopamine system primarily found that cannabis use was associated with abnormal striatal dopamine synthesis capacity, which was in turn correlated with clinical symptoms; (2) studies of the endocannabinoid system found that cannabis use and CUD are associated with lower cannabinoid receptor type 1 availability and global reductions in fatty acid amide hydrolase binding; (3) studies of brain metabolism found that individuals who use cannabis exhibit lower normalized glucose metabolism in both cortical and subcortical brain regions, and reduced cerebral blood flow in the lateral prefrontal cortex during experimental tasks. Heterogeneity across studies prevented meta-analysis.Conclusion: Existing PET imaging research reveals substantive molecular differences in cannabis users in the dopamine and endocannabinoid systems, and in global brain metabolism, although the heterogeneity of designs and approaches is very high, and whether these differences are causal versus consequential is largely unclear.