Is resting-state functional connectivity altered in regular cannabis users? A systematic review of the literature

Rationale: Regular cannabis use has been associated with brain functional alterations within frontal, temporal, and striatal pathways assessed during various cognitive tasks. Whether such alterations are consistently reported in the absence of overt task performance needs to be elucidated to uncover the core neurobiological mechanisms of regular cannabis use. Objectives: We aim to systematically review findings from studies that examine spontaneous fluctuations of brain function using functional Magnetic Resonance Imaging (fMRI) resting-state functional connectivity (rsFC) in cannabis users versus controls, and the association between rsFC and cannabis use chronicity, mental health symptoms, and cognitive performance. Methods: We conducted a PROSPERO registered systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched eight databases. Results: Twenty-one studies were included for review. Samples comprised 1396 participants aged 16 to 42 years, of which 737 were cannabis users and 659 were controls. Most studies found greater positive rsFC in cannabis users compared to controls between frontal-frontal, fronto-striatal, and fronto-temporal region pairings. The same region pairings were found to be preliminarily associated with varying measures of cannabis exposure. Conclusions: The evidence to date shows that regular cannabis exposure is consistently associated with alteration of spontaneous changes in Blood Oxygenation Level-Dependent signal without any explicit cognitive input or output. These findings have implications for interpreting results from task-based fMRI studies of cannabis users, which may additionally tax overlapping networks. Future longitudinal rsFC fMRI studies are required to determine the clinical relevance of the findings and their link to the chronicity of use, mental health, and cognitive performance.