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.

Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users: a systematic review of fMRI studies.

RATIONALE: Regular cannabis use (i.e. ≥ monthly) is highly prevalent, with past year use being reported by ~ 200 million people globally.High reactivity to cannabis cues is a key feature of regular cannabis use and has been ascribed to greater cannabis exposure and craving, but the underlying neurobiology is yet to be systematically integrated. OBJECTIVES: We aim to systematically summarise the findings from fMRI studies which examined brain function in cannabis users while exposed to cannabis vs neutral stimuli during a cue-reactivity fMRI task. METHODS: A systematic search of PsycINFO, PubMed and Scopus databases was pre-registered in PROSPERO (CRD42020171750) and conducted following PRISMA guidelines. Eighteen studies met inclusion/exclusion criteria. Samples comprised 918 participants (340 female) aged 16-38 years. Of these, 603 were regular cannabis users, and 315 were controls. RESULTS: The literature consistently reported greater brain activity in cannabis users while exposed to cannabis vs neutral stimuli in three key brain areas: the striatum, the prefrontal (anterior cingulate, middle frontal) and the parietal cortex (posterior cingulate/precuneus) and additional brain regions (hippocampus, amygdala, thalamus, occipital cortex). Preliminary correlations emerged between cannabis craving and the function of partially overlapping regions (amygdala, striatum, orbitofrontal cortex ). CONCLUSIONS: Exposure to cannabis-cues may elicit greater brain function and thus trigger cravings in regular cannabis users and thus trigger cannabis craving. Standardised and longitudinal assessments of cannabis use and related problems are required to profile with greater precision the neurobiology of cannabis cue-reactivity, and its role in predicting  cravings and relapse.