Brain reward function in people who use cannabis: a systematic review.

Rationale: Cannabis is one of the most widely used psychoactive substances globally. Cannabis use can be associated with alterations of reward processing, including affective flattening, apathy, anhedonia, and lower sensitivity to natural rewards in conjunction with higher sensitivity to cannabis-related rewards. Such alterations have been posited to be driven by changes in underlying brain reward pathways, as per prominent neuroscientific theories of addiction. Functional neuroimaging (fMRI) studies have examined brain reward function in cannabis users via the monetary incentive delay (MID) fMRI task; however, this evidence is yet to be systematically synthesised. Objectives: We aimed to systematically integrate the evidence on brain reward function in cannabis users examined by the MID fMRI task; and in relation to metrics of cannabis exposure (e.g., dosage, frequency) and other behavioural variables. Method: We pre-registered the review in PROSPERO and reported it using PRISMA guidelines. Literature searches were conducted in PsycINFO, PubMed, Medline, CINAHL, and Scopus. Results: Nine studies were included, comprising 534 people with mean ages 16-to-28 years, of which 255 were people who use cannabis daily or almost daily, and 279 were controls. The fMRI literature to date led to largely non-significant group differences. A few studies reported group differences in the ventral striatum while participants anticipated rewards and losses; and in the caudate while participants received neutral outcomes. A few studies examined correlations between brain function and withdrawal, dosage, and age of onset; and reported inconsistent findings. Conclusions: There is emerging but inconsistent evidence of altered brain reward function in cannabis users examined with the MID fMRI task. Future fMRI studies are required to confirm if the brain reward system is altered in vulnerable cannabis users who experience a Cannabis Use Disorder, as postulated by prominent neuroscientific theories of addiction.