Abstract Increased extracellular glutamate concentrations in the brain can cause neuronal injury. Cannabinoid use has been demonstrated to reduce extracellular glutamate levels in the brain in many animal models. However, there are no systematic reviews published evaluating the effect of cannabis on glutamate levels in the human brain. This review aimed to review studies that investigated the effect of cannabinoids on glutamate levels in the living human brain using neuroimaging methods and to provide evidence gathered from biomedical databases such as MEDLINE and EMBASE. Nine randomized controlled trials (RCTs) and ten observational studies met the eligibility criteria for this review. The articles included in...