PURPOSE OF REVIEW: This review examines the literature associating cannabis with schizophrenia, glutamate dysregulation in schizophrenia, and cannabis involvement in glutamate pathways. Cannabis use is widespread among adolescents world-wide and is sold legally in many countries for recreational use in a variety of forms. Most people use it without lasting effects, but a portion of individuals have negative reactions that manifest in acute psychotic symptoms, and in some, symptoms continue even after the use of cannabis has ceased. To date, there is a huge gap in our understanding of why this occurs. RECENT FINDINGS: Recent studies have focused on abnormalities in the glutamate pathway in schizophrenia, the effect of cannabis on the glutamate system, and the role of glutamate in the brain Default Mode Network. SUMMARY: Given these observations, we hypothesize that perturbance of glutamate neuronal connectivity by cannabis in the brains of individuals genetically at high risk for psychosis will initiate a schizophrenia-like psychosis. Future studies may tie together these diverse observations by combining magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) of the default resting state network in patients with new onset schizophrenia who do and do not use cannabis compared with nonpsychotic individuals who do and do not use cannabis.