As Cannabis becomes increasingly available, adverse effects of Δ9-THC are increasing. The current understanding
of THC use makes it clear that there are many psychosis related side effects. This review investigated the metabolic,
molecular and cellular pathways of metabolizing and clearing THC to better understand how THC affects the brain,
which would help improve patient outcomes for chronic and acute complications of THC use. A comprehensive
literature search was conducted using utilized Pubmed, Google Scholar, and Cochrane with keywords and phrases such as “THC and Psychosis” and “schizophrenia,” including articles to studies focused on Cannabis related
psychosis and excluding studies focused on other mental health disorders. It was found that Δ9-THC and 11-OHΔ9-THC, a metabolite from CYP2C9, bind to cannabinoid receptors (CB1R) which affect dopamine, GABA, and
glutamate levels, resulting in both acute THC-induced-psychosis and chronic schizophrenia. The risk is further
increased based on the THC/CBD ratio, age of first exposure, dose, and presence of polymorphisms for CYP2C9.
To better treatment protocols in patients using Cannabis, physicians can employ strategies targeted at minimizing
adverse effects by using the lowest effective dose calculated through genetic profiles while also watching for acute
symptoms of psychosis before the patient develops schizophrenia. Further research is needed to observe long-term
brain effects of chronic THC use longitudinally.
