What is the neurobiological mechanism linking cannabis to psychosis?

The cannabis-psychosis link involves multiple converging neurobiological pathways. Primary mechanism: THC disrupts striatal dopamine regulation by activating CB1 receptors on glutamatergic inputs to the striatum, causing excessive dopamine release — the same neurochemical signature seen in schizophrenia. Secondary: THC impairs prefrontal cortical regulation of subcortical dopamine, reducing top-down inhibitory control. Third: THC activates the hypothalamic-pituitary-adrenal (HPA) axis, elevating cortisol, which sensitizes dopamine systems. Genetic vulnerability is critical — individuals with COMT Val158Met polymorphism, AKT1 variants, or family history of psychosis have substantially elevated risk. High-potency THC (>15%) and early onset use (before age 16) are the strongest environmental risk factors. CBD appears to counteract some of these effects by reducing striatal dopamine synthesis capacity.