The Neurobiology of Pain, Emotion, and Stress Regulation in Suicide: Role of Cannabinoid, Opioid, Vanilloid, and Galaninergic Systems – A Systematic Review of Postmortem Evidence

This systematic review investigates the association between the endocannabinoid, vanilloid, opioid, and galaninergic systems and suicide, focusing on post-mortem evidence. Findings indicate increased cannabinoid receptor 1 (CB1) densities in the prefrontal cortex, particularly in individuals with alcohol use disorder and mood disorders who died by suicide. Conversely, a decrease in CB1 receptors was observed in individuals with schizophrenia treated with antipsychotics, suggesting that this reduction may be more closely related to underlying psychopathology than directly to suicidal behavior. Limited evidence on the vanilloid system suggests stress-related alterations could influence suicide, warranting further exploration. Similarly, the opioid and galaninergic systems show alterations in individuals who died by suicide, with increased mu-opioid receptor (MOR) expression possibly representing an adaptive response to altered endogenous peptide levels. The review underscores the need for more extensive research to clarify the roles of these biological pathways in suicide, advocating for studies comparing individuals who died by suicide with and without psychiatric disorders to non-psychiatric controls to advance our understanding of these complex interactions and their implications.