Characterizing chronic non-suicidal self-injury and other forms of repetitive and escalating suicide behaviour as endocannabinoid-mediated pain and reward disorders

Suicide is a devastating complication of psychiatric disorders characterized by despair, hopelessness, and overwhelming mental distress or pain. Non-suicidal self-injury (NSSI), suicide ideation (SI) and suicide attempts (SA) all fall under the umbrella of suicide behaviour (SB). Several biopsychological theories describe SB as an attempt to relieve mental pain. They comment on the role of tolerance-habituation to the rewarding effects of SB-induced emotional regulation, as well as increasing physical or somatic pain tolerance, both of which contribute to the escalating patterns of repetitive SB. The endocannabinoid system (ECS) is involved in a wide range of homeostatic and neuromodulatory functions including appetite/feeding, sleep, motor control, pain perception, cognition, mood/affect, and reward processing. The downregulation of endocannabinoid signalling has major implications for affective disorders, pain disorders, and substance use disorders. SB can be seen as a manifestation of these disorders and has also been linked to ECS dysfunction. Drawing from both animal and human studies, we aim to understand repetitive SB as an endocannabinoid-mediated pain and reward disorder. We hypothesize that mental distress triggers the first incidence of NSSI or SB, from which patients derive stress-induced endocannabinoid-mediated analgesia. As patients become increasingly tolerant to this mechanism of analgesia, SB escalates to override increasing mental distress. This hypothesis calls for more research on endocannabinoid-based therapies to prevent the progression from NSSI or SI to fatal SA.