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The literature provides partial support for the hypothesis that some suicide attempters develop a behavioral addiction to suicidal behavior (SB). We hypothesized that major suicide repeaters (MR) (≥5 lifetime suicide attempts) are addicted to suicide attempts as measured by modified DSM-IV criteria for substance dependence. In this cross-sectional study with 13 psychiatric controls (PC), 55 non-major suicide attempters (NMR), and 9 MR we found that MR are characterized by emotional abuse and neglect, as well as higher scores on the Personality and Life Event scale (short version). The levels of 8 AM serum ACTH, cortisol and β-endorphin were elevated in all three groups. Serum β-endorphin (pg/mL) was particularly high in PC diagnosed with schizophrenia 220.34 (±56.30). The level of 8 AM serum β-endorphin rose with increased numbers of criteria met for addiction to SB from 130.31 (±88.16) (≥ 3 criteria met for addiction to SB) to 174.84 (±114.93) (≥ 6 criteria met for addiction to SB) whereas serum ACTH and cortisol did not change. SB addicts (≥ 6 criteria) displayed higher serum β-endorphin concentrations than non-addicts (174.84 ± 114.93 vs. 116.93 ± 61.70, FET p = 0.09). The present study brings some support to the addictive hypothesis of SB. Our results delineate β-endorphin as a promising biomarker of SB addiction, and offer a good basis for future studies that test whether buprenorphine can be used to prevent repetitive suicide attempts, non-suicidal-self-injury (NSSI), and the development of an addiction to SB., Competing Interests: Declaration of Competing Interest In the last two years, Dr. Hilario Blasco-Fontecilla has received lecture fees from AB-Biotics, Rovi, Praxis, and Shire. He has been paid by Praxis for the elaboration of an article. He was the recipient of a FIPSE Grant. He is involved in two clinical trials (ESKETINSUI2002, and NEWROFEED). The remaining authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Purpose of Review: The current serotonin-based biological model of suicidal behavior (SB) may be too simplistic. There is emerging evidence that other biomarkers and biological systems may be involved in SB pathophysiology. The literature on the endocannabinoid (EC) systems and SB is limited. The objective of the present article is to review all available information on the relationship between cannabinoid receptors (CB 1 and CB 2 receptors), and SB and/or psychological pain., Recent Findings: Our review is limited by the small number and heterogeneity of studies identified: (1) an autopsy study describing elevated levels of CB 1 receptor activity in the prefrontal cortex and suicide in both depression and alcoholism and (2) studies supporting the involvement of both CB 1 and CB 2 receptors in the regulation of neuropathic pain and stress-induced analgesia. We conclude that cannabinoid receptors, particularly CB 1 receptors, may become promising targets for the development of novel therapeutic tools for the treatment of SB.