Cannabinoid Receptors, Mental Pain and Suicidal Behavior: a Systematic Review.

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 (CB1 and CB2 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 CB1 receptor activity in the prefrontal cortex and suicide in both depression and alcoholism and (2) studies supporting the involvement of both CB1 and CB2 receptors in the regulation of neuropathic pain and stress-induced analgesia. We conclude that cannabinoid receptors, particularly CB1 receptors, may become promising targets for the development of novel therapeutic tools for the treatment of SB.

Serum endocannabinoid levels in suicide attempters: A pilot study.

The search for a biomarker for suicide risk is a longstanding pursuit in clinical psychiatry. Literature addressing the role of endocannabinoids in suicide attempters (SA) is sparse. This cross-sectional study is aimed at comparing 8 AM serum concentrations of 4 endogenous cannabinoids (anandamide, AEA; 2-arachidonoylglycerol, 2-AG; N-palmitoiletanolamida, PEA; and oleoylethanolamide, OEA) in 30 suicide attempters (SA) and 12 psychiatric controls (PC). 8 AM AEA and PEA serum levels were higher in SA compared to PC without controlling for cannabis use (n = 42) (3.58 ± 5.77 vs. 1.62 ± 2.49, F = 3.04, P = 0.089; and 3.31 ± 4.82 vs. 1.21 ± 1.20, F = 6.22, p = 0.017, respectively). Serum ACTH was higher in PC compared to SA (32.11 ± 21.60 vs. 20.05 ± 9.96, F = 9.031, p = 0.0.005). After controlling for cannabis use in the urine test (n = 28), 8 AM AEA and PEA serum levels remained higher in SA compared to PC (4.57 ± 6.38 vs. 0.64 ± 1.11, F = 4.852, P = 0.037; and 4.35 ± 5.46 vs. 1.21 ± 1.25, F = 4.125, p = 0.053, respectively). The present study offers preliminary evidence about the role of AEA and PEA in suicidal behavior (SB). Furthermore, in the context of the mental pain model of SB, our findings suggest that some endocannabinoids may play a role in the pathophysiology of SB. Our pilot study deserves replication by other studies with bigger sample sizes.

Serum ß-endorphin levels are associated with addiction to suicidal behavior: A pilot study.

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 ß-endorphin were elevated in all three groups. Serum ß-endorphin (pg/mL) was particularly high in PC diagnosed with schizophrenia 220.34 (±56.30). The level of 8 AM serum ß-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 ß-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 ß-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.