The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders

Abstract

Endogenous and exogenous cannabinoids bind to central cannabinoid receptors to control a multitude of behavioral functions, including aggression. The first main objective of this review is to dissect components of the endocannabinoid system, including cannabinoid 1 and cannabinoid 2 receptors; the endogenous cannabinoids anandamide and 2-arachidonoylglycerol; and the indirect cannabinoid modulators fatty acid amide hydrolase and monoacylglycerol lipase; that have shown abnormalities in basic research studies investigating mechanisms of aggression. While most human research has concluded that the active ingredient of marijuana, Δ9-tetrahydrocannabinol, tends to dampen rather than provoke aggression in acute doses, recent evidence supports a relationship between the ingestion of synthetic cannabinoids and emergence of violent or aggressive behavior. Thus, another objective is to evaluate the emerging clinical data. This paper also discusses the relationship between prenatal and perinatal exposure to cannabis as well as use of cannabis in adolescence on aggressive outcomes. A final objective of the paper is to discuss endocannabinoid abnormalities in psychotic and affective disorders, as well as clinically aggressive populations, such as borderline personality disorder and antisocial personality disorder. With regard to the former condition, decreased anandamide metabolites have been reported in the cerebrospinal fluid, while some preliminary evidence suggests that fatty acid amide hydrolase genetic polymorphisms are linked to antisocial personality disorder and impulsive-antisocial psychopathic traits. To summarize, this paper will draw upon basic and clinical research to explain how the endocannabinoid system may contribute to the genesis of aggressive behavior.

Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11C]CURB positron emission tomography study

“…These analyses were exploratory and would not survive Bonferroni correction. However, given that an EC signaling system may be relevant to manifestation of aggression [ 68 ], we believe that it is justified to pursue these results. Hostility in BPD is also highly clinically relevant, as its expression is linked to the presence, number, and severity of suicide attempts [ 69 ], in addition to completed suicide in this population [ 70 ].…”

CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population

“…While CNR1 has been widely investigated, only a few number of authors studied the role of CNR2 in psychiatric disorders. CNR2 receptors are chiefly found in the immune cells, however they have also been identified in some regions of the rat brain, such as cerebral cortex, striatum, amygdala, thalamus, cerebellum, spinal nucleus, olfactory nucleus, and hippocampus [30]. Further investigation searched whether cannabinoid CB2 receptor knockout (CB2KO) mice similarly showed a higher aggression compared with wild-type during the social interaction test and resident-intruder paradigm [31].…”

The comparison of violence, and the relationship with childhood trauma in Turkish men with alcohol, opiate, and synthetic cannabinoid use disorder

“…Among the studies examining the relationship between violence and substance abuse, opioid use was found to have less relation with violence as well as the alcohol was found to be highly related than the other substance uses. 5 , 8 , 47 In this context, we can make an assumption that SCs, as drugs that were already reported to be in a relation with violence and aggressive behavior, 19 , 20 should be considered as a potential cause of drug-related violence.…”

“… 19 However, it is unclear whether use of SCs leads to aggression and violent behavior or if aggressive tendencies of youths make them more prone to experiment with SCs. 20 …”