Fact or Faction Regarding the Relationship between Cannabis Use and Violent Behavior.

The relationship between cannabis use and violence, and to what extent this association is causal in nature, remains unclear. The aim of this scoping review was to ascertain whether cannabis use increases the risk of violence and aggression in adults. Because cannabis use can result in irritability, disinhibition, and altered cognition, it is plausible that its use increases the risk of violence and aggression and that this association is exacerbated in psychiatric illness. A search of the literature using PubMed, Scopus, and PsycINFO databases was performed; all materials published in English until April 2020 were considered. Peer-reviewed publications that assessed cannabis use and perpetration of violence or aggression in adults were included in this review. Of the 327 articles that were screened for eligibility, 19 articles met inclusion criteria for this review. Results suggest that there is a link between cannabis use and violence; however, this relationship is strictly correlational, and the strength of this relationship varies depending on the population (e.g., populations with severe and persistent mental illness versus the general population). These findings have important ramifications for treatment considerations and for public health and safety approaches.

DAT1 polymorphism associated with poor decision-making in males with antisocial personality disorder and high psychopathic traits.

Studies suggest that abnormalities of the dopaminergic system underlie decision-making deficits, a hallmark of antisocial personality disorder (ASPD) and psychopathy. The dopamine transporter gene (DAT1) is of particular interest due to a polymorphism that controls dopamine transporter (DAT) activity. However, the association between DAT1 genotypes and decision-making in ASPD has never been studied. The current study investigated the effect of DAT1 genotype on decision-making, as measured by the Iowa Gambling Task (IGT), in ASPD and healthy controls. A total of 17 participants with ASPD and 16 healthy control participants without ASPD were sampled. The Hare Psychopathy Checklist-Revised and the IGT were administered to all participants. All participants provided blood samples for genotyping. Data revealed a novel interaction effect between DAT1 genotype and diagnosis, whereby ASPD participants with low DAT activity genotypes performed significantly worse on the IGT and selected from disadvantageous decks more often, whereas the low DAT activity genotype in the healthy control group was associated with better performance on the IGT, and they selected from disadvantageous decks less often. We demonstrate, for the first time, that low DAT activity genotypes in ASPD with high psychopathic traits contribute to poor decision-making.

Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review.

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

Translocator Protein Distribution Volume Predicts Reduction of Symptoms During Open-Label Trial of Celecoxib in Major Depressive Disorder.

BACKGROUND: Gliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO VT), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO VT in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder. METHODS: A total of 41 subjects with treatment-resistant major depressive disorder underwent one [18F]FEPPA positron emission tomography scan to measure PFC and ACC TSPO VT. Open-label oral celecoxib (200 mg, twice daily) was administered for 8 weeks. Change in symptoms was measured with the 17-item Hamilton Depression Rating Scale (HDRS). RESULTS: Cumulative mean change in HDRS scores between 0 and 8 weeks of treatment was plotted against PFC and ACC TSPO VT, showing a significant nonlinear relationship. At low TSPO VT values, there was no reduction in HDRS scores, but as TSPO VT values increased, there was a reduction in HDRS scores that then plateaued. This was modeled with a 4-parameter sigmoidal model in which PFC and ACC TSPO VT accounted for 84% and 92% of the variance, respectively. CONCLUSIONS: Celecoxib administration in the presence of gliosis labeled by TSPO VT is associated with greater reduction of symptoms. Given the predictiveness of TSPO VT on symptom reduction, this personalized medicine approach of matching a marker of gliosis to medication targeting effects of gliosis should be applied in early development of novel therapeutics, in particular for treatment-resistant major depressive disorder.