Lifetime cannabis use and childhood trauma increase risk of psychosis in carriers of CNR1 genetic variants: findings from the STREAM study

Objectives: Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. Methods: Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. Results: Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. Conclusion: Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.

Levels of impulsivity in individuals with cannabis use disorder

Abstract Introduction Substance use disorder consists of the presence of cognitive, behavioral, and physiological symptoms, indicating continuous use of one or more substances by the individual. The literature points to the existence of a relationship between impulsive behavior, in which individuals tend to act thoughtlessly and with a lower level of planning, and consumption of substances including cannabis. Objectives To examine the presence and severity of impulsivity in individuals with cannabis use disorder and investigate associations between sociodemographic and clinical characteristics and impulsivity. Method Participants completed a sociodemographic data sheet and the Barratt Impulsiveness Scale (BIS-11). A total of 122 subjects with a diagnosis of cannabis use disorder participated, with a mean age of 34.46 years (standard deviation = 9.62). Results The prevalence of high levels of impulsivity in the sample ranged from 30 to 33%; the BIS-11 total score was significantly associated with cohabitation and alcohol use. The BIS-11 scores for motor impulsivity and attentional impulsivity were also associated with consumption of alcohol. No associations were found between impulsivity and the variables age, education, use of tobacco, or use of cocaine/crack. Conclusion This study contributes to understanding of substance dependence, especially cannabis. It found presence of impulsive behavior among individuals with cannabis use disorder, which is corroborated by reports in the literature.