A putative interaction between cannabis and variation at rs4680 within the catechol-methyl-transferase (COMT) gene on psychosis has been reported, but not adequately replicated.
Cannabinoid receptor 1 (CNR1) gene polymorphisms have been associated with central and peripheral effects of cannabis and schizophrenia pathophysiology.
Cannabis has been reported as a likely risk factor for the development of psychosis, and a gene × environment interaction with the catechol-O-methyltransferase (COMT) gene has been proposed.
Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMTVal(158)Met) gene moderate the psychosis-inducing effect of cannabis.
In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype.
CNR1 haplotypes were formed from four CNR1 SNPs (rs806368, rs1049353, rs2023239, and rs6454674) and tested with level of cannabis exposure to assess their interactive effects on the lingual gyrus, cingulum (right and left) and rolandic operculum, regions showing cannabis exposure effects in the SPM8 analyses.
Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free.
Epidemiological and retrospective studies suggest a cannabis x catechol-O-methyltransferase (COMT) Val(158)Met interaction effect on development of psychosis.
A single nucleotide polymorphism in the cannabis receptor-1 gene (CNR1), rs2023239, has been associated with CD diagnosis and intermediate phenotypes, including abstinence-induced withdrawal, cue-elicited craving, and parahippocampal activation to cannabis cues.
A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val(158)Met) appears to influence the immediate cognitive and psychotic effects of cannabis, or ∆(9)-tetrahydrocannabinol (THC), its primary psychoactive ingredient.
Since marijuana intoxication has a potent blocking effect on short-term memory we examined the association between the CNR1 alleles and the P300 wave amplitude at three electrodes in 35 alcohol and drug addicts, by MANOVA.
CNR1 variation emerged as a moderator of the relationship between trait impulsivity and marijuana problems, thus suggesting that marijuana users with CNR1 risk variants and a higher trait impulsivity are at greater risk for developing marijuana-related problems and supporting a role for CNR1 in a broader impulsivity phenotype.
The findings confirm that in people with psychometric evidence of psychosis liability, COMTVal(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.
We studied four single-nucleotide polymorphisms (SNPs) in the CNR1 gene for association with having one or more symptoms of cannabis dependence in 541 adolescent subjects who had all tried cannabis five or more times.
Then, we studied whether functional variation in CNR1 and cannabis exposure interact in modulating prefrontal function and related behavior during working memory processing.
These findings are in accord with earlier reported associations between CNR1 and FAAH and CD intermediate phenotypes, and suggest that the underlying mechanism of these genetic effects may be enhanced neural response in reward areas of the brain in carriers of the CNR1 G allele and FAAH C/C genotype in response to marijuana cues.