A family history of alcoholism is linked to differences in how the brain responds to a drug that blocks NMDA glutamate receptors. Healthy young adults with at least two relatives who had ethanol dependence received intravenous infusions of a low or high dose of ketamine, an NMDA receptor antagonist, or a placebo. Compared to those with no family history of alcoholism, individuals with a family history reported fewer perceptual changes and less dysphoric mood during ketamine infusion. These findings suggest that inherited alterations in NMDA receptor function may influence the subjective effects of alcohol and contribute to the risk of developing alcoholism.
A genome-wide association study of long-term cannabis users identified a significant signal at the CHRM3 gene linked to cannabis-induced hallucinations. The strongest association was found in European Americans, with the lead SNP rs115455482 reaching genome-wide significance. The risk allele was associated with lower CHRM3 expression in the thalamus, and CHRM3 was co-expressed with three psychosis risk genes in brain tissues. Findings did not replicate in an independent sample, though meta-analysis strengthened the association. No significant signals were found in African Americans. The results suggest CHRM3 may contribute to cannabis-induced hallucinations and point to the thalamus's potential role.