Alcohol is consumed by nearly half the U.S. population aged 12 or older, and heavy drinking contributes to over 140,000 deaths annually. Alcohol use disorder (AUD) has a current U.S. prevalence of 11%, yet less than 15% of individuals with a lifetime diagnosis receive treatment. Risk is nearly equally genetic and environmental. AUD responds to psychosocial treatments like cognitive-behavioral therapy and to pharmacotherapy. Three FDA-approved medications—disulfiram, naltrexone, and acamprosate—are underprescribed despite being first-line treatments. Off-label topiramate and gabapentin show efficacy, and novel candidates like psychedelics and phosphodiesterase-4 inhibitors are promising but need further evaluation. AUD remains highly stigmatized.
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.