Nicotine receptor gene linked to cannabis abuse

A genetic marker for cannabis use disorder is reported in a genome-wide association study published this week in Nature Neuroscience. This marker is also implicated in control of the levels of a brain receptor that binds to nicotine.

Cannabis is the most frequently used illicit psychoactive substance worldwide, and around one in ten users become dependent. As with other forms of addiction, cannabis use disorder (CUD) develops by frequent and harmful use of cannabis and involves engaging less in personal relationships and pleasurable activities, and experiencing cravings and withdrawal symptoms when the drug is not taken. As legalization makes cannabis products increasingly accessible, the incidence of the disorder is also expected to increase.

Ditte Demontis and colleagues used a nationwide Danish cohort to analyze the genomes of more than 2,000 individuals with CUD and the genomes of nearly 50,000 control individuals to establish links between common genetic variants and CUD. They found that the disorder was associated with a genetic variant that controls the expression of CHRNA2, a gene encoding a brain receptor for the neurotransmitter acetylcholine, which also binds to nicotine. The authors then replicated these findings in a genetic analysis of an additional 5,500 individuals with CUD and more than 300,000 control individuals from an Icelandic genetics cohort. They also found that presence of an overall higher number of genetic variants linked to decreased cognitive performance was associated with increased risk for CUD.

The authors conclude that this is the first large-scale study to link a specific gene to CUD. Further research is needed to understand the biological mechanisms by which these genetic differences contribute to the development of the disorder and how this information could be used to improve treatment.

doi: 10.1038/s41593-019-0416-1

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