A Cannabinoid Receptor Gene Variant Influenced How Much Nicotine Withdrawal Disrupted Brain Function | Research

The takeaway

A variant of the cannabinoid receptor 1 gene (CNR1) moderated nicotine withdrawal-related cognitive disruption, with homozygous carriers of the major allele showing greater brainwave changes during nicotine deprivation.

Researchers studying the genetics of nicotine addiction and the connection between cannabinoid and nicotine systems.

CNR1 rs806379 moderated withdrawal-related cognitive disruption (p=0.004)

What the researchers found

Researchers tested whether genetic variation in the cannabinoid receptor 1 gene (CNR1) affected how much nicotine withdrawal disrupted cognitive function, as measured by resting brainwave (EEG) patterns.

Seventy-three Caucasian smokers (15+ cigarettes/day) completed two lab sessions: one after smoking nicotine cigarettes and one after smoking placebo cigarettes following overnight deprivation. Three CNR1 gene variants were tested.

One variant (rs806379) significantly moderated the effect of nicotine deprivation on slow-wave EEG activity (a marker of cognitive disruption). Smokers homozygous for the major allele showed greater nicotine withdrawal-related cognitive disruption, suggesting they might benefit most from cannabinoid receptor-targeted smoking cessation medications.

Why it matters

This study suggests the endocannabinoid system influences vulnerability to nicotine withdrawal, and that genetic variation in cannabinoid receptors could predict who struggles most with quitting smoking. This could eventually support personalized smoking cessation treatment.

The numbers in context

73 smokers (15+ cigarettes/day). CNR1 variant rs806379 moderated withdrawal EEG effects (p=0.004). Homozygous major allele carriers showed greater cognitive disruption during withdrawal.

How the study worked

Within-subject crossover design. 73 Caucasian non-Hispanic smokers visited the lab twice following overnight nicotine deprivation. Either nicotine or placebo cigarettes were smoked before resting EEG was recorded across 17 electrodes. Three CNR1 polymorphisms were tested as moderators.

What this study cannot tell us

Small sample size (73 participants). Only Caucasian non-Hispanic smokers were included. EEG changes are a proxy for cognitive disruption and may not perfectly predict real-world quit outcomes. The specific functional effect of the rs806379 variant is not fully characterized.

How to read the evidence

This is a relatively small genetic study with a within-subject design. While the finding is statistically significant, replication in larger and more diverse samples is needed.

When this study was published

Published in 2016. Pharmacogenetics of smoking cessation has continued to develop.

The bigger picture

The overlap between the cannabinoid and nicotine systems is increasingly recognized. This study provides genetic evidence for this connection and suggests that cannabinoid receptor drugs might help specific subgroups of smokers who experience the most severe cognitive disruption during withdrawal.

Questions still open

Would CB1 receptor antagonists help smokers with this genetic profile quit more successfully? Does this same genetic variant influence cannabis withdrawal severity?

Common questions

What does this mean for quitting smoking?

This study found that people with a certain cannabinoid receptor gene variant experience more cognitive disruption during nicotine withdrawal. In the future, genetic testing might help identify smokers who would benefit from specific medications targeting the endocannabinoid system to manage withdrawal symptoms.

How are the cannabinoid and nicotine systems connected?

CB1 cannabinoid receptors and nicotinic receptors are both found in brain regions involved in reward, cognition, and attention. The endocannabinoid system modulates nicotinic signaling, and genetic variation in cannabinoid receptors has been linked to nicotine dependence and withdrawal severity.

Read the original research

Cannabinoid receptor 1 (CNR1) gene variant moderates neural index of cognitive disruption during nicotine withdrawal.

Genes, brain, and behavior, 15(7), 621-6

View on PubMed ↗Publisher’s paper ↗

Citation

Evans, D E; Sutton, S K; Jentink, K G; Lin, H-Y; Park, J Y; Drobes, D J. (2016). Cannabinoid receptor 1 (CNR1) gene variant moderates neural index of cognitive disruption during nicotine withdrawal.. Genes, brain, and behavior, 15(7), 621-6. https://doi.org/10.1111/gbb.12311