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Research Summary

Cannabinoids, GABA-Benzodiazepine Receptors, and Alcoholism

Twin and other genetic studies have clearly demonstrated that biology contributes substantially to the risk of alcohol dependence. Two recent studies, which add to this evidence, identified a link between central nervous system mechanisms and alcoholism.

In one study, researchers administered the intravenous benzodiazepine midazolam to 11 men with alcohol dependence who were abstinent at enrollment and 10 men without dependence who drank.

  • Neither GABA*-benzodiazepine receptor occupancy (measured by positron emission tomography) nor the plasma concentration of midazolam differed significantly between the groups.
  • However, sleep time after the midazolam infusion (which was measured by electroencephalography and reflects GABA-benzodiazepine receptor function) was significantly lower in men with alcohol dependence (16 versus 34 minutes).

In the second study, two strains of mice were given a choice between ethanol and water. CB1 knockout mice (mice bred to have no cannabinoid CB1 receptors) drank significantly less ethanol than did wild-type mice (who have these receptors).


The first study implies that men with alcohol dependence have significantly different GABA-benzodiazepine receptor function, which could explain the need for more alcohol to achieve effects. The mouse study found that receptors that play a role in marijuana intoxication and dependence, and obesity are also associated with alcohol intake. Both studies suggest possible etiologies for alcohol dependence and potential targets for alcoholism treatment.

Richard Saitz, MD, MPH
*Gamma-aminobutyric acid


Lingford-Hughes AR, Wilson SJ, Cunnigham VJ, et al. GABA-benzodiazepine receptor function in alcohol dependence: a combined 11C-flumazenil PET and pharmacodynamic study. Psychopharm. 2005;180(4):595–606.

Thanos PK, Dimitrakakis ES, Rice O, et al. Ethanol self-administration and ethanol conditioned place preference are reduced in mice lacking cannabinoid CB1 receptors. Behav Brain Res. 2005;164(2):206–213.