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ARRA Investments in Mechanisms of Alcohol and Nicotine Codependence


Public Health Burden
In any given year, 18 million Americans age 18 or older suffer from alcohol use disorders, including dependence, which put them at increased risk for alcohol-related injuries and disease.  Within this population, a subgroup of alcohol dependent individuals also suffers from nicotine dependence, increasing their risk for developing certain cancers and cardiovascular diseases due to the synergistic effects of the two substances.  Research to date suggests that both substance-specific and shared genetic and environmental influences play a role in the development of alcohol and nicotine dependence.  Researchers also hypothesize that interactions between and among these factors may underlie the co-occurrence of alcohol and tobacco addictions.  Understanding how dependence on alcohol affects the development and treatment of nicotine dependence and vice versa will lead to improved strategies for prevention and treatment of codependence.

Elucidating the Mechanisms Underlying Co-occurring Alcohol and Nicotine Dependence
ARRA supported projects will help to understand the molecular changes in the brain that result from co-occurring alcohol and nicotine use and the mechanisms by which these substances influence dependence on one another.  The findings could lead to improved treatment strategies for codependent individuals.  Examples of ARRA funded projects investigating these mechanisms include those that:
  • Study microglia (specialized immune cells of the central nervous system) as sites of interaction of alcohol and nicotine.1
  • Use animal models to elucidate mechanisms of cross-sensitization in which one substance increases the positive reinforcing effects of the other.2
  • Evaluate human brain regions implicated in the development of alcohol and nicotine dependence for gene expression changes in alcohol dependent individuals with histories of smoking.3
  • Examine the role of nicotinic acetylcholine receptors in the brain and the potential influence of genetic variability of the receptors in response to the medication varenicline, with an overall goal of generating new medications and treatment strategies.4



  1. 1RC2AA019388-01 -- Mechanism of Alcohol and Nicotine Interaction -- Narahashi, Toshio (IL)
  2. 1RC2AA019366-01 -- Ethanol and nicotine co-abuse: cross sensitization of their reinforcing actions -- McBride, William Joseph (IN)
  3. 1RC2AA019382-01 -- Next-gen sequencing: searching for mechanisms of alcohol and nicotine dependence -- Mayfield, Roy D (TX)
  4. 1RC2AA019429-01 -- Characterizing Alpha5* Nicotinic Receptors in Alcohol and Nicotine Co-Dependence -- Bartlett, Selena E. (contact); White, Raymond L (CA)


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