Department of Psychiatry Faculty

Education

1983-1987, B.S., Pharmacy, M.S. University, Vadodara, India
1987-1992, Ph.D., Pharmacology and Toxicology, Purdue University

Research Interest

Cigarette smoking and heavy alcohol drinking account for some of the most significant health problems in the United States and other parts of the world. Our research focuses on understanding and developing treatments for these addictive behaviors in adults and adolescents.

In the area of alcohol drinking, we are interested in understanding alcohol drinking behavior and evaluating the efficacy of new medications in reducing drinking behavior. This research is conducted using a human laboratory alcohol drinking paradigm for adult heavy drinkers developed by our group at Yale. Using this paradigm to evaluate naltrexone, one of two FDA approved medications for alcoholism, we recently demonstrated that naltrexone reduced drinking only in individuals with a positive family history of alcoholism. These data suggest that the efficacy of naltrexone, while modest in unselected samples, may be maximized by targeting the treatment to those with a genetic risk for alcoholism.

In the area of adult tobacco our research focuses on understanding the bio-behavioral mechanisms underlying the high co-occurrence of smoking and heavy alcohol consumption. We discovered that HPA or stress axis response to challenge with an opioid antagonist is suppressed in those who use either tobacco or alcohol alone, but not in those who use both substances. These novel findings suggest that concurrent use of alcohol and tobacco may be an attempt to maintain normal stress responses and that it would be imprudent to target one addiction to the exclusion of the other – such an approach might subsequently compromise ability to deal with stress. Most recently, in an intensive study of symptoms that emerge during abstinence from tobacco, we found that smokers who drink heavily experience more severe tobacco withdrawal as well as greater craving in response to withdrawal as well as negative affect cues than smokers who do not drink heavily. My team is currently probing the nature of these findings, if substantiated they have practical import for the treatment of smokers.

Tobacco and alcohol use are established during adolescence. Smoking in adolescence sets the stage for poor school performance, health consequences and lifelong addiction. Unfortunately, we know little about what maintains smoking in adolescents and there are no empirically validated treatments for this population. Our research has demonstrated that tobacco and alcohol are the most commonly and concurrently used substances during adolescence. We have also shown for the first time that while adolescent smokers show minimal symptoms on traditional withdrawal measures during abstinence from cigarettes, there are clinically significant gender-related changes in stress responses, cognition and pain; with girls being most affected. These findings suggest that adolescents may be smoking to modulate stress reactivity and cognitive performance and emphasize the need for gender-specific treatments addressing tobacco-abstinence induced changes. Recently, we have also been conducting innovative developmental work on the use of Contingency Management (CM) techniques for smoking cessation in adolescents. CM is an approach that reinforces target behaviors (such as abstinence) and has had a profound effect on the field of behavioral therapies for substance use in adults, but has not been tested in adolescents. We have adapted this approach to the unique needs of adolescent smokers and have developed a high school based smoking cessation intervention that combines CM with CBT based smoking cessation counseling. Initial results from this program are extremely promising and suggest that CM could be used to initiate abstinence in this high risk population of smokers.

Laboratory Personnel

Dana Cavallo, Ph.D.
Anne Smith, Ph.D.
Tricia Dahl, Research Assistant
Thomas Liss, Research Assistant
Amanda McFetridge, Research Assistant

Publications of Note

1. Krishnan-Sarin, S., Duhig, A., McKee, S., McMahon, T.J., Liss, T., McFetridge, A., Cavallo, D.A. (2006) Contingency Management for Smoking Cessation in Adolescent Smokers. Experimental and Clinical Psychopharmacology 14(2).

2. Rasmusson, A.M., Picciotto, M.R., Krishnan-Sarin, S. (in press) Smoking as a Complex but Critical Covariate in Neurobiological Studies of PTSD: A Review. Journal of Psychopharmacology.

3. O’Malley, S.S., Cooney, J., Krishnan-Sarin, S., Dubin, J.A., McKee, S., Cooney, N., Blakeslee, A., Meandzija, B., Romano-Dahlgard, D., Wu, R., Makuch, R., Jatlow, P. (2006). A Controlled Trial of Naltrexone Augmentation of Nicotine Replacement for Smoking Cessation. Archives of Internal Medicine 166:667-674

4. Adinoff, B., Junghanns, K., Kiefer, F., Krishnan-Sarin, S. Suppression of the HPA Axis Stress-Response: Implications for Relapse (2005) Alcoholism: Clinical and Experimental Research 29(7):1351-5.

5. Sacco, K.A, Termine, A., Seyal, A.A., Dudas, M.M., Vessicchio, J.C., Krishnan-Sarin, S., Wexler, B.E., George, T.P. (2005) Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: Involvement of nicotinic receptor mechanisms. Archives of General Psychiatry 62:649-659.

6. Duhig A., Cavallo, D., McKee, S., George, T.P., Krishnan-Sarin, S. (2005) Daily patterns of cigarette, marijuana and alcohol use in adolescents. Addictive Behaviors 30:271-283

7. Jamner, L.D., Whalen, C.K., Loughlin, S.E., Mermelstein, R., Audrain-McGovern, J., Krishnan-Sarin, S., Worden, J.K., Leslie, F.M. (2003). Tobacco use across the formative years: A road map to developmental vulnerabilities. Nicotine and Tobacco Research 5(Supplement 1): S71-S88.

8. Krishnan-Sarin, S., Meandzija, B., O’Malley, S.S. (2003). Naltrexone and nicotine patch in smoking cessation: a preliminary study. Nicotine and Tobacco Research 5(6): 851-857.

9. O'Malley, S.S., Krishnan-Sarin, S., Farren, C.F., Sinha, R. and Kreek, M.J. (2002). Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis. Psychopharmacology 160:19-29.

10. Krishnan-Sarin, S., Rosen, M.I. and O'Malley, S.S. (1999). Naloxone challenge in smokers: Preliminary evidence of an opioid component in nicotine dependence. Archives of General Psychiatry 56:663-668.

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