Mehmet Sofuoglu MD, PhD

Professor of Psychiatry; Director of VA New England Mental Illness Research, Education and Clinical Center (MIRECC)

Research Interests

Tobacco addiction; Cocaine addiction; Clinical trials; Human laboratory studies

Current Projects


Ongoing projects include:
    • Sex differences in the reinforcing threshold for intravenous nicotine self-administration in male and female smokers.
    • Genetic factors influencing the rewarding effects of intravenous nicotine in male and female smokers.
    • Testing the efficacy of carvedilol, an adrenergic blocker, for cocaine addiction in a randomized clinical trial.
    • Evaluating the genetic moderators of intravenous nicotine sensitivity using an intravenous nicotine administration paradigm.
    • Testing the efficacy of galantamine, a cognitive enhancer, in combination with contingency management for the treatment of cocaine addiction.

Research Summary

Our research is focused on development of novel medications for cocaine and nicotine dependence. Our program seeks to bridge the gap between human laboratory studies examining the medical safety and potential efficacy of new medications for substance dependence and outpatient trials directly examining these medications in drug relapse. Among the key findings is our work on sex and menstrual cycle influences on cocaine responses in humans. To explain our novel observations on sex and menstrual cycle effects on cocaine responses, we proposed progesterone’s role as a modulator of cocaine effects. We tested this hypothesis with a series of systematic human studies ranging from human laboratory to clinical trials examining the potential utility of progesterone as a treatment for cocaine and nicotine addiction. Following those seminal contributions, progesterone is considered a key modulator of drug use behavior, and an active area of research at the international level. Similarly, we were among the first to examine the contribution of the adrenergic system in cocaine responses with novel findings for effects of an alpha- and beta-adrenergic blocker, carvedilol. These novel human laboratory findings led to a new potential treatment approach using carvedilol for cocaine as well as methamphetamine addiction that is being pursued by other research research groups. More recently, we have developed a novel intravenous nicotine self-administration model which allows examination of both rewarding and aversive effects of nicotine in male and female smokers. This model has a great utility for early human screening for potential medications for tobacco addiction.

Extensive Research Description

Our research is focused on development of novel medications for cocaine and nicotine dependence. Our program seeks to bridge the gap between human laboratory studies examining the medical safety and potential efficacy of new medications for substance dependence and outpatient trials directly examining these medications in drug relapse. Among the key findings is our work on sex and menstrual cycle influences on cocaine responses in humans. To explain our novel observations on sex and menstrual cycle effects on cocaine responses, we proposed progesterone’s role as a modulator of cocaine effects. We tested this hypothesis with a series of systematic human studies ranging from human laboratory to clinical trials examining the potential utility of progesterone as a treatment for cocaine and nicotine addiction. Following those seminal contributions, progesterone is considered a key modulator of drug use behavior, and an active area of research at the international level. Similarly, we were among the first to examine the contribution of the adrenergic system in cocaine responses with novel findings for effects of an alpha- and beta-adrenergic blocker, carvedilol. These novel human laboratory findings led to a new potential treatment approach using carvedilol for cocaine as well as methamphetamine addiction that is being pursued by other research research groups. More recently, we have developed a novel intravenous nicotine self-administration model which allows examination of both rewarding and aversive effects of nicotine in male and female smokers. This model has a great utility for early human screening for potential medications for tobacco addiction. We are currently using this model to test potential GABA medications for tobacco addiction and to determine the genetic moderators of nicotine's rewarding and cognitive-enhancing effects.


Selected Publications

  • Sofuoglu M, DeVito EE, Waters AJ, Carroll KM. Cognitive enhancement as a treatment for drug addictions. Neuropharmacology. 2013;64:452-63. PMCID: PMC 3445733.
  • Herman AI, Jatlow PI, Gelernter J, Listman JB, Sofuoglu M. COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers. The pharmacogenomics journal. 2013. PMCID: PMC3675163.
  • Sofuoglu M, Herman AI, Nadim H, Jatlow P. Rapid nicotine clearance is associated with greater reward and heart rate increases from intravenous nicotine. Neuropsychopharmacology 2012;37(6):1509-16, PMCID: 3327855.
  • Sofuoglu M, Waters AJ, Poling J, Carroll KM. Galantamine improves sustained attention in chronic cocaine users. Exp Clin Psychopharmacol. 2011 Feb;19(1):11-9. PubMed PMID: 21341919.
  • Sofuoglu M, Mouratidis M, Mooney M. Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers. Psychoneuroendocrinology. 2011 Jan;36(1):123-32. Epub 2010 Aug 2. PubMed PMID:20675057; PubMed Central PMCID: PMC2987547.
  • Sofuoglu M. Cognitive enhancement as a pharmacotherapy target for stimulant addiction. Addiction. 2010 Jan;105(1):38-48. Review. PubMed PMID: 20078461; PubMed Central PMCID: PMC2808705.
  • Herman AI, Sofuoglu M. Cognitive effects of nicotine: genetic moderators. Addict Biol. 2010 Jul;15(3):250-65. Epub 2010 Apr 29. Review. PubMed PMID: 20456288; PubMed Central PMCID: PMC2903639.
  • Sofuoglu, M. and Mooney, M Subjective responses to intravenous nicotine: greater sensitivity in women than men. Experimental and Clinical Psychopharmacology 17: 63-9, 2009
  • Sofuoglu, M., Yoo, S., Hill, K, and Mooney, M: Self-administration of intravenous nicotine in male and female cigarette smokers Neuropsychopharmacology 33:715-20, 2008.

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