Mehmet Sofuoglu MD, PhD

Associate Professor of Psychiatry; Acting Director of VA VISN 1 MIRECC

Research Interests

Addiction; Clinical trials; Human laboratory studies

Current Projects

• • 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