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Fyn Kinase Inhibitors and Alcohol Drinking Behaviors in Heavy Drinkers (Project Completed)


Principal Investigator: Dr. Suchitra Krishnan-Sarin. This protocol examined the influence a Src/Fyn protein tyrosine kinase inhibitor (that modulates NMDA-R signaling via Fyn inhibition), when compared with a matched placebo on alcohol drinking behaviors among heavy drinkers with alcohol use disorder. Alcohol drinking behaviors were assessed using an experimental alcohol drinking paradigm (ADP) which involves exposure to a priming drinking of alcohol and subsequent ad-lib drinking of up to 12 drinks over the three-hour period. Participants completed a baseline ADP and were then randomized to receive active study medication or placebo for a 7-8 day period; participants were seen or contacted daily to observe medication administration and check for adverse events. At the end of this period they completed the second ADP. The primary outcome included the number of drinks consumed, and alcohol craving during the second ADP. Participants also completed a one week follow and one-month follow up appointments.


This randomized, placebo-controlled trial in non-treatment seeking heavy drinkers was conducted from 2017-19. We are currently in the process of finalizing data analysis.

In addition to this study, we are also in the process of conducting another trial examining the safety and tolerability of another medication in combination with alcohol. Please see Project 3b for more information.

Relevant Publications

  1. Krishnan-Sarin, S., Krystal, J.H., Shi, J., Pittman, B., O’Malley, S.S. (2007). Family history of alcoholism influences naltrexone-induced reduction in alcohol drinking. Biological Psychiatry. 62: 694-697.
  2. Krishnan-Sarin, S., O’Malley, S.S., Krystal, J.H. (2009). Treatment Implications: Using Neuroscience to Guide the Development of New Pharmacotherapies for Alcoholism. Alcohol Research and Health 31 (4): 400-407.
  3. Krishnan-Sarin, S., O'Malley, S.S., Franco, N., Cavallo, D.A., Morean, M., Shi, J., Pittman, B., & Krystal, J.H., (2015). N-methyl-D-aspartate receptor antagonism has differential effects on alcohol craving and drinking in heavy drinkers. Alcoholism: Clinical and Experimental Research. 39(2): 300-307.
  4. Krishnan-Sarin, S., O'Malley, S.S., Franco, N., Cavallo, D.A., Tetrault, J.M., Shi, J., Gueorguieva, R., Pittman, B., Krystal, J.H. (2020). Influence of combined treatment with naltrexone and memantine on alcohol drinking behaviors: a phase II randomized crossover trial. Neuropsychopharmacology. 45 (2):319-326.