Kappa-PET Imaging and Naltrexone in Alcohol Drinking Behaviors

The primary purpose of the study is to increase our knowledge of receptor function in the brains of people who are heavy drinkers and taking naltrexone (NTX), a medication that has been approved for the treatment of alcohol dependence. Receptors are special molecules in the brain to which other molecules (neurotransmitters) attach during the normal every-day workings of the brain. Drugs can bind to those receptor molecules as well. Recent evidence suggests that kappa opioid receptors (KOR's) may play an important role in alcohol drinking behavior. This study will try to determine if naltrexone's ability to attach to these receptors is related to its effectiveness. We will use PET (positron emission tomography) for this study. PET is a type of imaging device found in nuclear medicine. It is used for tracking the presence of injected radioactive materials in the body.

Alcohol, Drinking, Drinkers, Alcohol Drinking, Naltrexone, Alcohol Dependence, Alcohol Abuse, Alcohol-Related Disorders, Ethanol, Alcoholism

To determine the degree to which occupancy of KORs by a 100 mg/day dose of NTX mediates (influences the strength of) responsivity to NTX treatment in all heavy drinkers.

To determine whether the relationship between NTX responsivity and occupancy of KOR is different in family history positive vs. family history negative heavy drinkers. Evaluations were done with a logistic regression which included years of drinking (a covariate), family history status, and occupancy of KOR. The logistic model calculated a probability of response, defined as a 50% or greater reduction in drinking after naltrexone, for every participant. Reported outcome is the area under the ROC produced by the model. The closer the value is to 100 percent probability, the better the model is at correctly classifying the observations.

To determine if baseline levels of KOR differ between family history positive (FHP) and family history negative (FHN) heavy drinkers and to determine if baseline KOR level is related to either baseline drinking or responsivity to NTX.

Inclusion Criteria: Ages 21-50 Able to read English at 6th grade level or higher and to complete study evaluations Regular alcohol drinker Exclusion Criteria: Individuals who are seeking alcohol treatment Medical conditions that would contraindicate the use of study medication Regular use of other substances

de Laat B, Goldberg A, Shi J, Tetrault JM, Nabulsi N, Zheng MQ, Najafzadeh S, Gao H, Kapinos M, Ropchan J, O'Malley SS, Huang Y, Morris ED, Krishnan-Sarin S. The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving. Biol Psychiatry. 2019 Dec 1;86(11):864-871. doi: 10.1016/j.biopsych.2019.05.021. Epub 2019 Jun 8.