title: Antagonist Models for Relapse Prevention and Reducing HIV Risk.
abstract: Naltrexone is an antagonist that binds tightly to μ-opioid receptors and blocks the subjective and analgesic effects of opioids. It does not produce physiologic dependence and precipitates withdrawal if administered to an opioid dependent person, thus starting it must begin with detoxification. It was first available in the mid-1970s as a 50 mg tablet that blocked opioids for 24-36 h if taken daily, or every 2-3 days at higher doses - for example: 100 mg Monday and Wednesday, 150 mg on Friday. From a pharmacological perspective it worked very well and was hoped to be an effective treatment but results were disappointing due to low patient interest and high dropout followed by relapse. Interest in it waned but rose again in the late 1990's when injecting opioid use and the rapid spread of HIV in the Russian Federation converged with an international interest in reducing the spread of HIV. One result was a series of meetings sponsored by the U.S. National Institute on Drug Abuse (NIDA) and Pavlov State Medical University in St. Petersburg, Russian Federation, on ways to reduce the spread of HIV in that country. Addiction treatment was a clear priority and discussions showed that naltrexone could have a role since agonist treatment is against Russian law but naltrexone is approved and the government funds over 25,000 beds for detoxification, which is the first step in starting naltrexone treatment. These meetings were followed by NIDA studies that showed better compliance to oral naltrexone than in prior U.S. studies with the expected reductions in HIV injecting risk for those that stayed in treatment. These events and findings provided a background and identified an infrastructure for the study that led to FDA approval of extended release injectable naltrexone for preventing relapse to opioid dependence. This paper will briefly review findings from these studies and end with comments on the potential role of extended release naltrexone as a meaningful addition to current pharmacotherapies for treating opiod dependence and reducing HIV risk.
authors.affiliation: Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 3440 Market Street; Suite 370, Philadelphia, PA, 19104, USA. woody@tresearch.org.
authors.forename: George E
authors.initials: GE
authors.lastname: Woody
authors.affiliation: Department of Addictions, St. Petersburg Bekhterev Research Psychoneurological Institute, St. Petersburg, Russia.|Department of Pharmacology, St.-Petersburg State Pavlov Medical University, St. Petersburg, Russia.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Krupitsky
authors.affiliation: Department of Addictions, St. Petersburg Bekhterev Research Psychoneurological Institute, St. Petersburg, Russia.
authors.forename: Edwin
authors.initials: E
authors.lastname: Zvartau
mesh_terms: D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D009271:Naltrexone / Q000494:pharmacology / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000453:epidemiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology; D055502:Secondary Prevention / Q000379:methods* / Q000639:trends
chemical_list: D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone
keywords: HIV risk; Opiod dependence