This study is being submitted for review under the R21 (exploratory grant) mechanism, Its purpose is to explore whether the addition of very low doses of naltrexone to a methadone tapering schedule for opiate detoxification is safe, decreases withdrawal intensity and enhances patient treatment compliance. Although many different techniques for opiate detoxification have been employed, there is a continuing search for more effective approaches to reduce the duration and discomfort of withdrawal. Recent attempts have included the use of opiate antagonists to induce """"""""ultra rapid"""""""" detoxification. However, the resulting need for heavy sedation or anesthesia to control withdrawal intensity and the increased possibility of medical complications has discouraged and limited the use of this approach. By contrast, there is experimental evidence that very low doses of naltrexone administered in the presence of opiates has analgesic and dependency reducing properties, suggesting that the use of very low dose naltrexone in the clinical management of opiate detoxification might be a useful strategy. To test this hypothesis, 360 volunteer opiate dependent subjects, admitted to the inpatient detoxification program of a community hospital and placed on a 4-day detoxification schedule, will be randomly assigned to receive one of three different low-dose naltrexone schedules or placebo in addition to their routine methadone tapering treatment. The four groups will be compared with respect to behavioral, biological and subjective withdrawal signs and symptoms, detoxification completion rates, acceptance of referral to outpatient treatment, and one and seven day post-detoxification follow-up evaluations. If the administration of low-dose naltrexone (antagonist) at the same time as methadone (agonist) is found to be more effective than placebo in reducing withdrawal discomfort, the findings will have clear treatment implications and raise important questions about the mechanisms of opiate agonist and antagonist interactions at the receptor.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Grants (R21)
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Application #
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Oversby, Steven
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Duke University
Schools of Medicine
United States
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Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S et al. (2013) Smoking and opioid detoxification: behavioral changes and response to treatment. Nicotine Tob Res 15:1705-13
Mannelli, Paolo; Peindl, Kathleen S; Lee, Tong et al. (2012) Buprenorphine-mediated transition from opioid agonist to antagonist treatment: state of the art and new perspectives. Curr Drug Abuse Rev 5:52-63
Mannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy et al. (2012) The combination very low-dose naltrexone-clonidine in the management of opioid withdrawal. Am J Drug Alcohol Abuse 38:200-5
Mannelli, Paolo; Peindl, Kathleen S; Wu, Li-Tzy (2011) Pharmacological enhancement of naltrexone treatment for opioid dependence: a review. Subst Abuse Rehabil 2011:113-123
Mannelli, Paolo; Peindl, Kathleen; Patkar, Ashwin A et al. (2011) Problem drinking and low-dose naltrexone-assisted opioid detoxification. J Stud Alcohol Drugs 72:507-13
Mannelli, P (2010) Agonist-antagonist combinations in opioid dependence: a translational approach. Dipend Patologiche 5:17-24
Mannelli, Paolo; Peindl, Kathi; Patkar, Ashwin A et al. (2010) Reduced cannabis use after low-dose naltrexone addition to opioid detoxification. J Clin Psychopharmacol 30:476-8
Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathi et al. (2009) Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial. Addict Biol 14:204-13
Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen et al. (2009) Early outcomes following low dose naltrexone enhancement of opioid detoxification. Am J Addict 18:109-16
Mannelli, Paolo; Patkar, Ashwin; Rozen, Steve et al. (2009) Opioid use affects antioxidant activity and purine metabolism: preliminary results. Hum Psychopharmacol 24:666-75

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