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Psychopharmacology (Berl). 2006 Nov;189(1):37-46. Epub 2006 Sep 14.

Depot naltrexone: antagonism of the reinforcing, subjective, and physiological effects of heroin.

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Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.



Naltrexone is an opioid antagonist that is currently approved as a treatment for opioid and alcohol dependence. Although it is highly effective in completely antagonizing the effects of opioids, medication noncompliance is a difficult obstacle to treatment. Therefore, a sustained-release form of naltrexone may improve treatment outcome.


The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex).


Five heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, the effects of a range of heroin doses (0, 6.25, 12.5, and 25 mg, i.v.) were examined. Participants then received 384 mg naltrexone base. The effects of heroin were again evaluated for the next 6 weeks. One dose of heroin was tested per day and the entire dose range was tested each week. Doses were administered in non-systematic order. During a morning sample session, participants received a dose of heroin and $20 and subjective, performance, and physiological effects were measured both before and after drug administration. During an afternoon choice session, participants were given the opportunity to choose the sampled heroin dose and/or amount of money using a modified progressive ratio procedure.


Depot naltrexone antagonized both the reinforcing and subjective effects of heroin for 4-5 weeks. Subjective ratings of withdrawal were reduced after week 2 and throughout the remainder of the study. The effects of heroin on mean trough pupil diameter began to emerge by week 5. There were no clinically significant effects on respiratory or cardiovascular function.


The present results extend our previous findings by showing that the reinforcing effects of heroin were reduced for 4-5 weeks after administration of 384 mg depot naltrexone.

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