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


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sullivan
Maria A
MA
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.
Vosburg
Suzanne K
SK
Comer
Sandra D
SD
D000328:Adult; D000339:Affect / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D003932:Heroin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006556:Heroin Dependence / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009294:Narcotics / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D012646:Self Administration; D013997:Time Factors; D014040:Token Economy
D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; D003932:Heroin