Innovations in Opiates Dependency Treatment (Heroin, Morphine, Methadone, others).
The Role of Naltrexone in Long Lasting Formulations
Naltrexone, an opiate treatment medication, is used to help patients make the transition from illicit opiate use to a drug-free life. Patients in naltrexone treatment are first detoxified from their dependence on opiates and then take thrice-weekly doses of naltrexone and participate in weekly group therapy sessions.
The medication provides a safety net for patients because it blocks the euphoric effects they normally would feel if they slip and use heroin or any other opiate. As a result, even relapse, which is common in addiction treatment, may have a therapeutic effect as repeated failure to get high may eventually break the neurobiological and behavioral links between taking drugs and the rewards that lead patients to resume regular drug use. With successful naltrexone treatment, slips to drug use become less frequent, the medication is discontinued, and patients continue behavioral treatment if needed.
Naltrexone treatment has been successful mainly with patients who are highly motivated to stop using opiates. Such patients include health care professionals who must stop using opiates to retain their licenses to practice medicine and individuals subject to criminal justice sanctions for relapse to illicit opiate use. The severe penalties that these patients would incur if they fail treatment enable them to overcome naltrexone's main drawback: It eliminates the powerful rewarding effects of opiates without any replacement to help patients cope with lingering effects of withdrawal.


Long-Lasting Formulation Also May Increase Naltrexone Compliance Research Findings

NIDA NOTES Vol. 17, No. 6 (March 2003)

NIDA (USA National Institute of Drug Abuse)-supported researchers have been testing a long-lasting "depot" formulation of naltrexone that is aimed at reducing the three-times-a-week frequency with which patients must now take the medication to prevent them from getting high if they use heroin. The formulation is packaged in microcapsules injected under the skin that slowly release medication for several weeks. The sustained release of naltrexone is meant to maintain enough medication in the patient to suppress heroin's euphoric effects for an extended time.

Clinical trials now under way are assessing the safety and efficacy of depot naltrexone. In a recent trial, Dr. Sandra D. Comer and a team of researchers from the New York State Psychiatric Institute and Columbia University tested depot naltrexone in an 8-week inpatient study with 12 heroin-dependent subjects to see how long the medication remains active in the human body and blocks heroin's effects.

After detoxification, six patients received a low dose (192 mg) and six received a high dose (384 mg) of the medication. Patients in both groups subsequently were given a placebo or intravenous heroin once a day from Monday through Friday for 6 weeks. Each week, daily doses of heroin started at 6.5 mg and increased to 12.5, 18.75, and 25 mg; the placebo was administered randomly on one of the days.

Researchers assessed subjective, performance, and physiological effects after each dose of heroin or placebo and measured plasma levels of naltrexone over the course of the study. They found that both doses of depot naltrexone substantially suppressed the patients' ratings of heroin's pleasurable effects and how much they "liked" the drug and wanted to take it again. With the high dose of naltrexone, patients' positive ratings of heroin's pleasurable effects remained low for 5 weeks. In the 6th week, ratings increased significantly relative to week one after patients received the 18.75- and 25-mg injections of heroin. The low dose suppressed positive ratings of heroin for 3 weeks. Plasma levels of naltrexone remained above 1 ng/mL for 4 weeks with the high dose and 3 weeks with the low dose. Though these levels are low compared to those resulting from standard naltrexone treatment doses, other studies have reported that even with negligible plasma levels, naltrexone continues to counter heroin's effects. Other than initial discomfort at the site of naltrexone injection, there were no untoward side effects.

The results suggest that once-a-month administration of the depot formulation can provide safe, long-lasting blockade of the effects of intravenous "streetlevel" heroin doses in patients who have undergone detoxification. Future studies will address questions that remain about optimal dose levels for naltrexone treatment of heroin dependence, such as what effects different doses have on withdrawal, craving, and the ability to reduce heroin use.


Source:
Comer, S.D., et al. Depot naltrexone: Long-lasting antagonism of the effects of heroin in humans. Psychopharmacology 159:351-360, 2002.