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Long-Acting Opioid-Agonists in the Treatment of Heroin Addiction: Why Should We Call Them "Substitution"?

NCJ Number
Substance Use & Misuse Volume: 44 Issue: 5 Dated: 2009 Pages: 663-671
G. Gerra; I. Maremmani; B. Capovani; L. Somaini; S. Berterame; J. Tomas-Rossello; E. Saenz; A. Busse; H. Kleber
Date Published
9 pages
This study reviewed the literature on the pharmacological differences between long-acting opioids (L-AOs), such as methadone and buprenorphine, which are used in the treatment of heroin addiction, and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, and effects on the endocrine and immune systems.
The study concludes that the evidence indicates L-AOs, such as methadone and buprenorphine, should not be viewed as replacements (substitution) for the rewarding effects of heroin, but rather as medications for heroin addiction. This argument is based primarily on the ability of these L-AOs to reduce craving and control addictive behavior. There are sufficient examples of the significant differential effects of short-acting and long-acting opioids to justify calling the latter “maintenance agents” or “long-acting opioid agonist” rather than “substitute agents.” Protocols of oral self-administration in experimental animals has demonstrated that oral methadone did not act as a reinforcer, suggesting reduced effects of the L-AO on the reward system (Vivian, Liang, Higley, Linnoila, and Woods, 1999). Similarly, despite the high affinity of buprenorphine for the mu opioid receptor, this L-AO is apparently a safe drug, with a benign overall side effect. Pharmacokinetic evidence also suggests that the L-AO agonists used in heroin-addiction treatment should not be considered as simple substitutions for heroin. Further, a variety of evidence has shown that neuroendocrine function is significantly changed in humans who receive any narcotic on a short-term basis or short-acting narcotics on a chronic basis. In contrast, long-term, steady-state methadone treatment of former heroin addicts has been reported to induce a normalization of the opioid system and hypothalamic-pituitary-adrenal axis function. 20 references