and relapse prevention. NIDA's Medications Development Division has made important contributions in the development of pharmacotherapies for drug addiction and has served as a catalyst in promoting drug development (IOM, 1995b). Medications development for the treatment of heroin and cocaine addictions is discussed more fully in a recent Institute of Medicine report (IOM, 1995b).

Two opiate agonist medications, methadone and LAAM (levo-alpha-acetylmethadol), have been approved for the treatment of opiate addiction. Agonists act by substituting at the opioid receptor site, thereby blocking the euphoria of subsequently administered opiates (via crosstolerance) and inhibiting the symptoms of acute and chronic abstinence. Methadone was approved for use in 1972, and there are currently an estimated 650 methadone maintenance programs throughout the United States (IOM, 1995a,b). The data supporting the efficacy of methadone maintenance have been reviewed extensively (e.g., Ball and Ross, 1991; Kreek, 1992). In 1993, LAAM was approved for use in treating opiate dependence; this medication has the advantage of requiring three doses per week rather than daily doses, thus freeing subjects from daily clinic attendance. Clinical guidelines for the use of each of these medications have recently been published by the Substance Abuse and Mental Health Services Administration (SAMHSA, 1993, 1995c).

Naltrexone, an orally effective and long-acting opiate antagonist, has been shown effective in preventing relapse to opiate dependence in highly motivated patients (e.g., probationers, parolees, health care providers) who are under strong external pressure to remain opiate free (Brahen et al., 1978). Naltrexone has also been found to reduce relapse to alcohol dependence (Volpicelli et al., 1992). A newer opiate antagonist, nalmafene, which is currently undergoing testing, appears to have positive effects similar to those of naltrexone (Mason et al., 1994). Opiate antagonist medications work by binding to the opioid receptor site, preventing receptor activation by the abused drug and thereby blocking the drug's euphorigenic and dependence-producing effects. This blockade represents competitive antagonism, and thus its clinical efficacy can be modified by the dose of the antagonist, the time elapsed since the antagonist was taken, and the dose of the abused drug.

Buprenorphine is a partial opiate agonist that produces less physiological dependence than methadone or LAAM and is currently in clinical trials (Bicket and Amass, 1995; Cowan and Lewis, 1995). It has been shown to be effective in maintenance therapy, in retaining patients in treatment, and in facilitating abstinence from illicit opiates Johnson et al., 1992; Kosten et al., 1993). Buprenorphine is currently being tested in combination with naloxone in a sublingual preparation to reduce its abuse liability. The eventual goal is to develop a pharmacotherapy that avoids



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