Opioid Dependence: Rationale for and Efficacy of Existing and New Treatments

Yale University, New Haven, Connecticut, United States
Clinical Infectious Diseases (Impact Factor: 8.89). 01/2007; 43 Suppl 4(Supplement 4):S173-7. DOI: 10.1086/508180
Source: PubMed


Opioid dependence is a chronic and relapsing medical disorder with a well-established neurobiological basis. Opioid agonist
treatments, such as methadone and the recently approved buprenorphine, stabilize opioid receptors and the intracellular processes
that lead to opioid withdrawal and craving. Both methadone and buprenorphine have been proven effective for the treatment
of opioid dependence and can contribute to a decreased risk of human immunodeficiency virus (HIV) transmission. In addition,
a buprenorphine/naloxone combination appears to have a decreased potential for abuse or diversion, compared with that associated
with methadone. Largely because of these properties, recent legislation now affords an unprecedented opportunity for general
physicians to offer opioid agonist treatment through their offices. This review focuses on the neurobiological basis of opioid
dependence, the rationale for methadone and buprenorphine treatments, and issues in prescribing these medications to patients
with HIV infection.

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    • "Pharmacological treatments available for opioid addicts include opioid agonists (methadone and buprenorphine) and opioid antagonists (naltrexone), which bind to opioid receptors to either mimic or block the effects of heroin. Although these medications are safe, effective, and decrease the risk of human immunodeficiency virus transmission (Fiellin et al., 2006), less than 20% of opioid addicts in the United States are treated with these medications and even fewer in many other countries (Tang and Hao, 2007; Mendelson et al., 2008; Krupitsky et al., 2010; Lobmaier et al., 2010). Compliance with antagonist use is low (O'Malley et al., 2000) and agonists have a high abuse potential, risk of diversion, and relatively short duration of efficacy, limiting their appeal and necessitating tight regulation. "
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    ABSTRACT: Morphine conjugate vaccines have effectively reduced behavioral effects of heroin in rodents and primates. To better understand how these effects are mediated, heroin and metabolite distribution studies were performed in rats in the presence and absence of vaccination. In non-vaccinated rats 6-monoacetylmorphine (6-MAM) was the predominant opioid in plasma and brain as early as 1 minute after i.v. administration of heroin and for up to 14 minutes. Vaccination with morphine conjugated to keyhole limpet hemocyanin (M-KLH) elicited high titers and concentrations of antibodies with high affinity for heroin, 6-MAM, and morphine. Four minutes after heroin administration vaccinated rats showed substantial retention of all three opioids in plasma compared to controls, and reduced 6-MAM and morphine, but not heroin, distribution to brain. Administration of 6-MAM rather than heroin in M-KLH vaccinated rats showed a similar drug distribution pattern. Vaccination reduced heroin-induced analgesia and blocked heroin-induced locomotor activity throughout 2 weeks of repeated testing. Higher serum opioid-specific antibody concentrations were associated with higher plasma opioid concentrations, lower brain 6-MAM and morphine concentrations, and lower heroin-induced locomotor activity. Serum antibody concentrations over 0.2 mg/ml were associated with substantial effects on these measures. These data support a critical role for 6-MAM in mediating the early effects of i.v. heroin and suggest that reducing 6-MAM concentration in brain is essential to the efficacy of morphine conjugate vaccines.
    Preview · Article · Dec 2012 · Journal of Pharmacology and Experimental Therapeutics
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    • "Methadone and buprenorphine are full and partial muopioid receptor agonists, respectively, that are utilized as medications in the treatment of opioid dependence. Medication-assisted treatment (MAT) has been shown to be highly effective in reducing heroin and illicit prescription opioid use, promoting retention in treatment (Fiellin, Friedland, & Gourevitch, 2006; Mattick et al., 2008; Mattick, Breen, Kimber, & Davoli, 2009; O'Connor & Fiellin, 2000; Schwartz et al., 2006; Sees et al., 2000; Weiss et al., 2011), and reducing risk factors for the transmission of HIV and other blood-borne diseases (Gowing, Farrell, Bornemann, & Ali, 2008; Metzger et al., 1993). Despite the multiple positive outcomes demonstrated, the majority of opioid-dependent patients are not enrolled in MAT (Friedman et al., 2004; Stancliff, Myers, Steiner, & Drucker, 2002). "
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    ABSTRACT: Medication-assisted treatment for opioid dependence is safe and effective, yet negative perceptions about methadone and buprenorphine may discourage patients from entering treatment. One source of information that may influence viewers' perceptions is television. We performed a content analysis of a popular reality television program on addiction treatment. Although many patients had histories of opioid use, there were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information.
    Full-text · Article · May 2012 · Substance Use & Misuse
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    • "These results have been attributed to the similarities between the effects of d-amphetamine and those of cocaine and the usefulness of d-amphetamine to serve as a replacement drug in cocaine-dependent individuals (Grabowski et al. 2004b; Shearer 2008). This idea of agonist replacement therapy was first proposed for the treatment of opiate dependence (Dole et al. 1966; Kreek 2000), and is currently a primary line of treatment for heroin and prescription opiate dependence (e.g., methadone maintenance and levo-alphaacetyl-methadol treatment; Fiellin et al. 2006; Kreek and Vocci 2002) as well as tobacco smoking (i.e., nicotine replacement therapy; Fiore 2000; Stead et al. 2008). "
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    ABSTRACT: Recent studies have investigated D-amphetamine as a potential agonist medication for cocaine dependence. In rats, a 14-day continuous infusion of D: -amphetamine via osmotic mini-pump has been shown to decrease cocaine-reinforced responding under a progressive ratio (PR) schedule of reinforcement. This study was designed to assess the influences of the D-amphetamine treatment dose and self-administered cocaine dose on the magnitude of this effect. Experiment 1: rats were trained to self-administer 1.5 mg/kg/inj cocaine under a PR schedule, then implanted with D-amphetamine mini-pumps for 14 days (days 1-7, 5 mg/kg/day; days 8-14, 7.5 mg/kg/day). Breakpoints were evaluated throughout the treatment period and 14 days post-treatment. Experiment 2: rats were trained to self-administer cocaine under a PR schedule and initial dose-response curves were determined before implantation of D-amphetamine mini-pumps. During the 14-day D-amphetamine (5 mg/kg/day) treatment period, rats self-administered one of four cocaine doses (0.19, 0.38, 0.75, or 1.5 mg/kg/inj). A post-treatment PR dose-response curve and responding under a fixed ratio 1 (FR1) schedule were evaluated after mini-pump removal. Experiment 1: breakpoints for 1.5 mg/kg/inj cocaine were unchanged by the increasing dose of D-amphetamine. Experiment 2: the PR dose-response curve was shifted downward after the treatment period in rats that had self-administered 0.19 and 0.38 mg/kg/inj cocaine. In contrast, rats in the 0.75 and 1.5 mg/kg/inj groups demonstrated increased rates of cocaine intake under an FR1 schedule after the treatment period. These data suggest that continuous D-amphetamine treatment attenuates the reinforcing effects of cocaine.
    Preview · Article · Sep 2009 · Psychopharmacology
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