Clinical Update of Opioid Agonist and Partial Agonist Medications for the Maintenance Treatment of Opioid Addiction

After years of failures in managing heroin addiction by both supportive and punitive abstinence-based treatment modalities or incarceration, with or without initial short-term detoxification using an opioid agonist, research into the potential use of primarily mu opioid receptor directed agonist (or use of a partial agonist) in the chronic maintenance treatment of long-term opiate (primarily heroin) addiction was performed and such treatments have been developed. Of these treatments, chronic “maintenance” with the long-acting, orally effective, synthetic opioid methadone has been shown to be both highly effective and very safe. The extent of its effectiveness is directly related to its appropriate use in maintenance treatment, combining the use ofproperdoses of methadone (60 to 120 mg/day in most patients) with adjunctive treatment, including counseling and access to medical, behavioral, and psychiatric care. More recently, a second long-acting opioid,l-α-acetylmethadol (LAAM) has been approved for chronic maintenance of opiate addiction. This agent has also been shown to be safe and effective when used in appropriate doses and with adjunctive treatment as needed by each individual. A third agent, a partial agonist (or mixed agonist–antagonist) buprenorphine, is currently under rigorous study in the United States and is already being used in other parts of the world in the chronic maintenance treatment of opiate addiction. Other novel approaches such as using a kappa opioid receptor agonist, like the natural opioid receptor peptide dynorphin A, or a synthetic peptide or heterocyclic congener thereof, are now under study. This paper presents a historical review of the development, the pharmacokinetic and pharmacodynamic properties of each agent, their neurobiological effects and safety, and efficacy in treatment. A formulation of the rationale for use of these and other opioid agonist-like compounds which might be developed in the future for the treatment of opioid addiction will be discussed.