For decades, the mainstay of evidence-based OD treatment has been the pairing of supportive social services with opioid substitution therapy.4, 5 Methadone is an inexpensive and long-acting synthetic opioid, and like the most frequently abused opioids it is a potent μ-opioid receptor agonist.6 Methadone maintenance therapy (MMT) can therefore be used to treat abuse by pharmacologically substituting for other opioids, such as morphine or heroin. MMT reduces craving, withdrawal symptoms, and risk of relapse.6 The initial, or induction, stage of MMT requires considerable care: excessive methadone doses are dangerous,7 while overly conservative dosing is ineffective at preventing relapse to illicit opioid use.8 Determining the clinically optimal dose, one that provides clinical benefit to a particular individual without causing sedation or respiratory depression, is time consuming. Methadone dosing must be adjusted based on clinical signs and symptoms, and patients differ greatly in their dose requirements. Despite the clinical challenges posed by methadone administration, and resistance to MMT for social and cultural reasons,9, 10 MMT remains a vitally important treatment strategy for hundreds of thousands of patients in the United States.11
