Methadone is a long-acting opioid with considerable unexplained interindividual variability in clearance. Cytochrome P450 2B6 (CYP2B6) mediates clinical methadone clearance and metabolic inactivation via N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). Retrospective studies suggest that individuals with the CYP2B6*6 allelic variant have higher methadone plasma concentrati...

Background Methadone, a full opioid agonist, and buprenorphine, partial agonist at the receptor, are established first-line medications for maintenance therapy. Transition from methadone to sublingual buprenorphine may precipitate withdrawal is usually performed only in patients on low dose of (<30–40 mg). novel subcutaneous depot (Buvidal) has not been previously described.Objectives To test h...

BACKGROUND Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older. Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of Basel-City, Switzerland. METHODS The study included methadone patients between April 1,...

AIMS Methadone treatment has been shown to be an effective intervention that can lower the risk of heroin-induced overdose death. Recent reports have suggested increases in methadone-induced overdose deaths in several locations in the USA and in Europe. This study investigated the role of methadone and opiates in accidental overdose deaths in New York City. DESIGN We analysed data from the Of...

BACKGROUND Opioids enhance and prolong analgesia when applied as adjuvants to local anaesthetics (LAs). A possible molecular mechanism for this property is a direct inhibition of voltage-gated Na(+) channels which was reported for some opioids. Methadone is an effective adjuvant to LA and was recently reported to inhibit cardiac Na(+) channels. Here, we explore and compare LA properties of meth...

Homomeric 5-hydroxytryptamine (5-HT)(3A) and heteromeric 5-HT(3AB) receptors mediate rapid excitatory responses to serotonin in the central and peripheral nervous systems. The alkaloid morphine, in addition to being a mu-opioid receptor agonist, is a potent competitive inhibitor of 5-HT(3) receptors. We examined whether methadone, an opioid often used to treat morphine dependence, also exhibite...

We report persistent galactorrhoea and raised prolactin in a woman taking methadone, which is commonly prescribed for the treatment of opiate dependence. A heroin smoking 28 year old mother of two (younger child aged 4), with hepatitis C (of nine years’ duration), weighing 50 kg, was first prescribed 30 mg methadone a day for opiate dependence. She reported newly emergent galactorrhoea after fo...

PURPOSE To define the dose ratio between morphine and methadone in relation to the previous morphine dose and the number of days needed to achieve the same level of analgesia in a group of patients with advanced cancer with pain who switched from morphine to oral methadone. PATIENTS AND METHODS A cross-sectional prospective study of 38 consecutive cancer patients who switched from morphine to...

The peripheral conversion of testosterone to estradiol by aromatase is the primary source of endogenous estrogen in postmenopausal women. Studies indicating that placental aromatase is able to metabolize methadone to its primary metabolite, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidin (EDDP), led us to test the hypothesis that methadone is able to act as an inhibitor of aromatase. Using r...

BACKGROUND The first evidence that the hazard ratio (HR) for methadone-specific death rises more steeply with age-group than for all drug-related deaths (DRDs) came from Scotland's cohort of 33,000 methadone-prescription clients. We aim to examine, for England, whether illicit opioid users' risk of methadone-specific death increases with age; and to pool age-related HRs for methadone-specific d...