Méthadone

Méthadone is a synthetic opioid used medically for pain relief and, importantly, for the treatment of opioid use disorder. It is a long-acting mu-opioid receptor agonist that can suppress withdrawal symptoms and cravings, supporting maintenance therapy in appropriate programs. It is available in oral solutions, tablets, and concentrated formulas.

In clinical practice, methadone serves two main roles: analgesia for chronic or cancer-related pain, and opioid substitution therapy (OST) to reduce illicit opioid use and improve treatment retention. In OST, methadone maintenance helps stabilize individuals by providing a stable, longer-acting opioid effect, which lowers the risk of withdrawal and craving between doses.

Pharmacology and pharmacokinetics: methadone is a synthetic compound with two enantiomers; the R-enantiomer is the primary active form at the mu-opioid receptor. It has a relatively long and highly variable half-life, typically ranging from about 8 to 59 hours, which contributes to its gradual onset and prolonged effect. Methadone is mainly metabolized in the liver by several enzymes, including CYP3A4, CYP2B6, and CYP2D6, and it produces active and inactive metabolites such as EDDP. Because of its pharmacokinetics, dosing is individualized and often initiated or adjusted under medical supervision.

Safety and adverse effects: common effects include constipation, drowsiness, sweating, and nausea. Serious risks include respiratory depression, especially with concurrent Central Nervous System depressants or in overdose, and QT interval prolongation, which can lead to torsades de pointes in some patients. Methadone can cause dependence and withdrawal upon abrupt discontinuation; it should be used with caution in liver impairment and in those with significant heart rhythm abnormalities.

History: methadone was discovered in 1937 in Germany and introduced into clinical practice in the mid-20th century. It has since become a standard option in opioid dependence treatment worldwide, alongside other therapies such as buprenorphine.