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Methadone , sold under the brand name Dolophine among others, is an opioid used for opioid maintenance therapy in opioid dependence and for chronic pain management. Side effects are similar to those of other opioids. Methadone is used for the treatment of opioid use disorder. It may be used as a maintenance therapy or in shorter periods for detoxification to manage opioid withdrawal symptoms. Treatment of opioid-dependent persons with methadone follows one of two routes: maintenance or detoxification. It is usually prescribed as a single daily dose medication for those who wish to abstain from illicit opioid use. Treatment models for MMT differ. It is not uncommon for treatment recipients to be administered methadone in a specialist clinic, where they are observed for around 15—20 minutes post dosing, to reduce risk of diversion of medication. The duration of methadone treatment programs range from a few months to several years. The length of time a person remains in treatment depends on a number of factors. While starting doses may be adjusted based on the amount of opioids reportedly used, most clinical guidelines suggest doses start low e. Chronic methadone dosing will eventually lead to neuroadaptation, characterised by a syndrome of tolerance and withdrawal dependence. However, when used correctly in treatment, maintenance therapy has been found to be medically safe, non-sedating, and can provide a slow recovery from opioid addiction. Methadone is approved in the US, and many other parts of the world, for the treatment of opioid addiction. Its use for the treatment of addiction is usually strictly regulated. Methadone is used as an analgesic in chronic pain, often in rotation with other opioids. Adverse effects of methadone include: \\\\\\\\\\[ citation needed \\\\\\\\\\]. Physical symptoms \\\\\\\\\\[ citation needed \\\\\\\\\\]. Cognitive symptoms \\\\\\\\\\[ citation needed \\\\\\\\\\]. Methadone withdrawal symptoms are reported as being significantly more protracted than withdrawal from opioids with shorter half-lives. Methadone is sometimes administered as an oral liquid. Methadone has been implicated in contributing to significant tooth decay. Methadone causes dry mouth , reducing the protective role of saliva in preventing decay. Other putative mechanisms of methadone-related tooth decay include craving for carbohydrates related to opioids, poor dental care, and general decrease in personal hygiene. These factors, combined with sedation, have been linked to the causation of extensive dental damage. The respiratory depression of an overdose can be treated with naloxone. As naltrexone has a longer half-life, it is more difficult to titrate. If too large a dose of the opioid antagonist is given to a dependent person, it will result in withdrawal symptoms possibly severe. When using naloxone, the naloxone will be quickly eliminated and the withdrawal will be short lived. A common problem in treating methadone overdoses is that, given the short action of naloxone versus the extremely longer-acting methadone , a dosage of naloxone given to a methadone-overdosed person will initially work to bring the person out of overdose, but once the naloxone wears off, if no further naloxone is administered, the person can go right back into overdose based upon time and dosage of the methadone ingested. As with other opioid medications, tolerance and dependence usually develop with repeated doses. There is some clinical evidence that tolerance to analgesia is less with methadone compared to other opioids; this may be due to its activity at the NMDA receptor. Tolerance to the different physiological effects of methadone varies; tolerance to analgesic properties may or may not develop quickly, but tolerance to euphoria usually develops rapidly, whereas tolerance to constipation, sedation, and respiratory depression develops slowly if ever. Methadone treatment may impair driving ability. In the study of a group of drug abusers, most of them poly-drug abusers, 17 were involved in crashes killing people, compared with a control group of other people randomly selected having no involvement in fatal crashes. The license will be issued for 12 months at a time and even then, only following a favourable assessment from their own doctor. In the United States, deaths linked to methadone more than quadrupled in the five-year period between and According to the U. National Center for Health Statistics, \\\\\\\\\\[43\\\\\\\\\\] as well as a series in the Charleston Gazette West Virginia , \\\\\\\\\\[44\\\\\\\\\\] medical examiners listed methadone as contributing to 3, deaths in That number was up from in Approximately 82 percent of those deaths were listed as accidental, and most deaths involved combinations of methadone with other drugs especially benzodiazepines. Although deaths from methadone are on the rise, methadone-associated deaths are not being caused primarily by methadone intended for methadone treatment programs, according to a panel of experts convened by the Substance Abuse and Mental Health Services Administration , which released a report titled 'Methadone-Associated Mortality, Report of a National Assessment'. The consensus report concludes that 'although the data remains incomplete, National Assessment meeting participants concurred that methadone tablets or diskettes distributed through channels other than opioid treatment programs most likely are the central factors in methadone-associated mortality. In , the U. The change deleted previous information about the usual adult dosage. The bioavailability and elimination half-life of methadone are subject to substantial interindividual variability. Its main route of administration is oral. Adverse effects include sedation, hypoventilation , constipation and miosis , in addition to tolerance, dependence and withdrawal difficulties. The withdrawal period can be much more prolonged than with other opioids, spanning anywhere from two weeks to several months. The metabolic half life of methadone differs from its duration of action. The metabolic half life is 8 to 59 hours approximately 24 hours for opioid-tolerant people, and 55 hours in opioid-naive people , as opposed to a half life of 1 to 5 hours for morphine. Methadone has been shown to reduce neuropathic pain in rat models, primarily through NMDA receptor antagonism. Glutamate is the primary excitatory neurotransmitter in the central nervous system. NMDA receptors have a very important role in modulating long-term excitation and memory formation. Acting as an NMDA antagonist may be one mechanism by which methadone decreases craving for opioids and tolerance, and has been proposed as a possible mechanism for its distinguished efficacy regarding the treatment of neuropathic pain. The dextrorotary form dextromethadone , which acts as an NMDA receptor antagonist and is devoid of opioid activity, has been shown to produce analgesia in experimental models of chronic pain. Methadone has a slow metabolism and very high fat solubility , making it longer lasting than morphine-based drugs. Methadone has a typical elimination half-life of 15 to 60 hours with a mean of around However, metabolism rates vary greatly between individuals, up to a factor of , \\\\\\\\\\[49\\\\\\\\\\] \\\\\\\\\\[50\\\\\\\\\\] ranging from as few as 4 hours to as many as hours, \\\\\\\\\\[51\\\\\\\\\\] or even hours. Many substances can also induce, inhibit or compete with these enzymes further affecting sometimes dangerously methadone half-life. A longer half-life frequently allows for administration only once a day in Opioid detoxification and maintenance programs. People who metabolize methadone rapidly, on the other hand, may require twice daily dosing to obtain sufficient symptom alleviation while avoiding excessive peaks and troughs in their blood concentrations and associated effects. The analgesic activity is shorter than the pharmacological half-life; dosing for pain control usually requires multiple doses per day normally dividing daily dosage for administration at 8 hour intervals. The most common route of administration at a methadone clinic is in a racemic oral solution, though in Germany, only the R enantiomer the L optical isomer has traditionally been used, as it is responsible for most of the desired opioid effects. Methadone is available in traditional pill, sublingual tablet, and two different formulations designed for the person to drink. Drinkable forms include ready-to-dispense liquid sold in the United States as Methadose , and 'Diskets' known on the street as 'wafers' or 'biscuits' which are tablets designed to disperse themselves rapidly in water for oral administration, used in a similar fashion to Alka-Seltzer. The liquid form is the most common as it allows for smaller dose changes. Methadone is almost as effective when administered orally as by injection. Oral medication is usually preferable because it offers safety, simplicity and represents a step away from injection-based drug abuse in those recovering from addiction. Methadone pills often contain talc that, when injected, produces a swarm of tiny solid particles in the blood, causing numerous minor blood clots. Information leaflets included in packs of UK methadone tablets state that the tablets are for oral use only and that use by any other route can cause serious harm. In addition to this warning, additives have now been included into the tablets formulation to make the use of them by the IV route more difficult. Methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine EDDP , are often measured in urine as part of a drug abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims, or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Methadone usage history is considered in interpreting the results as a chronic user can develop tolerance to doses that would incapacitate an opioid-naive individual. Chronic users often have high methadone and EDDP baseline values. The protonated form of methadone takes on an extended conformation, while the free base is more compact. Methadone was developed in in Germany by scientists working for I. In the s, pethidine meperidine went into production in Germany; however, production of methadone, then being developed under the designation Hoechst , was not carried forward because of side effects discovered in the early research. The records on the research work of the I. Farbenkonzern at the Farbwerke Hoechst were confiscated by the U. Department of State and then brought to the US. In the early s, methadone most times the racemic HCl salts mixture was also investigated for use as an antitussive. Isomethadone , noracymethadol , LAAM , and normethadone were first developed in Germany, United Kingdom, Belgium, Austria, Canada, and the United States in the thirty or so years after the discovery of pethidine, the first synthetic opioid used in medicine. These synthetic opioids have increased length and depth of satiating any opiate cravings and generate very strong analgesic effects due to their long metabolic half-life and strong receptor affinity at the mu opioid receptor sites. Therefore, they impart much of the satiating and anti-addictive effects of methadone by means of suppressing drug cravings. It was only in that the drug was given the generic name 'methadone' by the Council on Pharmacy and Chemistry of the American Medical Association. Since the patent rights of the I. Farbenkonzern and Farbwerke Hoechst were no longer protected each pharmaceutical company interested in the formula could buy the rights for the commercial production of methadone for just one dollar MOLL Methadone was introduced into the United States in by Eli Lilly and Company as an analgesic under the trade name Dolophine. Therefore, Dolophine literally means 'pain end'. Methadone maintenance clinics in the US may be covered by private insurances, Medicaid , or Medicare. People on methadone maintenance in the US either have to pay cash, or if covered by insurance must complete a pre-determined number of hours per month in therapeutic groups or counseling. Methadone maintenance treatment MMT cost analyses often compare the cost of clinic visits versus the overall societal costs of illicit opioid use. As of China had the largest methadone maintenance treatment program with over , people in over clinics in 27 provinces. Methadone substitution as a treatment of opioid addiction has been criticized in the social sciences for its role in social control of addicts. Several authors apply a Foucauldian analysis to the widespread prescription of the drug and use in institutions such as prisons, hospitals and rehabilitation centres. Thus methadone, which mimics the effects of opioids and renders the addict compliant, is labeled as a 'treatment' and so achieves the disciplinary objectives of managing the 'undesirables'. In most countries of the world, methadone is similarly restricted. The salts of methadone in use are the hydrobromide free base conversion ratio 0. In Russia , methadone treatment is illegal. Instead, doctors encourage immediate cessation of drug use, rather than the gradual process that methadone substitution therapy entails. People are often given sedatives and non-opioid analgesics to cope with withdrawal symptoms. From Wikipedia, the free encyclopedia. Not to be confused with Methoxydone or Morphodone. For the fly genus, see Metadon fly. IUPAC name. Interactive image. Elsevier Health Sciences. Acta Anaesthesiologica Scandinavica. Postgraduate Medical Journal. Archived PDF from the original on 2 May Archived from the original on 23 December Retrieved 22 December American Family Physician. Archived from the original on 5 September Pharmacy and Therapeutics. Age-adjusted drug-poisoning and opioid-analgesic poisoning death rates: United States, —' PDF. Archived PDF from the original on 23 November Morbidity and Mortality Weekly Report. Archived from the original on 3 August Annals of Internal Medicine. CRC Press. Encyclopedia of Drug Policy. World Health Organization model list of essential medicines: 21st list Geneva: World Health Organization. Archived PDF from the original on 2 June Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Archived from the original on 1 January Mattick, Richard P ed. Expert Opinion on Pharmacotherapy. Methadone maintenance treatment. World Health Organization. The Mount Sinai Journal of Medicine. Health Technology Assessment. Revista Brasileira de Anestesiologia. International Journal of Clinical Practice. Cochrane Database Syst Rev. Archived from the original on 8 September Archived from the original on 27 February Archived from the original on 3 September Archived from the original on 4 March Cardiology Research and Practice. Archived from the original on 8 March Retrieved 23 October Archived from the original on 4 September Dental Update. Retrieved 20 November National Institutes of Health. Archived from the original on 17 October September Addiction Treatment Forum. Substance Abuse Treatment, Prevention, and Policy. Institute for Metropolitan Affairs, Roosevelt University. Royal College of General Practitioners. Archived from the original on 11 April Charleston Gazette. Archived from the original on 13 February Opioids in Cancer Pain 2nd ed. October The Journal of Pharmacology and Experimental Therapeutics. Journal of Addictive Diseases. Heroin Addiction and Related Clinical Problems. Clinical Pharmacokinetics. Journal of the American Osteopathic Association. Archived from the original on 20 May J Anal Toxicol. Archived from the original PDF on 11 May Canadian Journal of Ophthalmology. Irish Journal of Medical Science. European Respiratory Journal. Disposition of Toxic Drugs and Chemicals in Man 8th ed. Nature New Biology. Brain Research Bulletin. Justus Liebigs Annalen der Chemie in German. Myths and facts'. Bull Anesth Hist 25 3 : —6. In Tober, G. In: Methadone Matters. Taylor and Francis Group. Archived from the original on 20 November Retrieved 9 July GoodRx, Inc. Archived from the original on 11 September Retrieved 30 August Archived from the original on 19 September Retrieved 2 November Drug Policy Alliance Lindesmith Library. Archived from the original on 11 May Archived from the original on 15 February Health and History. Archived from the original on 2 March Retrieved 28 February Retrieved 16 May The New York Times. Archived from the original on 7 December Analgesics N02A , N02B. Meloxicam Piroxicam. Meclofenamic acid Mefenamic acid. Cannabidiol Cannabis Nabilone Nabiximols Tetrahydrocannabinol dronabinol. Carbamazepine Lacosamide Local anesthetics e. Neuropathic pain and fibromyalgia pharmacotherapies. SNRIs e. Anticonvulsants e. Treatment of drug dependence N07B. Salvia divinorum. Ionotropic glutamate receptor modulators. Monoamine reuptake inhibitors. Others: Antihistamines e. Others: A Amoxapine Antihistamines e. Amiodarone Amphetamines e. Nicotinic acetylcholine receptor modulators. Opioid receptor modulators. Medicine portal. Hidden categories: Articles with inconsistent citation formats CS1 errors: missing periodical All articles with dead external links Articles with dead external links from July Articles with permanently dead external links Articles with dead external links from October Webarchive template wayback links All pages needing factual verification Wikipedia articles needing factual verification from December CS1 German-language sources de Use dmy dates from December Template:drugs. Namespaces Article Talk. Views Read Edit View history. In other projects Wikimedia Commons. By using this site, you agree to the Terms of Use and Privacy Policy. Rapid \\\\\\\\\\[4\\\\\\\\\\]. Urine, faeces \\\\\\\\\\[3\\\\\\\\\\]. Sources: See template.
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