Detail:

        Methadone is an opioid used to treat pain and as maintenance therapy or to help with tapering in people with opioid dependence.Detoxification using methadone can either be done relatively rapidly in less than a month or gradually over as long as six months. While a single dose has a rapid effect, maximum effect can take five days of use. The pain relieving effects last about six hours after a single dose, similar to that of morphine. After long term use, in people with normal liver function, effects last 8 to 36 hours. Methadone is usually taken by mouth and rarely by injection into a muscle or vein.

        Side effects are similar to those of other opioids. Commonly these include dizziness, sleepiness, vomiting, and sweating. Serious risks include opioid abuse and a decreased effort to breathe. Abnormal heart rhythms may also occur due to a prolonged QT interval. The number of deaths in the United States involving methadone poisoning declined from 4,418 in 2011 to 3,300 in 2015. Risks are greater with higher doses. Methadone is made by chemical synthesis and acts on opioid receptors.

        Methadone was developed in Germany around 1937 to 1939 by Gustav Ehrhart and Max Bockmühl. It was approved for use in the United States in 1947. Methadone is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Globally in 2013, about 41,400 kilograms were manufactured. It is regulated similarly to other narcotic drugs. It is not particularly expensive in the United States.

Methadone maintenance:

       Methadone is used for the treatment of opioid dependency. It may be used as a long-term maintenance therapy or in shorter periods for detoxification without withdrawal symptoms.

        A 2009 Cochrane review found methadone was effective in retaining people in treatment and in the reduction or cessation of heroin use as measured by self-report and urine/hair analysis but did not affect criminal activity or risk of death.

        The treatment of opioid-dependent persons with methadone will follow one of two routes. Methadone maintenance therapy (MMT) usually takes place as an outpatient. It prescribed once or twice daily, who wish to abstain from illicit drug use.

        The duration of methadone treatment ranges from a few months to several years, or even lifelong. Methadone reduction, called detoxification, are suitable for persons who wish to completely stop using drugs. The length of time a person remains in treatment depends on a number of factors. The starting dose depends on the type and quantity of drugs being used at onset of treatment. It also depends on how long the person was using and the method oral, inhaled, or injected.

        In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with opiate injection, such as hepatitis B and C, and/or HIV. The principal goals of methadone maintenance are to relieve opioid cravings, suppress the abstinence syndrome, and block the euphoric effects associated with opioids.

        Both methadone abuse and lawfully prescribed use will eventually lead to 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. It is also indicated for pregnant women addicted to opioids.

Pain:

        Methadone is used as an analgesic in chronic pain. Due to its activity at the NMDA receptor, it may be more effective against neuropathic pain; for the same reason, tolerance to the analgesic effects may be less than that of other opioids.

        People with long-term pain will sometimes have to perform so-called opioid rotation. Opioid rotation involves switching from one opioid to another, usually at intervals of between a few weeks, or more commonly, several months. Opioid rotation may allow for a lower equivalent dose, and hence fewer side effects may be encountered to achieve the desired effect. Then, over time, tolerance increases with the new opioid, requiring higher doses. This, in turn, increases the possibility of adverse reactions and toxicity. Then it is time to rotate again to another opioid. Such opioid rotation is standard practice for managing people with tolerance development. Usually when doing opioid rotation, one cannot go down to a completely naive dose, because there is cross-tolerance carried over to the new opioid. Compared to other opioids, methadone has a lower cross-tolerance when switching to it from other opioids. This means that methadone can start at a comparatively lower dose than other opiates, and the time for the next switch will be longer.

Opioid detoxification:

        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. In the US, outpatient treatment programs must be certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA) in order to prescribe methadone for opioid addiction.

Adverse effects:

        On 29 November 2006, the U.S. Food and Drug Administration issued a Public Health Advisory about methadone titled "Methadone Use for Pain Control May Result in Death and Life-Threatening Changes in Breathing and Heart Beat". The advisory said that "the FDA has received reports of death and life-threatening side effects in patients taking methadone. These deaths and life-threatening side effects have occurred in patients newly starting methadone for pain control and in patients who have switched to methadone after being treated for pain with other strong opioid pain relievers. Methadone can cause slow or shallow breathing and dangerous changes in heartbeat that may not be felt by the patient." The advisory urged that physicians use caution when prescribing methadone to people who are not used to the drug and that people take the drug exactly as directed.

Route of administration:

        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. The single-isomer form is becoming less common due to the higher production costs.

        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" 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. In fact, injection of methadone does not result in a "rush" as with some other strong opioids such as morphine or hydromorphone, because its extraordinarily high volume of distribution causes it to diffuse into other tissues in the body, particularly fatty tissue; the peak concentration in the blood is achieved at roughly the same time, whether the drug is injected or ingested.[citation needed] 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. U.S. federal regulations require the oral form in addiction treatment programs. Injecting methadone pills can cause collapsed veins, bruising, swelling, and possibly other harmful effects. Methadone pills often contain talc that, when injected, produces a swarm of tiny solid particles in the blood, causing numerous minor blood clots. These particles cannot be filtered out before injection, and will accumulate in the body over time, especially in the lungs and eyes, producing various complications such as pulmonary hypertension, an irreversible and progressive disease. The formulation sold under the brand name Methadose (flavored liquid suspension for oral dosing, commonly used for maintenance purposes) should not be injected either. While it has been done in extremely diluted concentrations, instances of cardiac arrest have been reported, as well as damaged veins from sugars (even sugar-free syrups may cause this damage due to the presence of similarly-damaging artificial sweeteners). U.S. federal regulations require the oral form in addiction treatment programs.

        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.

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