Also known as

Amidone, chocolate chip cookies, fizzies, maria, pastora, salvia, street methadone, wafer, dollies, dolls, mud, phyamps, red rock, tootsie roll, balloons, breaze, burdock, buzz bomb, cartridges, jungle juice, junk, meth, green, linctus, physeptone, juice, methadone hydrochloride, amps


Narcotic analgesic, CNS depressant


Methadone is a prescription only medicine that can be taken orally and is used mainly to treat opioid addiction. Is was initially developed as a painkiller but now it is much more widely used to treat people who have got stuck on heroin or other opioid drugs (such as prescription painkillers). Methadone is a powerful opioid drug, so it has similar effects to drugs like codeine, morphine, and heroin. It lasts much longer in the body than heroin, and therefore it is used to stabilise people currently using heroin (or other opioid drugs) and then help them get off opioid drugs completely.

Methadone should not be confused with mephedrone, they are completely different drugs. Anyone taking methadone when they are looking for mephedrone risks extreme danger [1].

Methadone is a prescription drug, and is part of a group of drugs known as opioids. Opioids are depressant drugs, which means they slow down the messages travelling between the brain and the rest of the body [2].

Methadone is taken as a replacement for heroin and other opioids as part of treatment for dependence on these drugs. Replacing a drug of dependence with a prescribed drug in this way is known as pharmacotherapy. As well as improving wellbeing by preventing physical withdrawal, pharmacotherapy helps to stabilise the lives of people who are dependent on heroin and other opioids, and to reduce the harms related to drug use [3].

Methadone is also used to relieve pain following heart attacks, trauma and surgery [4].

Methadone is the leading drug for substitute prescribing for heroin and other opiates and can be used to maintain or detox [5].

Methadone is a synthetic opiate used as a strong painkiller and as a substitute for heroin in the treatment of heroin dependence.

Like heroin, it is a sedative drug that can produce feelings of relaxation and can reduce physical and psychological pain, but methadone doesn't deliver the same degree of pleasurable effects as heroin.

When a heroin user first begins treatment they are given a level of methadone (or other substitute drug) that is enough to minimise the withdrawal symptoms from the heroin [6].

The idea is that methadone will -

  • suppress symptoms of opioid withdrawal,
  • decrease cravings for opioids and hence illicit opioid use,
  • change risky behaviour such as injecting and sharing needles,
  • stop the need to commit crimes to fund the heroin habit,
  • help patients stay in treatment [6].

Methadone is controlled as a Class A drug under the Misuse of Drugs Act. Unauthorised possession can lead to up to seven years in jail. Supply can lead to life imprisonment and/or an unlimited fine.

Methadone, as with all the stronger opioids, can itself become addictive.

It is very important that methadone should be kept out of the reach of children. There have been fatalities from children drinking the liquid which they may find particularly attractive due to its vivid green colour [6].

Methadone is the mainstay of drug treatment in the UK. Recently some practitioners have returned to the 80's mantra that maintaining anyone on opiates/opioids rather than trying to detoxify them is merely trading one addiction for another. Consequently, these people tend to focus most of their frustrations on methadone.

There are plenty of research papers from all across the world supporting methadone, and it is undeniably effective for a very large number of people who are able to rebuild their lives while on long-term maintenance 'scripts'.

It can also be used as a short term community based reducing dose detox therapy (in which context it is rather less successful). Methadone is less sedating than heroin and offers less of a 'high'. It has a very long half-life (usually over 24 hours) and consequently can be used once daily (although some users will split their daily dose into two).

Anecdotally, there is some evidence that heroin users disappointed with the effect of methadone may gravitate towards 'potentiators' (other substances that increase the 'buzz', such as alcohol, gabapentin, or a benzodiazepine like temazepam). This dynamic is hardly unique to methadone, but again, its prominence ensures that these issues are not ignored.

There are a number of health considerations that often occur when methadone is discussed - tooth decay (a sugar free version is available), libido (absolutely - most opioids and opiates reduce the sex drive in the medium/long term) and somatic (bone) pain or calcium deficiency (limited evidence from a research but strong anecdotal evidence from users) [7].

A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough centre and may be given to control intractable cough associated with terminal lung cancer. Methadone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence [8].

Medical usage

Methadone mixture is used in the management of opiate - mainly heroin - dependence. Methadone linctus is used as a cough suppressant and occasionally as a pain killer [9]. Its mostly used as a substitute medication for people addicted to opioids such as heroin. It is occasionally prescribed as a pain-killer [1].

  • Maintenance (long-term programmes) - may last for months or years, and aim to reduce the harms associated with drug use and improve quality of life.
  • Withdrawal (short-term detoxification programmes) - run for approximately 5 - 14 days and aim to ease the discomfort of stopping the use of heroin [10].

For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain [8].

What does it look like?

It is available on the street, and usually comes in the form of a sticky green liquid; the liquid mixture is made in other colours however, and also in tablet form [7]. It is usually a green liquid although there is a blue liquid that is much more concentrated. Methadone also comes as tablets but this preparation is rarely used [1]. Liquid mixture, most frequently green, but also blue, orange, yellow or clear; tablets; ampoules for injection [11].


Methadone hydrochloride is a white crystalline powder or colourless crystals. Available primarily in tablet or liquid form [12]. On prescription from a GP or doctor in a drug dependency clinic, or diverted from either [9]. Prescribed drug, also sold illicitly [11].

Street price

When sold on the streets, ampoules typically sell for £20 or more, and are not relatively scarce as a street drug; tablets are increasingly scarce and could cost a few pounds each. Methadone Mixture is hugely variable in price at a street level - from £10 for a small volume up to £30 or £40 for a larger dose [11]. The current price for a methadone 10mg tablet is £3 [13].

Why take it?

Sought after effects

  • long-lasting and smooth action,
  • prevents heroin withdrawal symptoms [7].

Undesired effects

  • none of the pleasurable effects attributed to recreational opiate use [7].
  • light-headedness,
  • dizziness,
  • sweating,
  • dry mouth,
  • nausea,
  • vomiting,
  • drowsiness [9].




  • threshold 1 - 3 mg,
  • light 3 - 5 mg,
  • common 5 - 15 mg,
  • strong 15 - 30 mg,
  • heavy 30 mg + [14].

What are the different forms of methadone?

Methadone usually comes in liquid form that can be swallowed. It is usually a green liquid although there is a blue liquid that is much more concentrated. Methadone also comes as tablets but this preparation is rarely used.

Methadone is used illicitly, there is a street value for methadone that has been diverted from medicinal use. Most people use it illicitly in the same way as prescribed. As methadone is a powerful opioid drug it is very dangerous for people who are not tolerant to opioid drugs [1].

How does methadone work in the body and brain?

Methadone is an opioid drug. It mimics the body's natural pain-killing chemicals, endorphins. Therefore it can relieve pain, cause drowsiness, can cause mild euphoria, slow breathing, slow the bowels causing constipation, and cause other side-effects of opioids [1].

How long do its effects last?

Onset of effects

  • oral - 20 - 90 minutes [14], 45 - 90 minutes [15].
  • all ROA's - 45 - 120 minutes [16], 45 - 90 minutes [16].


  • oral - 6 - 8 hours [14].

Duration of effects

  • oral - 6 - 12 hours [15].


  • oral - 1 - 24 hours [14].
  • all ROA's - 1 - 48 hours [16].


Methadone is a full agonist at the mu (µ) opioid receptor (see Morphine for more details on opioid receptors) in the central and peripheral nervous systems. This produces the typical opiate effects of analgesia, sedation, etc. and slight euphoria, although at higher doses it blocks the euphoric effects that are seen by other opiates such as morphine and heroin. It also seems to have an affinity (ability to bind) to NMDA receptors which are receptors that release the neurotransmitter glutamate. This is thought to make methadone particularly effective in the treatment of neuropathic pain compared with other opioids [7].

Opioids exert their effects by binding to and activating the μ-opioid receptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. The way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement. The bioavailability of orally administered methadone can vary from 40% to around 99%. Methadone is metabolised by the cytochrome P450 system.

Unlike most opioids, methadone is a weak serotonin reuptake inhibitor as well as a week NMDA antagonist. Similarly to dextropropoxyphene, methadone is a nicotinic acetylcholine receptor antagonist [17], [14].


Methadone is a long acting m opioid receptor agonist with potent central analgesic, sedative, and antitussive actions. Methadone inhibits ascending pain pathways, alters perception of and response to pain (dissociative effect), and produces generalised CNS depression. Respiratory depression also occurs due to complete blockade of respiratory centers to pCO 2. (S)-Methadone lacks significant respiratory depressive action and addiction liability [12].

Methadone is a synthetic opioid analgesic with multiple actions quantitatively similar to those of morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, Methadone is more active and more toxic than morphine. Methadone is indicated for relief of severe pain, for detoxification treatment of narcotic addiction, and for temporary maintenance treatment of narcotic addiction. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. The Methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe [8].


When administered orally, methadone is rapidly absorbed from the gastrointestinal tract and can be detected in the blood within 30 minutes. Oral bioavailability varies from 41% - 99% and plasma protein binding is 60% - 90%. After repeated administration there is gradual accumulation in tissues. As for most lipid soluble drugs, a large between and within subject variability is observed. The half-life of (R,S)-methadone is 15 - 60 hours, and 10 - 40 hours for (R)-methadone. Methadone undergoes extensive biotransformation in the liver primarily to two inactive metabolites, 2-ethylidene-1.5-dimethyl-3.3diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP), through N-demethylation and cyclization. These are eliminated by the kidney and excreted through the bile. In total, nine metabolites have been identified including two minor active metabolites, methadol and normethadol [12].

Methadone is quickly absorbed from the stomach and intestines, stored in the liver, and released into the bloodstream over time. Plasma levels peak at around two to four hours after dosing [18].

Route of administration

Oral ingestion, intravenous, intramuscular or subcutaneous injection [12].


Well absorbed following oral administration [8].


  • oral 75% - 97% (Mean 86%),
  • rectal 70% - 81% (Mean 76%) [16].

The bioavailability of methadone ranges between 36% to 100% [8].


Hepatic. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine [8].


  • between 15 - 60 hours [12], 12 - 18 hours on the first dose, 13 - 47 on concurrent [16], 24 - 36 hours [8].


The elimination of methadone is mediated by extensive biotransformation, followed by renal and faecal excretion. Unmetabolised methadone and its metabolites are excreted in urine to a variable degree [8].

Lethal dosage

LD50 - 30 mg/kg [19], 3.5250 mol/kg in rats [8].


  • full tolerance is reached develops with prolonged and repeated use,
  • decreases to half after 3 - 7 days,
  • returns to baseline after 1 - 2 weeks,
  • cross-tolerance with all other opioids [14].

Tolerance to methadone can also occur with frequent administration, though studies have shown that a user's tolerance may not increase if prescribed correctly [20].

Mechanism of action

Methadone is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone's efficacy is unknown. Other NMDA receptor antagonists have been shown to produce neurotoxic effects in animals [8].

Fillers and additives

The inside of your stomach is a churning, acidic place. Anything that hits this caustic environment is broken down almost immediately. In order to help methadone reach the stomach, rather than being broken down in the mouth or in the throat, manufacturers create a bubble around the active ingredient in these oral medications [21]. Those additives can include -

  • glycerin,
  • food colouring,
  • flavouring,
  • sorbitol [21].

Some of these ingredients simply won't break down inside the veins, and no matter how much you might try to filter out all of the particulates, some tiny bits might remain and they might work like little missiles, zooming to your heart or to your lungs and causing very serious damage. Injecting this material can also damage your veins, causing them to block up and bleed [21].

Mode of use

  • swallowed - both the liquid and tablet forms are made for swallowing (ingesting),
  • injected - ampoules for injection are produced but are prescribed to relatively few heroin users [7].

Methadone is dispensed primarily in oral forms, including tablets, powder, and liquid for the treatment of narcotics addiction. Single doses, which should not exceed 80 - 100 milligrams daily, can last anywhere from 24 - 36 hours depending on user characteristics (e.g. age, weight, level of addiction, and tolerance); the long-acting nature of the drug is a distinct advantage since it requires less frequent administration, limiting potential harmful effects (0472). Tablet forms of the drug, sometimes called diskettes, contain approximately 40 milligrams of methadone and are often dissolved in water and ingested orally. There is also a white crystalline powder form available that is dissolved in water and swallowed. Illicit methadone is sometimes administered through injection (injection is not a valid route of administration in treatment) directly into the bloodstream. This form subjects users to increased risks of a variety of diseases, including HIV/AIDS [22].

Methadone mixture and methadone linctus are taken orally, physeptone ampoules are injected. The tablets are taken orally but are sometimes injected [9].

Methadone mixture is designed to be taken orally; it contains additives which cause irritation and discomfort when injected. This irritation combined with the large volumes and associated vein damage make methadone an unpopular choice for injectors.

Tablets are also designed to be taken orally. However some users grind up tablets and inject them.

Injectable ampoules are intended for intramuscular use; concentrated 50mg/ml were not originally intended for intravenous use, and can cause irritation and significant vein damage when injected in to a vein. Some users will dilute the ampoules to reduce the discomfort of injecting this highly acidic compound [11].

What are the effects of methadone?

As an opiod, it mimics the body's natural pain-killing chemicals, endorphins. Therefore it can relieve pain, cause drowsiness, can cause mild euphoria, slow breathing, slow the bowels causing constipation, and other side-effects of opioids. As it takes longer to build up in the body and takes longer to come out of the body it causes much less euphoria than heroin. However, most people report being drowsy, mentally slowed, and often a bit sweaty taking methadone every day [1].

Short-term effects

Physical effects

  • restlessness,
  • vomiting,
  • nausea,
  • slowed breathing,
  • itchy skin,
  • pupil contraction,
  • severe sweating,
  • constipation,
  • sexual dysfunction,
  • death [20].

Long-term effects

Physical effects

  • lung and respiration problems [20].

Physical effects

  • physical euphoria,
  • pupil constriction,
  • appetite suppression,
  • cough suppression,
  • orgasm suppression,
  • pain relief,
  • respiratory depression,
  • sedation,
  • constipation,
  • difficulty urinating,
  • itchiness,
  • nausea [14].

Cognitive effects

  • cognitive euphoria,
  • compulsive redosing,
  • dream potentiation,
  • anxiety suppression,
  • decreased libido [14].

Minor effects

Incidence not known

  • absent, missed, or irregular menstrual periods,
  • anxiety,
  • blurred or loss of vision,
  • confusion about identity, place, and time,
  • constipation,
  • decreased interest in sexual intercourse,
  • disturbed colour perception,
  • double vision,
  • false or unusual sense of well-being,
  • halos around lights,
  • erectile dysfunction,
  • irritability,
  • lack or loss of strength,
  • loss of libido,
  • night blindness,
  • overbright appearance of lights,
  • redness, swelling, or soreness of the tongue,
  • restlessness,
  • stopping of menstrual bleeding,
  • tunnel vision,
  • weight changes,
  • welts [23].

Major effects

Incidence not known

  • black, tarry stools,
  • bleeding gums,
  • blood in the urine or stools,
  • blurred vision,
  • change in the ability to see colours, especially blue or yellow,
  • changes in skin colour,
  • chest discomfort or pain,
  • confusion,
  • convulsions,
  • cough,
  • coughing that sometimes produces a pink frothy sputum,
  • decreased urine output,
  • difficult or troubled breathing,
  • difficult, fast, noisy breathing, sometimes with wheezing,
  • difficulty with swallowing,
  • dilated neck veins,
  • dizziness,
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position,
  • dry mouth,
  • extreme fatigue,
  • fainting,
  • fast, slow, or irregular heartbeat,
  • headache,
  • hives, itching, or skin rash,
  • increased sweating,
  • increased thirst,
  • irregular heartbeat,
  • irregular, fast or slow, or shallow breathing,
  • loss of appetite,
  • muscle pain or cramps,
  • nausea or vomiting,
  • numbness or tingling in the hands, feet, or lips,
  • pain,
  • cyanosis,
  • pinpoint red spots on the skin,
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue,
  • seizures,
  • sweating,
  • swelling of the face, fingers, feet, or lower legs,
  • tenderness,
  • trouble sleeping,
  • trouble urinating,
  • unusual bleeding or bruising,
  • unusual tiredness or weakness,
  • weight gain [23].


  • euphoria,
  • pain relief,
  • elevated mood,
  • overall feeling of contentedness [15].



  • nausea,
  • constipation,
  • CNS depression,
  • drowsiness,
  • hot/cold flashes,
  • dizziness,
  • vomiting,
  • urinary retention [15].


The most common side-effects of methadone are -

  • sweating (drink at least 2 litres of water each day to prevent dehydration),
  • difficulty passing urine
  • loss of appetite,
  • nausea and vomiting,
  • abdominal cramps,
  • constipation,
  • aching muscles and joints,
  • tooth decay,
  • irregular periods,
  • low sex drive,
  • rashes and itching,
  • sedation [2], [7].
  • light-headedness,
  • dizziness,
  • dry mouth [9].


  • slowed breathing,
  • sleepiness,
  • muscle weakness,
  • cold, clammy skin,
  • narrowed or widened pupils,
  • slowed heartbeat,
  • coma,
  • death [24],
  • shallow breathing,
  • low body temperature,
  • low blood pressure,
  • poor circulation,
  • dizziness,
  • cyanosis,
  • mental numbness,
  • occasional seizures [25].

Dose-related effects

Some people on methadone programs will experience unwanted symptoms during their treatment due to their dosage not being right for them. This occurs particularly at the beginning of treatment [26].

If the dose is too low, the following symptoms may be experienced -

  • runny nose and sneezing,
  • yawning, feeling weak and difficulty sleeping,
  • high temperature but feeling cold and sweating with goose-bumps,
  • tears, irritability and aggression,
  • loss of appetite, nausea and vomiting,
  • abdominal cramps and diarrhoea,
  • tremors, muscle spasms and jerking,
  • back and joint aches,
  • cravings for the drug they were dependant on [2], [25].


Medications that are meant to be swallowed often contain time-release properties, meaning that a tiny amount of the drug becomes active at a time. This allows people to take the drug and feel the effects of the drug over a long period of time. If you inject time-release methadone, you'll get the entire impact of the drug all at once. Even a dose you might take orally with no issues could cause an overdose if you inject it, simply because you'll have the full impact hitting your body at the exact same time. Death can quickly follow a methadone overdose [21].

If the dose is too high, the following symptoms may be experienced. If any of the following effects are experienced an ambulance should be called, ambulance officers don't need to involve the police.

  • pinpoint pupils,
  • slow pulse,
  • shallow breathing,
  • low body temperature,
  • low blood pressure,
  • poor circulation,
  • dizziness,
  • cold clammy skin and bluish tinge,
  • mental numbness,
  • occasional seizures [4].
  • slow shallow breathing,
  • cyanosis,
  • stomach spasms,
  • clammy skin,
  • convulsions,
  • weak pulse,
  • coma,
  • death [27].


If someone takes an overdose of an opioid drug they can die quickly. This is usually by respiratory depression. Anyone not used to opioid drugs would be much more at risk of this. Methadone is often reported as a contributory cause of death in opioid drug-related overdoses. It is particularly dangerous if mixed with other drugs such as heroin, alcohol, and benzodiazepines.

The risks of death by overdose increase when many substances are taken together for example alcohol and benzodiazepines which also have effects on breathing. Methadone decreases control and impairs judgment, making the risk of accidents much higher. This means activities like driving under the influence of methadone are potentially very dangerous. If you are prescribed methadone by your doctor you must inform the DVLA and they have to make a decision whether you are still safe to drive [1].


  • tolerance,
  • overdose which can be fatal [9].


  • dependence,
  • withdrawal symptoms [9].

Are there health conditions that make methadone more dangerous?

The risks of depressed breathing caused by methadone may be increased in people with conditions such as muscle weakness (e.g. myasthenia gravis), sleep apnoea, or lung disease/breathing disorders [1].


Addiction to methadone can be defined as the condition of being habitually or compulsively occupied with, or involved in the use and abuse of methadone [28]. There are two main components of the definition of methadone addiction -

  1. The first symptom of addction is that individuals who are addicted to methadone use this medication regularly and habitually despite the harms it causes.
  2. The second main symptom of addiction is the occurrence of compulsive methadone use which is generally beyond the individual's conscious control [28].

How addictive is methadone?

One-off or occasional use of methadone is very unlikely to result in the development of dependence. However, taking methadone regularly over a sustained period can cause serious physical and psychological addiction. People who become dependent on methadone may become tolerant to the drug's effects and experience withdrawal symptoms without it. Users may crave the drug and feel unable to cope without it. The longer the drug is taken, the higher and more regular the dose and the stronger the methadone, the higher the risk of dependence [1].

Psychological signs

  • loss of interest in activities once cared about, and a distancing from friends and family members who shared those activities,
  • mood swings,
  • irrational anger,
  • secretive behaviour, including absences from work or school that are unexplained, and excuses that seem thin or unrealistic,
  • stealing/borrowing money
  • neglecting responsibilities at home, work or school
  • losing interest in personal hygiene/appearance [29].

Physical signs

  • sweating,
  • flushing,
  • drowsiness,
  • nausea and vomiting,
  • swelling of the extremities,
  • sleeplessness,
  • lack of interest in sex,
  • rash or hives,
  • seizures [29].
  • constipation,
  • constricted pupils,
  • increase in pain,
  • slowed respiration [28].

Can you get addicted

Taking methadone regularly over a sustained period can cause serious physical and psychological addiction [1].


People who become dependent on methadone may become tolerant to the drug's effects and experience withdrawal symptoms without it. Users may crave the drug and feel unable to cope without it [1].


One-off or occasional use of methadone is very unlikely to result in the development of dependence. The longer the drug is taken, the higher and more regular the dose and the stronger the methadone, the higher the risk of dependence [1].

Dangerous interactions

Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption [14].

  • Depressants (1,4-Butanediol, 2m2b, alcohol, barbiturates, benzodiazepines, GBL / GHB, methaqualone) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Stimulants - It is dangerous to combine methadone, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of methadone, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of methadone will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only taking a certain amount of methadone.
  • Psychedelics - Methadone is well known to lower seizure threshold and psychedelics also cause occasional seizures [14].
  • 5-Hydroxytryptophan,
  • MAOI,
  • Serotonin,
  • Serotonin-norepinephrine reuptake inhibitors [14].


  • Ketamine - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
  • MXE - This combination can potentiate the effects of the opioid.
  • DXM - CNS depression, difficult breathing, heart issues, hepatoxic, just very unsafe combination all around. Additionally if one takes dxm, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
  • Cocaine - Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
  • Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely
  • GBL / GHB - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position
  • Tramadol - Concomitant use of tramadol increases the seizure risk in patients taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present
  • Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Blackouts/memory loss likely [16].


  • PCP - PCP can reduce opioid tolerance, increasing the risk of overdose.
  • Nitrous oxide - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.
  • Amphetamines - Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
  • MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhoea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases [16].


Methadone is dangerous if mixed with alcohol, benzodiazepines or heroin. Taking methadone with depressant drugs increases the risk of depressing breathing. Additionally, the effects of methadone may be masked if taken with a stimulant, which can lead to an overdose if a lot of the drug is taken and then the stimulant wears off. Certain medications (e.g. some antidepressants) may also interact with methadone to increase sedative effects [1].

Dangers of mixing methadone and alcohol

Methadone and alcohol are two substances that should not be used together. The effects of mixing methadone and alcohol can be profound. Methadone increases the effects of alcohol in some people, so taking the two together might make you become drunk more quickly and may inhibit your motor skills. Further, because alcohol is a nervous system depressant, taking it with methadone can lead to dangerous complications, including respiratory problems, low blood pressure, a weak heart rate, and coma. Taking both methadone and alcohol at the same time can also increase the risk of an overdose [30].

Methadone and alcohol overdose

Like any other drug, especially any narcotic, methadone can be purposefully or unintentionally abused and present serious health risks when taken with other drugs. Overdose can happen when more than the prescribed dose is taken, when methadone is injected or when methadone is taken with other drugs, such as alcohol or minor tranquillizers. When an individual takes methadone and alcohol together, he or she can experience a wide range of physical and emotional problems [30].

Overdose of methadone and alcohol can cause the following side-effects -

  • anxiety,
  • body aches,
  • dizziness or faintness,
  • fainting,
  • hallucinations,
  • nausea,
  • palpitations,
  • respiratory and heart problems,
  • shortness of breath,
  • unconsciousness,
  • vomiting [30].

Alcohol can also speed up the methadone withdrawal process, which can cause an individual severe physical pain and mental stress that may lead them back to using more dangerous opiates. At worst, mixing methadone and alcohol can lead to death [30].

Methadone and alcohol deaths

Most cases of overdose and death related to methadone intake involved mixing methadone with another depressant drug, especially alcohol, against doctor's orders. Alcohol and methadone are CNS depressants and taking them simultaneously increases the cumulative depressive effects on the brain's respiratory centres. This could lead to respiratory depression and coma followed by death [30].

Is it safe to drink on methadone?

Alcohol and methadone simply do not mix. In fact, alcohol taken with any substance of abuse is a leading cause of drug-related deaths. Even a modest amount of alcohol combined with methadone can slow methadone metabolism and make the drinker dangerously intoxicated. The person may pass out and choke to death on his/her own vomit [30].

What are the harms of opioid addiction and withdrawal?

A period of sustained dependence on any drug can be debilitating and prevent people from working and leading an active life. It may also cause mental and physical harm and opioid withdrawal can be very unpleasant.

Acute withdrawal effects from methadone can be intense, although for many they will be milder than those from heroin. Acute withdrawal effects include shivering, yawning, feeling cold and clammy, goose-bumps on the skin, diarrhoea and vomiting, flu-like symptoms, agitation, anxiety, insomnia and sensitivity to sound/light. Opioid withdrawal symptoms are unpleasant but do not endanger life.

Potential effects of long term methadone use include constipation, tiredness, sedation. People often have problems with their teeth as methadone reduces your natural saliva which protects the teeth against dental caries [1].

What are the long term effects of methadone on health and wellbeing?

Long-term risks of methadone are low if it is used as prescribed [1]


Methadone withdrawal develops more slowly and is less intense than withdrawal from heroin. Withdrawal symptoms are similar to those listed under 'Dose-related effects' under 'too low' dose. Most of these effects will begin within 1 - 3 days after the last dose and will peak around the 6th day, but can last longer [2], [7].

Withdrawal symptoms can begin within 12 hours of missing a dose and can last for several days. They include -

  • anxiety,
  • muscle pain,
  • sweating,
  • dilated pupils,
  • nausea,
  • agitation,
  • paranoia [29].
  • cravings,
  • depression,
  • diarrhoea,
  • flu like symptoms (fever, sweating and chills),
  • hallucinations,
  • increased heart rate,
  • insomnia,
  • irritability,
  • loss of energy,
  • muscle aches and pains,
  • nausea and/or vomiting,
  • paranoia,
  • stomach cramps,
  • suicidal thoughts [28].
  • yawning,
  • coughing,
  • sneezing,
  • runny nose,
  • lachrymation,
  • raised blood pressure,
  • increased pulse,
  • dilated pupils,
  • cool, clammy skin,
  • diarrhoea,
  • nausea,
  • fine muscle tremor,
  • restlessness,
  • irritability,
  • sleep disorders,
  • depression,
  • drug craving,
  • abdominal cramps [31].

Harm reduction advice

Methadone is one of the most researched medicines available, and if used correctly, is safe. Specific care should be taken to keep out of the reach of children, they seem to find the green syrup visually attractive. This is another area where methadone receives negative attention as thoughtless storage has caused infant fatalities leading to a call for stricter controls.

Methadone is available as a mixture, tablets, ampoules and suppositories. The usual strength is Mist. Methadone 1:1 (Drug Tariff Formula). The tablets are 5 mg, white

Although they are relatively rare, there is some concern over the acidity of methadone ampoules. Certain clients seem to suffer tissue damage at injection sites. Injecting oral methadone in any of its formulations should not be attempted.

Dosing levels are, of course, critical to the success of any treatment intervention. The evidence shows that doses between 60 - 120mg of methadone daily are most effective at reducing heroin use and improving health and social functioning. Many services are not yet up to speed on this, but the situation is slowly improving in most areas. Release's survey of 2002 found that of 1689 Heroin users questioned, 728 were on methadone scripts and on top of these another 116 (16%) of people regularly increased their intake by buying extra 'grey' market supplies, this strongly suggests many are on inadequate doses [7].

Getting the dose right

The client is given a starting dose and this is increased until no withdrawal symptoms can be observed. This may take three days returning to the unit, or in reviews, disputes or unusually high dose cases a period as an inpatient. Before commencing, a positive urine (for opiates) will be required and a drug history taken. If you are already on a 'script', and moving area, you should be able to keep your dose, but will need to be assessed.

Methadone 'failures' are, in reality, often less a fault of the drug itself than either the way it is delivered (inappropriate dose, inconvenient collection regimes) or an unrealistic expectation on the part of the prescriber/clinic or client. Being a long acting agonist it accumulates in the body and offers an alternative to the sedation/withdrawal cycle evident with street heroin or morphine. This is why stability is often mentioned in connection with methadone maintenance therapy.

The advantages are clear; the drug is legal and its strength/purity guaranteed. Dosing is once daily and oral formulations are clearly less risky than injecting. If dosed properly it has a blockade effect on other opiates/opioids.

However, in comparison with heroin, the drug is not euphoric. Much has been written on it's overdose potential, particularly in combination with alcohol and anxiolytics. Withdrawal unless handled extremely competently can be protracted and difficult. Methadone, like other opioids reduces the sex drive (one potential reason for their popularity with people with non-tactile and poor attachments in childhood) [7].

  • Mixing - Use of methadone with heroin or other opiates increases the risk of overdose. Patients receiving methadone should be advised of this risk and discouraged from using other opiates alongside methadone.
    • Where patients do use heroin or other opiates on top, it should be stressed that the person would need to use a lot less heroin than normal - or would be risking a fatal overdose.
    • Patients should also be advised that mixing other depressant drugs - especially alcohol or benzos - increases risk of overdose.
  • Dental care - Patients worried about dental health while using methadone could look at using a straw to take their methadone, chewing gum afterwards and rinsing mouth with milk or water. Discourage tooth brushing straight after use as the acid may have softened dental enamel. Consider use of sugar-free preparations. See a dentist regularly.
  • General health - maintain healthy diet and exercise to reduce weight gain exacerbated by methadone, and to improve bowel health and movement; increase fluid intake if experiencing substantial perspiration.
  • Children - don't allow children to get access to methadone; store it safely out of reach [11].

How much are you taking? How often?

If taken according to prescription then methadone is very safe [1].

Are you taking it with anything else? Mixing drugs is risky

Mixing with benzodiazepines and alcohol is potentially very dangerous. Also if other opioid drugs are used, although initially methadone would usually block the effects, eventually you can over-whelm the methadone and accidentally overdose [1].

Drug testing

Estimating how long methadone is detectable in the body depends on several factors, including which kind drug test is being used. Methadone - also known as Westadone, Dolophine, Methadose - can be detected for a shorter time with some tests, but can be 'visible' for up to three months in other tests.

The timetable for detecting methadone in the system is also dependent upon each individual's metabolism, body mass, age, hydration level, physical activity, health conditions and other factors, making it almost impossible to determine an exact time methadone will show up on a drug test.

How long methadone has been used, the frequency of use and the dosage can also be factors in how long it might be detectable in drug testing [24].

The following is an estimated range of times, or detection windows, during which methadone can be detected by various testing methods -

How long does methadone stay in urine?

Methadone can be detected in a urine test for up to 6 - 12 days [24].

How long does methadone remain in the blood?

Blood tests for Methadone can detect the drugs for up to 24 hours [24].

How long can methadone be detected in saliva?

A saliva test can detect Methadone for 1 - 10 days [24].

How long does methadone remain in hair?

Methadone, like many other drugs, can be detected with a hair follicle drug test for up to 90 days [24].


Class A drug (unless it has been prescribed to you). Penalties for possession are up to seven years in prison and/or an unlimited fine. Supply holds penalties of up to life in prison and/or an unlimited fine. Remember 'looking after' someone else's methadone is still an offence.

Your driving licence is invalid on a methadone treatment programme unless agreed by the DVLA following receipt of supportive medical advice [32].


Cracker - device used for opening methadone cartridges [20]. Brown medicine bottles for mixture and linctus; syringes, ampoules, tourniquet etc if injected [9].

Addiction treatment options

Advantages of methadone maintenance over heroin use

  • using methadone on its own is unlikely to result in an overdose,
  • methadone maintenance keeps the person stable while they make positive changes in their life,
  • health problems are reduced or avoided, especially those related to injecting, such as HIV, hepatitis b and hepatitis c viruses, skin infections and vein problems,
  • doses are required only once a day, sometimes even less often, because methadone's effects are long lasting,
  • methadone is much cheaper than heroin [33], [25].


When a heroin user first begins treatment they are given a level of methadone (or other substitute drug) that is enough to minimise the withdrawal symptoms from the heroin [34].

The idea is that methadone will -

  • suppress symptoms of opioid withdrawal,
  • decrease cravings for opioids and hence illicit opioid use,
  • change risky behaviour such as injecting and sharing needles,
  • stop the need to commit crimes to fund the heroin habit,
  • help patients stay in treatment [34].

Getting off methadone can be difficult, but rewarding. In fact, many users consider withdrawing from methadone more difficult and painful than withdrawing from heroin, so detox can be a significant challenge [35]. Detoxification requires a tapering off of the drug, with typical withdrawal symptoms following within 24 hours, including -

  • depression,
  • anxiety,
  • excessive sweating,
  • irritated eyes,
  • lightheadedness,
  • nausea,
  • vomiting,
  • diarrhoea,
  • strong drug cravings,
  • uncontrollable shaking [35].

Addiction treatment

Methadone abuse treatment usually consists of two different approaches. The first is gradually cutting down the dose of methadone. This approach is often the least effective, as the person is left to deal with the physical and psychological withdrawal symptoms alone. The second is to go through an official detoxification programme, usually held at a hospital or rehab centre. This can be attended as either an outpatient or an inpatient. People with severe addictions may be advised to stay under hospital supervision, so they can benefit from complete medical supervision. People who want to stop taking methadone need constant support on their road to recovery. A drug rehabilitation program will usually last for around 90 days. The trained staff will work at breaking down a person's psychological dependence on methadone, as well as offering treatment to cope with the physical symptoms. The programme involves teaching people new coping strategies, so they are better equipped to handle stressful situations. They will also be encouraged to face their methadone triggers. This will help them learn what to avoid and where [36].


Methadone overdose can also occur if a person takes methadone with certain painkillers. These painkillers include oxycontin, hydrocodone (Vicodin), or morphine [37].

Before calling the emergency

Have this information ready -

  • the person's age, weight, and condition,
  • name of the medicine (strength, if known),
  • time it was swallowed,
  • amount swallowed [37].

What to expect at the hospital

Take the container with you to the hospital, if possible.

The staff will measure and monitor your vital signs, including temperature, pulse, breathing rate, and blood pressure. Symptoms will be treated as appropriate [37]. You may receive -

  • activated charcoal (to induce vomiting, to remove the methadone),
  • blood and urine tests,
  • breathing support, including tube through the mouth and breathing machine (ventilator),
  • chest x-ray,
  • ECG,
  • fluids through a vein (by IV),
  • laxatives,
  • medicine to reverse the effects of the methadone (an antidote) and to treat other symptoms,
  • tube from the mouth into the stomach to empty the stomach (gastric lavage) [37].


According to the Drug Enforcement Administration -

  • In 2012, almost 2.5 million people over the age of 12 reported abusing methadone in their lifetime; marking an increase from 2.1 million in 2011.
  • In 2011, more than 65,000 emergency room visits were related to methadone use.
  • From 1999 to 2005, methadone overdose deaths increased by about 460% [38].


Methadone was developed in 1937 in Germany by scientists working for the Nazi conglomerate I G Farbenindustie. The reason for its swift abandonment as an alternative to morphine was due to the adverse effects it had in early trials. The doses used were however colossal by modern standards.

After the war, all German patents, trade names and research records were requisitioned and expropriated by the Allies, as reparations.

Despite some early trials, It was not until studies in New York City by Professor Vincent Dole along with Marie Nyswander that methadone was systematically studied as a potential substitution therapy. Their studies introduced a sweeping change in the notion that drug addiction was not necessarily a simple character flaw, but rather a disorder to be treated in the same way as other diseases. Dole and Nyswander are seminal figures in the history of drug treatment. Sadly, methadone rather than taking a place in the armatorium of possible pharmacological treatments for opiate dependence it has emerged as the treatment of choice (alone with Subutex/Suboxone), at the expense of a wider range of choices amongst which it once stood [7].

Methadone was developed in Germany in 1937 by Gustav Ehrhart and Max Bockmühl, that could be created with readily available precursors.

On September 11, 1941 Bockmühl and Ehrhart filed an application for a patent for a synthetic substance they called Polamidon, and whose structure had only a slight relation to morphine or other opiate alkaloids. It was brought to market in 1944 and was widely used by the German army during World War 2.

Methadone was introduced into the United States in 1947 by Eli Lilly and Company, as an analgesic under the trade name Dolophine [15].

The chemical structure of methadone was first produced in the 1930's as a team of German scientists was searching for a pain-killing drug (analgesic) that would not be as addictive as morphine. In 1937, two scientists (Max Bockmhl and Gustav Ehrhart) uncovered a synthetic substance that they called Hoechst 10820 or polamidon. Years later during World War II another team of German scientists expanded on earlier research and began synthesising the substance as a result of short supplies of morphine and other analgesics [39]. By the end of the war, the United States had obtained the rights to the drug from war requisitions and later coined the name methadone. Soon after in 1947 methadone was introduced into the United States to be used as a pain reliever for a variety of conditions, but eventually uncovered its usefulness in treating narcotic addictions [39]. Until the 1960's, little scientific advancement was made with regard to methadone. But with a resurgence of heroin addiction, researchers began to search for a substance that could reduce or eliminate drug craving and withdrawal signs and symptoms [40]. The idea behind this research was that methadone could be used to manage or maintain heroin addiction. In 1964, the effectiveness and usefulness of using methadone maintenance (i.e., using it as a substitute narcotic to prevent withdrawal) was realized. In the spring of 1971, methadone treatment for opiate dependence began to expand. That year the Federal Government developed regulations governing the use of methadone in the treatment of heroin addiction; final regulations were published in December 1972. Few advancements were made until 2001 when regulations over methadone were modified to allow physicians and other health care professionals to provide methadone more effectively and consistently [41].


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