Methadone is a popular synthetic opioid utilized for the treatment of opioid dependence as a “replacement therapy.” Individuals addicted to highly potent opioidergic agents (e.g. heroin) are often prescribed methadone as a transitory “replacement” drug. Administration of methadone as a replacement over heroin is preferred because it is medically viewed as being slightly less addictive. It also effectively mitigates full-blown discontinuation symptoms of heroin, allowing addicts to stabilize (get their life back on track) before attempting to attain sobriety.
Upon ingestion, methadone functions primarily as a full mu-opioid receptor agonist (and to a lesser extent an NMDA antagonist), thereby aiding in the management of opioid dependence. Mu-receptor agonism is known to generate production of beta-endorphin and enkephalin, leading to effects such as: analgesia (pain relief), physical relaxation, mood elevation (euphoria), and pleasure. As a result of these effects, many individuals undergoing opioid replacement therapy essentially replace one addiction for another, becoming equally (or more) addicted to the methadone than the original drug they attempted to kick (e.g. heroin).
Evidence suggests that methadone is among the world’s most addictive drugs. Though some people respond well to using methadone as a replacement agent, others experience adverse effects and deleterious long-term effects such as: sedation, digestive problems, dizziness, fatigue, muscle weakness, hallucinations, and heart problems. For these reasons and a variety of others (desire to be sober / mandatory drug testing / etc.) – many people have discontinued methadone and want to fully clear it from their systems.
How long does Methadone stay in your system?
Assuming you’ve completely ceased usage and dealt with (or are currently facing) methadone withdrawal symptoms, you probably want to know how long methadone stays in your system. After taking just one methadone pill, the therapeutic effects are known to last up to 8 hours. However, just because the therapeutic effects wear off within 8 hours doesn’t mean that the drug will be cleared from your body.
Most sources are in conflict regarding the average elimination half-life of methadone. Examples of some cited methadone half-lives include: 24 to 36 hours, 13 to 47 hours, 15 to 40 hours, and 8 to 59 hours. This indicates that the half-life of methadone is highly-variable between individuals. Since the 8 to 59 hour elimination half-life encompasses the others mentioned, we shall use it to estimate possible average clearance times of methadone.
Assuming 50% of the methadone is cleared from your system in 8 to 59 hours, it will likely take between 1.83 days and 13.52 days for complete systemic clearance. It is important to realize that this clearance range is just an average estimate. Certain individuals may take longer than 13.52 days to completely excrete methadone (and its metabolites) from their body.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/methadone
Factors that influence how long Methadone stays in your system
The significant variability in systemic clearance time of methadone is due to a variety of factors. Examples of these factors include things like: the individual (i.e. the person taking it), frequency of ingestion, the dosage, modality of administration, and co-ingestion of other substances. It is these factors that may facilitate expedited clearance (less than 2 days) in one person and prolonged clearance (2 weeks) in another.
If two people each take a 10 mg methadone pill simultaneously, why will one individual excrete the drug quicker from their system than the other? Excretion times are subject to significant variation based on the person taking the methadone. Individual factors that affect methadone absorption, metabolism, and clearance include: a person’s age, body mass, genetics, and liver functionality.
Age: Elderly individuals (ages 65+) are known to metabolize and excrete drugs at a slower rate than adults and adolescents. This is generally due to a variety of reasons including: reduced hepatic blood flow, poorer organ functionality (liver/kidneys), other health problems, slower metabolism, less efficient physiologic function, and/or ingestion of other medications. For these reasons, an individual’s age may affect clearance.
Body height/weight/fat: A person’s body mass index (BMI) relative to the dosage of methadone ingested may affect systemic clearance speed. Generally, the greater the amount of a drug a person ingests relative to their body mass, the longer it will remain in their system; vice-versa also applies. This means that administration of a 10 mg methadone pill to a 6’6″ 240 lb. person should get excreted quicker than the same pill to a 4’4″ 100 lb. individual.
Body fat also seems to affect methadone clearance in that the more fat a person has, the longer they are likely to retain the drug prior to excretion. Methadone is considered lipid-soluble and accumulates in fatty deposits throughout the body. Therefore individuals with less overall body fat will not accumulate as much methadone and are likely to clear it at a faster pace.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22898875
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23129867
Genetics: Individuals with certain genetic polymorphisms may metabolize (and ultimately excrete) methadone at a different rate than others. Genes responsible for regulating CYP450 (cytochrome P450) enzymes within the liver (specifically CYP3A4 isoenzyme) can affect how quickly you’re able to process and clear methadone from your system. A person who’s considered a “rapid metabolizer” as a result of certain genes may clear methadone faster than someone classified as a “poor metabolizer” (based on their genes).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/015501692
Food intake: It is unclear as to whether taking methadone with food (vs. on an empty stomach) could affect its absorption, metabolism, and clearance. Some speculate that a high-fat meal may enhance its absorption and increase its bioavailability, but this claim lacks scientific support. It is possible that ingestion of food with methadone may have a slight impact on its clearance. In addition the specific type of food may matter.
Liver function: Methadone is metabolized by various CYP450 enzymes within the liver (most notably CYP3A4). Individuals with hepatic impairment may be unable to metabolize nor excrete the drug as quickly as those with normative liver functionality. One case study analyzed the effect of methadone on an individual diagnosed with cirrhosis.
Methadone accumulated to 4-fold the extent of a healthy individual – indicating impaired metabolism. As a result of slower metabolism in a person with compromised hepatic function, methadone’s half-life may be substantially prolonged.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11965098
Metabolic rate: Your BMR (basal metabolic rate) indicates how much energy your body is expending at rest. Individuals with higher BMRs may clear methadone from their system at a faster rate than those with lower BMRs. This is due to the fact that high BMRs are associated with quicker drug metabolism and less body fat. People with low BMRs tend to metabolize drugs more slowly, and usually have more body fat (allowing for greater accumulation of methadone).
Pregnant women: Research shows that pregnant women tend to clear methadone from their systems faster than non-pregnant women. One study conducted on 23 pregnant women found that during pregnancy, methadone was eliminated at a faster constant rate and had a lower half-life compared to a control group (16 non-pregnant women). The expedited clearance speed is thought to result from decreases in methadone absorption.
Another study found that plasma concentrations of methadone were significantly lower among pregnant women than non-pregnant counterparts. While women are pregnant, less of a methadone dosage is absorbed, metabolism is enhanced, and elimination is expedited. If you are pregnant, it is likely that methadone will be cleared from your system quicker than if you weren’t.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10631963
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3981450
Urinary pH: When it comes to drug excretion, the more acidic your urinary pH – the faster you’ll clear it from your system. An individual with a highly acidic urine is likely to excrete methadone faster than someone with a urinary pH of high alkalinity. Highly alkaline urine often results in drug reabsorption (prior to excretion), prolonging the clearance.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17500
Frequency of use
How often a person uses methadone can influence how quickly it is cleared from their system. Frequent methadone users tend to accumulate increasing amounts of the drug within lipid stores with each consecutive usage. When administered at a frequent rate, a user will have added additional methadone to their lipid stores prior to clearance of the already-present methadone.
A frequent user will accumulate a substantially greater amount of methadone within their system, resulting in substantially prolonged clearance times compared to infrequent users. An infrequent user (or a single-dose user) may never accumulate “peak levels” of methadone within lipid stores. Though some of the drug will be retained in fat stores, it will not reach a maximal level like it would in a frequent user.
- Accumulation in lipids: The more frequent someone ingests methadone, the greater the extent to which it will accumulate within lipid stores. Reduced frequency of usage will prevent significant methadone accumulation.
- Dosage: It isn’t rocket science to assume that more frequent users take greater dosages. This is due to the fact that frequent users may build up tolerance to lower doses of methadone and require dosage increases. Higher doses are thought to extend clearance times.
- Peak concentrations: An infrequent user may not reach a peak concentration of the drug within their system compared to a frequent user. Someone taking the drug daily (3x per day) will likely reach peak levels of methadone compared to someone taking the drug once per month (1x per day).
- Time of dosing: Frequent users may administer their last dose of methadone in the afternoon, whereas a single-dose user may take the drug just once in the morning. Administration later in the day means metabolism won’t start until later in the day – resulting in a new half-life for the later dose. A single-dose user may have already excreted a significant portion of the drug by the afternoon.
Different types of patients receiving methadone tend to exhibit different half-lives. For example, methadone’s half life in healthy patients is thought to be 33 to 46 hours, but significantly longer in a chronic pain patient. The longer half-lives of methadone in certain patients are usually due to increased frequency of administration.
- Chronic pain: When taking methadone for the treatment of chronic pain, the half-life could reach 120 hours. In this case, the drug is frequently administered and tends to accumulate within the body. This means that it could take 27.5 days upon cessation of methadone for the drug to fully clear from a chronic pain patient’s system.
- Healthy individuals: Reports suggest that methadone’s half-life in healthy patients is approximately 33 to 46 hours. In part, this is due to the fact that healthy individuals aren’t usually taking the drug with high frequency, resulting in less overall accumulation. Methadone clearance in healthy individuals is usually complete within 10.55 days.
- Opioid dependence: Some research suggests that clearance of methadone is likely longer in opioid dependent patients compared to healthy individuals. The half-life of methadone among those with opioid dependence is thought to range from 47 to 75 hours. In other words, it could take 10.77 to 17.81 days for complete elimination of methadone.
- Postoperative: When administered to postoperative purposes, methadone can exhibit a half-life of up to 87 hours. Clearly 87 hours is at the upper-end of the half-life spectrum and unlikely for most postoperative patients. However, this indicates that complete clearance of methadone could take up to 20 days.
Dosage (5 mg to 40 mg)
The greater the dosage of methadone a person ingests, the longer it may take to clear from their system. On the other hand, the smaller the dose ingested, the quicker it may be cleared from the body. Individuals taking smaller doses don’t have as much of the drug to process, and thus it is efficiently metabolized by the liver.
Those taking high doses may accumulate a greater amount of the drug within lipids and overwhelm various enzymes in the liver such as CYP3A4. Furthermore, other physiologic alterations resulting from high dosages may prolong excretion times. The dosage ingested (especially relative to body mass) will impact clearance.
Taking other drugs (that affect CYP3A4)
Enzymes within your liver are responsible for the metabolism of methadone. In particular, the enzyme CYP3A4 is thought to have the biggest impact on the breakdown of methadone. If you are taking any drugs (or supplements) other than methadone, it is necessary to realize that they may alter its metabolism.
Drugs known as CYP3A4 inhibitors tend to interfere with methadone’s metabolism, leading to prolonged clearance terms. Examples of various potent CYP3A4 inhibitors include: Ritonavir, Indinavir, Clarithromycin, Ketoconazole, and Nefazodone. Even grapefruit juice (which contains “bergamottin”) is known to inhibit CYP3A4, leading to an extended clearance term.
Other drugs are known to enhance CYP3A4 activation and are therefore considered “inducers.” CYP3A4 inducers are known to speed up metabolism (and likely excretion) of methadone. Examples of various CYP3A4 inducers include: Carbamazepine, Phenobarbital, St. John’s wort, Rifampicin, Glucocorticoids, and Modafinil.
Methadone: Absorption, Metabolism, Excretion (Details)
Following oral administration of methadone, the drug is efficiently absorbed by the gastrointestinal (GI) tract. Upon gastrointestinal tract absorption, levels of methadone are apparent in plasma within 30 minutes, and concentrations peak approximately 4 hours post-ingestion. Its bioavailability ranges between 36% and 100%, but in most cases is around 80%.
Steady-state levels and maximal effects aren’t typically attained for at least 3 to 5 days of treatment. After absorption, up to 90% of methadone binds to plasma proteins (chiefly a1-acid glycoprotein) and is distributed widely throughout bodily tissues. When administered repeatedly, methadone continues to accumulate within tissues and lipids as a result of its high lipophilicity.
Enzymes within the liver are largely responsible for the metabolism of methadone. Cytochrome P450 (CYP) isoenzyme 3A4, also called “CYP3A4” breaks down the majority of ingested methadone. CYP3A4 facilitates N-demethylation to form the metabolite EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene) and which is pharmacologically inactive. To a lesser extent, various other isoenzymes such as CYP2B6, CYP2C19, CYP1A2, CYP2C9, and CYP2D6 contribute to metabolism of methadone to form EMDP (2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline) and other secondary metabolites.
Most of the ingested parent metabolites (i.e. EDDP) are excreted via urine. Smaller amounts are eliminated through bile, feces, and sweat. A very tiny amount of methadone is excreted unchanged via the urine. Since the half-life ranges from 8 to 59 hours, the intermediary half-life would be 33.5 hours. This means that for complete excretion of methadone, it will likely take around 7.68 days.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/methadone
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7403680
Types of Methadone Drug Tests
There are a variety of drug tests that can be administered to determine whether an individual currently has methadone in their system and/or recently ingested it. Though the most common type of screening is a urine test, other methadone drug tests include: saliva tests, hair tests, and blood tests. Each of the following tests has its own set of advantages and disadvantages for methadone detection.
Urine tests: The most common way to determine if someone ingested methadone is via a urine test. A urine test requires a fresh urine sample from a prospective methadone user. This sample is then sent to a laboratory for analysis (urinalysis). The urinalysis will accurately determine whether methadone metabolite EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene) appears above a specific threshold.
Methadone is thought to become detectable on a urine test within an hour of ingestion, and for up to 2 weeks post-ingestion. Due to the fact that urine tests are non-invasive, convenient, and offer a long detection period – they are commonly preferred over blood tests. For this reason, most employment-related methadone screenings involve collection of urine samples.
Blood tests: If you take methadone pills orally, the drug can be detected within 30 minutes of ingestion. Levels will peak in the bloodstream within 4 hours, making it even easier to detect. Detection times of methadone within the blood will be subject to significant individual variation, but should remain detectable for at least several days following ingestion.
Though blood tests can accurately detect the presence of methadone for days after ingestion, they are seldom utilized as a “drug test.” They are most commonly used to determine adherence to methadone treatment as an opioid replacement therapy. Some view blood tests as problematic in that they are invasive, costly, and offer a shorter window of detection compared to urine tests.
Hair tests: The greater the amount of methadone a person ingests, the higher the levels of the “EDDP” metabolite will appear in the hair. An effective way to determine whether someone has ingested methadone over a longer period is via a hair test. A hair test involves collecting a sample of hair follicles and sending them to a laboratory for analysis via gas chromatography/mass spectrometry (GC/MS).
In frequent users, methadone will already be present in the hair. In a new user, it may take days or weeks for methadone to accumulate in outgrowths of the hair. Proximal hair segments (those closest to the head) are best for determining how much methadone a person ingested compared to distal segments (further from the head). Hair tests are advantageous over other testing modalities due to the fact that they can detect methadone for up to several months after administration.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25869947
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11248447
Saliva tests: Collecting a sample of oral fluid (saliva) can effectively determine whether someone had ingested methadone. Salivary levels of methadone (and other drugs) tend to correlate well with blood levels. For this reason, saliva tests offer a relatively similar window of detection compared to blood tests. Methadone may become detectable on a saliva test within 30 minutes of ingestion, and remain detectable for over several days thereafter.
Utilizing saliva to detect methadone is advantageous in that it is relatively non-invasive and highly convenient. In most cases, saliva samples are sent to a laboratory to confirm the presence of methadone, but new technological devices are being engineered for rapid detection (without need for a lab). Saliva testing is employed mostly for scientific research, but may be used to determine methadone adherence in the future.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11599594
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16175130
Who may get tested for Methadone?
Standard drug tests such as the SAMHSA-5 are capable of detecting opioids such as heroin, opium, codeine, and morphine – but not methadone. For this reason, methadone testing is usually reserved for select individuals. Examples of people that may get tested for methadone include: addicts, athletes, criminals, employees, and military members.
- Addicts in rehab: Drug addicts attending a rehabilitation facility may be closely monitored for opioid ingestion and even methadone ingestion. At rehab facilities, some individuals will take any drug (including methadone) in attempt to attain a “high.” Should an addict test positive for methadone, he/she may require additional time at the rehab facility.
- Athletes: Though methadone is far from a performance enhancing drug, athletes are sometimes administered extensive drug tests that may detect it. Should an athlete get caught with methadone in their system, he/she may get fined, suspended, or banned from competition. That said, it is uncommon for athletes to use methadone.
- Criminals: If a law enforcement agent suspects that a criminal may be “high” on an opioid, they may administer a standard drug test. If nothing is detected on the standard test, an extensive test may be administered to detect methadone. Should an individual get caught having illicitly ingested methadone, they may be subject to additional legal penalization.
- Employees: Though not all employers will test current (and prospective) employees for methadone, some are legally required to. Jobs in which individuals operate heavy machinery and/or motor vehicles are often tested for methadone. This is because ingestion of methadone is known to impair motor skills, which could cause an accident, injury, or death.
- Military personnel: Individuals in the military are expected to serve their country in a state of sobriety. Ingestion of methadone could impair ability to follow commands, operate machinery, and/or handle dangerous weaponry. For this reason, extensive drug tests (capable of detecting methadone) are sometimes administered to military members. Should a soldier get caught with methadone in their system, they may be delisted without compensation.
Tips to clear Methadone from your system
There are several ways in which a person can potentially speed up the clearance of methadone from their system. Understand that these methods should be discussed with a medical professional prior to actual implementation. Also realize that while they may be effective in maximizing clearance speed for certain individuals, they may not help others.
- Acidify urinary pH: Studies have shown that urinary pH can serve to speed up or prolong clearance of methadone from a person’s system. The more alkaline a person’s urinary pH, the more likely they are to reabsorb the drug and excrete it at a slow rate. When urinary pH is acidified, clearance rates are markedly enhanced.
- CYP3A4 inducers: Drugs (or other substances) that induce CYP3A4 activity could expedite the body’s ability to metabolize and excrete methadone. Though taking a CYP3A4 inducer specifically to maximize clearance cannot be recommended, it may be effective. If you are already taking a CYP3A4 inducer, methadone is likely to have a shorter half-life.
- Reduce body fat: Methadone has a high affinity for body fat. If you have a high percentage of body fat, understand that you may have accumulated a significant amount of methadone in fatty tissues. This accumulation can significantly prolong clearance. Eating healthy, exercising, and doing what you can to reduce body fat should speed up methadone excretion.
- Exercise: Going for a run, jog, or doing some sort of cardio is beneficial for clearing methadone from your system quickly. Cardio exercise speeds up metabolism, burns fat, and can improve blood flow/circulation to organs such as the liver and kidney. The combination of a metabolism jolt, fat burning, and superior liver/kidney functionality from exercise can help you increase clearance speed of methadone.
- Stay hydrated: Methadone is excreted primarily through your urine. If you don’t stay hydrated, your urinary flow will be compromised and less methadone will get eliminated. Dehydration promotes reabsorption and inefficient excretion, whereas sufficient hydration will ensure that methadone is eliminated in an optimal amount of time.
How long has Methadone stayed in your system?
If you’ve taken methadone, share how long you believe it stayed in your system after your last dose. To help others understand your situation, mention factors that may have expedited or prolonged clearance of methadone from your system. Examples of factors to mention include: how long you were taking methadone, how often you took it, your dosage, whether you took other drugs, etc.
If you were drug-tested for methadone, feel free to share whether you passed (tested negative) or failed (tested positive). It is important to realize that there is substantial individual variability in methadone clearance time. That said, your average person will have fully cleared the drug from their system within 2 weeks after discontinuation.