What Is Methadone Addiction

Home
Methadone

Jump To:

Heading 2 Example

KEY TAKEAWAYS

Methadone addiction:

Occurs when users become physically dependent, caused by opioid receptor desensitisation
Becomes psychological dependence when methadone is used for its sedative effects to mask past trauma and current triggers
Results in fatigue, aches and pain during periods of non-use, necessitating rehabilitation

Defining Methadone Addiction

Methadone addiction begins when mu and NMDA receptors become habituated to methadone, so more is needed to experience sedation and detachment, creating a cycle of physical dependence.

Psychological dependence on methadone is caused by repeated overuse to mask pain, depression and anxiety - this results in methadone being used as an unhealthy coping mechanism.

Physical dependence occurs when methadone, a full opioid agonist, binds to mu receptors that become habituated over ~2 weeks, depending on dosage.

Methadone addiction results in persistent drowsiness and pain relief over 24-36 hours, compared to 3-5 for heroin, providing a longer time for users to become addicted.

Although methadone provides a less intense high than heroin, users may stock up on doses and take more than recommended to experience euphoria.

Physiological Indicators Of Methadone Addiction

Nausea And Constipation

Methadone-dependent patients experience 33.4% more constipation due to a lack of fluid in the bowels [1].

Methadone patients are 3.89 times less likely to have clear intestinal linings due to reduced peristalsis, resulting in less nutrient absorption and discomfort passing bowels [2].

Nausea and vomiting are physical signs of methadone dependency, resulting from stimulation of the Chemoreceptor Trigger Zone (CTZ) and dizziness from a sensitive vestibular system [3].

Disrupted Sleep And Libido

33.9% of users experience sleep latency - the time it takes to fall asleep - and struggle to remain asleep at night [4].

23.1% of users supplement with sleeping aids, such as melatonin, to help with sleeping problems [5].

A disrupted sleep-wake cycle caused by methadone dependency results from GABA inhibition, keeping the brain active at night.

Sexual libido is decreased in 14% of male methadone users, caused by inhibition on the hypothalamic-pituitary-gonadal axis [6].

Methadone consumption for 6+ months results in a 22% decrease in testosterone levels, causing reduced libido in both males and females [7].

Respiratory And Cardiovascular Dysfunction

Two months of methadone doses of 60-100mg+ result in hypoventilation due to CO2 accumulation and hypoxia [8].

Shallow breathing and a low breathing rate (<12/minute) occur when doses three times higher than recommended are consumed, caused by blood oxygen levels decreasing to 75% [9].

Heart palpitations and fainting episodes during methadone dependence are caused by QT prolongation of the heart (615ms ± 77) compared to normal readings (440-460ms) [10].

Wheezing, shortness of breath and rapid pulse occur during anaphylaxis and methadone overdose, caused by histamine release in the body during dependency [11].

Psychological Indicators Of Methadone Addiction

Rationalising Methadone Addiction

Methadone users perceive methadone as a necessary drug that replaces heroin, adding to psychological dependence.

Continued use of methadone results in psychological reliance on the drug as users associate the drug with emotional stability and normal daily functioning.

Normalising methadone use as a prescription medication is harmful when overuse is not viewed as addiction, as professional help is not sought.

Depression And Anxiety

A psychological indicator of methadone dependency is fear of withdrawal symptoms, causing continued use in 30% [12].

Confusion and anxiety are psychological indicators of serotonin syndrome caused by misuse and overdose of methadone.

Negative self-talk about methadone use is an indicator of addiction, as users are aware of the consequences but cannot stop taking methadone without professional methadone treatment.

Behavioural Indicators Of Methadone Addiction

Behavioural indicators of methadone addiction are:

Rationalising use by obtaining methadone legally via medically authorised prescriptions, as it can be deemed as 'safe' and 'necessary' for health
Seeking surplus doses of methadone that do not fit the medication timeframe, as this indicates doses higher than recommended have been consumed
Being resistant to changing methadone dispensaries out of fear of stricter monitoring and potential cuts in supply, especially when patients are using more than recommended
Stockpiling and hiding excess methadone tablets from family members to conceal dependence

Who Is Most Likely To Develop A Methadone Addiction?

	Addicted To Methadone Alone	Methadone Addiction From Heroin Addiction	Methadone And Heroin Addiction
Reason For Initial Methadone Use	Medicating chronic pain Borrowing medication	Heroin detox or maintenance medication	Harm reduction Heroin craving management
Prescribed Or Illicit?	Prescribed and illicit - case dependent	Prescribed	Prescribed and illicit
Impact On Daily Functioning	Pain management Drowsiness	Decreased heroin cravings Increased methadone cravings Risk of heroin relapse	Gastrointestinal discomfort Low functioning because of polydrug use
Treatment Required	Methadone rehab Slow tapered doses Close monitoring	Methadone rehab Behavioural therapy	Heroin and methadone rehab - residential Buprenorphine, Suboxone or Buvidal Behavioural therapy

Legal Status Of Methadone Dependence

Methadone is classified as a Class A substance under the Misuse of Drugs Act 1971, making possession, supply and production illegal in the UK; however, having methadone dependence itself is not illegal.

Methadone is a Schedule 2 controlled drug under the Misuse of Drugs Regulations 2001, making it a legally accessible option to maintain methadone dependence.

Strict rules on providing handwritten signatures for methadone orders prevent prescriptions from being fabricated and methadone being handed out to illicit dependent users.

Formal risk assessments take place to ensure that patients with a history of opioid dependence are assessed before methadone is issued, avoiding the risk of dependence.

Methadone 'take home' prescriptions are collected by the patient only, except under exceptional circumstances, to prevent misuse and dependency in others [13].

Methadone regulations do not allow an 'emergency supply' or the collection of repeat prescriptions before the date of issue to mitigate risks of misuse or overdose.

What Changes Methadone Dependency?

Medication Interactions

Heart palpitations occur when methadone is combined with haloperidol, as this combination results in a prolonged QT interval over 500ms.

55μM of fluoxetine reduces the enzyme breakdown of methadone by 50%, resulting in higher levels of circulating methadone and respiratory depression [14].

There is a 4.8 times increased risk of fatal toxicity when methadone is combined with benzodiazepines due to respiratory depression [15].

St John's Wort reduces the blood concentration of methadone by 47% by inducing the enzyme CYP3A4 [16].

Methadone Legality

Country	Legal Status	Overdose/Fatality Rate
UK	Class A	Overdose deaths: 1.37% [17]
USA	Schedule II Controlled Substance	Overdose deaths: 3.2% [18]
Australia	S8 (controlled drug)	Overdose deaths: 1.27% [19]
Sweden	Schedule II controlled substance	Responsible for 46% of drug-related deaths [20]
Russia	Schedule I prohibited substance	Data not available
Saudi Arabia	Schedule I prohibited substance	Data not available
Iran	Schedule II Controlled Narcotic	Responsible for 35.8% of drug-related deaths [21]

Country	Police Approach To Illicit Use	Primary Use of Methadone
UK	Possession: < 7 years imprisonment	Methadone Maintenance Therapy Chronic pain management
USA	Possession: < 1 year imprisonment	Methadone Maintenance Therapy Pain management
Australia	Possession: < 3 years imprisonment	Methadone Maintenance Therapy Pain management
Sweden	Police engage with drug services Possession: < 6 months imprisonment	Methadone Maintenance Therapy: 20+ year olds End-of-life care
Russia	Possession: < 3 years imprisonment	No legal use for methadone
Saudi Arabia	Possession: < 2 years imprisonment	No legal use for methadone
Iran	Possession: months - years (case dependent)	Methadone Maintenance Therapy

Method Of Administration

Oral and nasal administration of methadone results in 85% bioavailability, leading to rapid absorption and physical dependence [22].

Injectable methadone has the most potential for developing dependence as 100% of the drug enters the bloodstream.

Injectable methadone is not available for take-home use and is administered by a healthcare professional, limiting the possibility of maintaining self-managed dependence.

Physical dependence occurs quicker in rectal methadone compared to oral use, where peak blood methadone concentration occurs in 3-4 hours [23].

References

[1] Verma, Siddharth. “Chronic Methadone Use, Poor Bowel Visualization and Failed Colonoscopy: A Preliminary Study.” World Journal of Gastroenterology, vol. 18, no. 32, 2012, p. 4350. Accessed 2 Dec. 2021. “MD patients had significantly greater percentage of solid stool (i.e., poor visualization) compared to C (40.3% vs 6.9%, P < 0.001).”
[2] Verma, Siddharth. “Chronic Methadone Use, Poor Bowel Visualization and Failed Colonoscopy: A Preliminary Study.” World Journal of Gastroenterology, vol. 18, no. 32, 2012, p. 4350. “Under univariate analysis, factors significantly associated with MD group were presence of fecal particulate [odds ratio (OR), 3.89, 95% CI: 1.33-11.36, P = 0.01] and solid stool (OR, 13.5, 95% CI: 4.21-43.31, P < 0.001). Fair (OR, 3.82.”
[3] Pacini, Matteo. “Echoing the Patient’s Lack of Insight: A Role We Must Avoid Playing.” Heroin Addiction and Related Clinical Problems, vol. 11, no. 3, Associazione per l’Utilizzo delle Conoscenze Neuroscientifiche a fini Sociali, Sept. 2009, pp. 45–48.
[4] Habibolah Khazaie, et al. “Sleep Disorders in Methadone Maintenance Treatment Volunteers and Opium-Dependent Patients.” Addiction & Health, vol. 8, no. 2, Apr. 2016, p. 84. Accessed 10 June 2025. “Sleep latency 22 (33.9).”
[5] Habibolah Khazaie, et al. “Sleep Disorders in Methadone Maintenance Treatment Volunteers and Opium-Dependent Patients.” Addiction & Health, vol. 8, no. 2, Apr. 2016, p. 84. “Use of sleep medication 15 (23.1).”
[6] Wehbeh, Leen, and Adrian S. Dobs. “Opioids and the Hypothalamic-Pituitary-Gonadal (HPG) Axis.” The Journal of Clinical Endocrinology & Metabolism, vol. 105, no. 9, Aug. 2020, pp. e3105–13. Accessed 1 Apr. 2021.
[7] Petrov, S., et al. Evaluation of Gonad Function in Men Undergoing Methadone Treatment Hypothalamus-Pituitary-Gonad Axis and Erectile Function in Patients on Methadone Maintenance Treatment (MMT). no. 6, Nov. 2021, pp. 48–54.
[8] Santiago, T. V., et al. “Control of Breathing during Methadone Addiction.” The American Journal of Medicine, vol. 62, no. 3, Mar. 1977, pp. 347–54. Accessed 2 Aug. 2022. “Thus, during the first two months of methadone maintenance, there is continual alveolar hypoventilation due to depression of both central (CO2) and peripheral (hypoxia) chemoreception.”
[9] Mégarbane, Bruno, et al. “Case Report: Quantification of Methadone-Induced Respiratory Depression Using Toxicokinetic/Toxicodynamic Relationships.” Critical Care, vol. 11, no. 1, 2007, p. R5. Accessed 18 Apr. 2022. “In our overdosed patient, the maximal observed R,S-methadone concentration was approximately three times higher than the reported peak levels in patients treated with a daily therapeutic dosage of more than 80 mg.”
[10] Krantz, Mori J., et al. “Dose-Related Effects of Methadone on QT Prolongation in a Series of Patients with Torsade de Pointes.” Pharmacotherapy, vol. 23, no. 6, June 2003, pp. 802–5. “The mean QTc interval was 615 ± 77 msec. Multiple linear regression indicated that only the daily methadone dose was predictive of the QTc interval (r = +0.51, p=0.03).”
[11] Di, G., et al. “Histamine Release from Rat Mast Cells Induced by the Metabolic Activation of Drugs of Abuse into Free Radicals.” Inflammation Research, vol. 47, no. 3, Springer Science+Business Media, Mar. 1998, pp. 122–30. Accessed 10 June 2025. “These results suggest that morphine, cocaine and methadone are activated into free radicals which produce membrane lipid perturbation and histamine release.”
[12] Stotts, Angela L., et al. “A Stage I Pilot Study of Acceptance and Commitment Therapy for Methadone Detoxification.” Drug and Alcohol Dependence, vol. 125, no. 3, Oct. 2012, pp. 215–22. Accessed 28 Nov. 2021. “In 1980, Milby et al. (1980) identified among methadone maintenance clients an ‘iatrogenic detoxification phobia,’ which can be reliably detected and was present in almost 30% of the sample examined.”
[13] NHS Lothian. Edition 3 Guidelines for Dispensing and Supervised Self Administration of Methadone by Community Pharmacists. Mar. 2009. “It is not recommended that ‘take home’ doses are given to anyone other than the patient except under exceptional circumstances.”
[14] Iribarne, C., et al. “In Vitro Interactions between Fluoxetine or Fluvoxamine and Methadone or Buprenorphine.” Fundamental & Clinical Pharmacology, vol. 12, no. 2, 1998, pp. 194–99.
[15] Caplehorn, John R. M., and Olaf H. Drummer. “Fatal Methadone Toxicity: Signs and Circumstances, and the Role of Benzodiazepines.” Australian and New Zealand Journal of Public Health, vol. 26, no. 4, Aug. 2002, pp. 358–62. Accessed 17 May 2022. “Benzodiazepines were significantly more likely to have contributed to deaths from methadone toxicity among maintenance patients and people taking methadone tablets for pain relief than deaths involving diverted methadone syrup and deaths to which methadone did not contribute (OR 4.8, 95% 1.7 to 14.4).”
[16] Eich-Höchli, D., et al. “Methadone Maintenance Treatment and St. John’s Wort.” Pharmacopsychiatry, vol. 36, no. 1, Jan. 2003, pp. 35–37. “The study was proposed to addict patients about to start an antidepressant therapy. Introduction of St. John’s wort resulted in a strong reduction of (R,S)-methadone concentration-to-dose ratios in the four median patients included, with a median decrease to 47 % of the original concentration (range: 19 % - 60 % of the original concentration).”
[17] Marteau, Dave, et al. “The Relative Risk of Fatal Poisoning by Methadone or Buprenorphine within the Wider Population of England and Wales.” BMJ Open, vol. 5, no. 5, May 2015, p. e007629. “the pooled overdose death rate was 0.137/1000 prescriptions of methadone.”
[18] Jones, Christopher M., et al. “Methadone-Involved Overdose Deaths in the US before and after Federal Policy Changes Expanding Take-Home Methadone Doses from Opioid Treatment Programs.” JAMA Psychiatry, July 2022. “The percentage of overdose deaths involving methadone declined at similar rates, approximately 0.05% to 0.06%, before and after the take-home policy change, with 4.5% of overdose deaths involving methadone in January 2019 and declining to 3.2% by August 2021.”
[19] Sordo, Luis, et al. “Mortality Risk during and after Opioid Substitution Treatment: Systematic Review and Meta-Analysis of Cohort Studies.” BMJ, vol. 357, no. 357, Apr. 2017, p. j1550. “Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person.”
[20] Andersson, Lisa, et al. “Investigating Opioid-Related Fatalities in Southern Sweden: Contact with Care-Providing Authorities and Comparison of Substances.” Harm Reduction Journal, vol. 17, no. 1, Jan. 2020. Accessed 5 Mar. 2023. “Of the investigated deaths, nearly half, 46%, were caused by methadone.”
[21] Rostam-Abadi, Yasna, et al. “Public Health Risks Associated with Methadone in Iran: A Systematic Review and Meta-Analysis.” The International Journal on Drug Policy, vol. 100, Feb. 2022, p. 103529. “Methadone was reported as a cause of death in 53.5% of substance-related deaths referred to the Legal Medicine Organization while being the only cause in 35.8% of all cases.”
[22] Dale, O. “Disposition of Nasal, Intravenous, and Oral Methadone in Healthy Volunteers.” Clinical Pharmacology & Therapeutics, vol. 72, no. 5, Nov. 2002, pp. 536–45. Accessed 8 May 2020. “Both nasal and oral bioavailabilities were 0.85.”
[23] F. Moolenaar, et al. “Preliminary Study on the Absorption Profile after Rectal and Oral Administration of Methadone in Human Volunteers.” Pharmaceutisch Weekblad Scientific Edition, vol. 6, no. 6, Springer Science+Business Media, Dec. 1984, pp. 237–40. Accessed 10 June 2025. “The peak plasma concentration was only reached 3–4 h after administration, whereas the relative bioavailability up to 8 h after dosing ranged from 35–58%.”

About the author

Philippa Scammell

Philippa Scammell MSci holds an integrated Master's degree in Psychology
from the University of York and has completed undergraduate statistical studies at Harvard University. Philippa has substantial experience in inpatient psychiatric care (Foss Park Hospital York), Research in Psychology at University of York, and group therapy facilitation (Kyra Women's Project). Philippa writes on clinical psychology and addiction recovery. Content reviewed by Laura Morris (Clinical Lead).

Share 0

Last Updated: January 9, 2026