This Week’s Focus: Methadone

This week’s briefing focuses on Methadone because we were asked how methadone might differ from buprenorphine, which was addressed last week. Methadone is a long-acting synthetic opioid primarily used in medication-assisted treatment (MAT) for opioid use disorder (OUD, unlike shorter-acting opioids like heroin, fentanyl, or oxycodone.

Unlike short-acting opioids, which produce rapid and intense euphoria and carry a high risk of addiction and overdose, methadone works by stabilizing people and reducing cravings. While effective, methadone can be misused, especially when combined with depressants, due to its long half-life and potential for accumulation.

The latest NDEWS Special Report shows EMS nonfatal opioid encounters with methadone mentioned in the record from 2023 to 2025. Identified in the report are the top 10 counties across the four regions of the US. To harmonize the information, the NDEWS Web Monitoring Report focuses on Reddit discussions where commenters reference interest in methadone outside of prescribed or supervised use.

Lastly, we invite you to join us for the upcoming Our Community, Our Health Town Hall NDEWS Webinar with the National Association of State Controlled Substances Authorities (NASCSA) on January 20, 2026 from 2:00 pm - 3:00 pm ET: The National Drug Early Warning System: Emergency Overdose Trends, Emerging Drugs of Abuse and Why this Matters to States. Register here on this or any other topic. If you have ideas on what we might focus on, please let us know.

As always, we welcome your input.

Out of 10,040 EMS encounters involving nonfatal opioid overdoses mentioning methadone from January 1, 2023 to December 31, 2025, 1,713 (17.1%) occurred in Western states, 1,413 (14.1%) in Midwestern states, 3,643 (36.3%) in Southern states and 3,271 (32.6%) in Northeastern states.
To view the entire Special Report from the weekly briefing, click here.

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Why are we reporting on this? Methadone is a long-acting synthetic opioid widely used for medication for opioid use disorder (MOUD) and, less commonly, for chronic pain management (CDC, 2024). While it remains a critical evidence-based opioid use disorder treatment option, Reddit discussions reference methadone outside of prescribed or supervised use. Online conversations highlight interest in methadone’s euphoric or reinforcing effects, nonmedical and recreational use, diversion of take-home doses, and use in combination with other substances. These discussions raise public health concerns related to overdose risk, prolonged withdrawal, and polysubstance use involving methadone.

What is Methadone? Methadone is a full opioid agonist with a long and variable half-life that is primarily dispensed through regulated opioid treatment programs or prescribed for pain management (SAMHSA, 2025). It reduces opioid cravings and withdrawal symptoms by maintaining stable opioid receptor activation. Due to its pharmacological properties, methadone can accumulate in the body, interact with other central nervous system (CNS) depressants, and alter the effects of other opioids taken concurrently or afterward.

Public Health Impacts: Across multiple Reddit discussions, commenters report concerns related to methadone use beyond prescribed treatment parameters. Multiple discussants describe increased risk when methadone is combined with other CNS depressants, including benzodiazepines, alcohol, and non-benzodiazepine sleep medications, with reports of excessive sedation and respiratory suppression. Discussants also frequently mention prolonged and challenging withdrawal experiences following methadone dose reductions or discontinuation, including persistent fatigue, low mood, sleep disturbances, and gastrointestinal symptoms. Additional commonly reported effects include constipation, sweating, weight changes, and difficulty managing tolerance, particularly when methadone is used alongside other opioids.

How is it Being Discussed? Reddit users frequently discuss methadone in relation to its ability to reduce or “block” the effects of other opioids, with many asking how long methadone must be discontinued to feel substances such as oxycodone, fentanyl, or heroin again. There is substantial discussion of using methadone nonmedically, including taking higher or supplemental doses to achieve sedation or mood elevation, using diverted take-home doses, or employing methadone for unsupervised tapering from other opioids.

Polysubstance use is a dominant theme, particularly combining methadone with benzodiazepines, z-drugs, alcohol, stimulants, or additional opioids to enhance effects or manage anxiety, sleep, or withdrawal symptoms. Users also speculate about methadone’s pharmacology, including its NMDA receptor activity and whether this contributes to dissociative, mood-altering, or reinforcing effects. Practical discussions include managing clinic attendance requirements, obtaining or losing take-home privileges, traveling while enrolled in methadone treatment, and navigating drug testing.

CDC. “Treatment of Opioid Use Disorder.” Overdose Prevention, 12 Aug. 2024, www.cdc.gov/overdose-prevention/treatment/opioid-use-disorder.html.

SAMHSA. “What Is Methadone? Side Effects, Treatment & Use.” Samhsa.gov, 29 Mar. 2024, www.samhsa.gov/substance-use/treatment/options/methadone.

Click here to read more about NDEWS Online Monitoring.

A cross-sectional MRI study in Acta Neurologica Belgica by Shamooshaki et al. investigated the potential presence of brain disorders, particularly hypoxia, in individuals misusing methadone compared with individuals who use opium regularly. Significant hypoxia appeared in 16.7% of the methadone group, with no cases observed in the opium or control groups. Notably, 3 of 5 hypoxia cases involved concurrent methadone and alcohol use. Authors highlighted methadone’s unique neurotoxic potential—especially with alcohol—and call for routine MRI monitoring, stricter oversight of non-prescribed methadone, and targeted public health education to reduce hypoxia-related harm. Read the full study here.

 A recently published study in the Journal of Health Economics by Donahoe et al. examined a supply-side drug control policy. In 2008, the US Drug Enforcement Administration banned 40mg methadone diskettes due to overdose risks, which led to prescriptions of lower-dose 5mg and 10mg methadone tablets. The study showed that the targeted restriction prevented an estimated 1,661 overdose deaths in 2.5 years. Read the full study here.

A recently published study in the Journal of Substance Use and Addiction Treatment by Roy et al. examined whether states that opted out of expanded methadone take-home policies after initially adopting them saw changes in methadone-related overdose deaths. Using a difference-in-differences approach with CDC mortality data, researchers compared three opt-out states to 16 states that maintained the policy. Read the full study here.

An article published by Mental Health Providers highlights the warning signs of methadone misuse. Methadone treatment is used to help individuals recover from heroin or prescription opioid addiction, but the article points out that misuse can be dangerous and even life-threatening. The article identifies physical, behavioral, and psychological signs and symptoms of misuse, while also providing treatment options and resources for individuals who wish to seek help. Read the full article here.

A new report from the State of Connecticut Office of Inspector General (OIG) investigated two in‑custody deaths at Garner Correctional Institution in July 2024. Both men had recently begun the facility’s methadone program despite negative opioid screens and prolonged abstinence—factors identifying them as opioid‑naïve and high‑risk for toxicity. Each was also prescribed multiple sedating antipsychotic or benzodiazepine medications known to potentiate methadone‑induced respiratory depression. Autopsies determined both deaths resulted from acute intoxication due to methadone combined with other medications. The OIG found no criminal actions but identified significant deviations from best‑practice induction protocols. The Department of Corrections is implementing corrective actions, including adding addiction‑medicine oversight and reviewing all methadone induction procedures. Read the full report here.