How Effective Is Methadone Treatment for Fentanyl Addiction?

The use of illegal fentanyl has surged in recent years because it is a cheap and highly potent opioid. Even though fentanyl is one of the strongest opioids, there is evidence that methadone treatment for fentanyl addiction can be effective in supporting long-term recovery goals.

How Common Is Fentanyl Addiction?

Fentanyl is a synthetic opioid, which means it is a pain-relieving drug that is made in a lab. In high enough doses or when taken when you are not in pain, opioids cause euphoria, or a “high,” which makes them very addictive. Fentanyl is 100 times stronger than morphine. Providers only prescribe fentanyl for severe pain, such as breakthrough cancer pain in people who cannot take other opioids.1

In 2016, there were 19,413 overdose deaths from synthetic opioids alone.2 Recently, most overdose deaths from synthetic opioids have involved illegal fentanyl analogues. Because fentanyl is both effective and life-threatening at extremely low amounts, it has a higher risk of overdose than other drugs, especially if another pill or powder is contaminated with fentanyl. Deaths due to overdose of illegal fentanyl have risen 56% from 2020 to 2021.1

What Is Methadone Treatment for Fentanyl Addiction?

Methadone is one of three medications approved by the U.S. Food and Drug Administration (FDA) to treat opioid use disorder (OUD). It has been used for over 70 years and is the most widely used to treat OUD.3,4

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For fentanyl, in particular, methadone is a first-line treatment and may be preferable to other OUD treatment medications. This is because methadone treatment for fentanyl addiction is associated with higher rates of treatment completion.

Research indicates that completing an opioid addiction treatment program is crucial at reducing the risk of relapse and overdose. Using fentanyl is an identified risk factor for dropping out of treatment because the potency makes it even more addictive compared to other opioids and the withdrawal symptoms can be severe.5

How Does Methadone Treatment for Fentanyl Addiction Work?

Methadone is an opioid agonist, which means it acts like an opioid when it attaches to opioid receptors in your brain. Other medications used to treat opioid addiction work differently. Buprenorphine, another medication to treat opioid use disorder (OUD), is a partial opioid agonist, which means that it does not fully create opioid effects in your brain but partially creates them.5

If you are physically dependent on fentanyl, your brain is used to the stimulation from fentanyl that it reaches the point of needing the substance to function. In turn, if you stop using fentanyl abruptly, it can cause withdrawal, which is a painful and uncomfortable experience as your body struggles to function without fentanyl.

Methadone treatment for fentanyl misuse gives your brain the opioid effects it currently depends on while also reducing your fentanyl cravings and withdrawal symptoms. Methadone reaches the brain quickly and stays in the body at a consistent level over a long period of time.

When treating OUD, providers prescribe methadone in lower doses than they do when prescribing it to treat pain. This is one of the primary reasons that the risk of addiction to methadone is low during methadone treatment for fentanyl addiction.6

What Are Typical Methadone Doses?

Recently, providers have recommended higher doses of methadone when treating fentanyl addiction compared to addiction to other opioids.5 This might be because fentanyl is a much stronger opioid, being about 50 times stronger than heroin.

Experts are making this recommendation after seeing some research results showing that those with fentanyl addiction improved with higher doses of methadone.5,7

The starting dose of methadone for fentanyl addiction is 30 mg. Your provider will generally increase it by 10 to 15 mg about every five days until a dose of 100-120 mg is reached. You slowly take higher doses over time as a way to avoid methadone overdose. When you reach a dose that is stable, you enter methadone maintenance, where your dose may not be adjusted for a longer period of time.5

If you are at high risk for overdosing on fentanyl or are just starting your methadone treatment, your provider might also prescribe slow-release oral morphine (SROM) at the same time. This supplements the methadone and reduces withdrawal symptoms and cravings while you are taking low doses of methadone.5

Scientists recommend SROM doses begin at 200 mg per day. Your prescriber may keep this dose throughout your treatment or slowly increase it while they increase your methadone dose.5

Who Is a Candidate for Methadone Treatment?

Methadone is used to treat physical dependence on fentanyl. You are an appropriate candidate for methadone treatment if you:3,8,9

  • Have experienced withdrawal from fentanyl or take fentanyl to avoid withdrawal symptoms
  • Have been taking higher mounts of fentanyl to feel the same effects
  • Have been abstinent from fentanyl but were physically dependent on it in the past
  • Have never experienced a drug overdose before
  • Do not have a history of another substance use disorder
  • Do not use fentanyl in very high amounts
  • Are motivated to get a comprehensive treatment that includes daily methadone clinic visits and counseling

It is a good idea to start methadone treatment even if you have been abstinent from fentanyl. This is because you have a high chance of relapsing to fentanyl use and methadone reduces cravings.9

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Methadone is generally considered safe, but your provider will increase your methadone dose at a slower rate if you are at high risk for methadone toxicity. You will be at high risk if you are also:5

  • Using high doses of benzodiazepines, such as for treatment of an anxiety disorder
  • Drinking alcohol in large amounts or in treatment for alcohol addiction
  • Of older age
  • Using medications that make you sleepy (i.e., sedatives)
  • New to using methadone

Does Methadone Work for Fentanyl Addiction?

Methadone is both safe and effective in treating opioid use disorder (OUD). Researchers have found methadone to protect against fentanyl overdose, even among those who continue to use fentanyl while on treatment. This is why experts recommend switching to methadone from another opioid addiction treatment medication if a patient continues to use fentanyl while in treatment.5

Methadone treatment has also been shown to significantly reduce mortality as well as illegal opioid use. Studies suggest that patients f receiving methadone treatment remain in treatment longer compared to those who receive buprenorphine.5

A recent study of 121 patients who used fentanyl and received methadone treatment found that 75% of the individuals achieved remission within 12 months after starting treatment. About 64 of the patients completed the full 12 months of treatment, and 63 of those individuals achieved remission.10

Methadone is also a versatile medication because it can be taken by those who engage in injection opioid use, are pregnant, have another mental health diagnosis, or also use stimulants.

Experts recommend that treatment also include treating the co-occurring physical or mental health disorders because they can impact opioid use disorder and vice versa. For instance, depression can contribute to fentanyl use, and fentanyl use can contribute to depression symptoms.5

What Safeguards Are Available During Methadone Treatment?

Your provider works closely with you to ensure that you are getting the benefits of methadone treatment while minimizing the risks side effects. They provide education on methadone and harm reduction strategies. These strategies are actions you take to help minimize the risk common side effects, severe side effects, and rare potential methadone toxicity, which is a life-threatening emergency.5

Harm reduction strategies to practice if you continue to use fentanyl while on methadone treatment include:5

  • Not using fentanyl alone
  • Calling 911 if someone gets unusually sleepy after using fentanyl
  • Administering naloxone until paramedics arrive

Naloxone (Narcan) is a medication that reverses a fentanyl overdose. It does this by attaching to the opioid receptors in your brain and blocking the fentanyl. Naloxone temporarily restores breathing during an overdose, but it is not a replacement for medical intervention.11

Signs of a fentanyl overdose include:11

  • Breathing or heartbeat is very slow or has stopped
  • The person cannot be awakened or cannot speak
  • The body is limp
  • The face is extremely pale or feels clammy
  • Fingernails or lips have a blue or purple tinge
  • The person is vomiting or making gurgling noises

Because some risk exists for methadone overdose, experts recommend that physicians start prescribing take-home doses of methadone after at least the first 1-2 months of administering the medication daily at the office. Your provider gives you a limited number of doses to take home, usually one week’s worth of methadone at one time.5

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Are There Alternative Treatments for Fentanyl Addiction?

If you are not a good candidate for methadone treatment for fentanyl addiction, other medications are available. Health providers will also recommend these alternatives if you:8

  • Have a history of another substance use disorder
  • Have experienced a drug overdose before
  • Use fentanyl in high quantities
  • Have an occupation that does not allow treatment with opioid agonists or partial agonists

Buprenorphine is another medication for opioid use disorder (OUD) and it is safer than methadone in terms of overdose risk. It also does not depress the respiratory system as much as methadone does.8

Naltrexone is another medication for fentanyl addiction that has no misuse potential. Some experts recommend naltrexone for mild opioid addiction and for patients who are highly motivated for treatment.8

Recovery is possible. For help with finding treatment providers for fentanyl addiction, please call 800-994-1867Who Answers? to learn more about your treatment options, available toll-free 24/7.


  1. United States Drug Enforcement Administration. (n.d.). Facts about fentanyl.
  2. Jones, C.M, Einstein, E.B., & Compton, W.M. (2018). Changes in synthetic opioid involvement in drug overdose deaths in the United States, 2010-2016. Journal of American Medical Association, 319(17), 1819-1821.
  3. National Institutes of Health. (2021). Medications to Treat Opioid Use Disorder Research Report. National Institute on Drug Abuse.
  4. Rosic, T., Naji, L., Bawor, M., Dennis, B.B., Plater, C., Marsh, D.C., Thabane, L., & Samaan, Z. (2017). The Impact of Co-morbid Psychiatric Disorders on Methadone Maintenance Treatment in Opioid Use Disorder: A Prospective Cohort Study. Neuropsychiatric Disease and Treatment, 13, 1399-1408.
  5. Bromley, L., Kahan, M., Regenstreif, L., Srivastava, A., & Wynam, J. (2021, June 30). Methadone treatment for people who use fentanyl: Recommendations.
  6. Jordan, C.J., Cao, J., Newman, A.H., & Xi, Z. (2019). Progress in agonist therapy for substance use disorders: Lessons learned from methadone and buprenorphine. Neuropharmacology, 158.
  7. Centers for Disease Control and Prevention. (2022, February 23). Fentanyl facts.
  8. Centers for Disease Control and Prevention. (n.d.). Module 5: Assessing and Addressing Opioid Use Disorder (OUD).
  9. American Psychiatric Association. (2013). Substance-related and addictive disorders. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Publishing.
  10. Stone, A.C., Carroll, J.J., Rich, J.D., & Green, T.C. (2020). One year of methadone maintenance treatment in a fentanyl endemic area: Safety, repeated exposure, retention, and remission. Journal of Substance Abuse Treatment, 115.
  11. Substance Abuse and Mental Health Services Administration. (2018). Opioid Overdose Prevention Toolkit.
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