Methadone Treatment for Opioid Use Disorder: How It Works

Methadone is a long-acting opioid medication that’s been used for decades to treat opioid use disorder (OUD). Taking methadone under medical supervision can help people manage OUD by reducing opioid cravings, easing withdrawal symptoms, and lowering the risk of overdose.

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Although methadone isn’t a quick fix for OUD, it can help many people stay in treatment longer. In this article, we’ll explore how methadone works, along with its potential risks and benefits.

What Is Methadone?

Methadone is a synthetic (lab-made) opioid medication that’s approved by the U.S. Food and Drug Administration (FDA) for:

• Moderate to severe pain that doesn’t respond to nonnarcotic pain medications
• Medically supervised withdrawal from opioids
• Ongoing maintenance treatment for OUD

Because methadone is FDA-approved for OUD, it’s part of a group of drugs called medications to treat opioid use disorder (MOUDs). Other MOUD options include buprenorphine and naltrexone. Methadone is also sold under the brand names Diskets, Dolophine, and Methadose.

How Does Methadone Work?

Methadone blocks and reduces the effects of opioids in the brain. To understand how this drug works, it helps to know a little more about how opioids work in the brain.

Opioids Affect the Brain

Opioids — such as fentanyl (prescription) and heroin (nonprescription) — attach to proteins in the brain called mu-opioid receptors. These receptors help control pain, pleasure, and other functions. When opioids bind to mu-opioid receptors, they trigger the brain to release endorphins — chemicals that tell the brain to feel good. This creates the euphoria or “high” that often drives opioid misuse.

Repeated opioid use changes the way the brain functions, lowering endorphin production. This can result in tolerance (needing more of the drug to achieve the same effect) and dependence (experiencing withdrawal symptoms when not taking opioids). These changes make quitting opioids extremely difficult without medical support.

Methadone Is a Long-Acting Opioid

Like other opioids, methadone also activates mu-opioid receptors (making it an opioid agonist). At first, it may seem surprising that an opioid is used to treat OUD. However, methadone is a long-acting opioid. This means methadone activates the receptors more slowly than other types of opioids and stays in the body much longer — typically 24 to 36 hours.

Because it works more gradually, methadone produces a steadier effect without the intense highs and lows of other opioids. This can help reduce withdrawal symptoms and curb opioid cravings without causing a high.

How Do You Take Methadone for OUD?

Methadone is just one part of a comprehensive treatment plan for OUD, which also includes counseling and behavioral therapy. It’s available in different forms, including a liquid, powder, or diskette (a tablet that dissolves in water). Your healthcare team will work with you to find the right dosage form that best fits your needs and treatment goals.

To start methadone treatment, you must be enrolled in an opioid treatment program (OTP) certified by the Substance Abuse and Mental Health Services Administration (SAMHSA) and registered with the Drug Enforcement Administration (DEA). In some cases, methadone treatment may also begin during a hospital stay. Never start methadone therapy on your own — the dose must always be supervised to avoid serious complications.

Most people will start with a dose of 10 to 30 milligrams of methadone. Your healthcare team will monitor you closely for several hours after your first dose. If your opioid tolerance is low — such as when restarting methadone after a relapse — your starting dose may be lower.

Lower doses of methadone may improve opioid withdrawal symptoms. However, higher doses may be needed to control cravings. Your healthcare team will slowly increase your dose over several weeks to help you find the right balance between managing cravings and limiting side effects.

Maintenance Treatment

When you first begin methadone treatment, you’ll go to your OTP location every day to get your medication. After you’ve been stable on treatment and making progress in your recovery for some time, you may be able to take home up to a 28-day supply between visits to your OTP.

Health experts recommend continuing methadone maintenance treatment for at least 12 months. However, there’s no limit on how long you can stay on treatment for OUD. Many people require long-term methadone treatment.

What Are the Risks of Methadone?

Like all medications, methadone has risks, including side effects and drug interactions. Your healthcare team can help you weigh the risks and benefits of methadone treatment based on your individual needs and treatment goals.

Side Effects

Methadone can cause side effects, especially at the beginning of treatment while your dose is being adjusted. After a few days, most people develop a tolerance to the more common side effects, which may include:

• Nausea and vomiting
• Small (“pinpoint”) pupils
• Itching
• Slowed breathing
• Sweating
• Constipation
• Dry mouth
• Lowered sex drive
• Drowsiness
• Low blood pressure

Especially at higher doses (more than 200 milligrams a day), methadone has been linked to serious heart rhythm problems. During treatment, your healthcare provider will monitor your heart regularly. Serious symptoms that could indicate a problem include chest pain, lightheadedness, and a fast or pounding heartbeat.

The most serious side effect of methadone is respiratory depression, which can be life-threatening. This is why methadone therapy must be supervised by a medical professional and doses increased gradually. If methadone toxicity occurs, it can be reversed with naloxone.

Methadone should be tapered gradually. Stopping suddenly can lead to withdrawal symptoms such as restlessness, tremors, and a fast heartbeat.

Talk with your healthcare provider if you experience any unusual effects. Additional serious side effects to watch for include:

• Difficulty breathing
• Dizziness or lightheadedness
• Rash
• Facial swelling
• Hallucinations
• Confusion

Methadone can also pass from the pregnant parent’s blood to the fetus and is present in breast milk. Your healthcare team will help you weigh the benefits and risks if you are pregnant or breastfeeding.

Food and Drug Interactions

Methadone can interact with several medications and even some foods. These interactions can cause methadone levels to become too high (raising the risk of overdose) or too low (leading to withdrawal symptoms).

Examples of medicines and foods that may increase the risk of overdose when taken with methadone include:

• Antibiotics such as ciprofloxacin
• Antifungals such as fluconazole
• Benzodiazepines such as alprazolam
• Antidepressants such as fluoxetine
• Antipsychotics such as quetiapine
• Other opioid medications
• Alcohol
• Grapefruit and grapefruit juice

Examples of drugs that may lower methadone levels and lead to withdrawal symptoms include:

• Antivirals such as efavirenz
• Antibiotics such as rifampin
• Anti-seizure drugs such as phenytoin and carbamazepine

This isn’t a complete list of medicines and foods that can interact with methadone. To help avoid dangerous drug interactions, always tell your healthcare team about all the medications, supplements, and foods you’re taking.

What Are the Benefits of Methadone Treatment?

When taken as prescribed and under medical supervision, methadone is a safe and effective treatment for OUD. Research shows that methadone can reduce opioid use, lower the risk of overdose, and help people stay in treatment longer.

A 2022 study in Ohio found that people taking methadone were more likely to continue treatment compared with those taking buprenorphine or naltrexone. Staying in treatment is important because the longer you remain engaged, the greater the benefits for your recovery and overall quality of life.

Even though research shows that methadone and other MOUDs are effective treatments, it’s estimated that less than 20 percent of people with OUD receive them. If you’re considering treatment, your healthcare provider can help you weigh the risks and benefits of methadone.

Join the Conversation

On MyOpioidRecoveryTeam, people share their experiences with opioid use disorder, get advice, and find support from others who understand.

Have you taken methadone or another type of medication to treat opioid use disorder? How did it work for you? Let others know in the comments below.