Medications for Opioid Use Disorder

Opioid use disorder is a complex, treatable chronic medical condition from which people can recover. A person is diagnosed with opioid use disorder if they have two or more of the symptoms and behaviors related to their opioid use listed in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5^th Edition.

For example, they may use opioid drugs more or for longer than intended, experience a strong desire to use opioid drugs (cravings), continue to use opioid drugs even when knowing that it causes problems, or experience withdrawal symptoms when stopping opioid use.¹ To learn more, see the NIDA research topic about addiction science.

There are FDA-approved medications that can help people stop or reduce opioid use. They may also help treat withdrawal symptoms that occur when people stop taking opioids and reduce drug cravings without creating the strongly pleasurable effects of opioid drugs. These medications include methadone, buprenorphine, and naltrexone.² Another medication, lofexidine, is available to treat the acute symptoms of opioid withdrawal.³ 

Methadone is an opioid medication that has been used for more than 50 years to treat opioid use disorder.⁴  It binds to and activates the same molecules on neurons (nerve cells), called mu-opioid receptors, as heroin, fentanyl, and other opioid drugs. However, methadone activates these receptors more slowly than those drugs and also remains in the body longer. As a result, methadone produces less intense feelings of pleasure in people with opioid use disorder while reducing their withdrawal symptoms and drug cravings.⁵

In the United States, methadone is only available from approved opioid treatment programs when used to treat opioid use disorder. When people start opioid use disorder treatment, they usually must go to a program location every day or almost every day to receive their medication. However, since 2020, new regulations allow many people who have been in treatment for a while to receive up to 28 doses of methadone from their treatment program to take home with them.⁶ NIDA-funded studies have shown that allowing more take-home doses of methadone is safe and may help people stay in treatment, have better outcomes, and make more positive life changes.^{7, 8}

Buprenorphine is another opioid medication that is used to treat opioid use disorder. Buprenorphine also binds to and activates mu-opioid receptors in the brain, but to a lesser degree than methadone; it also can block other opioid drugs from attaching to those receptors. Like methadone, buprenorphine can reduce cravings and withdrawal symptoms without producing intense feelings of pleasure and intoxication in people who have opioid use disorder.

Several buprenorphine products are approved for treatment of opioid use disorder, including tablets that are placed under the tongue, extended-release injections, and implants. Other products contain buprenorphine together with the overdose-reversal medication naloxone, including tablets or film to put under the tongue or film to place in the cheeks.⁹

Methadone and buprenorphine can be equally effective in helping people reduce opioid use.¹⁰ Both medications help people stay in treatment. Methadone may help some people stay in treatment longer.¹¹

Unlike methadone, buprenorphine can be prescribed by many doctors, nurse practitioners, and physician assistants. There is no need to visit special treatment clinics.⁹ Since the COVID-19 pandemic, health care providers can even prescribe buprenorphine via telehealth services, making it easier for people to get buprenorphine and stay in treatment.¹²

Buprenorphine treatment can also be started in the emergency department to ease withdrawal and cravings after an overdose.¹³  This can help motivate people to begin long-term treatment.

Naltrexone is another medication approved for the treatment of opioid use disorder; it is also approved for the treatment of alcohol use disorder. Unlike methadone and buprenorphine, naltrexone works solely by blocking opioid receptors so that opioid drugs can no longer cause feelings of pleasure.¹⁴ Evidence also suggests that naltrexone reduces opioid cravings.¹⁵

Naltrexone is available as a long-acting injection (Vivitrol^®) that needs to be given once a month. Any health care provider can prescribe naltrexone. Naltrexone treatment is typically started after the person has completely stopped taking other opioid drugs; otherwise, the medication may cause withdrawal symptoms.¹⁶

Naltrexone can be as effective as buprenorphine in helping people avoid returning to drug use when it is taken for a long period of time. However, starting naltrexone treatment may be harder for people using opioid drugs than starting buprenorphine or methadone treatment. This is because a person usually needs to stop taking opioids for 7 to 10 days first.¹⁵ However, NIDA-supported research suggests that a faster treatment approach that reduces the waiting time to start naltrexone can also be effective.¹⁷

The medication lofexidine (Lucemyra^®) is approved for treatment of withdrawal symptoms that can happen when people suddenly stop taking opioids. These symptoms can include feeling sick, stomach cramps, muscle spasms, heart pounding, aches and pain, or sleep problems.¹⁸ Lofexidine is not used for long-term treatment of opioid use disorder.

Research has shown that methadone, buprenorphine, and naltrexone can reduce opioid use and other negative health outcomes. For example:

• People with opioid use disorder who are treated with methadone or buprenorphine are less likely to die or to have an overdose than those who do not receive treatment.^{19, 20}
• People with opioid use disorder who are treated with methadone or buprenorphine are less likely to engage in behaviors that put them at risk for HIV or hepatitis C virus infection, such as injecting drugs, sharing injection equipment, or having multiple sex partners.^{21, 22}
• People who are in prison or jail and receive treatment with methadone or buprenorphine are more likely to stay in treatment after release. They are also less likely to have an overdose or to be arrested or incarcerated again after release.^{23, 24}

Both methadone and buprenorphine bind to and activate the same mu-opioid receptors in the brain as do other opioid drugs. So, some people may think they are just substituting one drug for another. However, when taken as prescribed by people with opioid use disorder, methadone and buprenorphine prevent drug cravings and withdrawal symptoms without causing the intense feelings of pleasure (or “high”) that other opioid drugs produce. This makes methadone and buprenorphine less addictive.

Like many medications, methadone and buprenorphine do produce dependence. When a person suddenly stops taking their medication abruptly, they may experience withdrawal symptoms. However, these effects are milder than those produced by dependence on other opioid drugs and can be managed by slowly reducing the medication dose rather than stopping it abruptly.

Both methadone and buprenorphine can be misused to achieve rewarding effects if injected instead of taken by mouth as prescribed.² People without an opioid use disorder could experience a high when taking them orally. Studies show that the majority of people who misuse buprenorphine do so to control withdrawal symptoms form other opioids, not to experience a high.^{25, 26}

Naltrexone is not addictive. Although it also binds to the mu-opioid receptor, naltrexone blocks the receptor, rather than activates it.

Although medications are effective, less than 20% of people with opioid use disorder receive them.²⁷ Several factors may contribute to these low rates:

• People who live in rural or small suburban communities or who lack reliable transportation may not have an opioid treatment program nearby where they can receive methadone.²⁸
• Some people may have a hard time filling buprenorphine prescriptions because many pharmacies do not carry or dispense it.²⁹
• Stigma associated with substance use disorder treatment—both toward people in recovery and/or by their health care providers—may limit access to these medications.³⁰
• People from racial and ethnic minoritized groups may face more barriers to medication treatment for opioid use disorder than White individuals.^{31, 32}

Telehealth appointments can facilitate access to medications for opioid use disorder. They help engage and keep people in treatment, increase patient satisfaction with their care, and reduce many of the traditional barriers to treatment, including stigma.^{12, 33}

Treatment for opioid use disorder is important during pregnancy. Untreated, the disorder may harm the health of a pregnant woman and the developing baby in these ways: ^{34, 35}

• Pregnant women with untreated opioid use disorder may receive poor prenatal care or experience malnutrition.
• Exposure to drugs and drug withdrawal can harm the developing baby’s health and growth. They may be born too early, have a low birth weight, experience convulsions, or even die.
• Babies born to women with opioid use disorder also may experience withdrawal symptoms after birth. This is known as neonatal opioid withdrawal syndrome.

Yes. Treatment with methadone or buprenorphine is recommended for pregnant women with opioid use disorder. Buprenorphine treatment may lead to better health outcomes for infants than methadone treatment. For example, infants whose mothers were treated with buprenorphine were less likely to have neonatal opioid withdrawal syndrome or have a low birth weight than those whose mothers were treated with methadone.³⁶  NIDA-funded studies are investigating the best approach for treating opioid use disorder in pregnant women.

Medications for opioid use disorder are also safe for women who are breastfeeding and for their infants. Breastfeeding helps the mother and infant to bond, and it can ease the symptoms of neonatal opioid withdrawal syndrome and improve a baby’s health outcomes. Only minimal amounts of methadone or buprenorphine pass into breast milk.³⁷

Many people who are taking medications for opioid use disorder have acute pain—for example, after surgery—or live with chronic pain.³⁸ Pain management for these people requires special consideration. For example, some medications for opioid use disorder may make other opioid pain medications less effective in relieving pain.³⁹

Both methadone and buprenorphine can reduce pain. So, people with acute or chronic pain may be advised to continue using these medications. However, naltrexone blocks the effects of opioids. Health care professionals may advise that people treated with naltrexone should discontinue the medication before surgery if they are likely to need treatment with opioid pain medications afterwards.⁴⁰

In all patients with opioid use disorder who have acute or chronic pain, the American Society of Addiction Medicine recommends that medication-free treatments, such as physical therapy or behavioral therapy, or treatment with non-opioid pain medications should be tried first.^{40, 41}

NIDA plays a leading role in the National Institutes of Health HEAL (Helping to End Addiction Long-term®) Initiative, an effort to develop new scientific solutions to the overdose epidemic, including opioid and stimulant use disorders, and the crisis of chronic pain.