Substance use disorder medications explained

What substance use disorder medications are

Substance use disorder (SUD) medications are the FDA-approved treatments that reduce craving, block or replace the effect of the substance, or make using the substance unpleasant. They're used alongside counseling and mutual support (12-step, SMART Recovery, or other programs), but they aren't optional add-ons. For opioid use disorder in particular, the evidence is strong that medication treatment reduces overdose death and saves lives, and treatment without medication has much worse outcomes.

The class covered here includes medications for opioid use disorder (buprenorphine, methadone, naltrexone injectable and oral, naloxone for overdose reversal, lofexidine for withdrawal), alcohol use disorder (naltrexone, acamprosate, disulfiram), and tobacco use disorder (varenicline, nicotine replacement therapy, bupropion). Bupropion has a separate page as an antidepressant. Naltrexone-bupropion combined (Contrave) is used for weight, not SUD, but is included on the site.

How they work

The mechanisms differ by substance and by medication.

Opioid use disorder medications. Buprenorphine is a partial agonist at the mu opioid receptor. That means it activates the receptor, but only partly, so it eases withdrawal and craving without producing the full euphoric effect a full agonist like heroin or fentanyl would. Buprenorphine also has a ceiling effect on respiratory depression, which is a big part of why it's safer than full agonist opioids. Methadone is a long-acting full agonist at the mu opioid receptor. It occupies the receptor, prevents withdrawal, and blocks the effect of shorter-acting opioids taken on top. Naltrexone is a full antagonist. It blocks the mu opioid receptor completely, so opioids taken while on naltrexone don't produce a high. Because it's a full blocker, naltrexone can only be started after someone has fully detoxed, or it will precipitate withdrawal.

Alcohol use disorder medications. Naltrexone reduces alcohol craving and reduces the reward from drinking. The mechanism isn't entirely worked out, but it's thought to involve opioid receptor blockade in reward circuits. Acamprosate acts on glutamate and GABA signaling and is thought to reduce protracted withdrawal symptoms. Disulfiram works differently. It blocks the enzyme that breaks down acetaldehyde, an alcohol byproduct. If someone drinks on disulfiram, acetaldehyde builds up and produces a very unpleasant reaction (flushing, nausea, vomiting, headache, rapid heart rate). It's an aversion approach.

Tobacco use disorder medications. Varenicline is a partial agonist at the nicotinic acetylcholine receptor. It partly activates the receptor to reduce withdrawal and craving, and it partly blocks it so that smoking is less rewarding. Nicotine replacement therapy (NRT), including gum, patches, lozenges, inhalers, and nasal spray, delivers nicotine without the tobacco smoke, so cravings ease and the transition to no nicotine happens in stages. Bupropion, an antidepressant, reduces craving through effects on dopamine and norepinephrine.

Withdrawal medications. Lofexidine is an alpha-2 adrenergic agonist approved for opioid withdrawal. It doesn't treat opioid use disorder itself but reduces the autonomic symptoms of withdrawal (sweating, tearing, chills, cramping) during detox. Clonidine is used similarly off-label.

Overdose reversal. Naloxone is an opioid antagonist. It doesn't treat opioid use disorder but reverses an active opioid overdose. It's available as a nasal spray (Narcan and generics) and by injection. Everyone using opioids or in an opioid-using household should have it.

How the class developed

Each substance has its own history.

Methadone was first used for opioid use disorder in the 1960s in New York City by Vincent Dole and Marie Nyswander. Their observation was that people on stable methadone stopped seeking heroin, stopped injecting, and could return to work and family life. Methadone maintenance treatment became the standard for decades, though it was heavily regulated and mainly delivered in specialized clinics.

Buprenorphine, developed in the 1970s as a pain medication, was approved for opioid use disorder in the U.S. in 2002 under the Drug Addiction Treatment Act (DATA 2000). That law allowed office-based prescribing by qualified physicians, which was a major change from the clinic-only methadone model. The X-waiver requirement was eliminated in 2023, so any DEA-licensed clinician can now prescribe buprenorphine for opioid use disorder.

Naltrexone for alcohol use disorder was approved in 1994. The injectable form (Vivitrol) was approved in 2006 for alcohol use disorder and in 2010 for opioid use disorder. Acamprosate was approved in 2004, and disulfiram is much older, dating from 1951.

Varenicline was approved for smoking cessation in 2006. Nicotine replacement therapy started with nicotine gum in the 1980s and expanded to patches, lozenges, inhalers, and nasal sprays.

The clinical picture around SUD medication changed in the 2010s and 2020s. The opioid overdose crisis, driven by prescription opioids and later illicit fentanyl, pushed medication treatment for opioid use disorder toward being the standard of care rather than one option among many. ASAM (American Society of Addiction Medicine) and SAMHSA both recommend medication as first-line for opioid use disorder, with clear evidence that it reduces overdose death.

What they treat

• Opioid use disorder. Buprenorphine, methadone, and naltrexone are the three FDA-approved medications. All reduce use and improve retention in treatment.
• Alcohol use disorder. Naltrexone (oral or injectable), acamprosate, and disulfiram are the FDA-approved options.
• Tobacco use disorder. Varenicline, nicotine replacement therapy, and bupropion are the first-line treatments.
• Opioid withdrawal. Lofexidine is FDA-approved for reducing withdrawal symptoms during opioid detoxification. Clonidine is used similarly off-label.
• Opioid overdose reversal. Naloxone reverses an active opioid overdose. It's not itself a treatment for opioid use disorder but is essential in any household or setting where opioid overdose is a risk.

There aren't currently FDA-approved medications for stimulant use disorder (cocaine, methamphetamine) or cannabis use disorder, though several are studied. Contingency management remains the most evidence-based treatment for stimulant use disorder.

Individual medications in this class

• Buprenorphine (Subutex, Suboxone, Sublocade, Zubsolv). A partial opioid agonist. Available as sublingual tablets and films, buccal films, and a monthly extended-release subcutaneous injection (Sublocade). Suboxone is buprenorphine combined with naloxone to deter injection misuse. First-line for opioid use disorder.
• Methadone. A long-acting full opioid agonist. Delivered through federally regulated opioid treatment programs (OTPs), meaning specialized clinics. First-line for opioid use disorder, especially for people who haven't done well on buprenorphine.
• Naltrexone, oral (ReVia, Depade). A full opioid antagonist taken by mouth daily. Used for alcohol use disorder and opioid use disorder, though adherence to a daily pill is the main challenge.
• Naltrexone, injectable (Vivitrol). Extended-release naltrexone given as a monthly intramuscular injection. Approved for both alcohol use disorder and opioid use disorder. Requires full opioid detox before starting.
• Acamprosate (Campral). Alcohol use disorder. Reduces protracted withdrawal symptoms and supports abstinence. Taken three times daily.
• Disulfiram (Antabuse). Alcohol use disorder. Creates an unpleasant reaction if alcohol is consumed. Best used with supervision and a person committed to abstinence, not moderation.
• Varenicline (Chantix, Tyrvaso). Tobacco use disorder. Partial agonist at the nicotinic receptor.
• Nicotine replacement therapy (patch, gum, lozenge, inhaler, spray). Tobacco use disorder. Available over the counter.
• Bupropion (Wellbutrin, Zyban). Antidepressant that's also FDA-approved for smoking cessation (under the brand name Zyban).
• Lofexidine (Lucemyra). Alpha-2 agonist for opioid withdrawal.
• Naloxone (Narcan). Opioid antagonist for overdose reversal. Nasal spray available over the counter.
• Naltrexone-bupropion (Contrave). A combination used for weight, not SUD. Listed here for completeness because it appears on the site.

Common side effects across the class

Because the mechanisms differ, the side effects differ too. What's common by category:

Opioid use disorder medications.

• Buprenorphine: constipation, headache, nausea, sweating. Some people find the sublingual film unpleasant to taste.
• Methadone: sedation, sweating, constipation, weight gain over time. Prolonged QT interval is a specific concern at higher doses.
• Naltrexone: nausea, headache, fatigue. Injectable naltrexone can cause injection-site reactions. Precipitated withdrawal if given too soon after opioid use.

Alcohol use disorder medications.

• Naltrexone: nausea, headache, fatigue, injection-site reactions with the injectable form.
• Acamprosate: diarrhea is the most common.
• Disulfiram: fatigue, headache, metallic taste. The reaction with alcohol is severe and expected: flushing, nausea, vomiting, rapid heart rate, low blood pressure. This isn't a side effect but is the mechanism.

Tobacco use disorder medications.

• Varenicline: vivid or unusual dreams, nausea, headache, insomnia.
• NRT: skin irritation with the patch, throat and mouth irritation with gum or lozenge, mild sleep disturbance with higher-dose patches.
• Bupropion: insomnia, dry mouth, headache, agitation.

Serious warnings across the class

The warnings that matter most.

• Boxed warning for methadone regarding QT prolongation and serious arrhythmias, and separately regarding respiratory depression and death, especially during initiation and dose changes.
• Boxed warning for disulfiram regarding severe hepatotoxicity. Liver function tests are checked at baseline and periodically.
• Boxed warning for naltrexone regarding hepatotoxicity at high doses (though at usual treatment doses this risk is small).
• Precipitated withdrawal. Buprenorphine and naltrexone can trigger opioid withdrawal if started while opioids are still active. For buprenorphine, this means starting after mild-to-moderate withdrawal has begun (using COWS score guidance) or using a low-dose induction strategy. For naltrexone, full detox with a several-day opioid-free window is required, sometimes longer for long-acting opioids.
• Overdose risk. Opioid tolerance drops during any period off opioids (jail, hospital, residential treatment, sustained abstinence). Someone returning to their previous dose after a break is at high overdose risk. That's true whether they were on medication treatment or not.
• Interactions. Methadone and buprenorphine both interact with medications that affect CYP3A4 (some antifungals, some HIV medications, rifampin). Varenicline and disulfiram have their own interaction profiles.
• Neuropsychiatric effects. Varenicline previously carried a boxed warning about neuropsychiatric symptoms, which was removed in 2016 after the EAGLES trial found no significantly increased psychiatric risk versus placebo, patch, or bupropion. Attention to mood changes on any of these medications is still reasonable.
• Naloxone and community. Anyone with an opioid use history, or anyone in their household, should have naloxone. It's now available over the counter as a nasal spray. Recognizing overdose (unresponsive, slow breathing, blue lips) and giving naloxone can save a life.

What tips the choice within the class

For opioid use disorder. Buprenorphine and methadone both work well. Buprenorphine is usually first-line for someone who can access office-based prescribing and doesn't have very high opioid tolerance. Methadone is often preferred for people with high tolerance, for people who haven't done well on buprenorphine, or for people who prefer or need daily clinic contact. Naltrexone is a reasonable option for someone who has fully detoxed and prefers a non-opioid medication, though outcomes on average are less good than with buprenorphine or methadone.

For alcohol use disorder. Naltrexone (oral or injectable) is often the first-line choice, particularly for people who want to reduce drinking rather than eliminate it right away. Acamprosate suits someone who has already reached abstinence and wants support to stay there. Disulfiram works for someone committed to abstinence with structure (often supervised dosing).

For tobacco use disorder. Varenicline has the highest quit rates in most head-to-head trials, followed by combination NRT (patch plus short-acting form like gum or lozenge), then single-form NRT, then bupropion. Prior response and side-effect tolerance shape the choice.

Adherence and delivery. Daily oral medication (naltrexone, acamprosate, varenicline, bupropion) requires reliable daily use. Extended-release injections (buprenorphine Sublocade, naltrexone Vivitrol) remove the daily decision. Methadone requires daily clinic visits at first, with take-home doses earned over time.

Pregnancy. Buprenorphine and methadone are both compatible with pregnancy and are the standard for pregnant people with opioid use disorder. Untreated opioid use disorder in pregnancy carries much worse outcomes than either medication.

Guidance from ASAM and SAMHSA recommends medication as first-line for opioid use disorder, and against short-term detox without medication continuation, because relapse and overdose risk after detox-only approaches are very high.

Common questions

Isn't buprenorphine or methadone just trading one addiction for another? No. Both medications treat opioid use disorder by occupying the mu opioid receptor in a stable, controlled way that ends the cycle of craving, withdrawal, and use. On a stable dose, people don't get high, don't have withdrawal, and can work, care for family, and live their lives. The evidence is clear: buprenorphine and methadone reduce overdose death, reduce infectious disease transmission, and improve function. Untreated opioid use disorder has much worse outcomes than medication treatment.

Do I need to fully detox before starting naltrexone? Yes. Naltrexone is a full opioid antagonist. If it's started while opioids are still active in the body, it will precipitate severe withdrawal. That means at least seven to ten days opioid-free for short-acting opioids, and longer for long-acting ones like methadone. This is the main practical limitation of naltrexone for opioid use disorder. Buprenorphine has a lower threshold: it can be started after mild-to-moderate withdrawal has begun.

How long do people stay on medication for opioid use disorder? There's no fixed answer. For many people, indefinitely, in the same way someone with high blood pressure might stay on medication indefinitely. Coming off buprenorphine or methadone carries a high risk of relapse and overdose, and the decision to try tapering off is best made with a prescriber when someone is stable, has strong recovery supports, and understands the risks. Long-term medication treatment is safe and is not a sign of weakness or failure.

What is naloxone and who should have it? Naloxone is an opioid antagonist that reverses opioid overdose. It's available over the counter as a nasal spray (Narcan and generics). Anyone using opioids, anyone recently out of treatment (opioid tolerance drops during any opioid-free period), anyone on a high-dose prescribed opioid, and anyone with a family member or roommate in any of those categories should have naloxone easily accessible. It's inexpensive, easy to use, and saves lives.

Can I moderate my drinking on naltrexone, or do I have to be abstinent? Naltrexone can be used for either goal. The Sinclair Method uses naltrexone taken about an hour before drinking, with the goal of gradually reducing the reward from alcohol and drinking less over time. That's different from the abstinence-oriented approach, where naltrexone is taken daily. Both have evidence behind them. The right approach depends on someone's own goals and situation, and it's worth discussing with a prescriber. Disulfiram, by contrast, requires abstinence, because drinking on disulfiram causes a severe reaction.

Sources

This guide draws on current prescribing information and public health references. It's reviewed for clinical accuracy and updated as guidance changes. This is educational content, not medical advice.

1. U.S. Food and Drug Administration. Prescribing information.
2. MedlinePlus, U.S. National Library of Medicine.
3. National Institute on Drug Abuse.
4. Substance Abuse and Mental Health Services Administration (SAMHSA). TIP 63: Medications for Opioid Use Disorder.
5. American Society of Addiction Medicine (ASAM). National Practice Guideline for the Treatment of Opioid Use Disorder.
6. American Psychiatric Association. Practice guideline for the treatment of patients with substance use disorders.