The first evidence-based medication for methamphetamine use disorder
For the first time in the long and difficult history of methamphetamine addiction, science has offered something it never could before: a medication that measurably helps. A federally funded trial published in the New England Journal of Medicine found that combining bupropion and naltrexone produced significantly better outcomes than placebo for people with moderate-to-severe methamphetamine use disorder — a condition that, unlike opioid or alcohol dependence, has never had an FDA-approved pharmaceutical treatment. The gains are modest, the researchers are careful, and the real world will test what the clinic has only begun to prove — but for millions who have faced a medical dead end, there is now, at last, a door.
- Methamphetamine use disorder has long been a treatment orphan — while opioid and alcohol addiction had approved medications, meth left clinicians with nothing pharmaceutical to offer as overdose deaths climbed past 70,000 in 2019.
- A rigorously controlled trial of 403 participants found that 13.6% on the bupropion-naltrexone combination tested negative for meth use, compared to just 2.5% on placebo — a gap modest in absolute terms but significant in a field where zero had been the baseline.
- Patients on the active treatment also reported fewer cravings and improved quality of life, though side effects including nausea, vomiting, and constipation were more common than in the placebo group.
- The National Institute on Drug Abuse called the findings a watershed moment, while the researchers themselves cautioned that tightly monitored trial conditions may not reflect the messiness of real clinical practice.
- The field now faces its next challenge: determining whether these benefits hold in real-world settings, across longer timeframes, and for the full spectrum of patients who need help most.
For years, people struggling with methamphetamine addiction faced a particular kind of medical dead end. While doctors could prescribe medications to ease opioid cravings or help someone quit alcohol, nothing existed in the pharmaceutical toolkit for meth use disorder — and that absence has mattered enormously as the drug surged alongside a broader overdose crisis that claimed more than 70,000 lives in 2019 alone.
A federally funded clinical trial published this week in the New England Journal of Medicine offers the first concrete evidence that a two-drug combination can actually help. Researchers tested bupropion — an antidepressant already used to help people quit smoking — paired with naltrexone, a medication known to work against opioid and alcohol dependence. The trial enrolled 403 people with moderate-to-severe methamphetamine use disorder, randomly assigning them either the medication combination or a placebo.
The results diverged sharply: 13.6 percent of people on the medication combo tested negative for methamphetamine at least three out of four times, compared to just 2.5 percent on placebo. Participants in the treatment group also reported fewer cravings and noticeable improvements in their overall quality of life. No serious side effects emerged, though nausea, vomiting, and constipation were more common in the treatment group.
The researchers are careful not to oversell the gains. They note that the magnitude of improvement roughly matches what doctors see with established treatments for other serious conditions, including alcohol use disorder — meaningful context for a disease that can cause heart damage, brain injury, severe paranoia, hallucinations, and devastating dental deterioration.
Nora Volkow of the National Institute on Drug Abuse called the finding a watershed moment, but the authors acknowledge the work is far from finished. The trial was tightly controlled — real-world patients miss appointments, and life gets messy. Whether this combination holds up in actual clinical practice, and whether its benefits persist beyond the trial window, remains the next critical question. For now, though, there is something to build on.
For years, people struggling with methamphetamine addiction have faced a particular kind of medical dead end. While doctors could prescribe medications to ease opioid cravings or help someone quit alcohol, nothing existed in the pharmaceutical toolkit specifically designed to treat methamphetamine use disorder. That absence has mattered enormously as the drug has surged alongside the broader overdose crisis—more than 70,000 people died from overdoses in 2019 alone, and the numbers have only climbed since.
A federally funded clinical trial published this week in the New England Journal of Medicine offers the first concrete evidence that a two-drug combination can actually help. Researchers tested bupropion, an antidepressant already used to help people quit smoking, paired with naltrexone, a medication known to work against opioid and alcohol dependence. The trial enrolled 403 people with moderate-to-severe methamphetamine use disorder, randomly assigning them either the medication combination or a placebo. A second phase brought in 225 more participants from the placebo group who hadn't responded to treatment.
The numbers tell a cautious but real story of progress. Participants receiving the active treatment got naltrexone injections every three weeks plus a daily bupropion pill, while everyone—both treatment and control groups—met weekly with clinicians and underwent regular urine testing. When researchers defined success as testing negative for methamphetamine at least three out of four times, the results diverged sharply: 13.6 percent of people on the medication combo met that threshold, compared to just 2.5 percent on placebo. Beyond the drug tests, participants in the treatment group reported fewer cravings and noticeable improvements in their overall quality of life, though researchers note these self-reported measures carry less certainty than the objective testing.
The gains are modest, and the researchers are careful not to oversell them. No serious side effects emerged, though people on the active treatment did experience higher rates of nausea, vomiting, and constipation. But the authors point out that the magnitude of improvement here roughly matches what doctors see with established treatments for other serious conditions, including alcohol use disorder. For a disease that can cause heart damage, brain injury, severe paranoia, hallucinations, and the kind of tooth decay that leaves people unable to eat, even modest progress represents something genuinely new.
Nora Volkow, director of the National Institute on Drug Abuse, which helped fund the research, called the finding a watershed moment—evidence that medical treatment for methamphetamine use disorder can actually shift outcomes for patients. Yet the authors themselves acknowledge the work is far from finished. The trial was tightly controlled, with weekly clinical visits and regular monitoring. Real-world settings look different. Patients miss appointments. Life gets messy. The next phase of research will need to test whether this combination holds up when deployed in actual clinical practice and whether the benefits persist over months and years, not just the six-week trial window. For now, though, there is something to build on.
Notable Quotes
This advance demonstrates that medical treatment for methamphetamine use disorder can help improve patient outcomes— Nora Volkow, director of the National Institute on Drug Abuse
The Hearth Conversation Another angle on the story
Why does methamphetamine addiction seem so much harder to treat than opioid addiction?
It's partly neurochemistry—meth affects the brain differently than opioids do, and we've had decades to develop opioid treatments. But it's also about resources and attention. The overdose crisis focused heavily on opioids, so the research and medication development followed that money.
So this study is saying bupropion and naltrexone work together in a way neither does alone?
Not quite. Bupropion is an antidepressant that affects dopamine and norepinephrine. Naltrexone blocks opioid receptors. Together, they seem to reduce cravings and make it easier for people to stay engaged with treatment. But we don't fully understand the mechanism yet.
The success rate is still pretty low—13.6 percent. How is that hopeful?
Because it's the first time we've seen anything work at all. And that 13.6 percent is five times better than placebo. For a disease that's been completely untreatable, that's genuinely significant. It's a foothold.
What happens to the people in the study after six weeks?
That's the real question nobody can answer yet. The trial ended there. We don't know if people stay off meth, if they relapse, if they need the medication forever. Real life is messier than a controlled trial.
Does this mean people can get this treatment now?
Not automatically. The study provides evidence it works, but it still needs to move through the system—insurance coverage, clinical guidelines, training for providers. And doctors will want to see more data from real-world use before making it standard practice.