The United States has entered a sobering chapter in its battle against drug addiction—what public health experts are calling the “fourth wave” of the overdose epidemic. Unlike the previous waves driven largely by prescription opioids, heroin, and synthetic opioids like fentanyl, this newest wave is fueled by the explosive rise in methamphetamine use—often in dangerous combination with fentanyl. Addressing this crisis requires a strong focus on methamphetamine use disorder treatment to support those struggling and reduce the devastating impact of this epidemic.
This grim reality brings with it a critical challenge: there are still no FDA-approved medications for methamphetamine use disorder. But a new study, published in the peer-reviewed journal Addiction, is offering something we haven’t seen in a long time—hope. Researchers have found that a combination of two medications, naltrexone and bupropion, can reduce methamphetamine use by 27% compared to a placebo.
That breakthrough may seem modest on the surface, but in a landscape where effective pharmacological options are virtually nonexistent, it marks a monumental step forward in methamphetamine use disorder treatment.
Understanding the Fourth Wave: Meth and Fentanyl’s Dangerous Dance
The term “fourth wave” isn’t just a rhetorical flourish—it reflects a dramatic shift in the dynamics of overdose deaths in the U.S.
In 2020, stimulants like methamphetamine were involved in less than 1% of fentanyl-related overdose deaths. By 2021, they were involved in nearly one-third. That’s a staggering rise, and it underscores how methamphetamine has evolved from a fringe drug into a central player in America’s overdose crisis.
There are several reasons behind this increase. Methamphetamine is cheap, potent, and widely available, especially in regions like the western United States. But its rising use isn’t just a matter of accessibility—it’s also about poly-drug use. Many users report taking meth alongside fentanyl to enhance euphoria and counteract fentanyl’s sedative effects, a practice that intensifies both dependency and the risk of overdose.
This combination has proven lethal. Fentanyl already poses a severe overdose risk. Adding methamphetamine to the mix creates an unpredictable chemical cocktail. The need for effective methamphetamine use disorder treatment has never been more urgent.
A New Treatment Approach: The ADAPT-2 Trial
In the face of this crisis, researchers have been urgently seeking solutions. One of the most promising efforts is the ADAPT-2 trial—a multi-phase study funded by the National Institute on Drug Abuse (NIDA). The latest findings from phase two of this trial are providing a hopeful new direction.
Led by researchers at UCLA, the 12-week study involved 403 participants diagnosed with methamphetamine use disorder. They were randomly assigned to either a treatment group or a placebo group. Those in the treatment group received a combination of extended-release injectable naltrexone and extended-release oral bupropion.
- Naltrexone, commonly used to treat alcohol and opioid dependence, was administered as a 380-milligram intramuscular injection every three weeks.
- Bupropion, an antidepressant also used for smoking cessation, was given as 150-milligram tablets in weekly blister packs.
The results were clear: participants receiving the medication duo had significantly fewer methamphetamine-positive drug tests than those on placebo. This duo shows real promise as a foundation for methamphetamine use disorder treatment programs moving forward.
Closing a Gap in Behavioral Health
For clinicians, this research is especially important. While many substance use disorders—like opioid and alcohol use—have multiple medication-assisted treatment options, methamphetamine use disorder treatment has lagged far behind.
This absence of effective, FDA-approved treatments forces clinicians to rely entirely on behavioral therapies. While counseling, contingency management, and support groups are helpful, many patients need more support than therapy alone can offer. That’s why the development of a medication protocol, even one with incremental success, is a critical advancement.
The ADAPT-2 findings help establish a scientific base for methamphetamine use disorder treatment to expand in clinical settings, particularly for patients who also struggle with opioid use.
Why Gradual Progress Still Matters
The authors of the ADAPT-2 study emphasized that reductions in methamphetamine use tend to be gradual, not instant. But even small changes can significantly reduce health risks. Fewer uses mean fewer ER visits, lower chances of infectious disease transmission, and reduced risk of overdose.
“Less use is in turn associated with lower risk of comorbidities,” the study explains. These outcomes are the stepping stones toward recovery—and highlight how essential it is to develop and invest in methamphetamine use disorder treatment that is practical, accessible, and long-lasting.
Looking Ahead: Research, Hope, and Public Health Priorities
While this combination therapy hasn’t yet earned FDA approval, its success in clinical trials is a sign that targeted pharmacological support for methamphetamine use disorder may soon become a reality.
Further research is still needed, especially studies that assess treatment success beyond 12 weeks. But with each new phase of the ADAPT trial, the evidence is mounting that methamphetamine use disorder treatment can evolve—just as treatment for other substance use disorders has.
As policymakers, providers, and community health leaders digest these findings, it’s crucial that resources be allocated not only for further trials but for education, integration, and real-world application of these therapies.
Final Thoughts
We’re deep into the fourth wave of the overdose crisis—and it’s unlike anything we’ve faced before. But this time, amidst the devastation caused by fentanyl and methamphetamine, there is finally a viable lead for methamphetamine use disorder treatment.
For people in the grip of addiction, and for the families and providers supporting them, that kind of progress is everything. And while there’s still a long road ahead, the hope sparked by this study may be the beginning of something life-saving.
