The U.S. has entered the “fourth wave” of the overdose epidemic, characterized by skyrocketing use of stimulants like methamphetamine. 

A new study found that a duo of drugs is effective at curbing methamphetamine-positive drug tests by 27% compared to a placebo. 

“These findings have important implications for pharmacological treatment for methamphetamine use disorder,” Michael Li, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA and the study’s first author, said in a statement. “There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade.”

In 2020, stimulants were involved in less than 1% of fentanyl-related overdose deaths. In 2021, stimulants were involved in almost one-third. This increase resulted in researchers naming the current era of overdose deaths the “fourth wave.” 

Methamphetamine use has increased in part because of its availability and affordability. The drug also heightens the euphoria of fentanyl and reduces fentanyl’s depressant effects, known as the fentanyl “nod.”

The study, published in the peer-reviewed journal Addiction, involved a 12-week study of 403 people with MUD, including a placebo group.

Results indicate that extended-release injectable naltrexone in combination with extended-release oral bupropion resulted in significant reductions in methamphetamine use for up to 12 weeks.

Participants received 380 milligrams of naltrexone in single-use intramuscular injection kits every three weeks. Bupropion was provided in weekly blister packs including 150-milligram tablets.

The study was the second stage of a larger trial, called the ADAPT-2 trial, funded by the National Institute on Drug Abuse (NIDA). The first study demonstrated that the combination of drugs was effective for six weeks and the most recent stage demonstrated efficacy over a longer period. 

“Reductions in use during treatment tend to be gradual, and less use is in turn associated with lower risk of comorbidities,” the study’s authors wrote. “In these ways, our stage two findings extend on the efficacy of NTX + BUPN for reducing [methamphetamine] use, and allude to the possibility of additional benefit with longer treatment duration.”

The authors note that it is unclear if treatment past 12 weeks would result in sustained abstinence and that further research is needed.

The study’s findings are noteworthy because, while other substance use disorders (SUDs) can be treated with a variety of medications, no medications are currently available to treat methamphetamine use.

“The lack of FDA-approved medications for stimulant use disorders limits the clinical tools that are available and increases the complexity and intensiveness of treatment regimens for those with co-occurring opioid and stimulant use disorders, as well as those with primary stimulant use disorders,” the authors of a Millennium Health report published in February wrote.