By Lev Facher
When it comes to meth addiction, Thomas Robey has long been at a loss.
As an emergency room doctor, he treats a steady stream of patients who show up at Providence Regional Medical Center in Everett, Wash., after experiencing a methamphetamine overdose.
But he’s never had much to offer them. Despite the skyrocketing use of meth, a stimulant particularly common in the western U.S., there’s no medication currently approved to treat meth overdose or aid in long-term recovery. Doctors who want to help have few available options. Patients who seek help often leave hospitals hardly better off than when they arrived.
“I’d offer a turkey sandwich and some resources, and send them on their way,” Robey said. “That was the standard treatment: Compassion, reassurance, an exam to make sure there aren’t infections or injuries … and connect them with as many social resources as possible, which in a community setting is usually not very many.”
Recently, though, Robey has added a new weapon to his limited meth-treatment arsenal: A monoclonal antibody that binds to methamphetamine molecules and helps prevent them from entering the brain.
The new treatment has shown anecdotal promise in a pair of Phase 2 clinical trials being conducted at a handful of emergency rooms across the country, including Everett, a small city roughly 25 miles north of Seattle where the methamphetamine crisis has hit hard.
The monoclonal antibodies are just one of several promising new approaches to treating meth addiction. In another recent trial, researchers found that a combination of two drugs helped roughly 1 in 8 patients reduce methamphetamine use. Neither drug was developed to treat patients who use meth: One, naltrexone, is used to treat alcohol or opioid addiction, and the other, bupropion, is used as an antidepressant and to help people trying to quit smoking.
A third approach has also gained momentum in recent years: contingency management — essentially the practice of offering gift cards or cash payments to people who stop using meth. The Department of Veterans Affairs has used the strategy to treat thousands of patients in the past decade, and more recently, California launched a pilot program to fund contingency management via Medicaid, allowing patients to receive up to $599 over six months if they test negative on drug screens.
The new strategies are being implemented amid a dramatic rise in methamphetamine-related deaths, which roughly tripled between 2015 and 2019, according to the National Institute on Drug Abuse. Drug deaths that involve methamphetamine are now at an all-time high of roughly 24,000, and are expected to continue climbing.
Though meth use is just one element of the country’s multifaceted drug epidemic, it differs from alcohol and opioid addiction in a key respect: The availability of medications used to treat it.
To date, the Food and Drug Administration has approved three medications to treat opioid use disorder: Methadone, buprenorphine, and naltrexone. Naltrexone is also used to treat alcohol addiction. (Physicians, however, have long been criticized for underutilizing the medications.)
Meth addiction, by contrast, has no pharmacological treatment options at all — meaning that their approval would mark a change for patients seeking help, and doctors looking to provide it.
“I wish I could say that at this point, we had medications [for meth addiction] like we have for opioid use disorder,” Nora Volkow, the director of NIDA, told STAT in an interview. “And we currently have naloxone for opioid overdose — we have nothing like that for methamphetamine, and these monoclonal antibodies could act like that, by sequestering the drug in the blood and stopping it from actually binding into the relevant brain systems.”
Currently, the monoclonal antibodies are being tested in a pair of Phase 2 clinical trials: One is testing it as a treatment for meth overdose; the other is measuring its effectiveness as an aid in long-term recovery.
If the drug proves effective, though, it could eventually be used for both purposes at once, said Brooks Gentry, an anesthesiologist and professor of pharmacology and toxicology at the University of Arkansas for Medical Sciences who is coordinating the clinical trials. Ideally, he said, patients would receive the monoclonal antibody when they experience an overdose, and then receive continued doses to help prevent future use.
The drug “binds meth and keeps it from going to its sites of action in the brain, and in so doing, reduces its positive reinforcing effects,” Gentry said. “We think it will reduce some of the negative overdose effects, too. It’s not quite a sponge, but it functions kind of like one in the bloodstream.”
Monoclonal antibodies have existed since the 1970s, when researchers gained the ability to isolate cells that create antibodies with only one target. In theory, researchers can produce antibodies with nearly any target, making them tremendously valuable as a therapeutic — they’ve been used in dozens of applications ranging from cancer drugs to Covid-19 treatments. And since the antibodies remain in the body for weeks after they’re administered, even patients who resume meth use would theoretically experience a far weaker high.
The origin of the antibodies being used to treat meth overdose, known as IXT-m200, dates to the 1980s, when the physician-scientist Michael Owens began exploring the concept as a postdoctoral researcher.
It is largely a coincidence that the drug has shown promise exactly as the meth crisis has flared. NIDA, easily the country’s largest funder of addiction research, first awarded a grant to a team of UAMS researchers in 1999.
The drug’s development is now being overseen by UAMS and an affiliated biotech startup, InterveXion, where Gentry also works as chief medical officer, and Owens is the chief scientific officer.
Even optimistically, however, the drug is years away from winning approval and achieving widespread use, Gentry said. Robey, the Washington state-based doctor who is enrolling patients in one of the clinical trials, also noted that it’s being administered to patients experiencing relatively mild meth toxicity, as opposed to those experiencing an acute overdose. Those patients, he said, often need to be restrained or treated with sedatives — and their impairment makes them unable to consent to joining a medical study using an experimental treatment.
Still, the ongoing clinical trials highlight health providers’ increasing desperation for effective methamphetamine interventions, especially in states where attitudes toward drug use and local politics mean contingency management programs are not an option.
“Before, we had nothing, and now we might just be able to get people back to the lives they want to live,” Robey said. “I’ve seen it in 30 minutes: We give the drug, and they’re either clear-headed or they just go to sleep. They’re finally free of the agitation and anxiety that methamphetamine causes.”
The efforts also underscore the fact that governments, academics, and the biopharmaceutical industry have not yet devoted resources to the overdose crisis on par with that of other health emergencies, like Covid-19 or even the HIV/AIDS epidemic. The amount of money invested in addiction research as compared to diseases like Covid, Alzheimer’s, diabetes, or HIV, Volkow said, is “minuscule, a fraction of a fraction.”
The same phenomenon is largely true for cocaine addiction and overdose, which have also increased substantially in the past decade. There is also no FDA-approved medication used to treat cocaine overdose or addiction.
“These discrepancies are driven, really, by the stigmatization of addiction as a moral flaw, a character flaw, something a person does to themself,” Volkow said. “You see that in terms of how agencies are willing to put their relative resources for developing treatments for addiction, but also from industry — the industry has completely disengaged.”