Meth, Cocaine, and the GLP-1 Frontier: San Francisco's First-Ever Stimulant Trial

The Unmedicated Addiction

Addiction medicine has made real progress on several fronts. Buprenorphine and methadone help people with opioid use disorder. Naltrexone, disulfiram, and acamprosate are FDA-approved for alcohol use disorder. Nicotine patches, gums, and varenicline help smokers quit.

But stimulants — methamphetamine, cocaine, amphetamines — remain a pharmacological blind spot. Despite decades of research, the FDA has not approved a single medication to treat stimulant use disorder. The only evidence-based treatments are behavioral interventions like contingency management, which work for some people but have limited reach and durability.

This gap is not academic. Methamphetamine was present in approximately 46% of the 625 overdose deaths in San Francisco in 2025. Cocaine was present in around 40%. Nationally, stimulant-involved overdose deaths have been rising steadily alongside the opioid crisis, often in combination with fentanyl.

The San Francisco Trial

Dr. Philip Coffin, director of the Center on Substance Use and Health at the San Francisco Department of Public Health, first noticed the potential while treating patients at Ward 86, the HIV clinic at Zuckerberg San Francisco General Hospital. Some patients struggling with stimulant addiction happened to be taking GLP-1 medications for weight loss or diabetes — and he observed what he described as "pretty profound" benefits.

The trial is a two-phase pilot study. Phase 1 began in January 2026 with 25 participants receiving semaglutide (marketed as Wegovy) over a 12-week treatment period, with follow-up visits at week 20. Phase 1 data will be processed over the next year and a half before a larger Phase 2 launches at sites in both San Francisco and Portland, Oregon, with 100 to 170 participants.

Why Stimulants Are Different

Dr. Daniel Ciccarone, an addiction medicine professor at UCSF, explained why stimulant addiction has resisted pharmacological treatment. While conditions like opioid use disorder involve a relatively targeted receptor system, stimulants affect a wider range of neurotransmitter systems simultaneously — dopamine, serotonin, norepinephrine, and others.

This multi-target pharmacology is precisely why GLP-1 agonists are an intriguing candidate. Rather than targeting one specific receptor system (the way methadone targets opioid receptors), GLP-1 agonists modulate the downstream reward circuitry that all addictive substances converge on. If the craving itself can be dialed down — regardless of which neurotransmitter pathways generate it — GLP-1 drugs could theoretically work where substance-specific approaches have failed.

Preclinical evidence supports this theory. In rodent studies, the GLP-1 agonist exendin-4 reduced amphetamine-induced locomotor stimulation and attenuated cocaine self-administration. These effects were mediated through GLP-1 receptors in the VTA and nucleus accumbens — the same reward pathway nodes implicated across all addictive substances.

Healthy Skepticism

Ciccarone remains cautious. While he acknowledged enough evidence exists to support GLP-1 effectiveness for alcohol addiction, he characterized the application to stimulant use disorder as a hypothesis without preliminary human data.

But he also acknowledged the desperation in the field. Addiction medicine experts are "getting a little desperate" to address the stimulant side of the drug crisis, he said. Existing treatments are not FDA-approved, many prescribers are reluctant to use them, and they produce modest results at best.

"Even if the GLP-1s don't produce a definitive solution for everything, they're almost certainly going to be a major tool in the toolbox for treating these conditions going forward." — Dr. Philip Coffin, lead researcher, SF DPH

What Comes Next

Beyond the methamphetamine trial, Coffin's team is also preparing to test GLP-1 medications as an "added agent" for people with opioid use disorder who continue using fentanyl despite receiving buprenorphine treatment — a common and dangerous clinical scenario. The idea is that GLP-1 agonists could provide complementary craving reduction on top of existing OUD pharmacotherapy.

If either trial produces positive results, it would represent a paradigm shift: the first pharmacological tool for a class of addictions that has resisted medication treatment entirely.