GLP-1s for Cocaine Addiction: What Early Research Shows

There are no FDA-approved medications for cocaine use disorder. New research on semaglutide is changing the conversation. Here's what the science actually says.

The Problem: Zero FDA-Approved Treatments

Cocaine use disorder affects approximately 1.3 million Americans aged 12 and older, according to the American Addiction Center. Despite decades of research, there is no FDA-approved medication to treat it. Current treatment relies entirely on behavioral therapy — effective for some, but not for all.

This treatment gap has made cocaine addiction research a priority. The emergence of GLP-1 receptor agonists — and their unexpected effects on reward pathways — has opened a new avenue.

The University of Gothenburg Study

In September 2025, researchers from the University of Gothenburg (Sweden) and the University of Pennsylvania published the most comprehensive preclinical study to date on semaglutide and cocaine. The results, published in European Neuropsychopharmacology, were striking.

How the Study Worked

Male rats were trained to self-administer cocaine by pressing a lever. After establishing baseline cocaine-taking behavior, an experimental group received semaglutide at varying doses (0.013, 0.026, or 0.039 mg/kg) before access to cocaine.

The researchers measured three things:

• Cocaine intake — how much cocaine the rats took when given access
• Reinstatement — cocaine-seeking behavior after a period of abstinence (models relapse)
• Progressive ratio — how hard rats would work (more lever presses) to get cocaine (measures motivation)

The Dopamine Connection

What makes this study particularly interesting is that researchers also measured dopamine levels in the nucleus accumbens — the brain's "reward center."

Cocaine works by flooding this region with dopamine, creating intense euphoria. The researchers found that semaglutide suppressed cocaine-evoked dopamine spikes in this region. Importantly, semaglutide didn't affect baseline dopamine — it specifically blunted the dopamine surge triggered by cocaine.

"This is the first trial showing semaglutide's potential as a drug for cocaine dependence. The outcomes with cocaine seem to reflect previous findings on alcohol use." — Elisabet Jerlhag, PhD, Professor of Pharmacology, University of Gothenburg

Why Semaglutide Might Work Better Than Earlier GLP-1s

This isn't the first time GLP-1 drugs have been tested for stimulant addiction. Earlier studies with exenatide (Byetta) showed some reduction in cocaine-related behaviors in animals, but the effects were modest and didn't translate well to humans.

Researchers believe semaglutide may be different because:

• Higher potency — binds more tightly to GLP-1 receptors
• Longer half-life — maintains consistent brain levels with weekly dosing
• Better brain penetration — reaches reward circuits more effectively

The Human Trial: UTHealth Houston

In October 2025, the National Institute on Drug Abuse awarded $2.7 million to researchers at UTHealth Houston to study semaglutide for cocaine use disorder in humans — the first major funded trial of its kind.

"We think that semaglutide can help decrease the rewarding effects of stimulants such as cocaine. If you take semaglutide, you may experience less of that enjoyment, which would decrease the motivation to use cocaine." — Luba Yammine, PhD, UTHealth Houston

The Mechanism: How GLP-1s Might Fight Cocaine

Cocaine addiction hijacks the brain's reward system. When you use cocaine, dopamine floods the nucleus accumbens, creating intense pleasure. Over time, the brain adapts — you need more cocaine to feel the same effect, and normal pleasures become less satisfying.

GLP-1 receptors are expressed throughout this reward circuitry:

• Ventral tegmental area (VTA) — where dopamine neurons originate
• Nucleus accumbens — where dopamine creates reward feelings
• Prefrontal cortex — involved in decision-making and impulse control

When semaglutide activates these receptors, it appears to dampen the dopamine response to cocaine. The drug still releases dopamine, but less of it — potentially making cocaine use less rewarding.

Not Blocking, But Modulating

Importantly, semaglutide doesn't block dopamine or cocaine's receptor target. It modulates the system. This may explain why users report they can still enjoy food and other activities — the drug doesn't eliminate pleasure, it "turns down the volume" on reward signals.

Important Context: This Is Early-Stage Research

While the preclinical data is promising, several cautions apply:

• Animal studies often don't translate — many drugs that work in rats fail in humans
• No human data yet — the UTHealth trial is just beginning
• Side effects in cocaine users are unknown — semaglutide's GI effects combined with cocaine's cardiovascular effects could pose risks
• Insurance won't cover it — any off-label use would be expensive and unproven

The Broader Picture: GLP-1s and Addiction

The cocaine research is part of a larger trend. GLP-1 drugs are being studied for:

• Alcohol use disorder (most advanced research)
• Nicotine addiction
• Opioid use disorder
• Cannabis use disorder
• Gambling and compulsive behaviors

The common thread: GLP-1 receptors in reward circuits. If semaglutide can dampen reward-seeking behavior broadly, it could become a tool for multiple addictions — though each would require its own clinical trials and FDA approval.