GLP-1s could be a breakthrough treatment for addiction. Why is Big Pharma staying away?

The United States has an addiction crisis. Smoking kills 480,000 people a year, alcohol another 178,000, and opiate overdoses more than 100,000, up 500% since 2000. That’s over three-quarters of a million people every year, far outnumbering those killed by heart disease and cancer, before taking into account how much heart disease and cancer is caused by addiction.

In dollars spent and lives lost, addiction is the most destructive public-health issue in America. It creates a staggering financial impact on the country. A CDC and Joint Economic Committee effort estimated that the opioid epidemic alone cost nearly $1.5 trillion in 2020, and recent studies indicated a $600 billion bill for smoking and $250 billion for alcohol. 

Despite that, addiction-treatment options can be unappealing, ineffective, difficult to adhere to, or nonexistent. Methadone, a popular treatment for opioid-use disorder, requires getting a daily dose at a clinic. Naltrexone, prescribed for opioid- or alcohol-use disorders, means taking a pill every day or a monthly shot. Given options like these, perhaps it’s no surprise that only 3% of people with substance-abuse disorders receive any medication. There is no FDA-approved treatment for methamphetamine or cocaine-use disorder. 

There’s a potential solution right in front of us: GLP-1s, known by their brand names Ozempic, Wegovy, Mounjaro, and Zepbound. Small clinical trials and anecdotal success stories indicate that the drugs could be game changing in treating addiction. But the road to prescribing them is complicated and expensive. Pharmaceutical companies shy away from studying addiction, and conducting Phase III trials — the final step before submitting a New Drug Application to the FDA, which would allow doctors to prescribe GLP-1s for addiction if approved — would be an enormous undertaking. 

Still, addiction is the biggest untapped return on investment for public health. Even reducing substance-use disorders by 20% — a reasonable goal given indications from Phase I and Phase II trials — would save at least 150,000 lives and more than $400 billion annually in the US alone. It could also provide the drug’s two patent holders, Novo Nordisk and Eli Lilly, with a vast array of patients and the thing pharma companies love most: money. 

The promise is there

GLP-1s, first approved by the FDA in 2005 to treat Type 2 diabetes, increase the release of insulin while slowing gastric emptying. The result is a decrease in the feeling of hunger and a more consistent blood-sugar level that prevents sugar crashes or spikes.

The drug class rocketed into the public consciousness with the 2017 approval of Ozempic. While it still remains approved for Type 2 diabetes, it has become a popular off-label treatment for weight loss, so much so that diabetes patients have struggled to get their prescriptions filled. Similar drugs Wegovy and Zepbound are FDA-approved for weight loss, meaning a doctor can prescribe them for that reason. Serendipitous drug side effects are not new. In 1989, two doctors developed sildenafil citrate to treat high blood pressure. Clinical trials failed to show any effect, but the men in the studies did end up with erections. And Viagra was born.

Now, there’s a growing body of evidence that GLP-1s help fight addiction. While working as an editor for the Center for Addiction Science, Policy, and Research, I interviewed several people who shared their life-changing experiences. “I had no desire to take opiates and there was no dopamine rush when I took a pill — no buzz,” one of them told me. An addiction-medicine doctor, himself in recovery, started prescribing GLP-1s for his patients. He’s seen several people experience their longest periods of sobriety with the help of GLP-1s, and he now offers prescriptions to nearly all his patients with substance-use disorders. There’s nothing preventing a doctor from prescribing these drugs to a willing patient “off-label,” or for a use they haven’t been approved for, but it’s not something that scales very well. Off-label prescriptions are not covered by insurance, so patients are on the hook for the full cost of the drug, which can run up to $1,000 a month.

Small clinical trials and larger studies of patients prescribed GLP-1s for other symptoms have shown promising results when it comes to addiction treatment. A 48-patient Phase II study on non-treatment-seeking people with alcohol-use disorder demonstrated a significant reduction in drinking. A report this year from Morgan Stanley concluded that more than half of people on GLP-1s reduced their alcohol intake, with about 16% quitting entirely. A paper published in the medical journal JAMA Network Open found that people taking Ozempic for diabetes were less likely to suffer from opiate overdoses, while another large retrospective study reported a 40% decrease in opioid overdoses and 50% fall in alcohol intoxication for GLP-1 patients.

Something is clearly happening when it comes to GLP-1s and addiction. But what, exactly? We need Phase III trials to find out.

An investment worth making

Since there is no generic definition of substance-use disorder, separate Phase III trials would need to be conducted for alcohol, opiate, nicotine, and stimulant addictions. Each one is a large undertaking that can take more than four years to complete and cost north of $10 million. 

Typically, the patent-holding pharmaceutical companies step up, eager to find additional uses for their drug, and thus another possible population of patients. Recently, there have been successful Phase III trials for new applications of existing drugs, like the FDA’s 2010 approval of Vivitrol, a version of naltrexone that needs to be injected monthly rather than daily. But patent holders Novo Nordisk and Eli Lilly haven’t expressed interest in pursuing large trials for addiction treatments. 

Why? For pharma, addiction is a touchy subject. 

“The pharmaceutical industry has never spontaneously embraced us and said, ‘We want to help develop treatments,’” Nora Volkow, director of the National Institute on Drug Abuse, said earlier this year. Remarkably, the FDA hasn’t approved any new medication classes for substance-use disorders in 20 years. 

“Addiction is stigmatized, right?” Keith Humphreys, a professor of psychiatry and behavioral sciences at Stanford University, told Sherwood. “Some companies may be concerned about the effect on the brand if a drug that’s already selling well for safer, approved-of indications becomes known as a drug that helps addicts.”

The good news is that a drug company is not necessary for a Phase III trial, but it’s a battle. The Center for Addiction Science, Policy, and Research is investigating launching a Phase III trial with the Allegheny County Department of Human Services and others. That could happen by licensing a GLP-1, developing their own, or partnering with a drug company. And drug companies, whether existing patent holders or others, should be involved. They have the experience, infrastructure, and financial incentive to scale quickly and effectively.

While these are expensive and complex solutions, the opportunities, both financial and societal, are hard to ignore. 40 million Americans struggle with addiction. A series of successful Phase III trials would lead to relief for many — and rocket the $105 billion GLP-1 industry to new heights.

Noah Davis is a writer and a cofounder of Three Point Four Media.