Metabolic treatments show promise for psychiatric conditions
Anyone who has dieted may be familiar with the high-fat, low-carbohydrate, adequate-protein ketogenic diet, but they might not be aware of how it’s been used to treat epilepsy for more than 100 years, and more recently recognized for its potential in metabolic health. Also, in the last few years, a new class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists seems to have changed the metabolic treatment landscape overnight. These drugs — which include semaglutide (Ozempic) and tirzepatide (Wegovy, Mounjaro, and Zepbound) — have proven remarkably effective in curbing food cravings that can lead to obesity and type 2 diabetes.
Given this success, new questions have emerged from the Mass General Brigham Department of Psychiatry exploring further possibilities with these drugs and the ketogenic diet. Could these metabolic interventions also help people with substance use disorders reduce or even eliminate their cravings for unhealthy and dangerous substances? What about their effects on other psychiatric disorders?
Broad indications
Metabolic psychiatry is a key area of focus for Dost Öngür, MD, PhD, chief of McLean Hospital’s Division of Psychotic Disorders, who is studying the effectiveness of the ketogenic diet in regulating brain energy metabolism in people with bipolar disorder and schizophrenia.
“To a significant degree, patient experiences have been key drivers of innovation,” says Öngür. “Many psychiatric medications cause patients to gain weight. We recently started seeing patients with bipolar disorder or related conditions who decided to go on the ketogenic diet to counteract these effects. Not only do many of these patients lose weight, they also started reporting improvement in their psychiatric symptoms.”
In October 2026, McLean Hospital announced the creation of the McLean Center for Metabolic Psychiatry, with Öngür as its director, made possible by a $20 million gift from Baszucki Group. The center’s goal is to advance the field of metabolic psychiatry by scaling access to these therapies (starting with the ketogenic diet), sharing expertise through training and education, and supporting research into how metabolic therapies can best be prescribed.
At Brigham and Women’s Hospital, Joji Suzuki, MD, is studying whether GLP-1 receptor agonists can do for substance use disorders (SUDs) what they have done for obesity and diabetes. Suzuki is a faculty member in the Division of Addiction Treatment and Prevention and program director for the Addiction Medicine Fellowship Program.
“From the time I finished medical school in 2002 to now, I have seen the evolution of addiction treatment,” says Suzuki. “And the pace of this evolution has been extremely slow. We have good tools, but it’s been a long time since we had a new class of drugs for treating SUDs. That’s why GLP-1 receptor agonists are so exciting.”
Dost Öngür, MD, PhD
Surprising history
GLP-1 receptor agonists activate the GLP-1 receptor, which leads to reduced blood sugar, appetite, and energy intake. Interestingly, these receptors are found both in the pancreas and in the brain. Scientists knew about their properties for many years, but with a half-life of just a few minutes, they were not considered feasible as a therapy.
Approximately 30 years ago, an endocrinologist isolated a novel substance from Gila monster venom that seemed to mimic properties of human GLP-1, though with a much longer half-life. When the substance, exendin-4, was tested on mice with diabetes, their blood glucose levels went down. In 2005, the synthetic version, called exenatide, became the first FDA-approved GLP-1 agonist, ushering in a new era of treatment.
“We have not had a new class of medication to treat substance use disorders in over two decades,” Suzuki says. “I’m convinced that the next FDA-approved treatment for alcohol use disorder will be a GLP-1.”
Forward acceleration
Individual drugs have different properties and characteristics, which makes a one-drug-fits-all approach challenging, but Suzuki says it is not impossible.
“Most therapeutics are specific to a particular drug,” he says. “For example, nicotine replacement only works for tobacco. GLP-1 receptor agonists could be the first trans-diagnostic medications for addiction. Preliminary data point to their efficacy in treating alcohol use disorder, but we think they could also help with tobacco, cannabis, opioid, and stimulant use disorders.”
Over the last two years, Suzuki’s lab has been conducting clinical trials. He plans to publish a paper next year to report the results of a trial that is testing the effectiveness of semaglutide in helping those with opioid use disorder, as well as the results of a trial testing tirzepatide’s ability to treat alcohol use disorder.
As for Öngür, his lab is close to completing a three-year study that involves taking brain scans pre-diet, then administering the ketogenic diet — meals provided — and finally taking new brain scans approximately three months later. “We hypothesize that adherence to the ketogenic diet improves brain metabolism,” he says.
Öngür continues, “Existing treatments for psychiatric disorders are only partly effective and have undesirable side effects. For that reason, metabolic approaches like GLP-1 agonists and the ketogenic diet are extremely promising additions to our therapeutic arsenal.”
Continued philanthropic support will enable Mass General Brigham to lead further research into these paradigm-shifting therapies.
Joji Suzuki, MD