Researchers are on the trail of a new drug that has shown promising results in treating opioid use disorder (OUD) in rats. The drug is called troriluzole, a prodrug of the FDA-approved drug, riluzole. A “prodrug” is a carrier molecule that releases the drug (riluzole) into the bloodstream.

Interestingly, riluzole moderates the neurotransmitter glutamate. In a 2008 systematic review of riluzole use in treating psychiatric disorders, two researchers from the Mood and Anxiety Disorders Research Program at the National Institute of Mental Health wrote:

The glutamate system seems to be an important contributor to the pathophysiology of mood and anxiety disorders. Thus, glutamatergic modulators are reasonable candidate drugs to test in patients with mood and anxiety disorders.

Riluzole is approved by the FDA for the treatment of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease. It’s sold under the brand names Rilutek, Tiglutik, and Exservan. Riluzole inhibits glutamate release, helping reduce the toxic buildup of glutamate that damages nerve cells in ALS sufferers.

The prodrug troriluzole makes the drug riluzole easier to tolerate with better absorption. In tests with opioid-addicted rats, troriluzole showed the following results:

• reduced opioid self-administration
• inhibited food self-administration
• reduced withdrawal signs
• reduced opioid-induced respiratory depression

The overlap in the test results for troriluzole and GLP-1 drugs such as Ozempic is noteworthy. Both drugs affect glutamate receptors, and both appear to suppress the appetite for food as well as the appetite for opioids. The researchers make no mention of any connection with GLP-1 drugs.

The new study into troriluzole comes from the Center for Substance Abuse Research at the Lewis Katz School of Medicine at Temple University. The study with rats “found that it [troriluzole] significantly alleviated multiple adverse effects associated with long-term opioid exposure,” according to a summary of the study in Temple Now, a university publication, adding:

[T]he study found that troriluzole administration reduced the physical dependence, reinforcing effects and relapse-like behaviors caused by chronic opioid exposure.

The fact that troriluzole helps with cravings, cue sensitivity and withdrawal makes it a promising candidate for human trials against OUD. Co-author of the study, Dr. Scott Rawls, told Temple Now, “[Troriluzole], based on preclinical work conducted in our lab with methamphetamine, is also being currently tested in patients with methamphetamine use disorder in a National Institutes of Health (NIH)-funded clinical trial at [the] University of Kentucky.”

There are no FDA-approved drugs for methamphetamine use disorder (MUD). If troriluzole works, it will truly be “a game changer” in the fight against OUD, MUD, and possibly other substance use disorders.

Written by Steve O’Keefe. First published December 24, 2025.

Sources:

“New research could be key to combatting opioid addiction,” Temple Now, Temple University, December 18, 2025.

“Troriluzole attenuates opioid intake, reinforcing efficacy, seeking behaviours, physical dependence and antinociceptive tolerance in rats,” British Journal of Pharmacology, September 23, 2025.

“Riluzole in psychiatry: a systematic review of the literature,” Expert Opinion on Drug Metabolism & Toxicology, August 24, 2008.

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