PHILADELPHIA, PA — Researchers at Temple University Lewis Katz School of Medicine say a little-known compound could mark a major turning point in the fight against opioid addiction, showing promise in reducing drug use, dependence, and relapse in preclinical studies.
The research, conducted in collaboration with the Center for Substance Abuse Research, focuses on troriluzole, or TRLZ, a prodrug of the FDA-approved drug riluzole. The findings were recently published in the British Journal of Pharmacology.
In laboratory studies using rats trained to self-administer opioids, researchers found that TRLZ significantly reduced opioid intake, weakened the drug’s reinforcing effects, and sharply curtailed relapse-like behavior after periods of abstinence. The compound also diminished physical dependence, reduced tolerance to morphine’s painkilling effects, and lessened opioid-related respiratory depression.
“For us, this is exciting because what we found is that TRLZ has the potential to really alleviate multiple adverse effects associated with long-term opioid use,” said Scott Rawls, a professor of pharmacology at the Katz School of Medicine and senior author of the study. Rawls also holds faculty appointments at CSAR and Temple’s Department of Neural Sciences.
The study highlights a central challenge in treating opioid use disorder: relapse driven by both physical dependence and powerful psychological cravings. In the experiments, rats typically pressed a lever repeatedly to obtain opioids. After TRLZ was introduced, that behavior dropped sharply.
“Opioid intake dropped significantly with TRLZ treatment,” Rawls said. “The compound also reduced motivation to seek the drug and, perhaps most importantly, prevented relapse behaviors after a period of opioid abstinence.”
Researchers say those findings are particularly significant because relapse remains one of the most difficult hurdles in addiction treatment.
Troriluzole is already drawing attention beyond opioid research. Based on earlier preclinical work involving methamphetamine, the drug is currently being tested in patients with methamphetamine use disorder in a National Institutes of Health–funded clinical trial at the University of Kentucky. That trial has fueled optimism that TRLZ could have broad effectiveness across multiple classes of addictive substances.
The research has received funding from the National Institute on Drug Abuse, and plans are underway to explore a future clinical trial focused on opioid use disorder at Temple University Hospital.
Rawls collaborated on the study with Saadet Inan, an associate scientist at CSAR, Sonita Wiah, a research technician and laboratory manager, and Allen Reitz, CEO of Fox Chase Therapeutics Discovery, Inc., who discovered TRLZ and partnered with Biohaven for further clinical development. Additional contributors included researchers from Colgate University and the National Institute on Drug Abuse’s intramural research program in Baltimore.
“Addiction is a very real problem, and it’s difficult to treat,” Rawls said. “The great thing about TRLZ is that it seems to have effectiveness against different classes of addictive drugs, which means it could potentially help patients who misuse multiple substances.”
While the findings are preclinical, researchers say the results offer a hopeful glimpse of a future treatment that could blunt addiction’s grip — and help prevent the cycle of relapse that has fueled the opioid crisis for decades.
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