After several years of development, a promising drug designed to prevent relapse to opioid use and opioid overdose is taking a critical step by entering human testing.
In October, scientists at The University of Texas at San Antonio Health Science Center launched the first-in-human clinical trial of methocinnamox, or MCAM, a novel long-acting opioid receptor antagonist, under the direction of Charles P. France, PhD, professor of pharmacology at the Joe R. and Teresa Lozano Long School of Medicine.
If successful, the drug could offer a powerful tool for addressing one of the nation’s most devastating public health crises, the opioid epidemic and opioid overdose, which continue to claim thousands of lives each year.
“This is immensely exciting,” France said. “To have something that is this immediate, that is going into humans, and that I truly believe could save lives, that is deeply gratifying.”
A new approach to overdose prevention
MCAM belongs to a class of drugs known as opioid receptor antagonists, which block opioids like fentanyl from activating receptors in the brain that cause euphoria and respiratory depression, the primary driver of overdose death.
MCAM is unique because of its extraordinarily long duration of action.
Existing rescue drugs such as naloxone, commonly known as Narcan, reverse overdose for about an hour, often requiring repeated doses. In animal studies, MCAM has demonstrated the ability to block opioid effects for weeks following a single dose.
“That long duration of action is the novelty of this compound and also its potential value,” France said.
The extended protection could be transformative for people with opioid use disorder, who remain vulnerable to relapse and fatal overdose, particularly after periods of abstinence.
“Even one exposure can be fatal,” France said. “A medication that provides weeks of protection could dramatically reduce that risk.”
Moving toward clinical testing
France’s work in opioid pharmacology spans decades, but the idea that MCAM could become a medication with real-world clinical impact gained momentum about eight years ago, when he and his collaborators began moving the compound toward formal drug development.
Since then, the team has conducted extensive preclinical laboratory testing across multiple research models, demonstrating both strong safety profiles and the ability to block opioid activity for a prolonged period of time. That research has been supported largely through federal funding, including a $12 million National Institutes of Health grant awarded in 2024 to accelerate MCAM’s development.
This year, the project hit a major milestone when the team submitted an investigational new drug application to the U.S. Food and Drug Administration. Once approved, the researchers were cleared to begin phase 1 clinical testing.
Inside the first-in-human trial
The initial clinical trial is underway at a specialized facility in Kansas with expertise in substance use disorder studies. The study will include two components.
The first will be a safety trial involving healthy adult volunteers. Participants will receive one of three escalating doses of MCAM or a placebo, allowing researchers to monitor safety, tolerability and how the drug behaves in the body.
The second part will examine whether MCAM produces long-lasting opioid blockade in humans. During this portion, participants with prior opioid experience, but not current dependence, will receive a single dose of MCAM. They will then undergo controlled exposure to an opioid. Scientists will monitor physical responses such as pupil constriction and collect self-reported data on how participants feel, allowing them to determine whether MCAM successfully blocks opioid activity and how long that effect persists.
“This part is really proof of concept in humans,” France said. “If we see the long duration of action that we have observed in animals, it will be a strong signal to push this project forward.”
A potential breakthrough for public health
The public health implications of MCAM are substantial. Despite recent signs of stabilization, the opioid epidemic continues and opioid overdose remains a leading cause of accidental death in the United States, driven largely by fentanyl and other synthetic opioids.
France believes MCAM could complement existing tools such as naloxone and medication-assisted treatment, particularly for people at highest risk.
“We have become numb to the numbers,” he said. “We hear that deaths have declined, so instead of 12 people dying every hour, it’s eight. That is still eight too many.”
Because MCAM blocks opioid effects for weeks, it could provide a layer of protection during periods of vulnerability.
Years of persistence and collaboration
The journey to this point was long and complex. Drug development requires expertise that extends far beyond traditional academic research, and France credits a small, dedicated team for guiding MCAM through regulatory, manufacturing and commercialization challenges.
Along the way, the team has navigated manufacturing delays, regulatory hurdles and logistical complications.
“You learn very quickly that drug development is a world of details,” France said.
The road ahead
For France, MCAM represents the culmination of a career devoted to understanding how drugs affect the brain and translating that knowledge into meaningful public health impact.
As MCAM enters human trials, years of research and persistence converge on the ultimate goal of reducing overdose deaths and offering a new path forward in the fight against opioid addiction.
“To end my career with something that actually improves lives would mean everything,” he said. “This is about people. This is about lives.”
Read more:
UT Health San Antonio Professor France leads novel drug discovery research
University awarded $12 million to further develop opioid use disorder drug