Preventing opioid relapse
Methocinnamox, a novel compound for opioid use disorder treatment, advances toward clinical trials
By Claire Kowalick
Drug overdoses happen every day, every hour. “More people die from drug overdose than cars and guns put together. It is a shocking number,” said Charles France, PhD, a professor of pharmacology and psychiatry and the Robert A. Welch Distinguished University Chair in Chemistry at the Joe R. and Teresa Lozano Long School of Medicine.
Yet, few Food and Drug Administration-approved medications are available for opioid use disorder. While certain drugs have been around for decades to treat it, the problem persists, compounded in recent years by the explosive growth in the availability of synthetic opioids like fentanyl, said France. The problem, he said, is multifaceted due to the stigma surrounding addiction, lack of access to life-saving medication, inadequate mental health services and poor health care in general in the country.
“Certainly, people are not getting the health care they need for mental health disorders,” he said.
Current treatments
The three most common pharmaceutical interventions for opioid use disorder are methadone, buprenorphine and naltrexone, each of which has pros and cons.
Methadone is a full agonist that replaces the drug individuals are currently using. “It keeps people satisfied. They do not feel the need for the opioid, and they do not go into withdrawal,” France said.
Buprenorphine is a partial agonist that shares some properties with methadone but is not as strong. “Under the right conditions, it will help people from going into withdrawal and keep them from having cravings,” said France.
A drawback to both drugs is the potential for diversion and abuse.
Naltrexone, France said, is more advantageous in many ways because it is an antagonist, meaning it does not stimulate opioid receptors or replace the opioid. Rather, it blocks the effects of the administration of opioids. The drug’s action is short-lived, however, and if its effects wear off sooner than the effects of theopioid, the adverse effects of the opioid may return.
Vivitrol, an extended-release formula of naltrexone, lasts about a month but it is costly, requires special handling and its effectiveness varies markedly among individuals. It may, however, be an improvement over the shorter-acting formulation of naltrexone because the monthly dosing could increase treatment compliance.
Nalmefene, an opioid-receptor agonist nasal spray, was also approved in 2023 by the FDA.
Exploring a better option
Years of rigorous investigation at The University of Texas Health Science Center at San Antonio has laid the groundwork for an effective novel treatment for opioid use disorder that is safe, long lasting and inexpensive to manufacture.
France, the leading expert in the U.S. on the compound methocinnamox and its use as a treatment for opioid use disorder, has studied opioids for more than 40 years, 24 of those at his lab at the health science center. His work is predominantly funded through grants from the National Institutes of Health and the National Institute on Drug Abuse. Recent NIH UG3/UH3 funding aims to advance methocinnamox for use in a clinical setting.
First discovered in 1988 at the University of Bath, England, methocinnamox is what’s called a mu opioid receptor antagonist with a long duration of action that can block and reverse the effects of opioid drugs such as heroin, morphine, oxycodone and the synthetic opioid fentanyl.
France has been studying the drug in his lab for years and is in the process of moving it through drug development for the prevention of relapse and overdose in opioid-experienced individuals who are not currently taking an opioid.
According to France, some of the remarkable qualities of methocinnamox are that it is orally bioavailable, shelf stable and a single administrationblocks the effects of opioids for a very long time, despite the rapid clearance of the drug from the plasma. Studies in rats and non-human primates show methocinnamox to be extremely effective, even in small doses, and safe even at massive doses.
While France never thought, as a lifelong professor and researcher, that he would be in the drugdevelopment business, the extraordinary potentialof methocinnamox drew him into the process.
Currently, all investigational new drug-enabling studies required by the FDA are complete. If additional funding is secured, and the process moves along with “lightning speed,” France said there could potentially be a phase 1 clinical trial in humans by 2025.
If methocinnamox passes through its drugdevelopment hurdles, France hopes it will quickly become readily available to providers with patients who have used opioids or who want to refrain from using opioid.
