A research The University of Houston-led team has developed a vaccine that targets the dangerous synthetic opioid fentanyl that could block its ability to enter the brain, thereby eliminating the “high” of the drug. The breakthrough discovery could have major implications for the nation’s opioid epidemic by becoming a relapse prevention agent for people trying to stop using opioids. While research shows that opioid use disorder (OUD) is treatable, an estimated 80% of people dependent on the drug relapse.
The findings, published in the journal Pharmacy, could not be more timely or more in demand: More than 150 people die every day from overdoses of synthetic opioids, including fentanyl, which is 50 times stronger than heroin and 100 times stronger than morphine. Consuming about 2 milligrams of fentanyl (about the size of two grains of rice) is likely to be fatal depending on the size of the person.
“We believe these findings could have a significant impact on a very serious problem that has plagued society for years: opioid misuse. Our vaccine can generate anti-fentanyl antibodies that bind to consumed fentanyl and prevent it from entering the brain, allowing it to be eliminated from the body through the kidneys. Therefore, the individual will not feel the euphoric effects and can ‘get back on the bandwagon’ to sobriety,” said study lead author Colin Haile, an associate professor of psychology researcher at UH and the Texas Institute for Measurement, Evaluation, and Statistics (TIMES), and a founding member of the UH Institute for Drug Discovery.
In another positive finding, the vaccine did not cause any adverse side effects in the immunized rats involved in the laboratory studies. The team plans to begin manufacturing a clinical-grade vaccine in the coming months, and human clinical trials are planned soon.
Fentanyl is an especially dangerous threat because it is often added to street drugs like cocaine, methamphetamine, and other opioids like oxycodone and hydrocodone/acetaminophen pills, and even to counterfeit benzodiazepines like Xanax. These counterfeit drugs laced with fentanyl add to the number of fentanyl overdoses in people who don’t normally use opioids.
“The fentanyl antibodies were specific for fentanyl and a fentanyl derivative and did not cross-react with other opioids, such as morphine. That means a vaccinated person could still receive pain-relieving treatment with other opioids,” he said. Haile. .
The tested vaccine contains an E. coli-derived adjuvant called dmLT. An adjuvant molecule increases the immune system’s response to vaccines, a critical component for the efficacy of addiction vaccines. The adjuvant was developed by collaborators at the Tulane University School of Medicine and has proven vital to the efficacy of the vaccine. Also part of the team are Greg Cuny, Joseph P. & Shirley Shipman Buckley Professor of Drug Discovery in the UH School of Pharmacy along with investigators from Baylor School of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center. .
Current treatments for OUD are methadone, buprenorphine, and naltrexone, and their efficacy depends on formulation, adherence, access to medications, and the specific opioid misused.
Therese Kosten, professor of psychology and director of the UH Behavioral, Cognitive, and Developmental Neuroscience program, calls the new vaccine a potential “game changer.”
“The use and overdose of fentanyl is a particular treatment challenge that is not adequately addressed with current medications due to its pharmacodynamics, and the management of acute overdose with the short-acting naloxone is not adequately effective as often necessary multiple doses of naloxone to reverse the fatal effects of fentanyl,” said Kosten, the study’s lead author.
The study was funded by the Department of Defense through the Alcohol and Substance Use Disorders Program administered by RTI International’s Pharmacotherapies for Alcohol and Substance Use Disorders Alliance, which has funded Haile’s lab for several years to develop the vaccine against the fentanyl.