Summary: A newly developed vaccine blocks the opioid fentanyl from entering the brain, preventing “high” doses of the drug.

Source: University of Houston

A research team led by the University of Houston has developed a vaccine that targets the dangerous opioid fentanyl by blocking its ability to enter the brain, thereby eliminating the drug’s “high.”

The discovery could have major implications for the nation’s opioid epidemic as a relapse prevention agent for people trying to stop using opioids. Research shows that while opioid use disorder (OUD) is treatable, 80% of people who become dependent on the drug will relapse.

The findings are published in the journal PharmaceuticalsSynthetic opioids, including fentanyl, which is 50 times stronger than heroin and 100 times stronger than morphine, kill more than 150 people every day. Consumption of about 2 milligrams of fentanyl (the size of two grains of rice) can be fatal in humans.

“We believe these findings could have a significant impact on a very serious problem that has plagued society for years – opioid abuse.”

“Our vaccine binds to ingested fentanyl and generates anti-fentanyl antibodies that prevent it from entering the brain, allowing it to be excreted through the kidneys.

“So the person doesn’t feel euphoric and can go back to their senses,” said study lead author Colin Hailey, a research associate professor at UH and the Texas Institute for Measurement, Evaluation and Statistics. (TIMES), and a founding member of the UH Drug Discovery Institute.

In another positive finding, the vaccine did not cause any side effects in the vaccinated mice included in the laboratory studies. The team plans to begin production of a clinical-grade vaccine in the coming months with clinical trials on humans.

Fentanyl is a particularly dangerous threat because it is often added to cocaine, methamphetamine, and other opioids such as oxycodone and hydrocodone/acetaminophen pills, as well as benzodiazepines such as Xanax. These counterfeit drugs laced with fentanyl increase the rate of fentanyl overdose in individuals who do not use opioids.

“Anti-fentanyl antibodies are specific to fentanyl and fentanyl derivatives and do not cross-react with other opioids such as morphine. This means that a vaccinated person can still be treated with other opioids for pain relief,” Haile said.

The tested vaccine has an adjuvant from E. coli called dmLT. An adjuvant molecule enhances the immune system’s response to vaccines, which is a critical component of the effectiveness of anti-addiction vaccines. The adjuvant was developed by collaborators at Tulane University School of Medicine and proved to be critical to the vaccine’s effectiveness.

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In another positive finding, the vaccine did not cause any side effects in the vaccinated mice included in the laboratory studies. The image is in the public domain.

Also on the team are Greg Cooney, Joseph P. and Shirley Shipman Buckley, professor of drug discovery in the UH College of Pharmacy, researchers at Baylor College of Medicine, and Michael E. DeBakey, a researcher at the Veterans Affairs Medical Center.

Current OUD treatments include methadone, buprenorphine, and naltrexone, and their effectiveness depends on formulation, compliance, drug availability, and the specific opioid used.

Therese Kosten, professor of psychology and director of the Developmental, Cognitive and Behavioral Neuroscience Program at UH, called the new vaccine a “game changer.”

“Fentanyl use and overdose is a unique medical challenge, due to the pharmacodynamics that is inadequately responded to by current medications, and the management of acute overdose with short-acting naloxone is not necessarily effective, as multiple doses of naloxone are often required to reverse the lethal effects of fentanyl,” they said. said Costen, senior author of the study.

So opioids and addiction research news

Author: Laurie Fickman
Source: University of Houston
Contact: Laurie Fickman – University of Houston
Image: The image is in the public domain.

Preliminary study: Open Access.
Immunization alters distribution and decreases the anticancer, behavioral, and physiological effects of fentanyl in male and female mice.” by Colin N. Hailey et al. Pharmaceuticals

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Draft

Immunization alters distribution and decreases the anticancer, behavioral, and physiological effects of fentanyl in male and female mice.

Fentanyl (FEN) is a potent synthetic opioid associated with opioid use disorder (OUD) and fatal opioid overdoses. Immunosuppressive therapy can be an effective treatment method for FEN-related diseases.

Here, we extend our previous study in mice demonstrating the immunosuppressive and anti-antinociceptive efficacy of our FEN vaccine administered with adjuvant dmLT.

In this study, vaccinated male and female mice produced highly effective anti-FEN antibodies, abrogating FEN-induced antinociceptions in tail flick assay and hot plate assays.

The vaccine reduced brain levels of FEN following drug administration. Vaccination blocked FEN-induced, but not morphine-induced, disruptive effects on schedule-controlled responding.

The vaccine is inhibited. Physiological parameters (oxygen saturation, heart rate) and general activity decrease following FEN administration.

The effect of FEN on these measures was greater in unvaccinated male rats compared to other female rats. Cross-reactivity experiments showed that anti-FEN antibodies bound to FEN and sufentanil but not to morphine, methadone, buprenorphine, or oxycodone.

These data support further clinical development of this vaccine to address OUD in humans.

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