A new vaccine protects against fentanyl addiction by removing its high

Over 150 people a day die from fentanyl-related overdoses.
Loukia Papadopoulos

Researchers at the University of Houston have engineered a vaccine that may just provide effective protection against developing an addiction to the opioid fentanyl, according to a press release by the institution published on Monday. The vaccine blocks the drug’s ability to enter the brain, eliminating its powerful and seductive “high.” 

Tough to quit

Fentanyl is 50 times stronger than heroin and 100 times stronger than morphine and is responsible for the deaths of over 150 people every day. Currently, an estimated 80 percent of those dependent on the drug suffer a relapse when trying to quit. The new vaccine may change that.

“We believe these findings could have a significant impact on a very serious problem plaguing society for years – opioid misuse. Our vaccine can generate anti-fentanyl antibodies that bind to the consumed fentanyl and prevent it from entering the brain, allowing it to be eliminated out of the body via the kidneys. Thus, the individual will not feel the euphoric effects and can ‘get back on the wagon’ to sobriety,” said the study’s lead author Colin Haile, a research associate professor of psychology at UH and the Texas Institute for Measurement, Evaluation and Statistics (TIMES), and a founding member of the UH Drug Discovery Institute.  

Studies on the vaccine’s efficiency have thus far only been conducted on rats. However, the researchers have found that the vaccine did not cause any adverse side effects. The team now plans to conduct clinical trials in humans to see if the vaccine is as effective as it is in rats.   

“The anti-fentanyl antibodies were specific to fentanyl and a fentanyl derivative and did not cross-react with other opioids, such as morphine. That means a vaccinated person would still be able to be treated for pain relief with other opioids,” said Haile. 

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A new vaccine protects against fentanyl addiction by removing its high
The researchers at work.

The new vaccine contains an adjuvant derived from the bacteria E. coli named DMLT that accelerates the immune system’s response to vaccines. This is a key and vital criterion for the effectiveness of anti-addiction vaccines that was developed by the team with aid from researchers at the Tulane University School of Medicine.

Treatments are not always effective

Today, available treatments for opioid use disorder include methadone, buprenorphine, and naltrexone, but they do not always prove effective.  

Therese Kosten, professor of psychology and director of the Developmental, Cognitive & Behavioral Neuroscience program at the University of Houston calls the new vaccine a potential “game changer.”  

“Fentanyl use and overdose is a particular treatment challenge that is not adequately addressed with current medications because of its pharmacodynamics and managing acute overdose with the short-acting naloxone are not appropriately effective as multiple doses of naloxone are often needed to reverse fentanyl’s fatal effects,” said Kosten, senior author of the study. 

In the past, scientists from the Wake Forest School of Medicine with support from the National Institute on Drug Abuse developed a non-addictive painkiller to fight addictions to opioids. Called AT-12, the new chemical compound was proven to have a dual therapeutic action that suppressed the addictive effects of opioids and produced morphine-like analgesic effects in non-human primates. 

The findings are published in the journal Pharmaceutics.

Abstract:

Fentanyl (FEN) is a potent synthetic opioid associated with an increasing incidence of opioid use disorder (OUD) and fatal opioid overdose. Vaccine immunotherapy for FEN-associated disorders may be a viable therapeutic strategy. Here, we expand and confirm our previous study in mice showing immunological and antinociception efficacy of our FEN vaccine administered with the adjuvant DMLT. In this study, immunized male and female rats produced significant levels of anti-FEN antibodies that were highly effective at neutralizing FEN–induced antinociception in the tail-flick assay and hot plate assays. The vaccine also decreased FEN brain levels following drug administration. Immunization blocked FEN-induced, but not morphine-induced, rate-disrupting effects on schedule-controlled responding. Vaccination prevented decreases in physiological measures (oxygen saturation, heart rate) and reduction in overall activity following FEN administration in male rats. The impact of FEN on these measures was greater in unvaccinated male rats compared to unvaccinated female rats. Cross-reactivity assays showed 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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