Combatting the Zombie Drug: Developing a Vaccine for Xylazine

Xylazine is a sedative and pain reliever approved by the FDA for use in animals, but its use in humans has serious harmful effects. It is being illicitly mixed with opioids such as fentanyl and heroin, as well as cocaine, leading to a significant increase in overdose deaths. Chemical biologists at Scripps Research have created a vaccine to counteract the harmful effects of xylazine. The vaccine functions by teaching the immune system to combat the toxicity of xylazine.The drug’s effects are detailed in a recent article in Chemical Communications released on April 1, 2024.

The senior author of the study, Kim D. Janda, PhD, the Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research, states, “We have demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents. Currently, there is no known remedy for xylazine poisoning other than supportive care. Therefore, we believe that our research and the data we have provided will lead to an effective treatment for humans.”

The rapid rise in fatal drug overdoses linked to xylazine and fentanyl has led to action from the White House Office.The Office of National Drug Control Policy has declared the combination of xylazine and opioids an emerging threat to the United States. Intoxication with xylazine produces symptoms similar to opioid overdose, such as respiratory and central nervous system depression, and it can also intensify the effects of opioids. However, naloxone, which is typically used to reverse the effects of opioids, does not address the impact of xylazine. This underscores the need for effective measures to treat acute toxicity caused by xylazine.

Researchers believe that xylazine works by reducing blood flow to the brain and other areas of the body. The drug also causes non-healing skin lesions and wounds, often leading to serious health issues.present molecule that can trigger an immune response). The hapten-carrier complex can then stimulate the body to produce antibodies that can bind to the drug and prevent it from causing harm. This approach has shown promising results in animal studies, with the vaccinated animals exhibiting a strong immune response and resistance to the effects of xylazine. The next step is to conduct human trials to determine the vaccine’s safety and efficacy in people. If successful, this vaccine could be a game-changer for individuals who are at risk of xylazine-induced tissue damage. It could potentially save limbs and improve the quality of life for those affected by this dangerous drug.

The scientists in this study combined a xylazine hapten with various protein types to determine which combination would produce a strong immune response against xylazine. They tested three different vaccine formulations (labeled TT, KLH, and CRM197 based on the protein used) to determine which vaccine could protect rodents after being exposed to xylazine. The results showed that one of the vaccines (TT) significantly improved the movement of mice after xylazine exposure, while two of the vaccines (TT and KLH) led to better breathing.

The scientists also examined…The study aimed to understand how certain vaccines could reduce the permeation of xylazine across the blood-brain barrier (BBB), which is a mechanism that controls the entry of drugs into the brain. When xylazine was administered, it quickly entered the brain and bound to receptors. Normally, antibodies are unable to pass through the BBB, but two out of the three vaccines (TT and KLH) demonstrated a strong ability to prevent xylazine from reaching its receptors in the brain, thus reducing its harmful effects.

A provisional patent has been filed for this research. In the future, the team plans to use this research as a basis to develop a dual-function antibody that can counteract the toxicity of both fentanyl and xylazine simultaneously.

Simultaneously, a monoclonal antibody treatment can be administered alongside the vaccine to offer immediate and long-term protection against opioid substance use disorders and opioid-xylazine overdoses,” according to Janda. “This approach has the potential to have a significant impact on the opioid epidemic.”

The study titled “Evaluation of a Hapten Conjugate Vaccine Against the ‘Zombie Drug’ Xylazine” was co-authored by Mingliang Lin, Lisa M. Eubanks, Bin Zhou, and Kim D. Janda from Scripps Research.

The Shadek family and Pearson Foundation provided funding for the research.