Human Trials Begin for Fentanyl Vaccine to Prevent Overdoses

A vaccine that blocks the effects of fentanyl, including overdoses, is scheduled for Phase I human trials in the Netherlands in early 2026 to assess its safety. In previous rat studies, the vaccine blocked fentanyl from entering the rodents’ brain and also blocked the drug from depressing respiration and causing overdose. 

Opioids work by binding to opioid receptors in the brain and spinal cord, triggering changes in nerve cell signaling that prevent pain and can create a euphoric high. But these opioid receptors are also found in the part of the brain that controls breathing, which can be fatal. The vaccine, which is licensed by startup ARMR sciences, works in the circulatory system before the drug can reach the brain. However, to keep fentanyl from reaching the brain, the immune system must first recognize the drug. But since immune cells don’t naturally react to fentanyl’s presence, ARMR’s researchers chose a deactivated diphtheria toxin called CRM197, a compound already used in vaccines on the market. To boost the immune response, they added dmLT, a compound distilled from toxins produced by the Escherichia coli bacterium. They attached these two components to a synthetic piece of the fentanyl molecule that cannot cause a high or pain relief. When the immune system meets this combination, it builds antibodies that react to bind to the opioid, keeping it from crossing the blood-brain barrier and then clearing it from the body.

Forty people will be enrolled in the initial human trials and will focus on detecting any safety issues with the vaccines, such as unwanted or dangerous side effects. Researchers will also draw blood samples from participants to make sure the vaccine is spurring the creation of anti-fentanyl antibodies. If these trials are successful, Phase II trials will test the vaccine’s efficacy. The Phase II trials will also be dosed with safe levels of fentanyl used for pain relief in medical procedures under close supervision to check that the vaccine works in the presence of the drug.

This would be the first treatment that does not work on the opioid receptor.