More than 80,000 people died in the US from overdoses involving opioids in 2021, and this devastating statistic climbs every year (1). The growing opioid use disorder (OUD) crisis has prompted researchers to explore new approaches to reduce its fatality. Most recently, hope comes in the form of opioid vaccines.
Although vaccines are traditionally associated with preventing infectious disease, they have shown potential for addressing substance abuse issues. Instead of training the immune system to build up immunity to an infectious pathogen, opioid vaccines train the immune system to build an “immunity” to opioids by neutralizing their effects in the body. Indeed, these vaccines stimulate the immune system to generate antibodies that, when opioids are consumed, bind to the target opioid in the periphery. This prevents the opioid from entering the brain, mitigating its potential to cause an overdose. These vaccines could be given pre-emptively to groups at high risk of OUD, such as those with a history of opioid addiction, chronic pain patients, and individuals in opioid treatment programs.
While several opioid vaccines are in development, researchers are most excited about the fentanyl vaccine. Fentanyl, a potent synthetic opioid, is widely considered to be the main driver of the recent surge of fatal overdoses across the US. With a strength of 50 times that of heroin and 100 times that of morphine, only 2mg of fentanyl is considered lethal (2).
A study from the University of Houston demonstrated early success of an anti-fentanyl vaccine in preclinical studies involving rats (3). This study showed that the anti-fentanyl vaccine effectively generated significant levels of anti-fentanyl antibodies. These antibodies proved highly efficient in neutralizing fentanyl’s pain-relieving properties and reducing physiological measures associated with overdose.
Importantly, the vaccine exhibited specificity, binding only to fentanyl and its derivatives, with no cross-reactivity to other opioids. This means that it does not interfere with the body’s natural abilities to control pain or with other pain management therapies, it only neutralizes fentanyl’s effects.
Trials of this fentanyl vaccine, as well as a heroin vaccine developed as part of a multi-institutional effort funded by the National Institutes of Health, are expected to start phase I trials in humans in 2024. For now, the only opioid in human clinical trials is being developed at Columbia University against oxycodone. Oxycodone leads to far fewer overdoses every year compared to fentanyl, but it serves as an important validation for opioid vaccines more broadly.
While these results are encouraging, past human trials of substance abuse vaccines should dampen our expectations. Researchers have already brought nicotine and cocaine vaccines to human trials, and while these attempts were successful at generating antibodies against these drugs, they never managed to meet their intended purpose of altering the substance abuse of those who took them (4, 5).
These shortcomings highlight the fact that opioid vaccines are far from a complete solution to OUD, even if they manage to receive FDA approval. Indeed, opioid vaccines do not directly address the underlying issue of addiction. Instead, they focus on mitigating the harmful effects of opioids, particularly the risk of overdose. People struggling with OUD often face complex challenges, including physiological dependence and psychological aspects of addiction, which the vaccines do not directly address.
Addressing the OUD crisis in the US will continue to require a multifaceted approach, including behavioral therapy, counseling, support groups, and, in some cases, medication-assisted treatment (MAT) using drugs like methadone, buprenorphine, or naltrexone. MAT helps manage cravings and withdrawal symptoms, facilitating a person's ability to engage in the therapeutic aspects of recovery.
Therefore, while opioid vaccines are a promising tool in reducing the harm and fatality of the ever-worsening OUD crisis, a comprehensive strategy to combat opioid addiction should involve a combination of preventive measures, treatment options, and ongoing support for individuals on the path to recovery.
Author: Dane Callow
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