A new fentanyl vaccine looks promising – but treating drug addiction needs a more complex approach

The US and Canada are in the middle of an opioid epidemic. But opioid use is a growing problem in other countries too.

Opioid-related deaths make up the largest proportion of drug-related fatalities across the UK, with an average of 40 a week. From patients who have become dependent on prescription painkillers to people addicted to newer, more potent synthetic opioids called nitazenes, new treatments for opioid abuse are desperately needed.

Recent reports heralded the next stage of a 2022 US study. The study found a vaccine for fentanyl addiction showed promising results in rats. According to the reports, the study will soon go to human clinical trials. If effective in humans, the vaccine might prevent fentanyl abusers from feeling any of the euphoric effects of the drug, and could prove to be an important weapon in the war against opioid addiction. But it’s unlikely to be a silver bullet.

The vaccine works by getting our bodies to produce antibodies that are specific for the fentanyl molecule. These antibodies attach themselves to part of the fentanyl molecule, stopping the drug from crossing the blood-brain barrier. This means the fentanyl can’t activate the mu opioid receptors, which are critical for producing the euphoric effects of opioids.

In the 2022 study, male and female rats were given three doses of the vaccine in weeks one, three and six. The vaccine was found to have several effects. First, it increased the level of fentanyl antibodies in blood serum by the fourth week – and remained relatively stable until the final blood test in week ten.

Next, the rats faced the “tail flick” and “hot plate” tests to check for their perception of pain. Both tests measure how long it takes for the rat to move in response to heat. Typically, fentanyl and other painkillers will increase the time it takes for the rat to move – showing less sensitivity to pain. However, the vaccinated rats moved quickly in response to heat, showing that the painkilling effect of fentanyl was lost.

The study also found that the vaccine significantly reduced or completely inhibited fentanyl’s effects on blood oxygen saturation, heart rate and general activity (movement).

Finally, at week 20 of the experiment, rats were injected with a high dose of fentanyl, then anaesthetised and killed humanely. Their brains were then examined. Brain levels of fentanyl were very low in the vaccinated rats. The blood serum taken at this point was also tested against other opioids to determine how specific the vaccine was for fentanyl. While serum from vaccinated rats showed that the anti-fentanyl antibodies bound to fentanyl, these antibodies did not bind to morphine, methadone, buprenorphine or oxycodone antigens.

This final finding – that the anti-fentanyl antibody was specific for fentanyl and not the other opioids – is important. These other drugs can be clinically useful. Morphine, oxycodone and buprenorphine are effective painkillers, while methadone is used in treating opioid dependence.

Not there yet

The fentanyl vaccine study is not the first time researchers have tried to develop vaccines for drug dependency. Vaccines for cocaine, methamphetamine, nicotine and others have all been tested in rats and, in some cases, people.

A 2022 review article found that, of the 23 registered clinical trials examining vaccination for drug abuse, 15 were on nicotine, six were on cocaine and one each examined methamphetamine and opioids. So far, the clinical data do not support the use of a vaccine for drug dependency.

For example, a cocaine vaccine, despite producing high levels of anti-cocaine antibodies and being relatively safe to use, did not significantly reduce cocaine taking in a group of 130 people. Previous clinical studies had been more effective in drug addicts with high cocaine antibody levels. This may be due to those studies including psychotherapy and methadone in the treatment regimen along with the cocaine vaccine.

Not a perfect solution

Vaccines could be useful in the treatment of drug addiction – but there are significant barriers to overcome. For example, will those dependent on drugs be motivated to try a vaccine that blocks their high? Some users might be able to overcome the antibodies in the vaccine by taking larger doses of drugs, which could prove lethal.

Users might take a similar drug (a different opioid, say) that isn’t affected by the vaccine. Also, people have variable responses to vaccines so it may be more effective in some users than others. Treatment would have to include frequent vaccination because of the limited time of antibody production, which may prove expensive and inconvenient for users.

I have reviewed treatments for drug addictions and, fortunately, there are other developments in drug abuse therapies, an area with relatively few good treatments. For instance, similar to using methadone for heroin abuse, there are several maintenance or substitution treatments available or being developed for other drugs.

Although vaccines to treat drug dependence would be welcome, the root cause of addiction is rarely just a love of drugs – or that people started on painkillers and ended up on fentanyl. Those addicted to drugs are more likely to have complex psycho-social issues. People with deep psychological problems will have the same issues post-vaccine and could switch to other harmful substances – alcohol, methamphetamine, cocaine, for example – if the root of their addiction isn’t addressed.

As such, any vaccine would only be one aspect of holistic treatment of addiction, including psychotherapy.

Colin Davidson has previously received funding from the NIH (USA) and the EC for projects related to drug abuse. He is currently a consultant on novel psychoactive substances for the Defence Science Technology Labs and is on a Working Group on Synthetic Cathinones for the Advisory Council on the Misuse of Drugs (UK).