In development: a vaccine against addiction to the deadly drug that led to the opioid crisis

18-year-old Trinity Ripley from Maryland in the United States was a sociable girl, a gifted pianist who loved board games. In December 2023, Trinity took a painkiller, marketed as the drug Percocet, which contains oxycodone and acetaminophen (acetaminophen). But the pill she took was unbeknownst to her in a pirate drug lab, and even though it looked like any regular painkiller it also had a third substance in it: fentanyl. The result was tragic: shortly after Trinity swallowed the pill, she died of an overdose – from just one pill.

dictation Originally published on the Davidson Institute for Science Education website

Trinity’s story It was presented in the testimony of US Senator Chris Van Hollen (van Hollen) before a committee of the Senate, alongside other testimonies that revealed the inherent danger of fentanyl. After her death, Trinity’s father said, “I’m losing my mind thinking that one bullet is enough to kill.” Unfortunately, Trinity is not the only one. Data collected on the mortality of teenagers in the United States from fentanyl overdose in 2019-2021 reveals that in the vast majority of cases – 65 percent – There is no record of the drug victims having previously used fentanyland all the more that they were addicted to it.

Fentanyl is a synthetic substance pain reliever From the opioid family, given as a medicine for severe pain and also consumed as a mind-altering drug. Fentanyl is stronger than morphine (morphine) and heroin, although it is less well known than them. Due to its potency, even a tiny amount of two milligrams (thousandths of a gram) of fentanyl can cause serious harm and even death from an overdose. The danger is especially great for drug addicts and other people who use street drugs, as the substance they consume may have an unknown amount of fentanyl mixed in.

In addition to its action as a pain reliever, fentanyl also affects the respiratory center in the brain stem. This is an area that monitors breathing and we do not control it voluntarily – after all, we cannot decide to stop breathing. Due to the effect of fentanyl, the sensitivity of the brain to the levels of carbon dioxide in the blood decreases and it does not send a command to breathe more oxygen-rich air even when they rise. The suppression of breathing is why the drug is so deadly. Currently fentanyl is leading cause of death from overdose in the United States, and the number of its victims is high 18.5 times more than heroin.

The strength of fentanyl’s effect is due to its chemical structure. The molecule is fat soluble and therefore passes relatively easily and quickly the blood-brain barrierand affects the central nervous system faster than morphine and heroin. In case of overdose, prompt treatment Naloxone (Narcan), may save lives – this is a substance that binds to the opioid receptors and prevents the drug from binding to them itself. The substance is given by injection or as a sprayand will only work in the presence of opioids.

In addition to pain relief, fentanyl affects the mesolimbic pathway: a pathway in the brain that involves the neurotransmitter dopamine and creates feelings of pleasure, pleasure and motivation. Similar to heroin and other opioids, fentanyl creates a strong feeling of euphoria and is also consumed for this purpose, separate from its use as a pain reliever. This brain pathway is part of the reward system in the brain, which creates links between certain stimuli in reality and the sense of pleasure that people experience following them, and thus motivates to get more and more of the thing that caused the good feeling. This is why fentanyl is a highly addictive substance.

Uncontrolled administration of fentanyl for pain relief gave rise to the The opioid crisis in the United States. The health care system encouraged doctors to prescribe their patients strong painkillers, such as fentanyl, sometimes without a real medical need. Many of them developed a growing addiction and dependence on the drug, to the point that they switched to consuming it privately, as a street drug. Many found themselves spending all their savings on the drug, losing their jobs and becoming estranged from their family and friends.

One of the victims of the strong painkillers is the journalists Kathryn Kemp. in the book “Addicted to painkillers: from destruction to redemption”She said that she started consuming painkillers when the family doctor prescribed them for her due to pancreatitis. Later on, she experienced a difficult breakup and began to gradually increase the dose, thinking that “just one more wouldn’t hurt.” That’s how she went from a dose of eight pills a day to thirty. Kemp became addicted to fentanyl and became desperate, her life revolved around obtaining more and more prescriptions for the drug, because she was terrified of the withdrawal symptoms.

A new vaccine is now being developed designed to prevent the rapid passage of fentanyl into the brain. Already in 2009 an article was published that examined the The effectiveness of this vaccine on rats. It was found that following the vaccination, the rats produced specific antibodies in their bodies against fentanyl, but not against other opiate substances such as morphine, oxycodone and methadone, so it does not prevent the provision of other effective pain treatment. After the vaccination, fentanyl stopped relieving the pain of the vaccinated. Fentanyl levels in the brains of the vaccinated rats were very low compared to those that were not vaccinated. When rats were injected with increasing doses of fentanyl, the non-vaccinated rats exhibited difficulty breathing, while the vaccinated ones breathed normally and the level of oxygen saturation in the blood was normal.

the vaccinedeveloped by the biotechnology company ARMRis based on a small synthetic molecule of fentanyl, which is constructed so that it cannot induce a feeling of euphoria or relieve pain. to which they attached two molecules of inactive toxins of bacterial origin – a toxin of bacterial origin Diphtheria And another toxin produced by bacteria E. Coli. The toxins are inactive and therefore not dangerous, but stimulate the immune system to react against them. Their combination with fentanyl causes the immune system to produce antibodies that bind to fentanyl and prevent it from penetrating the brain and binding to the nerve cell receptors. Since it will not reach the brain, it will not create a feeling of euphoria nor will it depress the breathing of the users. In the absence of euphoria, they will not be motivated to consume the drug, and since the reward system will not be activated, they will not be able to become addicted to it either. NFirst clinical trial in a vaccinewhich will include several dozen people, began in March in Leiden in the Netherlands.

For Trinity Ripley, and many others, the new developments in research come too late. But if the clinical trial goes well, it is possible that in the near future we will have a vaccine that will help fentanyl users wean themselves off their dependence on the drug, and will even protect paramedics and other medical personnel who are exposed to the substance as part of their work, especially in emergency treatments on the battlefield or in accidents. If that happens, one wrong bullet will no longer be a death sentence.