Experimental vaccine blunts the deadliest synthetic opioids

As the opioid epidemic raged with even greater force during COVID-19, the Scripps research laboratory of chemist Kim Janda, Ph.D., was working on new therapeutic interventions that could cover most of the deaths due to opioid overdose. may occur.

Janda and his team developed experimental vaccines that have been shown in rodents to stop the deadly effects of fentanyl – which has driven the rise in opioid deaths – as well as the deadliest cousin, carfentanil, a growing source of overdoses and a chemical. terrorist threat.

“Synthetic opioids are not only extremely lethal, they are also addictive and easy to manufacture, making them a huge threat to public health, especially if the coronavirus crisis is adversely affecting mental health,” said Janda, the Ely R. Callaway, jr. Professor of Chemistry at Scripps Research. “We have shown that it is possible to prevent these unnecessary deaths by eliciting antibodies that prevent the drug from reaching the brain.”

Once in the brain, synthetic opioids cause the body to slow down breathing. If too much of the drug is consumed, which is easy to do, breathing can stop completely. In a series of experiments involving mice, Janda’s vaccines “sequestered” the powerful drug molecules to prevent them from interacting with the brain and body, obstructing dangerous respiratory symptoms.

Findings appear today in ACS Chemical Biology.

Janda foresees that the vaccine could be used in a number of scenarios, including emergency situations for the treatment of overdoses, as a therapy for those with drug abuse, and as a way to protect military personnel who may be exposed to opioids as chemical weapons . It can even be helpful for trained police dogs to search for these deadly drugs.

“The respiratory depression data we are showing is phenomenal for both fentanyl and carfentanil, giving us hope that this approach will work to treat a number of opioid-related diseases,” says Janda.

A long road of ‘miracle cure’

Opioids are a diverse class of medicines that have been used for over 200 years to relieve pain, although the landscape has begun to turn strong in recent decades. The painkiller morphine, isolated from opium, was announced as a miracle cure in the early 1800s. Not long after, drug manufacturers created a synthetic form, heroin, as a putative morphine substitute. (The problematic nature of the drug became apparent in the 1920s, which led to regulation.)

However, it was not until the late 1990s that opioids began to cause an emergency for public health, characterized by widespread overuse of opioid drugs, both by prescription and the illicit sale of the drug.

Today, the problem has reached a new crescendo. In December, the Centers for Disease Control and Prevention declared the highest number of overdose deaths ever recorded in a twelve-month period, with synthetic opioids – mainly fentanyl, created in illegal laboratories – as the main source.

Also considered a terrorist weapon

Fentanyl is much stronger than most other opioids, up to 100 times stronger than morphine. Carfentanil, meanwhile, is up to 10,000 times stronger than morphine, says Janda, making it the deadliest of all. It is often used in veterinary medicine to soothe large animals such as elephants.

Although carfentanil is not as well known as a drug on the street, it is increasingly used as an adultery in heroin and cocaine, leading to unexpected drug overdoses. It can also lead to overdose deaths due to accidental exposure, such as in the veterinary or police environment. Having an emergency vaccine on hand can reduce the risks.

Janda says synthetic opioids are also considered a terrorist weapon; it can be made in large quantities and in various forms, including tablets, powder and syringe. It is easily absorbed through the skin or by inhalation. A single terrorist attack with carfentanil could be fatal to large numbers of people, he says.

“Unfortunately, the increase in the causes of carfentanil and fentanyl overdose puts further strain on already overwhelming public health systems currently facing a pandemic,” says Janda. “We look forward to continuing our vaccine research and translating it into the clinic, where we can begin to make an impact on the opioid crisis.”