The experimental vaccine dulls the deadliest synthetic opioids

While the opioid epidemic spread with even greater force during COVID-19, chemist Kim Janda’s Ph.D. laboratory, Scripps Research, has been working on new therapeutic interventions that may be able to prevent most deaths from opioid overdose.

Janda and his team developed experimental vaccines that have been shown in rodents to mitigate the deadly effects of fentanyl – which has fueled the boom in opioid deaths – as well as its even more fatal cousin, carfentanil, a growing source of overdoses and a threatening chemical. terrorist.

“Synthetic opioids are not only extremely deadly, but also addictive and easy to manufacture, making them a formidable threat to public health, especially when the coronavirus crisis is negatively affecting mental health,” said Janda, professor at Ely R. Callaway Jr. Química at Scripps Research. “We have shown that it is possible to prevent these unnecessary deaths by producing antibodies that prevent the drug from reaching the brain.”

Once in the brain, synthetic opioids trigger the body to slow down breathing. When many of the drugs are taken, which is easy to do, breathing can stop completely. In a series of experiments involving mice, Janda’s vaccines “hijacked” the drug’s potent molecules to prevent them from interacting with the brain and body, thereby preventing dangerous respiratory symptoms.

The findings appear today in Chemical Biology ACS.

Janda predicts that the vaccine will be used in a number of settings, including emergency situations to treat overdoses, as a therapy for those with substance abuse disorder and as a means of protecting military personnel who may be exposed to opioids as chemical weapons. They can even be useful for police dogs trained in search of these deadly drugs.

“The respiratory depression data we show is phenomenal for fentanyl and carfentanil, which gives us hope that this approach will work to treat a range of opioid-related illnesses,” said Janda.

Far from the ‘miracle drug’

Opioids are a diverse class of drugs that have been used to relieve pain for more than 200 years, although the scenario has undergone a radical change in recent decades. The painkiller morphine, isolated from opium, was announced as a miracle drug in the early 19th century. Not long after, drug makers created a synthetic form, heroin, as a supposedly non-addictive substitute for morphine. (The problematic nature of the drug became clear in the 1920s, leading to regulation.)

However, it was not until the late 1990s that opioids began to trigger a public health emergency marked by the overuse of opioid medications, both by prescription and illegal drug sales.

Today, the problem has reached a new crescendo. In December, the Centers for Disease Control and Prevention declared the highest number of overdose deaths on record in a 12-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, in turn, is up to 10,000 times more potent than morphine, says Janda, making it the deadliest of all. It is often used in veterinary medicine to sedate large animals, such as elephants.

Although carfentanil is not as well known as a street drug, it is increasingly used as an adulterant in heroin and cocaine, leading to unexpected drug overdoses. It can also lead to overdose deaths due to accidental exposure, such as in veterinary or police environments. Having an emergency vaccine available can prevent these risks.

Janda says synthetic opioids are also considered a terrorist weapon; they can be made in large quantities and in various forms, including tablets, powder and spray. They are readily absorbed through the skin or by inhalation. A single terrorist attack using carfentanyl can be deadly to a large number of people, he says.

“Unfortunately, the rise in carfentanyl and fentanyl overdose incidents is putting even more pressure on the already overburdened public health systems that are currently fighting a pandemic,” said Janda. “We hope to continue our vaccine research and translate them into the clinic, where we can begin to impact the opioid crisis.”