A Fentanyl Vaccine Is a Horrible Idea

By Crystal Lindell

A few years ago, I saved a loved one’s life when he was overdosing on fentanyl.

His lips and fingertips were blue when I found him, and as I administered NARCAN (naloxone), all I could think at that moment was that if he was dead, I never got the chance to say good-bye.

It was one of the most traumatizing experiences of my life, and I’m forever grateful that my efforts to save him were successful.

Even with that experience, I’m here to tell you that a fentanyl vaccine is an absolutely horrible idea. And I pray that nobody I love ever takes it – even the man who’s life I saved.

This week, JAMA published an article about the current status of the fentanyl vaccine, which is in development.

In the article, Associate Managing Editor Kate Schweitzer interviews Collin Gage, a cofounder and chief executive officer of ARMR Sciences, which has begun early-phase human trials of a fentanyl vaccine in the Netherlands.

Schweitzer seems to think such a vaccine would be a net positive for the world.

"If proven safe and effective, it could become the first proactive pharmaceutical approach designed to prevent fentanyl overdose and, potentially, treat addiction," she writes.

However, as both a chronic pain sufferer and someone whose loved one struggled with fentanyl addiction, I’m here to tell you that this entire research project should be ended right now.  

First and foremost, my biggest concern is that such a vaccine would be pushed onto people who do not want or need it, including pain patients.

I can already see doctors having a policy where they won’t prescribe opioids unless the patient agrees to receive the fentanyl vaccine. They’ll claim the policy is meant to protect patients, when in reality, it would only cause them more harm.

The article even points out what those harms could look like. Schweitzer quotes Kathryn Frietze, PhD, associate professor of molecular genetics and microbiology at the University of New Mexico, who is one of many researchers working to develop vaccines against drugs of abuse.

Doctors, according to Frietze, have expressed concern about how a vaccine could complicate medical care, given that prescription fentanyl is a widely used medication for acute pain control and anesthesia.

“Can they increase the fentanyl dose medically if needed, or is it going to completely eliminate fentanyl as an option?” Fritze asked. 

Read that again. Do we really want to eliminate fentanyl as an option for pain control and anesthesia? This is a medication used in hospitals, usually on patients in severe trauma or undergoing surgery.

Do we really want a vaccine to make fentanyl ineffective for them? 

Do we really want a vaccine that requires more fentanyl to be administered?

In practice, either scenario could be disastrous, especially in an emergency situation where an unconscious patient would be unable to explain to doctors that they had the fentanyl vaccine.

The thing about fentanyl is that you have no idea that you might need it someday. We don’t usually know when we’ll need anesthesia or acute pain control.

That is particularly relevant in this situation, because the article quotes multiple experts who seem excited about pushing a fentanyl vaccine onto high-risk groups, such as college students and young adults, who are experimenting with drugs. They may not be aware that the counterfeit pill they bought or got from a friend has a lethal dose of fentanyl. 

“Overdose from fentanyl doesn’t just happen to people who are purposely taking fentanyl,” Frietze said. “People may be exposed without their knowledge.” 

So they want to go to college campuses and give students a vaccine against a very valid pain medication, when they have no idea if they will ever need it?

Schweitzer says a vaccine that specifically targets fentanyl could still allow for the use of other analgesics, such as morphine and propofol. 

As a pain patient, I’m skeptical about that. If a vaccine blocks the effects of one opioid, it may also dampen the effects of other ones.  

The other major issue with a potential fentanyl vaccine is a phrase coined by Richard Cowan in 1986: “The Iron Law of Prohibition.” That essentially means that when law enforcement targets a specific drug, the potency of other prohibited substances increases.

Or, as Cowan said, "The harder the enforcement, the harder the drugs."

If you give everyone fentanyl vaccines, people will just find even stronger drugs to take. And those drugs will likely be more deadly. It’s no coincidence that illicit fentanyl arrived on the black market just as opioid pain medication became harder to get. 

As such, a fentanyl vaccine could result in more overdose deaths, not less, as people seek substitute drugs that bypass the vaccine.

Gage’s response to that possibility is to call the fentanyl vaccine “a platform technology—one that we plan to adapt."

In other words, they will just make new vaccines for new drugs. But in practice, how long would it take to actually develop new ones? And how long would it take to get them to drug users, who are often difficult for the medical community to reach?

Trust me when I tell you that drug users and their dealers will move exponentially faster than any research and development team ever could.

In practice, the reason street fentanyl is so deadly is because it’s unregulated. Users don’t know how much they are taking or what is mixed in with it – and those two things make it more likely that the drug will cause an overdose.

The solution then is to offer drug users a regulated supply, which is what methadone treatment is. In a perfect world, if they really wanted to help fentanyl users, these researchers would be working to make methadone treatment more accessible.

Instead, they’d rather make it so patients can’t use one of the most effective pain and anesthesia medications on the market, while pushing them onto harder or less effective drugs.

It’s a bad idea, and I hope these researchers see the error of their ways before it’s too late.

Can Fentanyl Be ‘Rewired’ to Make It Safer?

By Pat Anson

Scientists at Scripps Research have found a way to change fentanyl’s molecular structure to reduce the risk of overdosing, while at the same time preserving its pain-relieving properties. 

The findings, published in the ACS Medicinal Chemistry Letters, suggest that next-generation synthetic opioids could have less risk of addiction, respiratory depression, and death. 

Fentanyl has been used safely and effectively for over 50 years as a surgical analgesic, and by patients with severe pain from cancer and other intractable pain conditions. Only in the past decade has illicit fentanyl emerged as a potent and deadly street drug that fueled the U.S. overdose crisis.

That has given fentanyl a bad name – and led to efforts to “rewire” fentanyl and other opioids to make them safer, but still effective as pain relievers.

“For decades, the pharmaceutical industry has been constrained by the assumption that major structural changes to opioids would eliminate their analgesic properties,” says senior author Kim Janda, PhD, Professor of Chemistry at the Skaggs Institute For Chemical Biology. 

“Our research has identified a different possibility—that fundamental structural redesign can preserve pain relief while improving safety.”

Janda and his colleagues used a medicinal chemistry strategy known as “bioisosteric replacement,” a method used to redesign molecules to have different effects than the original molecules. 

To engineer the change in fentanyl, scientists replaced the central ring structure of fentanyl molecules with an entirely different one called “2-azaspiro[3.3]heptane.” The new compound doesn’t bind as much to nerve receptors in the brain that regulate breathing. 

When the redesigned fentanyl was tested on laboratory mice, the team arrived at a dose that remained effective as an analgesic, while the mice “appeared normal with no indication of distress or signs of acute toxicity.” 

Slowed breathing in the mice occurred only at very high doses and was temporary, with breathing returning to normal within 25-30 minutes. The new analog has a short half-life of about 27 minutes – the amount of time it takes for the liver to metabolize and break down the drug. Other medicines have a long half-life of several hours or even days — which makes them potentially more toxic.

“Finding ways to preserve the analgesic properties of the synthetic opioids without encumbering the perils of respiratory depression could help derisk the toxicity associated with synthetic opioid use while providing a new conduit for pain management,” says Janda.

The research appears promising and may someday benefit pain patients, but it overlooks the fact that illicit fentanyl is involved in most overdoses. The drug cartels and street dealers that sell it will have little interest in changing the chemical structure of illicit fentanyl to make it safer.

LSD Won’t Make a Good Painkiller

By Roger Chriss, PNN Columnist

Recent news that a small pilot study found LSD has a “protracted analgesic effect” at low doses garnered a lot of enthusiasm and hype. Headlines declared that LSD “could replace opiates” and be a “potent weapon against pain.”

The study looked at two dozen healthy volunteers given low doses of LSD or a placebo and then subjected them to a “cold pressor test” – immersing a hand in near-freezing water. Researchers found that 20 micrograms of LSD “significantly increased the time that participants were able to tolerate exposure to cold (3°C) water.”

Despite this, LSD has a clear problem: Its therapeutic index is very low.

The therapeutic index is a measure of the relative safety of a drug, computed by dividing the toxic dose by the dose needed for a therapeutic response. A toxic dose represents a threshold beyond which undesirable side effects or adverse events become common.

A high therapeutic index is better. It signifies a broader range of possible doses, letting clinicians adjust a dose precisely for a specific patient. Body weight, age, gender and metabolic status all influence drug metabolism and a high therapeutic index improves clinical safety.

A high therapeutic index also means that the drug can be given in multiple doses. If an initial dose is inadequate, a second dose can be given. Or a dose of another medication from the same class can be given. Or the drug can be given repeatedly over a short time without risky cumulative effects. All of this is important, because acute pain associated with trauma, injury or surgery may last for days.

The therapeutic dose of LSD in the simulated pain study was 20 micrograms (lower doses were ineffective). In general, a hallucinogenic dose starts at 25 micrograms. This suggests that LSD’s therapeutic index is 1.25.

Other measures of drug safety look even worse. The measure known as the margin of safety looks at how a dose may be toxic for 1% of people while being clinically effective for the other 99 percent. This accounts for variations in dose-response curves. Since some people experience LSD’s psychoactive effects at well below the standard 25 microgram threshold, LSD’s margin of safety is also very low.

LSD probably has little future as an over-the-counter analgesic or in a standard clinical setting for acute or chronic pain. It may instead have potential as a narrow therapeutic index (NTI) drug, which the FDA defines as a drug “where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity.”

Current NTI drugs include lithium and methotrexate, which are used to treat serious conditions such as bipolar disorder and rheumatoid arthritis in carefully selected patients under close medical supervision. LSD could wind up being designated as an NTI drug, but only if clinical trials demonstrate safety and efficacy in the management of specific types of pain.

In general, however, LSD is unlikely to be a broadly useful analgesic. Pain relievers need to have a wide therapeutic index in order to succeed, and there seems to be no practical way to do this with LSD.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.