Forging a path to addiction-free painkillers

May 26 · 4 min read

“It’s not what we hire our staff to do,” a library director said after a man was found dead of an overdose in the library restroom. Overdue books, not overdose deaths, are librarians’ traditional realm. Yet American Libraries Magazine notes that plumbing clogged with needles is now a challenge in many public media centers.

In both public spaces and private homes, more than 70,000 deaths per year in the U.S. and Canada are linked to opioids. For many people, the problem begins innocently enough, while taking doctor-prescribed painkilling medicine that contains opioids. From there, taking safe doses can shift toward compulsive craving for excessive amounts, leading to Opioid Use Disorder, or OUD.

Can’t there be medicine that just kills pain and not people?

Advances in organoid research may light a path to addiction-free painkillers, and do so without testing animals or desperate human volunteers. The U.S. National Institutes of Health is fueling this innovation. The NIH’s “Helping to End Addiction Long-term” Initiative arrives astride the optimistic acronym HEAL. The initiative asks, how can organoids help?

Compulsive craving

“Opiates” and “opioids” are two different things. Opiates occur naturally, but opioids do not. To understand this, the pair can be thought of as the good opiates and the bad opioids.

Natural opiates are inborn, created by the human body. One familiar type, endorphins, are natural opiates generated by exertion, and have a calming effect.

In contrast, opioids are manufactured copies of opiates — with few or no natural ingredients. Opioids are concocted from chemical ingredients. The opioid Fentanyl is one example. Fentanyl is 50 to 100 times more powerful than morphine.

Inside the brain, opiates attach to receptor cells, because the receptors’ normal job is to “receive” opiates. But opioids can also latch onto the receptors, because they look like a twin of opiates. This tricks the receptors into welcoming them. Unfortunately, manufactured opioids are wolves in sheep’s clothing. They pretend to be naturally-occurring opiates, but they are not.

Natural opiates impact the brain in a different way than manufactured opioids do. Both of them bind to receptors — but after that, their paths diverge.

Bad opioids do dull or end severe pain — that’s their positive attribute. But they also burrow into the brain in a way that natural opiates do not, and that burrowing creates abnormal, uncontrollable craving. Once inside the brain, opioids cause changes that rob a person of everyday functioning. At that point, craving for more opioids overpowers all normal impulses, including those for survival. One expert describes opioids as “kidnapping the system” that motivates survival. This is how OUD wipes out the brain’s normal decision-making.

A chip off the old block

The name “organoids” refers to miniature human organs. They are seeded from human stem cells, and nurtured in a lab dish, where they grow to resemble real organs. The value of organoids, including mini-intestines, mini-kidneys and mini-colons, is that new treatments are tested on them.The word “proxies” has been used to describe organoids. There is no need for animal experiments, if experiments can instead be done on proxies.

Stem cells can come from patients’ skin, marrow or blood, and then used as seeds to grow organoids that match a patient’s genes exactly. Organoids are also called “tissue chips” because they are replicas of human tissue. Organoids are literally a “chip off the old block.” For this reason, they are used to safety-test new drugs before they are prescribed for humans. Organoids are like automobile crash-test dummies: they are used to test the impact before humans do.

Researchers at Harvard, Yale and many other universities have developed brain organoids. By using new information gleaned from brain organoids, rather than from animal experiments, scientists might be able to create non-addictive painkillers.

Hopes for HEAL

Per the NIH, organoid research is the focus of HEAL. “The HEAL Initiative will bolster research across NIH to improve treatment for opioid misuse and addiction and enhance pain management.”

British physicist Sir Arthur Eddington was renowned for translating his colleague Albert Einstein’s theories into the English language, at a time when world wars made it impossible for Einstein’s own German writing to be understood in other countries. Despite this vaulted pedigree, Eddington once described certain physics processes within the universe as, “Something unknown is doing we don’t know what.”

Likewise, when it comes to opioids, something unknown clearly has been doing we don’t know what.

But we’re on to something now.

Kathy Jean Schultz

Written by

Kathy Jean Schultz is a freelance medical writer who covers new experimental research.

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