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Drug can amplify naloxone's effect and reduce opioid withdrawals, study shows

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Drug can amplify naloxone's effect and reduce opioid withdrawals, study shows

Naloxone has long been hailed as a life-saving drug in the face of the opioid epidemic. But its capacity to save someone from an overdose can be limited by the potency of the opioid — a person revived by naloxone can still overdose once it wears off.

Stanford researchers have found a companion drug that can enhance naloxone’s effect — and reduce withdrawal symptoms. Their research on mice, led by Stanford University postdoctoral scholar Evan O’Brien, was published today in Nature.

Typically, overdose deaths occur when opioids bind to the part of the brain that controls breathing, slowing it to a stop. Naloxone reverses overdoses by kicking opioids off pain receptors and allowing normal breathing to resume.

However, it is only able to occupy pain receptors for 30 to 90 minutes. For more potent opioids, such as fentanyl, that may not be long enough.

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To determine how the naloxone companion drug, which researchers are calling compound 368, might boost naloxone’s effectiveness, researchers conducted an experiment on pain tolerance in mice, said Jay McLaughlin, a professor of pharmacology at the University of Florida. How quickly would mice pull their tails out of hot water, depending on which combination of opioids and treatments they were given?

Mice that were injected with only morphine did not respond to the hot water — given their dulled pain receptors. Mice given morphine and naloxone pulled their tails out within seconds. No surprises yet.

When the dosage of naloxone was reduced and compound 368 was added, the compound was found to amplify naloxone’s effects, as if a regular dose was used. When used on its own, the compound had no effect, indicating that it is only helpful in increasing the potency of naloxone.

What researchers did not expect, however, was that the compound reduced withdrawal symptoms.

McLaughlin said withdrawal is one reason that people who have become physically dependent on opioids may avoid naloxone.

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“Opioid withdrawal will not kill you, but I have talked to a number of people who have gone through it, and they have all said the same thing: … ‘I wished I was dead,’” McLaughlin said. “It has a massive range of nasty, horrible effects.”

The idea that the compound could amplify naloxone’s effect at a lower dosage, while limiting withdrawal symptoms, indicates that it may be a “new therapeutic approach” to overdose response, McLaughlin said.

The research team said their next step is to tweak the compound and dosage so that the effects of naloxone last long enough to reverse overdoses of more potent drugs.

Though the compound is not yet ready for human trials, the researchers chose to release their findings in the hope that their peers can double check and improve upon their work, said Susruta Majumdar, another senior author and a professor of anesthesiology at the Washington University School of Medicine in St. Louis.

“We may not be able to get that drug into the clinic, but somebody else may,” Majumdar said. He added: “Let them win the race.”

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What’s in a Name? For These Snails, Legal Protection

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What’s in a Name? For These Snails, Legal Protection

The sun had barely risen over the Pacific Ocean when a small motorboat carrying a team of Indigenous artisans and Mexican biologists dropped anchor in a rocky cove near Bahías de Huatulco.

Mauro Habacuc Avendaño Luis, one of the craftsmen, was the first to wade to shore. With an agility belying his age, he struck out over the boulders exposed by low tide. Crouching on a slippery ledge pounded by surf, he reached inside a crevice between two rocks. There, lodged among the urchins, was a snail with a knobby gray shell the size of a walnut. The sight might not dazzle tourists who travel here to see humpback whales, but for Mr. Avendaño, 85, these drab little mollusks represent a way of life.

Marine snails in the genus Plicopurpura are sacred to the Mixtec people of Pinotepa de Don Luis, a small town in southwestern Oaxaca. Men like Mr. Avendaño have been sustainably “milking” them for radiant purple dye for at least 1,500 years. The color suffuses Mixtec textiles and spiritual beliefs. Called tixinda, it symbolizes fertility and death, as well as mythic ties between lunar cycles, women and the sea.

The future of these traditions — and the fate of the snails — are uncertain. The mollusks are subject to intense poaching pressure despite federal protections intended to protect them. Fishermen break them (and the other mollusks they eat) open and sell the meat to local restaurants. Tourists who comb the beaches pluck snails off the rocks and toss them aside.

A severe earthquake in 2020 thrust formerly submerged parts of their habitat above sea level, fatally tossing other mollusks in the snail’s food web to the air, and making once inaccessible places more available to poachers.

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Decades ago, dense clusters of snails the size of doorknobs were easy to find, according to Mr. Avendaño. “Full of snails,” he said, sweeping a calloused, violet-stained hand across the coves. Now, most of the snails he finds are small, just over an inch, and yield only a few milliliters of dye.

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Video: This Parrot Has No Beak, But Is at the Top of the Pecking Order

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Video: This Parrot Has No Beak, But Is at the Top of the Pecking Order

new video loaded: This Parrot Has No Beak, But Is at the Top of the Pecking Order

Bruce, a disabled kea parrot, is missing his top beak. The bird uses tools to keep himself healthy and developed a jousting technique that has made him the alpha male of his group.

By Meg Felling and Carl Zimmer

April 20, 2026

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Contributor: Focus on the real causes of the shortage in hormone treatments

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Contributor: Focus on the real causes of the shortage in hormone treatments

For months now, menopausal women across the U.S. have been unable to fill prescriptions for the estradiol patch, a long-established and safe hormone treatment. The news media has whipped up a frenzy over this scarcity, warning of a long-lasting nationwide shortage. The problem is real — but the explanations in the media coverage miss the mark. Real solutions depend on an accurate understanding of the causes.

Reporters, pharmaceutical companies and even some doctors have blamed women for causing the shortage, saying they were inspired by a “menopause moment” that has driven unprecedented demand. Such framing does a dangerous disservice to essential health advocacy.

In this narrative, there has been unprecedented demand, and it is explained in part by the Food and Drug Administration’s recent removal of the “black-box warning” from estradiol patches’ packaging. That inaccurate (and, quite frankly, terrifying) label had been required since a 2002 announcement overstated the link between certain menopause hormone treatments and breast cancer. Right-sizing and rewording the warning was long overdue. But the trouble with this narrative is that even after the black-box warning was removed, there has not been unprecedented demand.

Around 40% of menopausal women were prescribed hormone treatments in some form before the 2002 announcement. Use plummeted in its aftermath, dipping to less than 5% in 2020 and just 1.8% in 2024. According to the most recent data, the number has now settled back at the 5% mark. Unprecedented? Hardly. Modest at best.

Nor is estradiol a new or complex drug; the patch formulation has existed for decades, and generic versions are widely manufactured. There is no exotic ingredient, no rare supply chain dependency, no fluke that explains why women are suddenly being told their pharmacy is out of stock month after month.

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The story is far more an indictment of the broken insurance industry: market concentration, perverse incentives and the consequences of allowing insurance companies to own the pharmacy benefit managers that effectively control drug access for the majority of users. Three companies — CVS Caremark, Express Scripts and OptumRx — manage 79% of all prescription drug claims in the United States. Those companies are wholly owned subsidiaries of three insurance behemoths: CVS Health, Cigna and UnitedHealth Group, respectively. This means that the same corporation that sells you your insurance plan also decides which drugs get covered, at what price, and whether your pharmacy can stock them. This is called vertical integration. In another era, we might have called it a cartel. The resulting problems are not unique to hormone treatments; they have affected widely used medications including blood thinners, inhalers and antibiotics. When a low-cost generic such as estradiol — a medication with no blockbuster profit margins and no patent protection — runs into friction in this system, the friction is not random. It is structural. Every decision in that chain is filtered through the same corporate profit motive. And when the drug in question is an off-patent estradiol patch that has negligible profit margins because of generic competition but requires logistical investment to keep consistently in stock? The math on “how much does this company care about ensuring access” is not complicated.

Unfortunately, there is little financial incentive to ensure smooth, consistent access. There is, however, significant financial incentive to steer patients toward branded alternatives, or simply to let supply tighten — because the companies aren’t losing much profit if sales of that product dwindle. This is not a conspiracy theory: The Federal Trade Commission noted this dynamic in a report that documented how pharmacy benefit managers’ practices inflate costs, reduce competition and harm patient access, particularly for independent pharmacies and for generic drugs.

Any claim that the estradiol patch shortage is meaningfully caused by more women now demanding hormone treatments is a distraction. It is also misogyny, pure and simple, to imply that the solution to the shortage is for women’s health advocates to dial it down and for women to temper their expectations. The scarcity of estradiol patches is the outcome of a broken system refusing to provide adequate supply.

Meanwhile, there are a few strategies to cope.

  • Ask your prescriber about alternatives. Estradiol is available in multiple formulations, including gel, spray, cream, oral tablet, vaginal ring and weekly transdermal patch, which is a different product from the twice-weekly patch and may be more consistently available depending on manufacturer and region.
  • Consider an online pharmacy. Many are doing a good job locating and filling these prescriptions from outside the pharmacy benefit manager system.
  • Call ahead. Patch shortages are inconsistent across regions and distributors. A call to pharmacies in your area, or a broader geographic radius if you’re able, can locate stock that your regular pharmacy doesn’t have.
  • Consider a compounding pharmacy. These sources can sometimes meet needs when commercially manufactured products are inaccessible. The hormones used are the same FDA-regulated bulk ingredients.

Beyond those Band-Aid solutions, more Americans need to fight for systemic change. The FTC report exists because Congress asked for it and committed to legislation that will address at least some of the problems. The FDA took action to change the labeling on estrogen in the face of citizen and medical experts’ pressure; it should do more now to demand transparency from patch manufacturers.

Most importantly, it is on all of us to call out the cracks in the current system. Instead of repeating “there’s a patch shortage” or a “surge in demand,” say that a shockingly small minority of menopausal women still even get hormonal treatments prescribed at all, and three drug companies control the vast majority of claims in this country. Those are the real problems that need real solutions.

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Jennifer Weiss-Wolf, the executive director of the Birnbaum Women’s Leadership Center at New York University School of Law, is the author of the forthcoming book When in Menopause: A User’s Manual & Citizen’s Guide. Suzanne Gilberg, an obstetrician and gynecologist in Los Angeles, is the author of “Menopause Bootcamp.”

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