The Nasal Spray that Was Supposed to Replace Sleep

What happened to Orexin-A, the wonder drug that was supposed to eliminate sleep?

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Jan 19 2016, 6:00pm

If you believed the headlines you read a decade ago, you might have thought that come New Year's Day in 2016, we'd be wide awake after a night of celebrations, high off the effects of a nasal spray wonder drug that has replaced sleep.

That drug is called Orexin-A, and in 2007 its reveal produced headlines like "Snorting a Brain Chemical Could Replace Sleep" and "DARPA Develops Brain Chemical to Replace Sleep."

At the time, a study led by UCLA professor Jerry Siegel introduced a "a totally new route for increasing arousal, and the new study shows it to be relatively benign," as he told ABC News at the time. Rumors floated that the drug could become an effective sleep replacement that didn't have the negative side effects, like addictive properties and mood swings, of its predecessors, like caffeine pills and stimulants or amphetamines, many of which can't produce positive effects without dragging a slew of problems along with them.

In the study, a group of lab monkeys were deprived of sleep for 30 to 36 hours, and then given either Orexin-A or a placebo. The monkeys were then presented with a series of cognitive tests to complete. As the researchers had suspected, the monkeys who were given Orexin-A nasal spray scored the same as monkeys who were not deprived of sleep, suggesting that the spray may have helped them stay alert on far less sleep. Meanwhile, group given a placebo performed poorly on the tests, as would be expected of a very tired monkey.

"It won't be a perfect drug, but no drug is."

So why aren't we all shooting sleep up our noses now? What happened to Orexin-A, the sleep wonder drug?

According to Siegel, work on Orexin-A is still alive and well, though it hasn't reached shelves yet. In fact, what most of the headlines that heralded the coming of Orexin-A failed to mention is that the drug isn't really meant to be a "sleep replacement" in the first place. It's intended for use by narcoleptics, people who suffer from a neurological disorder that prevents them from regulating their sleep-wake cycles.

"It's ridiculous," Siegel told Motherboard, about the first headlines that came out about Orexin-A. "I certainly never said that. I remember it coming out. There's no drug that can replace sleep. I don't think that's likely—or desirable."

But in terms of helping ease the symptoms of narcoleptics—meaning, creating a drug that could stave off both sleepiness and catoplexy (sudden physical collapse), Orexin-A could be a godsend: in both Siegel's monkey trials and in a series of trials on narcoleptics in Germany, the drug showed promising effects.

Still, nine years later, people who suffer from narcolepsy aren't using Orexin-A. The problem, as it boils down, lies with the pharmaceutical companies and money.

"It takes a lot of money to get a drug," said Siegel. "You have to enroll hundreds of people, and they all have to be seen by physicians."

What's more, it's not likely that a company would make a lot of money off Orexin-A. Because the substance it's extracted from, the neuropeptide orexin, occurs in naturally in the brain—and because Siegel has already published the results of his study—the drug and its method of administration (snorting) can't be patented.

"No drug company has undertaken to develop it because it's not worth their effort," he said.

Meanwhile, drug companies have developed Orexin-A's opposite: a sleep aid called Belsomra. While Orexin-A, an agonist, works by binding to receptors in the brain, Belsomra is an antagonist drug: it blocks molecules from binding at those receptors, and can be used to treat symptoms of insomnia, a sleep disorder that can be called the opposite of narcolepsy.

Belsomra succeeded where Orexin-A has not specifically because it can make more money. Even though the drug comes with serious side effects, including depression and suicidal thoughts, its market is huge. The number of people who suffer from insomnia in the US (60 million) is much higher than the number of people who have narcolepsy (200,000), and—excluding the market of college students who want to stay up all night to study for finals—therefore there is much greater demand for insomnia cures.

As for entirely "replacing" sleep, as some of the headlines had originally predicted, that may still be out of reach. According to Siegel, this is already possible with certain amphetamines—but not sleeping has dire effects. Orexin-A shouldn't be used this way, and would probably cause a host of problems if it was.

"It is likely that any drug radically changing the brain's balance to eliminate sleep would have similar effects," he said. "Orexin might also be addictive in the same way that opiates are addictive."

Still, Siegel hopes that Orexin-A will one day be able to help people with narcolepsy—without some of the negative side effects of existing drugs like Modafinil and Provigil.

"I hope that that it will be developed," he said, adding that there is at least one research group working on developing a pill form of the drug, but it release is still years away.

"I think it probably will be developed," he said. "It won't be a perfect drug, but no drug is."

You'll Sleep When You're Dead is Motherboard's exploration of the future of sleep. Read more stories.