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A new study could revive an abandoned theory on how to treat narcolepsy, the incurable disorder until now that makes people chronically sleepy. And it could also provide a new track on how to deal with addiction.
The article, published Wednesday in Science Translational Medicine, suggests that opioids can restore the ability of a narcoleptic person to produce a crucial neurotransmitter to regulate sleep. And because this same neurotransmitter plays a role in making people without narcolepsy vulnerable to addiction, finding a way to create the opposite effect could just help treat the addiction to seizure.
Narcolepsy affects at least 200,000 Americans. People with the disorder feel perpetually exhausted, often sleeping off throughout the day. But their fatigue is not caused by lack of sleep – on average, they sleep the same amount a day as anyone else. Instead, it's because they do not get enough REM sleep, a particularly restorative sleep stage (that's also the perfect time). Two-thirds of narcoleptics also suffer from cataplexy, which means that they suddenly lose control of their muscles when they are awake. The constant nodding, associated with episodes of cataplexy, explains the stereotypical representation of the narcoleptics who sleep at any moment.
The symptoms of narcolepsy, especially cataplexy, are caused by incredibly low rates of hypocretin (also called orexin). chemical in the brain that helps to govern our sense of enlightenment, among other things. And researchers in this study had previously discovered that dead narcoleptic brains had 90% fewer hypocretin-producing cells than healthy subjects.
One of the sound controls used in this study as a comparison is an interesting case themselves. The person, who had lived with a heroin addiction, had much higher amounts of hypocretin-producing cells than the other controls. Based on this strange finding, they decided to look at the brains of four people who had been addicted to opioids, finding the same pattern. These brains contained more cells producing hypocretin – 54% more on average – than the control subjects.
"So it was natural to ask if opiates reversed narcolepsy," says lead author Jerry Siegel, neuroscientist at the Brain Research Institute. The University of California at Los Angeles told Gizmodo.
In fact, they did it, at least in the mouse.
Narcoleptic mice given morphine for at least two weeks had their hypocretal cell levels return to normal, Siegel and his team found. They also had fewer episodes of cataplexy. And the effects seemed to last weeks after stopping the doses.
"In the past, two studies have shown that narcoleptics" accidentally "prescribed for opiates (for pain) had a reversal of symptoms, including cataplexy". baseline case reports published in the early 1980s. These studies led to an opioid test (using codeine) for patients with narcolepsy published in 1986. Unfortunately, the trial was largely considered to be a failure, as there was no objective change in the way in which sleeping people took opioids
. According to Siegel, it was understandable that doctors worry about unnecessarily giving addictive opioids to patients. This fear could have encouraged researchers to abandon the study of the link between opioids and narcolepsy after only one mediocre study. But even in the "failed" study, he notes, patients who were taking opioids still reported feeling better than those who did not have opioids. And research from his team suggests that the full effects of opioids might simply take longer than the study was allowed (patients received only a week of codeine).
There is also indirect evidence that this link operates in both directions. Narcoleptics are known to be less likely to develop a drug addiction than the general public, despite the fact that they often use powerful medications such as stimulants to keep them awake. And research in animals and humans has indicated that hypocretin is an important cog in the reward system that is hijacked by addictive drugs, alongside the neurotransmitter dopamine. According to the team, finding a way to safely reduce the number of hypocretin producing cells or block their production could bypass a person's addiction cycle.
People with narcolepsy have a dysfunctional immune system that kills the immune system. cells responsible for the manufacture of hypocretin. But opioids probably do not help the brain create more of these neurons, since the Siegel team has found no evidence of new neuron growth in mice. Instead, they appear to awaken some of the ability of surviving but dormant neurons to produce the chemical
"Understanding why opiates" awaken "these cells is a task for the future," Siegel said. . , Siegel and his team are once again looking to go ahead with the human trials of opioid treatment of narcoleptics, hoping to find the best dose and the best concentration of opioids needed to safely reverse the symptoms ( the ideal goal would be to develop a drug without dependence potential). In animals, they are also trying to find a way to reverse the drug addiction by altering the hypocretin system.
[Science Translational Medicine]
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