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New research reveals orexin antagonists as potential therapy for drug addiction

Substances that reduce the level of orexin neurons in the brain can prove useful in combating drug addiction. – Photo by Elsa Olofsson / Unsplash

In a recent study, Rutgers researchers observed that the use of insomnia medication and having a regulated sleep cycle could reduce addiction to drugs and abuse of other related substances.

Gary Aston-Jones, co-author of the review and director of the Rutgers Brain Health Institute, said the orexin system controls the brain’s reaction to sleep, appetite and emotional well-being by releasing orexin neurons when stimulated.

Typically, orexin levels increase when the human body is awake or encounters stress and then reduce when the body is sleeping or no longer stressed, he said. But substance abuse can prolong the influx of orexin to the body, which can leave a person in an overstimulated mental state.

"(In the addictive state, cells) keep expressing a lot of orexin as though you're always awake or as though you always have a stressor on," Aston-Jones said. "That, in turn, because of the function of the system makes the subject easily motivated to pursue a salient stimulus in the environment."

He said that when an individual addicted to cocaine, for example, no longer wants typical stimulants like eating, they search out another dosage of cocaine to force their body to increase orexin levels.

Morgan James, the co-author of the review and an assistant professor in the Department of Psychiatry at Robert Wood Johnson Medical School, similarly said the study’s results have shown that an increase in the number of orexin neurons is directly related to drug use.

He said this finding has been shown in various other studies, including one that found that opioid-addicted individuals tend to have higher numbers of orexin neurons in their bodies.

Aston-Jones said other addictive substances such as nicotine, alcohol and food consumption have also been shown to have a neurological connection with the orexin system.

"I think (orexin) is a common denominator across any number or maybe all highly salient rewards and associated conditioned responding," he said.

With respect to how sleep medications affect orexin and drug addiction, by extension, James said drug-addicted people often have irregular sleep cycles.

By taking orexin antagonists, which can block orexin signals, these individuals can have better sleep which may lessen their need to use drugs like cocaine to stay stimulated during the day, he said.

"Sleep is so fundamental to every physiological system in the brain and in the body, and just by normalizing sleep, it is probably pushing an animal or a human into a more normal state … which probably will add up to a healthier behavioral state," James said.

Aston-Jones said there are currently multiple orexin antagonists treatments for insomnia but also that these treatments can also prove useful for targeting addiction. He said unlike other medications like antidepressants, orexin antagonists are shown to impact the subject very quickly.

Various healthcare organizations and scholarly researchers have drawn their attention to the growing field of orexin medications and their relation to relieving drug addictions, he said.

"It's a really exciting time to be working on the system because there is all of a sudden a large amount of interest in the orexin system as a potential therapeutic target for addiction," James said.

Aston-Jones said he is interested in researching more about why orexin neuron levels sometimes remain high in the body and whether orexin from reserve cells targets any specific parts of the brain.

He said the orexin system impacts multiple processes beyond addiction and is connected to neurological issues like anxiety and schizophrenia.

"Addiction might be the tip of the iceberg, and new therapies that tailor treatments to include orexin antagonists — perhaps along with existing antagonists — might prove to be more effective because I'm sure the orexin system is involved in many disorders in the brain,” he said.


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