Individuals with narcolepsy have an unusual ability to resist addiction to amphetamines, the type of drug used to treat their condition. Because they have mutations at the genetic level for peptides called orexins, or their receptors, the potent amphetamines are not addictive, but are successful at keeping them awake.

This discovery has led several pharmaceutical companies to investigate whether the orexins might be helpful in treating addictions. The tiny proteins are what keep us awake and attentive during the day and they also govern some stimulation caused by the effects of addictive drugs. The drug companies are investigating whether the drugs that promise a good night’s sleep by blocking orexins may also help treat addictions.

The same drug companies that are now working to develop sleep aids based on orexins are investigating the same drugs’ role in addiction by testing its effects on animals. Researchers at GlaxosmithKline Medicines Research Center in Verona Italy are using an experimental orexin-blocker to test the effects on rats using amphetamine. When the rats are given the orexin blocker, they release less dopamine and are less sensitized to the stimulant. The effects remain the same, even with repeated doses.

David Quarta leads the research team and explains that the sensitized neurons grow extra receptors for the craved drug. The body then demands more of the drug to experience the same level of stimulation, creating an addictive cycle. The orexin blocker keeps the sensitization process from continuing.

Merck scientists are also doing similar research. The study, led by John J. Renger, showed that an orexin blocker, offered with amphetamine to rats, prevented sensitization. The same study also showed that relapse in nicotine addiction could be prevented by giving the animals orexin blockers.

Renger explains that amphetamines target orexins. The brain’s release of orexins enhances and increases the process of sensitization and addiction.

A lack of orexin can encourage sleep, so orexin-blocking sleep aids will provide a more natural sleep than that produced by the sleeping pills currently on the market. The sleeping pills being used depress all brain activity, including orexins, and make it hard for an individual to wake up.

Orexin-blockers as sleep aids may assist in overcoming addiction just by providing a healthy, natural night of sleep. It is harder for recovering addicts to avoid relapse when they are overly tired. If orexin-blockers could be used to keep patients taking amphetamines for medical reasons from becoming addicted, they could assist in avoiding many unintentional addictions.