Understanding how our brains work provides valuable insights into how addiction works, and how to treat it. A new study, published in Science Translational Medicine, suggests an interesting connection between opioid use and a neurotransmitter that regulates sleep. By manipulating hypocretin-producing cells in the brain.
Although the paper focused on narcolepsy, it actually studied two neurotransmitters related to the sleep and satisfaction systems of the brain: hypocretin, which regulates sleep, and dopamine, which controls mood. Hypocretin levels are very low in people who have the sleep disorder narcolepsy. Fewer hypocretin-producing cells translates to less good-quality sleep, but also less susceptibility to opiate addiction. Narcoleptics are less likely to develop substance use disorder than the average person, despite the fact they’re often prescribed powerful, addictive stimulants to keep them awake.
In comparison, the brains of people who lived with opioid use disorder were rich in hypocretin-producing cells. Their brains had more hypocretin-producing cells—an average of 54% more—than control subjects. The brains of narcoleptics had 90% fewer hypocretin-producing cells than healthy subjects. That suggests that people whose brains produce lots of hypocretin are more susceptible to developing substance dependency than the average person.
According to Gizmodo, “Plenty of research in animals and humans has indicated that hypocretin is an important cog in the reward system that gets hijacked by addictive drugs, alongside the neurotransmitter dopamine. So finding a way to safely reduce the number of hypocretin-producing cells or otherwise blocking its production, the team theorizes, might just short-circuit a person’s cycle of addiction.”
“So it was natural to ask if opiates would reverse narcolepsy,” senior author Jerry Siegel, a neuroscientist at the Brain Research Institute at the University of California, Los Angeles, told Gizmodo. The researchers dosed narcoleptic mice with morphine for at least two weeks and observed that the animals’ level of hypocretin-producing cells returned to normal. They also had fewer episodes of cataplexy, which is when a narcoleptic person will suddenly lose control of their muscles and appear to nod off or fall asleep.
According to Gizmodo, “opioids likely don’t help the brain create more of these neurons, since Siegel’s team found no evidence of new neuron growth in the mice. Instead, they seem to reawaken some of the surviving-but-dormant neurons’ ability to produce the chemical.”
Thomas Scammell, a narcolepsy expert at Harvard Medical School and Beth Israel Deaconess Medical Centre, said “If chronic use of opioids is increasing hypocretin production—and the authors show that nicely—then that could amplify the rewarding aspects of these drugs, making addiction all that much worse. I think that’s actually the most interesting part of their research.”
In future studies, the researchers plan to find a way to reverse drug addiction through tweaking the hypocretin system. Although substance use disorder is a complex illness, understanding more about how the brain’s chemistry impacts a person’s likelihood of developing it is very important. Just as breast cancer can be detected through early screening tests, we may one day have a similar screening process for substance use disorder.