The apnea and the ecstasy

Users of a popular club drug will be less than ecstatic to learn that the pill might be making it hard to breathe at night.

Researchers report online December 2 and in the December 8 issue of Neurology that regular users of the drug known as ecstasy were more likely than nonusers to show the cardinal signs of sleep apnea — stoppage of breath and gasping for air — during deep sleep.

In sleep apnea, muscle tone in the throat becomes unduly relaxed, resulting in airway blockage. An individual gasps for breath many times per hour of sleep, often leaving 10 seconds or more between breaths. Frequent gasping and arousal from sleep go unnoticed by the sleeper — until the next day. Sleep apnea can lead to daytime drowsiness, morning headaches, irritability, low energy and even driving accidents. It has also been associated with cognitive problems, stroke and heart disease.

Ecstasy would seem to have little to do with sleep problems. The popular drug is a synthetic psychoactive compound called MDMA (3,4-methylenedioxymethamphetamine), which brings on euphoria, emotional warmth, and distortions of time perception and tactile experiences, according to the National Institute on Drug Abuse, which provided funding for scientists who worked on this study.

But there is evidence that ecstasy is toxic to neurons in the brain that make serotonin, a multipurpose neurotransmitter. It has been hypothesized that serotonin-making neurons might somehow protect against sleep apnea, but how is unclear.

In the new study, scientists monitored the sleep of 62 people who had never taken ecstasy and 71 people who had used ecstasy at least 30 times but hadn’t taken it or any other illicit drug in the previous two weeks. The researchers rated sleep apnea as mild, moderate or severe based on the number of breath stoppages per hour. Volunteers ranged in age from 18 to 46, with an average age of 24, and none had been diagnosed previously with a sleep disorder.

The tests showed that eight of the ecstasy users had moderate obstructive sleep apnea and one had a severe case. None of the nonusers had such serious apnea. Roughly equal percentages of ecstasy users and nonusers had mild apnea, report physician Una McCann of Johns Hopkins School of Medicine in Baltimore and her colleagues. She and her colleagues accounted for differences among the volunteers in age, gender and weight.

The researchers also found that, among people who had taken ecstasy, those who took it most often were also the most likely to have sleep apnea.

“The results are intriguing,” says Sigrid Veasey, a physician and sleep researcher at the University of Pennsylvania School of Medicine in Philadelphia. “The critical question is whether individuals with pre-existing childhood or young-adulthood sleep apnea are more prone to use ecstasy … or whether the ecstasy causes or worsens sleep apnea.”

If there is a biological link between ecstasy and sleep apnea, it could be serotonin-making neurons. Writing in the same issue of Neurology, Nancy Chamberlin and Clifford Saper of Harvard Medical School point out that serotonin-making neurons might somehow sense carbon dioxide buildup in the blood or could play a role in a wake-promoting system.

“It would be interesting to see whether former [ecstasy] users have poor arousal responses,” they note, and to assess how these people react to high levels of carbon dioxide, which normally stimulate a person to take a breath.

Veasey cites her group’s research in dogs, which shows that sleep apnea may be worsened when serotonin signaling is blocked. Many young adults who already have some mild sleep apnea could be shifted into a more severe form by such a blockade, she says. But Veasey doubts that the loss of serotonin signaling alone would be enough to cause sleep apnea.