A synthetic cannabis-like pill was safe and effective in treating obstructive sleep apnea (OSA) in the first large multi-site study of a drug for apnea funded by the National Institutes of Health, conducted at Northwestern Medicine and the University of Illinois at Chicago (UIC). There is no current drug treatment for apnea, so such medication could be an alternative to continuous positive airway pressure (CPAP), oral appliances, and other treatments.
Breathing is interrupted in sleep apnea, which affects about 30 million people in the United States, and these pauses can last from a few seconds to minutes and may occur 30 times or more an hour. Untreated apnea raises the risk of heart disease, diabetes, sleepiness, cognitive impairment, and motor vehicle accidents. CPAP delivers air to prevent collapse of the airway and breathing pauses, but its use can be challenging, so many patients stop using it.
“There is a tremendous need for effective, new treatments in obstructive sleep apnea,” said David W. Carley, PhD, co-lead author of the study and the Katherine M. Minnich Endowed Professor Emeritus of Biobehavioral Health Sciences, Medicine, and Bioengineering at UIC.
The researchers investigated the effect of dronabinol, a synthetic version of the molecule Delta-9 tetrahydrocannabinol (THC), which is in cannabis, on sleep apnea in a Phase 2 trial. It was the largest and longest randomized, controlled trial to test a drug treatment for sleep apnea. The Food and Drug Administration approved dronabinol more than 25 years ago to treat nausea and vomiting in chemotherapy patients.
The drug treatment was a new approach, as it targeted the brain instead of the physical problem of collapsing airways. This reflects the new belief that sleep apnea is not just a physical problem but may be caused by multiple factors, such as poor regulation of the upper airway muscles by the brain, according to the researchers.
“The CPAP device targets the physical problem but not the cause,” said Phyllis Zee, MD, PhD, co-lead author and the Benjamin and Virginia T. Boshes Professor of Neurology at the Northwestern University Feinberg School of Medicine and director of the Northwestern Medicine Sleep Disorders Center.
“The drug targets the brain and nerves that regulate the upper airway muscles. It alters the neurotransmitters from the brain that communicate with the muscles,” said Zee. “Better understanding of this will help us develop more effective and personalized treatments for sleep apnea.”
CPAP is highly effective, the researchers note. But some patients simply refuse to use the machine, and even those who want to use it often only do so for about four hours a night on average, Carley said.
“So the best they can get is a roughly 50% improvement in their apnea,” said Carley. “When people take a pill to treat apnea, they are treated for the entire night.”
In the study, 73 adult patients with moderate or severe sleep apnea were divided into three groups. One group received a low dose of dronabinol. The second group was given a higher dose. The third group got a placebo. Subjects took the drug once daily before bed for six weeks.
Six weeks of treatment with the highest dose, 10 mg, was associated with a lower frequency of apneas or hypopneas (overly shallow breathing) during sleep, decreased subjective sleepiness, and greater overall treatment satisfaction compared to the placebo group. The severity of their disorder was reduced by 33% compared to complete compliance with the mechanical treatment, although complete compliance for the night is rare.
However, the researchers caution that ingesting or smoking marijuana won’t produce the same benefits for sleep apnea.
“Different types of cannabis have different ingredients,” said Zee. “The active ingredient may not be exactly the same as what’s indicated for sleep apnea.”
“Cannabis contains dozens of active ingredients, but we tested just purified delta-9 THC,” said Carley.
Larger-scale clinical trials are needed to clarify the best approach to cannabinoid therapy in OSA, the researchers said. UIC has licensed intellectual property related to the experimental drug treatment used in the study to RespireRx Pharmaceuticals. Researchers have attempted to identify drugs to treat sleep apnea for nearly 35 years, Carley said, but to no avail.
Carley developed the idea that dronabinol might be useful in treating sleep apnea more than 15 years ago. He and his colleagues tested the concept in an animal model of apnea, publishing their findings in 2002, and launched a subsequent pilot study in humans in 2007. Those findings formed the basis for the recent multi-center clinical trial.
“By providing a path toward the first viable obstructive sleep apnea drug, our studies could have a major impact on clinical practice,” said Carley.
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