Cannabinoid May Be First Drug for Sleep Apnea
By Nancy A. Melville / Medscape – Jan 25, 2018
Dronabinol, a synthetic form of the cannabis compound tetrahydrocannabinol (THC), shows efficacy in the treatment of obstructive sleep apnea, possibly representing a first pharmacologic approach to the tough-to-treat, but potentially serious, condition.
“These findings support the therapeutic potential of cannabinoids in patients with obstructive sleep apnea,” the authors, led by Phyllis Zee, MD, the Benjamin and Virginia T. Boshes Professor of Neurology at Northwestern University Feinberg School of Medicine and director of the Northwestern Medicine Sleep Disorders Center, Chicago, Illinois, write.
“In comparison to placebo, dronabinol was associated with lower AHI [apnea/hypopnea index], improved subjective sleepiness and greater overall treatment satisfaction,” they add.
The study was published in the January issue of Sleep.
With no approved pharmacotherapies available for sleep apnea, current first-line treatment is a continuous positive airway pressure (CPAP) device that applies continuous air pressure to keep the airways open during sleep. Though effective, the device can be cumbersome to wear, and long-term adherence is low.
Dronabinol, specifically a synthetic formulation of the molecule delta-9 THC and a nonselective cannabinoid type 1 and typ2 receptor agonist, was first approved in 1985 by the US Food and Drug Administration (FDA) for the treatment of nausea and vomiting associated with chemotherapy and is also indicated for appetite stimulation in AIDS-related wasting syndrome.
In previous studies involving rodents and a small pilot study of 17 humans, however, the authors of the current study noted that dronabinol also showed some signs of reducing spontaneous sleep apneas.
To expand on this research in the multisite, phase 2 Pharmacotherapy of Apnea by Cannabimimetic Enhancement (PACE) study, the authors enrolled 73 adult patients with moderate or severe sleep apnea.
Patients were randomly assigned to treatment with 2.5 mg of dronabinol (n = 21), 10 mg dronabinol (n = 27), or placebo (n = 25) 1 hour before bedtime for up to 6 weeks. They had a mean baseline body mass index (BMI) of 33.4 kg/m2 and a mean age of 53.6 years. The mean baseline AHI was 25.9 and mean Epworth Sleepiness Scale score was 11.5.
The primary endpoint was change from baseline in AHI after 6 weeks of treatment. The study showed significant improvements in the 2.5-mg group, with a reduction of 10.5 events per hour (P = .02), and in the 10-mg group, with a reduction of 12.9 events per hour (P = .004), in rapid eye movement (REM) as well as non-REM sleep, after adjustment for factors including age, race, ethnicity, and baseline AHI.
No significant changes were observed in the placebo group after adjustment, and the differences in improvement between the 2.5- and 10-mg groups were not statistically significant.
The 10-mg group also showed a significant reduction in the secondary primary endpoint of subjective daytime sleepiness, assessed by the ESS, with a reduction of 3.8 points from baseline (P < .0001), and a reduction of 2.3 points compared with placebo (P = .05), while the reductions in the ESS score in the 2.5-mg and placebo groups from baseline were not statistically significant.