in a new study.
A paper published in the January edition ofpresents data from a phase 2, blinded, randomized controlled trial of the nonselective cannabinoid 1 and cannabinoid 2 receptor agonist, dronabinol, in 73 adults with moderate or severe obstructive sleep apnea (OSA). No approved drug treatments for OSA exist, and this study provides results “from the largest and longest randomized controlled trial to date of any putative drug treatment for OSA,” the researchers wrote.
Patients were randomized to 2.5 mg dronabinol or 10 mg dronabinol daily for up to 6 weeks, or placebo. At the end of treatment, researchers saw significant increases in the apnea-hypopnea index among the patients on placebo, while those who received dronabinol showed decreases in the number of apnea and hypopnea events per hour. Patients given the 2.5-mg dose of dronabinol had a mean decrease of 10.7 events per hour, and those on the 10-mg dose had a mean decrease of 12.9 events per hour compared with placebo.
The difference between the placebo and treatment arms was significant for both dosages, and the apnea-hypopnea index decreases were similar between the two dosages of dronabinol.
These effects were largely due to reductions in apnea events; the largest reduction was seen in the REM apnea index in patients treated with the 10-mg dose of dronabinol. However, there were few effects on the expression of hypopneas, except in the higher-dose group.
After adjustment for age, race, ethnicity, and baseline apnea-hypopnea index, the increases seen in the placebo group were no longer significant, but the decreases from baseline seen in the treatment arms were greater.
Dronabinol treatment was also associated with significant decreases, compared with placebo, in non-REM apnea-hypopnea index and REM apnea-hypopnea index.
Patients’ self-reported daytime sleepiness, measured by the Epworth Sleepiness Scale, remained similar compared with baseline in those who received placebo and the 2.5-mg/day dose of dronabinol, but decreased significantly by a mean of −2.3 points compared with placebo in those on the higher dose of dronabinol.
There were no significant changes from baseline in objective sleepiness, as measured by the maintenance of wakefulness test, in any of the study groups. Researchers also saw no significant changes in sleep architecture, oxygenation, or the duration of supine sleep in any of the study groups, although the patients on the higher dose of dronabinol showed a slight increase in REM sleep and those on placebo showed a slight decrease.
Younger patients and those with a greater preponderance of REM-related apnea/hypopnea, and shorter average event duration were both more likely to respond to treatment, but apart from these factors there were no other influences on likelihood of patients responding to dronabinol.
David W. Carley, PhD, of the University of Illinois at Chicago, and his coauthors noted that there was a great need for pharmacological treatments for obstructive sleep apnea because positive airway pressure – while effective – has poor long-term adherence rates.
“Based on a series of animal investigations, we proposed that drugs which dampen afferent vagal feedback to the medulla may be effective in stabilizing respiratory pattern generation and increasing activation of upper airway dilating muscles during sleep,” they wrote.
One patient experienced diarrhea and vomiting that required admission to hospital, and which was judged as possibly related to the study medication. There were six other withdrawals due to adverse events including dizziness and vision changes, vertigo, ECG arrhythmias, and headache with dizziness and vomiting. Overall, nearly 90% of patients reported at least one adverse event, but the rates did not differ significantly between the treatment and placebo arms.
The researchers noted that significantly higher satisfaction scores were seen among patients receiving the higher dose of dronabinol.
“All of these observations argue that dronabinol, at doses from 2.5 to 10 mg/day, is safe for use by medically stable patients with moderate or severe OSA,” the authors wrote. “Participants also tolerated and adhered well to daily self-administration of dronabinol.”
The National Institutes of Health, National Heart, Lung, and Blood Institute, and National Center for Advancing Translational Sciences funded the study. One author declared grants from the National Institutes of Health for the study, and patents related to treatment of sleep-related breathing disorders by cannabinoid drugs. He also holds stock in RespireRx Pharmaceuticals, which holds an exclusive license to these and other related patents.
SOURCE: Carley D, et al. Sleep. 2018 Jan 1.