Patients with sleep apnea displayed lower apnea–hypopnea indexes and improved subjective sleepiness when treated with dronabinol compared with placebo, but clinical trials are warranted to identify the best approach to cannabinoid therapy in these patients, according to data presented at SLEEP 2017, the Annual Meeting of the Associated Professional Sleep Societies.
“At the present time there are no approved drug treatments for sleep apnea, and there remains an important unmet need for fully effective and acceptable treatments of the disorder,” David W. Carley, PhD, director of the Center for Narcolepsy, Sleep and Health Research at the University of Illinois at Chicago, said in a related press release.
In a previous small-scale clinical pilot study, Carley and colleagues found that the nonselective cannabinoid agonist dronabinol showed significant promise for treating sleep apnea. To expand on this research, the investigators initiated the current study — a fully-blinded two-center phase 2 randomized placebo controlled trial, PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement).
They randomly assigned 56 adults with BMI less than 45 kg/m², Epworth Sleepiness Scale (ESS) score greater than 7 and polysomnograph-documented apnea–hypopnea index (AHI) between 15 and 50 to receive either placebo (n = 17), 2.5 mg (n = 19) or 10 mg (n = 20) of dronabinol 1 hour before bedtime once a day for 6 weeks. Every 2 weeks, the researchers performed a repeat in-laboratory polysomnography and maintenance of wakefulness (MWT) testing. They also completed ESS and Treatment Satisfaction Questionnaire for Medications during each visit.
Among all treatment groups, baseline AHI was 26, MWT latency was 19.9 min and BMI was 33.8kg/m². There was a slight difference in ESS (P =.01) and age (P = .04) among treatment groups. The end of treatment changes in AHI were –13.2 (P = .001) for participants taking 10 mg of dronabinol and –9.7 (P = .02) for those taking 2.5 mg of dronabinol, compared with placebo. There was no significant change in ESS among participants receiving placebo or 2.5 mg of dronabinol; however, ESS decreased by 4 units for the 10
-mg group. MWT latency or BMI did not significantly change in any treatment group. These results remained even after controlling for baseline ESS and age.
“In comparison to placebo, 6 weeks of treatment by the highest dose of dronabinol (10 mg) was associated with a lower frequency of apneas or hypopneas during sleep, decreased subjective sleepiness, and greater overall treatment satisfaction,” Carley said. “Neither the amount of sleep nor objective sleepiness improved.”
“By providing a path toward the first viable obstructive sleep apnea drug, our studies could have a major impact on clinical practice,” he added. “However, expanded and pivotal clinical trials must still be conducted to fully establish the best approach to cannabinoid therapy in obstructive sleep apnea.” – by Alaina Tedesco
Carley DW, et al. Abstract 0558. Presented at: Sleep 2017, the Annual Meeting of the Associated Professional Sleep Societies; June 3-7, 2017; Boston.
Disclosure: The authors report funding by the NIH.