0558 DRONABINOL REDUCES AHI AND DAYTIME SLEEPINESS IN PATIENTS WITH MODERATE TO SEVERE OBSTRUCTIVE SLEEP APNEA SYNDROME

Abstract

Introduction: There remains an important unmet need for fully effective and acceptable treatments in OSA, and at present there are no approved drug treatments. We previously published findings from a small-scale clinical pilot study showing promise for the nonselective cannabinoid agonist dronabinol as a potential OSA pharmacotherapy. Here, we present initial findings of the PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully-blinded two-center Phase II randomized placebo-controlled trial of dronabinol in patients with OSA. Methods: By random assignment, 56 adult subjects with BMI<45, Epworth Sleepiness Scale (ESS)>7 and PSG-documented AHI between 15 and 50 received either placebo (N=17), 2.5mg (N=19) or 10.0mg (N=20) of dronabinol daily, one hour before bedtime for 6 weeks. Repeat in-laboratory PSG followed by maintenance of wakefulness (MWT) testing was completed every 2-weeks during the treatment period. At each visit, the ESS and Treatment Satisfaction Questionnaire for Medications also were completed. Results: Overall, baseline AHI was 26.0 ± 11.6(SD), MWT latency was 19.9 ± 12.0 min, BMI was 33.8 ± 5.4 kg/m2 and these were equivalent among all treatment groups. ESS and Age differed slightly among placebo, 2.5mg and 10mg treatment groups: ESS=11.5 ± 3.8, 10.1 ± 3.7, 13.7 ± 3.7 (p=0.01); Age=58.8 ± 6.1, 52.7 ± 7.7, 54.7 ± 7.0 (p=0.04), respectively. In comparison to placebo, the end of treatment changes in AHI were -13.2 ± 4.0 (p=0.001) and -9.7 ± 4.1 (p=0.02) for the 10 and 2.5mg dronabinol groups, respectively. ESS did not change significantly with treatment in the placebo or 2.5mg groups, but decreased by 4.0 ± 0.8 (p=0.0001) units for subjects receiving 10mg dronabinol. There were no significant changes in MWT latency or BMI with treatment in any group. The above conclusions were not altered after controlling for baseline ESS and Age. Subjects receiving 10mg dronabinol also expressed the greatest overall satisfaction with treatment (p=0.02). Conclusion: These findings support the therapeutic potential of cannabinoids in patients with OSA. In comparison to placebo, 6 weeks of treatment by 10mg/day dronabinol was associated with lower AHI, improved subjective sleepiness and greater overall treatment satisfaction, but objective sleepiness did not improve. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.