Treatment of Obstructive Sleep Apnea with a Cannabimimetic – Dude, Seriously?
Don’t let the fancy name of the medication fool you. The cannabimimetic is dronabinol, a synthetic non-selective CB1 and CB2 receptor agonist. But really, it’s marijuana. As medical and recreational use of marijuana becomes legal state by state, research that has been impossible has now become available. And the therapeutic effects of marijuana are extending beyond the well-known positive effects for chemotherapy patients. High on that list of benefits is, believe it or not, obstructive sleep apnea.
The clear leader in this research is Dr. David Carley, known for his long flowing hair, waist-length beard, paisley shirts and wild late-night parties, as well as his penchant for following the Grateful Dead around the country in his youth. I’m kidding. I think. I don’t really know if he was a Deadhead. And he does have some facial hair, but it is well-trimmed and neat.
During his long and fruitful collaboration with Dr. Miodrag Radulovacki at the University of Illinois, Chicago, Dr. Carley explored pharmacological interventions of sleep and sleep disorders. His research includes careful animal model studies of drug effects, including several experiments using a rodent model of sleep apnea. He was first “turned on” to the possibility of treating apnea with cannabinoids fifteen years ago using an animal model.1 Injection of dronabinol was associated with significant decreases in apnea during NREM and REM sleep in rats. The only side effect was that the rats kept asking for Doritos.
Seriously, though, there is some science behind this. One theory of the genesis of sleep apnea is that serotonin receptors, when over activated, cause perturbations of breathing. Dronabinol may improve breathing by blocking excessive serotonin activation. Carley speculates that the cannabinoid action occurs in the peripheral nervous system, in the nodose ganglion cells of the vagus nerve known to have serotonin receptors. Stimulation of the vagus nerve is a treatment for epilepsy, and is known to cause increases in episodes of sleep apnea.2
Dr. Carley recently teamed with Dr. Phyllis Zee and colleagues at Northwestern University to test the effects of dronabinol on obstructive sleep apnea patients.3 A sample of 73 adults was randomly assigned to placebo, low dose and high dose dronabinol. After six weeks of treatment the AHI was reduced in a dose-dependent fashion, with significant decreases at low and high doses. Patients in the high dose group also had a significant improvement in the Epworth Sleepiness Scale. Sleep architecture was not changed and the Maintenance of Wakefulness Test was not significantly different. Potential users will be pleased to know that there were no changes in BMI with nightly dronabinol. Side effects were mostly mild, with sleepiness, headache and nausea the most common issues.
The data presented are from a Phase II trial, and much work remains to be done. Larger patient populations, longer treatment durations and additional outcomes measures will be necessary to demonstrate effects and optimize treatment strategies. It remains to be seen whether dronabinol will reduce the consequences of untreated sleep apnea such as increased risk of cardiovascular events and hypertension.
One of the primary concerns with the use of CPAP for treatment of OSA is low adherence. If cannabinoids are shown to be an effective treatment I doubt that adherence will be an issue, especially among younger OSA patients. Oh, and don’t Bogart those Doritos, dude.
- Carley DW, Paviovic S, Janelidze M, Radulovacki M. Functional role for cannabinoids in respiratory stability during sleep. Sleep. 2002; 25 (4): 391–398.
- Ebben, M. R., Sethi, N. K., Conte, M., Pollak, C. P., &Labar, D. (2008). Vagus nerve stimulation, sleep apnea, and CPAP titration. Journal of Clinical Sleep Medicine, 4(5), 471–473.
- David W Carley, Bharati Prasad, Kathryn J Reid, RoneilMalkani, HryarAttarian, Sabra M Abbott, Boris Vern, Hui Xie, Chengbo Yuan, Phyllis C Zee; Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of Dronabinol in Obstructive Sleep Apnea, Sleep, zsx184, https://doi.org/10.1093/sleep/zsx184