Could a Synthetic Form of THC Solve Sleep Apnea?

by Eli Hendel, M.D. Medical Reviewer

The search for medical treatments for sleep apnea that do not involve the use of CPAP mask is ongoing. Many patients find CPAP masks cumbersome and would rather forgo them and face the (serious) consequences. The use of oral devices has not proven to be of significant help, and they can be quite expensive.

New studies published about a medicinal aid in the treatment of sleep apnea have garnered great attention. A December 2017 study on the latest treatment involves a rather controversial medicinal agent: The research done at Northwestern University tested dronabinol, a synthetic version of delta-9-tetrahydrocannabinol or THC, which is the compound responsible for the euphoric effects of marijuana.

The study: Does dronabinol help treat sleep apnea?

The study involved 56 patients diagnosed with severe obstructive sleep apnea (OSA) as measured by an Apnea Hypopnea Index (AHI) of greater than 30. These patients also had excessive daytime sleepiness as measured by an abnormal Epworth Sleepiness Scale (ESS). Baseline measurements were established, and after 12 weeks, the researchers compared the use of dronabinol at doses of 2.5 and 10 mg with a placebo. The researchers noted a significant reduction in the subjects’ AHI and an improvement in the ESS among the subjects given the drug, compared with the subjects on placebo.

This research was part of what is known as the Pharmacotherapy of Apnea by Cannabimimetic Enhancement (PACE) trial phase 2. This trial offered the basis for approaching the FDA to gain approval for a phase 3 trial that will lead to approval dronabinol’s use for sleep apnea. The drug is currently approved for the treatment of eating disorders associated with AIDS and for chemotherapy-induced nausea.

Dronabinol is available in 2.5 mg, 5 mg, and 10 mg tablets. It is considered a “schedule III drug,” meaning it has a low potential for abuse, but it is still monitored by the U.S. Drug Enforcement Agency (DEA) and its use is restricted for the two indications just mentioned. It cannot be used “off label” like some other drugs, despite the phase 2 findings. It is marketed under the brand name Marinol.

Does this mean marijuana can be used to help sleep apnea?

Although dronabinol, a synthetic form of tetrahydrocannabinol, the active ingredient of marijuana, is approved by the FDA for specific indications, it does not mean that marijuana has been approved for therapeutic use. It is unlikely that any “plant” can be approved as a medicinal treatment. The FDA approval process is contingent on reproducibility of the specific agent that’s responsible for its effect. We can’t really do that when it comes to a plant. Additionally, a synthetic compound can be monitored for purity of composition, whereas a plant when ingested or smoked contains numerous unaccounted-for ingredients.

The DEA has determined that smoked marijuana can contain more than 400 different chemicals, including some hazardous ones found in cigarette smoke. That’s precisely why we can’t just assume that marijuana can offer the same therapeutic benefits or safety profile, whether treating nausea or obstructive sleep apnea.

What do these results mean for people with sleep apnea?

Current standard of treatment for OSA is by a mechanical approach with a positive pressure mask (CPAP) to maintain an open airway during supine sleep. This study explores the possibility that there is a possible role for medications that influence the brain, helping the facilitation of regulating the muscles of the upper airway in order to maintain a patent, open airway.

Adherence to CPAP has had its problems including the noise it creates while in operation and discomfort when wearing the mask. Patients also often feel that the problem has been “cured” after CPAP is used for a certain duration of time. The possibility of treating the condition medically with the use of a pill may have strong allure, especially among patients diagnosed with the disease who don’t feel any profound symptoms. Those individuals are especially resistant to using CPAP therapy.

Findings from this study go beyond just the improvement in the patency of the airway from Marinol. Although the primary endpoints measured were improvements in the AHI, the secondary endpoints also showed improvements. Those include the improvements in the ESS (as previously mentioned), which measures a person’s subjective perception of daytime sleepiness, and improvements in the Maintenance of Wakefulness Test. This test measures the ability to stay awake during traditional waking hours. The study also measured the time it took to see a drop in the oxygen saturation of the blood and the perception of treatment satisfaction. It rated positively in all these measures.

It’s possible that the effect of dronabinol goes farther than improving the quality of sleep by avoiding obstruction of airways. It may be that dronabinol also has an intrinsic effect on the brain, improving the quality of sleep through other pathways. These are important considerations because they suggest impact of the drug on several parts of the brain.

Clearly, more research is needed to explore the therapeutic actions of dronabinol to see if it may be useful in the treatment of other sleep-related conditions.

Eli Hendel, M.D.
Meet Our Writer
Eli Hendel, M.D.

Eli Hendel, M.D., is a board-certified internist/pulmonary specialist with board certification in Sleep Medicine. An Assistant Clinical Professor of Medicine at Keck-University of Southern California School of Medicine, and Qualified Medical Examiner for the State of California Department of Industrial Relations, his areas include asthma, COPD, sleep disorders, obstructive sleep apnea, and occupational lung diseases. Favorite hobby? Playing jazz music.