Dronabinol for obstructive sleep apnea

Targeted Treatment of Obstructive Sleep Apnea With Dronabinol: Proof of Concept and Phase II Clinical Trial

This two-week treatment will test whether taking oral dronabinol lowers sleep apnea events in adults aged 18–65 with moderate-to-severe obstructive sleep apnea.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: N/A to 65 Years
• Sex: All
• Sponsor: VA Office of Research and Development (fed)
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT06477952 on ClinicalTrials.gov

What this trial studies

This open-label Phase 1/2 trial gives oral dronabinol daily for two weeks to Veterans with obstructive sleep apnea and measures apnea-hypopnea index before and after treatment using overnight polysomnography. Up to 120 Veterans will be screened so that about 45 can complete the two-week treatment and paired sleep studies. Clinical data (age, sex, BMI, comorbidities) and pretreatment polysomnographic endotypes (sleep architecture, respiratory disturbance, loop gain, arousal threshold, upper airway collapsibility and compensation) will be used to develop a prediction model for AHI reduction with dronabinol. The prediction model is intended to guide a future randomized clinical trial.

Who should consider this trial

Good fit: Veterans aged 18–65 with moderate-to-severe OSA (AHI 15–50) who are not regularly using positive airway pressure or other device therapies and who meet BMI and oxygenation eligibility criteria.

Not a fit: Patients with predominantly central or mixed apneas (>25%), BMI >45 kg/m2, significant overnight oxygen desaturation, recent upper airway surgery, or those adherent to PAP/HNS/oral appliance therapy are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, dronabinol could reduce apnea events and provide a non‑mechanical treatment option for patients who cannot tolerate CPAP.

How similar studies have performed: Small pilot studies of dronabinol have shown some reductions in AHI, but evidence is limited and larger randomized trials are lacking.

Eligibility criteria

Inclusion Criteria:

1. Adults 18 to 65 years of age.
2. AHI 15-50 per hour on pre-treatment polysomnography.

Exclusion Criteria:

1. Positive Airway Pressure (PAP) treatment of OSA: use \> 4 hours per day for 30% of days within 3 months of enrollment. PAP use will be determined from device download data.
2. Hypoglossal nerve stimulator (HNS) or oral appliance device treatment with use \> 4 hours per day for 30% of days within 3 months of enrollment. HNS use will be determined by device download and oral appliance use by self-report.
3. History of upper airway surgery for OSA (except adenotonsillectomy).
4. Central or mixed apneas \>25% of respiratory events on diagnostic polysomnography.
5. Arterial oxygen saturation \< 75% for \> 5% sleep time on pretreatment polysomnography.
6. Body mass index \> 45 kg/m2.
7. If post-bariatric surgery, weight must be stable ±5% (per electronic medical records) for at least 6 months before the first dose of the study drug.
8. Active enrollment in a weight loss program.
9. Shiftwork within 3 months of enrollment.
10. High-risk occupation: commercial driver and pilot.
11. Motor vehicle accident or near-miss incident within 1 year of enrollment.
12. Current drug or habitual alcohol use or positive urine drug screen.
13. Comorbid medical and psychiatric disorders:

    1. Primary sleep disorders: e.g., narcolepsy, restless legs syndrome.
    2. Uncontrolled mood disorder or a diagnosis of schizophrenia.
    3. Initiation of new antidepressant or antipsychotic medication within 3 months.
    4. Identified as high-risk for suicide in electronic health records.
    5. Uncontrolled medical disorders (coronary heart disease, arrhythmia, congestive heart failure, chronic obstructive pulmonary disease, chronic hypoxemic or hypercapnic respiratory failure, stroke within 6 months of enrollment, chronic liver or kidney disease, autoimmune disorders).
14. Use of sedative-hypnotic medications within 30 days of enrollment.
15. Complete blood count or liver function test values more than 1.5 times the upper limit of normal.
16. Pregnancy.
17. Allergy to cannabinoids or sesame oil.
18. Average weekly alcohol consumption of more than 10 servings.
19. Participation in other investigational protocols within 30 days of enrollment.

Where this trial is running

Chicago, Illinois

• Jesse Brown VA Medical Center, Chicago, IL — Chicago, Illinois, United States (RECRUITING)

Study contacts

• Principal investigator: Bharati Prasad, MD — Jesse Brown VA Medical Center, Chicago, IL
• Study coordinator: Bharati Prasad, MD

Conditions: Obstructive Sleep Apnea, OSA, sleep apnea, pharmacological treatment, Drug treatment