Single oral administration of dronabinol increases ocular blood flow in patients with glaucoma

Purpose: Glaucoma is a leading cause of irreversible blindness globally, primarily driven by elevated intraocular pressure (IOP). Still, some patients progress despite significant IOP lowering, potentially due to impaired ocular blood flow. This study aimed to evaluate the effects of dronabinol, a synthetic tetrahydrocannabinol derivative, on ocular blood flow in primary open-angle glaucoma (POAG) patients. Methods: This randomized, double-masked, placebo-controlled, cross-over study included 23 patients with treated POAG (mean age 68 ± 7 years). All participants received dronabinol (11 patients received 5 mg and 12 received 10 mg in a randomized fashion) on one study day and placebo on the other study day. The primary outcome was optic nerve head blood flow (ONHBF) measured by laser speckle flowgraphy. Mean blur rate was determined for the large vessel area (MV), the tissue area (MT) and the total ONH area (MA). Secondary outcomes included vessel densities assessed by optical coherence tomography angiography, IOP, and blood pressure. Results: Administration of 10 mg dronabinol significantly increased ONHBF (MA: 10.8 ± 20.6%, p = 0.018, MV: 12.0 ± 24.8%, p = 0.042, and MT: 11.0 ± 22.6%, p = 0.022, each vs. placebo) up to 4 h post-administration without affecting IOP or mean arterial pressure (p > 0.548 each). Additionally, a significant increase in vessel density in the superficial vascular plexus was found after administration of 10 mg dronabinol (6.7 ± 14.7%, p = 0.040 vs. 5 mg). Conclusion: This pilot study demonstrates that systemic dronabinol enhances ONHBF in glaucoma patients, suggesting its potential as adjunct therapy for glaucoma by targeting vascular dysfunction. Further longitudinal studies are needed to explore its long-term impact on disease progression and visual field preservation. Trial Registration: ClinicalTrials.gov ID: NCT04596826.