International forskning

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


Theresa Lindner 1, Viktoria Pai 1, Patrick Janku 1, Nikolaus Hommer 1 2, Anton Hommer 1 3, Marihan Abensperg-Traun 4, Liudmyla Petric 1, Leopold Schmetterer 1 5 6 7 8 9 10 11, Gerhard Garhöfer 1, Doreen Schmidl 1

  • 1Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
  • 2VIROS – Vienna Institute for Research in Ocular Surgery – Karl Landsteiner Institute, Hanusch Hospital, Vienna, Austria.
  • 3Hommer Ophthalmology Institute, Vienna, Austria.
  • 4Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
  • 5Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
  • 6Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.
  • 7SERI-NTU Advanced Ocular Engineering (STANCE), Nanyang Technological University, Singapore, Singapore.
  • 8School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
  • 9Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
  • 10Fondation Ophtalmologique Adolphe De Rothschild, Paris, France.
  • 11AIER Eye Hospital Group, Changsha, China.

Affiliationer

Abstract

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.

Keywords: cannabinoids; dronabinol–tetrahydrocannabinol; glaucoma; laser speckle flowgraphy; optic nerve head blood flow; optical coherence tomography angiography; randomized controlled clinical trial; vessel densities.