The Effect of Orally Administered Low-Dose Dronabinol on Retinal Blood Flow and Oxygen Metabolism in Healthy Subjects

J Ocul Pharmacol Ther. 2021 Jul-Aug;37(6):360-366. doi: 10.1089/jop.2020.0131. Epub 2021 May 17.

Abstract

Purpose: The present study was performed to investigate the effect of oral dronabinol, a synthetic tetrahydrocannabinol derivate, on retinal hemodynamics in healthy subjects in a randomized, double-masked, placebo-controlled, 2-way crossover design. Methods: Twenty-four subjects received 5 mg dronabinol on 1 study day and placebo on the other study day. Total retinal blood flow (TRBF) was measured using a custom-built Doppler Optical Coherence Tomography system. Oxygen saturation of major retinal vessels was measured with a commercially available Dynamic Vessel Analyzer. Based on these parameters, retinal oxygen extraction was calculated. Measurements were performed before and after drug administration on both study days. Results: Placebo had no effect on TRBF, retinal arterial or venous oxygen content, and retinal oxygen extraction (P > 0.1 each). In contrast, dronabinol induced a significant increase in TRBF from 38.9 ± 6.1 to 40.7 ± 6.7 μL/min (P < 0.001), which was accompanied by a significant increase in retinal venous oxygen content (from 0.129 ± 0.008 to 0.132 ± 0.009 mL O2/mL, P = 0.02). As no change in retinal arterial oxygen content occurred (P = 0.12), retinal oxygen extraction remained stable (2.2 ± 0.4 μL vs. 2.2 ± 0.4 μL O2/min, P = 0.29). Conclusions: These results indicate that orally administered dronabinol increases TRBF in healthy subjects without altering retinal oxygen extraction. The drug may therefore be a candidate for improving perfusion in patients with ocular vascular disease.

Keywords: Doppler optical coherence tomography; cannabinoids; dronabinol; randomized controlled clinical trial; retinal blood flow; retinal oxygen extraction.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Flow Velocity
  • Cannabinoid Receptor Agonists / administration & dosage
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dronabinol / administration & dosage*
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Oxygen / metabolism*
  • Regional Blood Flow*
  • Retinal Vessels / drug effects
  • Retinal Vessels / physiology*

Substances

  • Cannabinoid Receptor Agonists
  • Dronabinol
  • Oxygen