Orally administered dronabinol increases retinal blood flow without altering oxygen extraction in healthy subjects

Abstract

Purpose : We have shown previously that administration of low-dose oral dronabinol, a synthetic tretrahydrocannabinol derivate, increases optic nerve head blood flow in healthy subjects. The aim of the present study was to investigate whether dronabinol also has an effect on retinal blood flow and oxygen extraction.

Methods : A randomized, placebo-controlled, double-masked, two-way crossover study was performed in 24 healthy subjects. Two study days were scheduled for each participant, on which they either received capsules containing 5mg dronabinol or placebo capsules. 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 did not alter 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±6.7µl/min (p<0.001), which was accompanied by a significant increase in retinal venous oxygen content (from 0.129±0.008 to 0.132±0.009ml 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 vs. 2.2±0.4µl 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. To confirm this hypothesis, further studies in patients are needed.

This is a 2021 ARVO Annual Meeting abstract.