The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

Abstract

It has been hypothesized that besides its intraocular pressure (IOP) lowering potential, tetrahydrocannabinol (THC) may also improve ocular hemodynamics. The aim of the present study was to investigate whether single oral administration of dronabinol, a synthetic THC, alters optic nerve head blood flow (ONHBF) and its regulation in healthy subjects. The study was carried out in a randomized, placebo‐controlled, double‐masked, two‐way crossover design in 24 healthy subjects. For each study participant, 2 study days were scheduled, on which they either received capsules containing 5 mg dronabinol or placebo. ONHBF was measured with laser Doppler flowmetry at rest and while the study participants performed isometric exercise for 6 minutes to increase mean arterial blood pressure (MAP). This was repeated 1 hour after drug intake. Ocular perfusion pressure (OPP) was calculated as 2/3MAP–IOP. Dronabinol was well tolerated and no cannabinoid‐related psychoactive effects were reported. Neither administration of dronabinol nor placebo had an effect on IOP, MAP, or OPP. In contrast, dronabinol significantly increased ONHBF at rest by 9.5 ± 8.1%, whereas placebo did not show a change in ONHBF (0.3 ± 7.4% vs. baseline, P < 0.001 between study days). Dronabinol did not alter the autoregulatory response of ONHBF to isometric exercise. In conclusion, the present data indicate that low‐dose dronabinol increases ONHBF in healthy subjects without affecting IOP, OPP, or inducing psychoactive side effects. In addition, dronabinol does not alter the autoregulatory response of ONHBF to an experimental increase in OPP. Further studies are needed to investigate whether this effect can also be observed in patients with glaucoma.

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

“…Furthermore, no psychoactive effects, effects on IOP, or systemic hemodynamics were observed at the selected dose as reported previously. 16 This indicates that exogenous administration of a cannabinoid receptor agonist exerts vasoactive properties at the level of the retina and increases RBF in healthy subjects without altering OPP.…”

“…The screening examinations, inclusion/exclusion criteria, and study design have been published in a previous report and are only shortly summarized here. 16 In the 4 weeks before the first study day, a screening examination was performed, which included medical history survey; pregnancy test in women of childbearing potential; urine drug test and analysis; alcohol breath test; physical examination, including 12-lead ECG and measurement of systemic hemodynamics, blood draw for hematological status, clinical chemistry, and Hepatitis B, C, and HIV-Serology; a psychiatric examination using the modified Structured Clinical Interview (SCID-1) 19,20 test; and a routine ophthalmic examination comprising of assessment of best-corrected visual acuity, slit lamp biomicroscopy, indirect funduscopy, and measurement of IOP.…”

“…We have previously shown that low-dose oral administration dronabinol increases optic nerve head blood flow in healthy subjects without exerting psychoactive side effects. 16 In this study, we present data on the effect of single administration of 5 mg dronabinol on retinal blood flow (RBF) and retinal oxygen metabolism in healthy subjects. Dronabinol is currently approved for the treatment of anorexia due to acquired immunodeficiency syndrome or cancer, nausea, and vomiting related to cancer treatment in patients who have failed to respond adequately to other treatments and for pain management.…”

Cannabinoids in Glaucoma Patients: The Never-Ending Story

“…Another interesting aspect of cannabinoid usage in glaucoma is connected with the neuroprotective capabilities of these molecules. To date, there are few studies assessing neuroprotective effects of cannabinoids in humans in term of functional or structural changes, but many studies demonstrated better outcomes for retinal ganglion cell (RGC) after different types of injuries in animals ( Table 1 ) [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

“…Endogenous cannabinoids may inhibit Endothelin-1 and consequently could play a neuroprotective role thanks to a better optic nerve head blood supply [ 14 ]. Oral THC indeed demonstrated to increase retinal perfusion and optic nerve head blood flow even at low dosages [ 43 , 44 ]. THC may therefore represent a promising therapeutic strategy since the optic nerve’s hypoperfusion has been identified as an important risk factor for glaucoma development and progression [ 52 ].…”