Table 1.

Studies evaluating the efficacy of various cannabis compounds in healthy volunteers and patients with glaucoma

Authors	Drug and formulation	Population	Aim of the study	Study design	Sample size	Results
Mosaed et al. [31] (2020) and [32] (2021)	5.9 or 13.4 w/w % cannabis cigarette inhalation	Adult healthy subjects who are regular cannabis smokers	Evaluate the effect of inhaled cannabis on IOP	Prospective, randomized, double-blind, placebo-controlled study	11 participants in test group, 3 in placebo group	Significant lowering of IOP compared with baseline but no consistent difference compared with placebo
			Assess the correlation between plasma levels of THC plasma levels and reduction of IOP			Significant negative correlation between plasma THC levels and IOP.
Hommer et al. [33] (2020)	Dronabinol 5 mg orally	Healthy volunteers	Does it alter optic nerve head blood flow and vascular autoregulation?	Randomized, placebo-controlled, double-blind, two‐way crossover	12 in each group	Increase in optic nerve head blood flow without affecting IOP, OPP, or inducing psychoactive side effects
Plange et al. [34] (2007)	Dronabinol 7.5 mg orally	Healthy volunteers	Effect on retinal hemodynamics in healthy individuals	Self-experiment of medical doctors	8 subjects	Increase in human retinal hemodynamics accompanied by (but not attributable to) a marked decrease in IOP.
Tomida et al. [35] (2006)	Δ-9-THC (5 mg) and CBD (20 and 40 mg) sublingual spray	Patients with ocular hypertension or early POAG	Effect on IOP; safety and tolerability	Randomized, double-blind, placebo-controlled, four-way crossover	6 patients	Significant lowering of IOP compared with placebo at 2 h. CBD 40 mg produced a transient increase at 4 h. One patient experienced a transient and mild panic-like reaction with Δ-9-THC
Flach [36] (2002)	Oral THC 2.5 or 5 mg four times a day; Marijuana cigarettes containing 6 mg THC	Uncontrolled IOP while receiving maximally tolerated conventional glaucoma treatment	Effect on IOP and BP	Uncontrolled, unmasked, nonrandomized, prospective evaluation	9 subjects	May reduce IOP but with the development of tolerance and systemic adverse effects
Porcella et al. [37] (2001)	WIN55212-2, a synthetic and selective CB1 receptor agonist (25 or 50 μg eyedrop)	Patients with bilateral glaucoma (>22 mm Hg) being treated with multiple topical drugs	Effect on IOP in patients with glaucoma resistant to conventional therapies	Self-controlled study (one eye treated)	8 patients	Decrease in IOP within the first 30 minutes; maximum effect reached in the first 60 min
Tiedeman et al. [38] (1981)	Delta-1-THC derivatives BW146Y and BW29Y single oral dose	Ocular hypertensive patients	Effect on IOP and adverse effects	Single-dose, randomized, double-blind	BW146Y: 6 received placebo, 9 received 4 mg dose, 10 received 8 mg, 3 received 12 mg	BW146Y had a significant IOP-lowering effect independent of orthostatic BP changes, although some effects were observed. Both drugs produced mild subjective adverse effects
					BW29Y: 6 received placebo, 5 received 5 mg dose, 5 received 10 mg
Merritt et al. [39] (1980)	Marihuana 900 mg (2% Δ-9-THC) inhalation	Patients with heterogeneous glaucomas	Effect on IOP and blood pressure	Prospective, single-arm study`	18 subjects	Decrease in BP followed by IOP. Postural hypotension, tachycardia, palpitations, and alterations in mental status
Crawford et al. [40] (1979)	2.8% THC inhalation	Systemic normotensive (N = 8) and hypertensive (N = 8) open-angle glaucoma patients	Relationship between simultaneous changes in heart rate, blood pressure, and IOP	Prospective, controlled study	16 subjects	Increase in heart rate followed by a substantial decrease in systolic, diastolic, and IOP. The intensity and duration of the responses were greater in hypertensives