The Cannabis sativa plant contains around 540 natural compounds, of which more than 100 are classified as cannabinoids Of the identified cannabinoids, D9-tetrahydrocannabinol (THC) is recognized to be the primary psychotropic compound, and cannabidiol is the predominant non-psychoactive ingredient.
Studies have shown that THC may result in a reduction in IOP by 15-20% but the effect only lasts 3-4 hours. Interestingly, this effect has only been observed with intravenous systemic THC. Oral CBD or THC failed to demonstrate efficacy in lowering intraocular pressure. Inhalational THC also shows a decrease of approximately 25% but only lasted 2 -4 hours with the effect had completely worn off by 4 hours. One study which evaluated CBD showed an increase in IOP at 4 hours. Topical eye drops with cannabinoids have been investigated and despite numerous attempts have not been able to show efficacy in lowering IOP. The lack of efficacy is thought to be due to limited corneal permeability. Significant topical side-effects included ocular surface irritation and
The mechanism of how THC may reduce IOP remains unclear. One theory is that the lowering of IOP is directly a result of decreased blood pressure which also occurs with THC. However, studies have shown that there are cannabinoid receptors on both the ciliary body and trabecular meshwork suggest that other mechanisms of action may include decrease aqueous production and improved outflow.
Therefore, despite the appeal of having a new pharmacological treatment, there are several limitations in the practical use of cannabinoids.
- First, the effect is short-lived and for non- intravenous modes of delivery, the effect seems to last for 2-4 hours.
- Second, there is a body of evidence to suggest that repeated usage results in physiological tolerance and diminished therapeutic effect.
- Third, a range of systemic side-effects has been documented in studies that have been evaluating the role of cannabinoids in lowering IOP including postural hypotension.
There have been concerns that the reduction in blood pressure that can be associated with systemic cannabinoid administration may also compromise blood flow to the optic nerve, which might represent a further insult to an already vulnerable optic nerve. Other side-effects include tachycardia palpitations and mental alterations.
In summary, although cannabinoids demonstrate hypotensive and neuroprotective properties, their use is limited by a significant number of potential side effects. On account of the current evidence, the most recent position statement released by the American Glaucoma Society recommends against the use of cannabinoids for the treatment of glaucoma.