Glaucoma is an eye disorder that occurs as a result of an increase in eye fluid pressure (intraocular pressure/IOP) due to an increased release of aqueous humor (eye fluid) in the front region of the eye or impaired outflow or drainage of aqueous fluid.
There are two main types of glaucoma; primary open-angle glaucoma, which is the most common type, and acute angle-closure glaucoma.
Intraocular inflammation in the trabecular meshwork interferes with rates of aqueous fluid synthesis and fluid outflow, resulting in elevated IOP and onset of open-angle glaucoma. Patients suffering with uveitis (inflammation in uvea of the eye) tend to develop inflammation of the trabecular meshwork, resulting in inflammatory glaucoma (uveitic glaucoma). Inflammatory glaucoma causes a recurrent elevation of IOP, leading to progressive optic nerve strain with retinal nerve damage. These pathophysiological events results in visual field defects. Both of the primary types of glaucoma are symptomatically similar, while inflammatory glaucoma occurs as a complication of uveitis.
Prolonged, untreated glaucoma leads to the gradual deterioration of optic nerves and visual field defects, typically ending in blindness. Most glaucoma patients remain asymptomatic and often suffer irreversible optic nerve damage before they even get diagnosed.
An effective way to treat inflammatory glaucoma is to suppress the inflammation and the elevated IOP, by which the severity and frequency might be reduced.
Currently, medical treatments for primary open-angle glaucoma are not completely effective. Treatments including corticosteroids, anti-inflammatories, immunosuppressive drugs and beta-blockers; which may provide temporary relief and delay the worsening of disease.
Looking into the science of medical marijuana
Medical cannabis studies for the treatment of glaucoma date back to the 1970s, and back then studies showed weed smoking lowered IOP in glaucoma patients. Like many other diseases, glaucoma may be treated with medical marijuana due to the presence of cannabinoid receptors in the ciliary body, which regulate aqueous humor production. It has been shown that CB1 receptors are involved in IOP control, and THC administration may lower aqueous humor production.
Even synthetic CB1 receptor agonists are shown to reduce IOP in normal and glaucomatous animal eyes, possibly by decreasing aqueous flow. These results have given the basis of developing marijuana-based anti-glaucoma drugs.
In uncontrolled studies, smoking whole-plant cannabis, as well as oral and intravenous administration of THC have all lowered IOP in glaucoma patients. The IOP-lowering effect of THC has been reported by 60-65% of glaucoma and non-glaucoma subjects (reduction by approximately 25%, compared to pre-treatment IOP value). The change in IOP values appeared to have a dose-response relationship. Meaning, increasing the cannabinoid dose was associated with greater reduction in IOP value. The IOP-lowering benefit might be due to the peripheral vasodilatory effects of cannabinoids and decreased pressure in ciliary body vasculatures. The treatment benefit lasted only for 3-4 hours, and higher doses did not increase the duration of the effects.
Irrespective of route of administration, cannabis does lower IOP. However, the benefit lasts for about 3-4 hours, which is a major limitation of marijuana use for glaucoma treatment. Typically, glaucoma symptoms need to be under control 24/7; if you opt for medical cannabis, you need to administer cannabis at least 6-8 times a day to maintain optimal IOP, round the clock. Regular, repeated doses are not always possible in most patients due to the psychoactive effects, and missed doses are common.
To avoid these issues, researchers tried to employ topical eye drops with a formulation of THC. However, the occurrence of eye irritation and its stimulation of tears washed away the medication and prevented drug absorption. As the role of ocular cannabinoid receptors has been implicated in glaucoma, it is still worthy to pursue drug development in topical eye drop form with an effective drug delivery system without causing systemic adverse events.
It is NOT the limited efficacy of cannabis but rather prohibition that is preventing the development of cannabis-based topical application eye drops. In the United States, the chance of conducting this type of research is remote due to federal restrictions. We hope this situation will change in the near future.
In Jamaica Canasol, a cannabis-based eye drop formulation to treat glaucoma, is available. Due to its high efficacy, Canasol has a high demand in local and international markets.
The therapeutic role of other cannabinoids, including cannabigerol, has been identified. One experimental study found that the administration of a synthetic version of a non-psychoactive cannabinoid decreased IOP, and the effects lasted for 4 hours.
Animal studies have reported both THC and cannabigerol as having modest efficacy in lowering IOP without altering the rate of aqueous humor formation. On the other hand, these biomolecules significantly increased the outflow of aqueous humor (eye fluid drainage) and thereby lowered IOP. These results suggest that not only THC but also other phytocannabinoids may have therapeutic potential to treat glaucoma.
As of now, no clinical trial studies have been conducted to explore and demonstrate the efficacy of cannabinoids on inflammatory glaucoma. As a potent anti-inflammatory agent, cannabis could be a potential treatment for uveitis glaucoma or inflammatory glaucoma.
Cannabis has remarkable therapeutic value to control other symptoms of glaucoma including pain, nausea and vomiting. However, smoking weed is contraindicated in glaucoma patients, as it may worsen eye reddening (blood shot eyes). Instead, vaporized inhalers could be considered to avoid this side effect.
Is cannabis suitable for all?
At this time, there are too few research studies available to show the benefits and safety of cannabis for glaucoma patients.
Cannabis not only lowers IOP but also the blood pressure all over the body. So, marijuana may not be suitable for certain individuals with abnormally low blood pressure.
Even with its favorable safety profile, medical cannabis use for glaucoma treatment is limited due to cardiac-related effects in certain heart patients, temporary psychoactive effects and particularly, the fact that treatment benefits last only for a few hours.
These issues can be addressed by contraindicating THC use and cannabis smoking in cardiac patients. With scientific advancements, our scientific community can develop newer, novel drug delivery systems including topical formulations, which could eliminate all of these side effects, while increasing drug action duration to provide long-lasting treatment benefits.
What does the future hold?
As THC has low water-solubility, several effective drug delivering vehicles were identified in the early 1980s for the delivery of lipophilic agents, including THC. These vehicles permit internalization or encapsulation of lipid-soluble compounds into water-soluble esters, such as maleate salts. In this way, an excellent drug delivery platform for THC can be designed for effective drug action in lipid corneal epithelium, delivered through the aqueous tear environment of the eye.
This technique is similar to the ‘pro-drug’ approach, which offers great efficacy and drug penetration into the site of action, without causing psychoactive effects.
The availability of newer drug delivery platforms could be helpful for sustained, localized release of non-psychoactive cannabinoids into the affected eye(s). This approach could be a promising way to treat glaucoma in an effective and safer way than conventional treatments.
Compared to pill form, topical applications developed in this way have the advantage of employing the use of low drug mass per dose delivery volume. Meaning, one drop of medication may contain less than 2 mg of drug, which will reach the site of action without any drug loss. This approach ensures maximal and sustained efficacy, while the lack of adverse events such as psychoactive effects can eliminate the risk of potential abuse problems, which is noteworthy.