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Retinal Health and Cannabis- “Seeing” the Difference

Glaucoma was one of the first applications identified for medical cannabis treatment and remains one of the most common medical reasons for prescription. Why? In the 1970’s initial slew of cannabis-centric research, the Journal of the American Medical Association published a finding that individuals who smoked cannabis experienced lower intra-ocular (inner-eye) pressure. This was one of the first significant physiological findings regarding the effect of smoking cannabis. However, more importantly, it seemed to be an answer to glaucoma, a disease in which excess fluid builds up in the eye, causing higher pressure and cell damage. As a result, the study was duplicated often, and the results upheld the initial conclusion that cannabis could be an effective solution.

Unfortunately, cannabis research waned in popularity. Once cannabis was culturally cast in the same category as other recreational drugs, the idea that it would ever be prescribed legally for glaucoma lost traction. Fortunately, years later, as we experience a renaissance in both cannabis prescription and cannabis research, a new interest has arisen in the way the endocannabinoid system might be manipulated to treat retinal disease.

The endocannabinoid system, as some readers may be familiar with, is the system of cannabinoid receptors, natural cannabinoids that bind to them, and all the enzymes facilitating that process that are found in humans and most mammals. Recently we’ve learned that cannabinoid receptors are more complex than we imagined. Aside from cannabinoid receptors CB1 and CB2, vanilloid receptors (an entirely different chemical system), and orphan GPR-55 receptors are also capable of receiving cannabinoids, meaning that the line where the endocannabinoid system ends and another begins is somewhat blurred. Regardless, the cannabinoid system is present in multiple ways in the retina. CB1 receptors are found in the inner and outer plexiform layers of retina in many animals, specifically in the cones and rods that actually translate light radiation into chemical signals. CB2 receptors are likewise known to be present in both human and mouse eyes, especially in retinal pigment cells. Finally, vanilloid receptors and GPR-55 receptors are also found in rods of eyes of some mammals. The endocannabinoid system, which is activated by cannabis, is abundant throughout parts of the eye that may influence glaucoma or other retinal disease. In fact, their pattern of distribution hints that it plays an active role in eyesight, although that role is unclear at the moment. Researchers suspect the role involves the release of other neurotransmitters that affect visual processing.

In the case of glaucoma, which is the second leading cause of blindness worldwide, we’ve found that cannabis alone is not a full treatment. Cannabis and similarly, activating the CB1 and CB2 receptors through any means, does legitimately reduce eye pressure by affecting the tissues around the eye that control the influx and outflow of fluid. However, this drop in pressure is not enough to prevent the eye from going blind and is merely a small aid. Regardless, cannabis indeed appears to be helpful for glaucoma and other retinal disease for an entirely different reason; it attenuates cell death directly.

In the case of diabetic retinopathy, which is another common ocular disease, excess blood sugar affects the circulatory system of the retina, by reducing blood flow. Neurodegenerative effects, inflammation, and oxidative stress hasten this development. Recently created pharmaceuticals, known as anti-VEGF therapies, present the most likely solution for the disease by slowing the growth of the natural enzyme that forms new, faulty blood vessels. However, this treatment ignores both the neurodegenerative and inflammatory components of the disease. Effective treatment of glaucoma and diabetic retinopathy inevitably must involve these underlying causes, rather than simply the vascular results.

Specifically, with ischemia, or the limited blood supply that occurs in both diseases, cell death occurs through excitotoxicity, or over-activation of cell receptors. Cells respond to the decreased blood flow by releasing a flood of calcium ions, which ironically ends up being more than the cell can handle. THC and CBD, chemical components of cannabis, have been shown to shield retinal cells from this type of excitotoxic damage. Furthermore, synthetic cannabinoids that bond to the CB1 receptor have similar neuroprotective properties. Finally, not surprisingly, the body’s own version of THC, Anandamide, serves a protective role as well. Taken together, this hints that the CB1 receptor is the major agent of action in protecting retinal cells from excitotoxicity. However, recent evidence has found that vanilloid receptors may present another pathway. Researchers have observed that when the vanilloid receptor is blocked, effects stemming from cannabinoids (natural or otherwise) are also blocked, indicating that the vanilloid receptor plays a role in the process. Unfortunately, the reverse does not seem to be true: activating vanilloid receptors has not been found to be therapeutic. Regardless, fixing blood flow or ocular pressure alone does not prevent blindness once the cycle of neurodegeneration has been initiated. Cannabis has been demonstrated to be particularly effective in these areas, meaning that it may greatly assist the treatment of all sorts of retinal disease.

As a result, while cannabis alone is not an effective solution, it seems to play a strong beneficial role for those suffering from retinal disease and continues to offer promise for further pharmacological development involving the endocannabinoid system. Patients suffering from glaucoma will likely find that cannabis improves their condition noticeably, and we encourage physicians to include cannabis in the mainstream roster of treatment options. As medical cannabis use continues to increase globally, we remain hopeful for the future.



Works Cited

Despina Kokona, Panagiota-Christina Georgiou, et al. Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease. Neural Plasticity (2016) Volume 2016: Article 8373020. DOI: 10.1155/2016/8373020