Virginia Thornley, M.D.,  Neurologist, Epileptologist

February 28, 2018

Introduction

The endocannabinoid system is composed of 3 systems: (the cannabinoid receptors, (2) endocannabinoid transportation system and (3) enzymes that break down the ligands. Two endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) are elevated in response to a wide variety of pathological events. This suggests a compensatory response of endocannabinoids in response to damage or pathology within the system (3). Activation of the endocannabinoid system appears to correlate with cell repair and survival. The G-receptors discovered called CB1 and CB2 trigger transducer signal cascades and influence peripheral central cell functions.

Cannabidiol in glaucoma

Cannabidiol is becoming a topic of hot debate in pain, anti-tumor effects, epilepsy and in glaucoma.  Glaucoma can result in increased intraocular pressure resulting in damage to the optic nerve at the retinal attachment. There is the narrowing of the visual field and eventual blindness through retinal damage. Cannabinoid receptors have been found in the ocular cells leading to speculation of benefits of cannabinoids in glaucoma.

Mechanism for treating glaucoma

One possible mechanism in ameliorating intraocular pressure is by suppressing N-methyl D-aspartate or NMDA receptor excitability, increasing neural vasculature circulation, suppressing apoptosis and damaging free radicals. Separation of the novels effects appears possible from the toxic side effect through novel technique (2).

Involvement of cannabinoid and their receptors in retinal cells have been well documented in fish cells to primates and more recently in neurodegeneration and neuroprotection. There is a fine balance of biosynthetic and degrading enzymes that influence endocannabinoids and exert neuroprotection during trauma, inflammation, ischemia, and neurotoxicity found in brain damage (4).

THC studies and glaucoma

In a rabbit model, 9THC showed improved penetration to the anterior chamber with reduction of intraocular pressure using a prodrug. THC is an established neuroprotectant and has the possibility of being an effective IOP lowering agent. THC and THC-Val-HS reached the retina choroid(5).

In one study of 32 different types of cannabinoids, it was found that certain derivatives of delta 9THC and delta 8THC were more effective at lowering intraocular pressure in glaucoma than the parent derivative cannabidiol (1).

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References

1. ElSohly, et al, “Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure on rabbits,”Current Eye Research, 1984, Jun., 3(6):841-50.
2. Jarvinen, T., “Cannabinoids in treatment of glaucoma,” 2002, Aug., 95(2):203-20.
3.  Karanian, et al, “Cannabinoid drugs and enhancement of endocannabinoid responses: strategies for a wide array of disease states,” Current Molecular Med., 2006, Sep., 6(6):677-84.
4.  Rapino, et al, “Neuroprotection by endocannabinoids in glaucoma and retinal neurodegenerative diseases,” Current Neuropharmacology, 2017, Jul., doi:10.2174 (Epub ahead of print)
5.  Goutham, et al, ” Development of a 9tetrahydrocannabidiol amino acid dicarboxylate prodrug with improved ocular bioavailablity,” Investigative Ophthalmology and Visual Science, 2017, Apr., 58(4):2167-2179.