Medical Marijuana for Glaucoma Therapy

Despite the drug’s potential IOP-lowering capabilities, toxicity to the ocular surface is a major concern.

By Katherine Shen, OD
 

Over the past year, media coverage and national awareness of the legalization of marijuana for medical and recreational use have increased. Twenty-one states plus Washington, DC, have enacted laws that allow the use of medical marijuana with a doctor’s recommendation, and two of those states—Colorado and Washington—have legalized marijuana for recreational use.1 It is therefore important that eye care providers learn about medical marijuana for glaucoma therapy. This article reviews some of marijuana’s effects on the eye.

BACKGROUND

Marijuana (cannabis) is the drug most frequently used illicitly today. It is also one of the oldest drugs used for medical purposes. The drug’s therapeutic use was first recorded in a classical Chinese medical book in 2737 BC,2 and European doctors introduced marijuana to Western medicine in the 19th century. The cannabis plant has more than 480 chemical constituents and 60 compounds that only contain carbon, hydrogen, and oxygen known as cannabinoids.3 The main psychoactive constituent of cannabis is the cannabinoid delta-9-tetrahydrocannabinol (THC). In 1988, a specific protein receptor (CB1) for THC was discovered on mouse nerve cells. CB1 mediates most of the central nervous system (such as the brain and spinal cord) and certain peripheral tissues, including the lungs, heart, urogenital and gastrointestinal tracts, and the eye.4 In 1993, a second receptor (CB2) for THC was identified in cells and tissues associated with the immune system such as the tonsils, spleen, and leucocytes.4

IOP-LOWERING EFFECT

According to the American Glaucoma Society, the mainstay of treatment for glaucoma patients is to lower IOP.5 Although, historically, three modalities (medication, laser treatment, and surgery) have been used to decrease IOP, it has been demonstrated that smoking marijuana lowers the IOP of both healthy and glaucomatous eyes.6

In 1971, Heplar and Frank reported that smoking marijuana reduced IOP by 25% to 30% in 11 youthful subjects.6 The duration of action after smoking the drug was 3 to 4 hours, and a dose-response relationship was present. Conjunctival hyperemia, reduced tear production, and a change in pupillary size were also observed. Acute systemic effects included the reduction of systemic blood pressure and tachycardia. Psychotropic effects included euphoria or dysphoria, disruption of short-term memory, cognitive impairment, a distorted sense of time, reduced coordination, and sleepiness. Dawson et al reported an equal reduction in IOP between nonusers and long-term (10 years or more) users of marijuana.7

Different cannabinoid compounds have reduced IOP through oral, intravenous, sublingual, and topical administration pathways.8 Although the exact mechanism by which cannabinoids regulate IOP is unknown, CB1 and CB2 have been identified in ocular tissues, with CB1 as the main cannabinoid receptor at the ocular level. The location of the CB1 cannabinoid receptors and their effect on cyclic adenosine monophosphate suggest that CB1 influences the production of aqueous. In 1999, ocular cannabinoid receptors were identified via immunohistochemistry, with the greatest density found in the trabecular meshwork, the nonpigmented ciliary epithelium, and the ciliary muscles; a lesser density of ocular cannabinoid receptors was found in Schlemm canal.9 The presence of CB1 receptors at the nonpigmented epithelium of the ciliary body and in the choroidal vessels could be one of the main mechanisms through which cannabinoid agonists lower IOP by diminishing the production of aqueous humor.10 How CB2 receptors reduce IOP has not been established.

NEUROPROTECTIVE PROPERTIES

Cannabinoids’ full mechanism of action in the human eye is not fully understood. Numerous studies have demonstrated that cannabinoids increase neuron survival in neurodegenerative diseases.11 In glaucoma, the final pathway leading to vision loss is the selective death of retinal ganglion cells through apoptosis, which is initiated by axonal injury at the optic disc by either compression or ischemia. In ischemia, the release of glutamate activates the N-methyl-D-aspartate receptor. Such activation is one of several pathways to apoptotic cell death. It causes an influx of calcium into the cells and generates free radicals.12 THC can inhibit the release of glutamic acid by increasing potassium and decreasing calcium permeability, and it can also block the activation of glutamate and N-methyl-Daspartate.12

Cannabinoids also have antioxidant and vasorelaxant properties, and they may increase ocular blood flow.4 Patients with open-angle glaucoma may experience an abnormal increase in plasma endothelin-1 in response to vasospastic stimuli.4 Marsicano et al demonstrated that cannabinoids reduced endothelin-induced calcium mobilization, thus inhibiting vasoconstriction.11 Cannabinoids may therefore be of benefit to eyes with ischemia-induced optic nerve damage. On the other hand, inhaled THC can cause systemic hypotension, which could harm optic nerve perfusion.13

CONCLUSION

Cannabinoids are a potential IOP-lowering treatment for glaucoma. They seem to have neuroprotective properties, which may or may not be applicable to retinal ganglion cells or other visual pathway neurons.4 The use of eye drops containing THC has been investigated, but it has not been possible to formulate sufficiently concentrated therapy due to the low water solubility of the active ingredients. Additionally, the formulations created have been toxic to the ocular surface and have not been tolerable due to local side effects.14 At this time, marijuana’s side effects and short duration of action preclude recommending this drug in any form for the treatment of glaucoma.

Katherine Shen, OD, is an associate at Specialty Eyecare Group in Seattle and Kirkland, Washington. Dr. Shen may be reached at drshen@specialtyeye.com.

  1. 21 legal medical marijuana states and DC. ProCon.org website. http://medicalmarijuana.procon.org/ view.resource.php?resourceID=000881. Updated April 25, 2014. Accessed April 30, 2014.
  2. Robson P. Therapeutic aspects of cannabis and cannabinoids. Br J Psychiatry. 2001;178:107-115.
  3. Dewey WL. Cannabinoid pharmacology. Pharmacol Rev. 1986;38:151-178.
  4. Tomida I, Pertwee RG, Azuara-Blanco A. Cannabinoids and glaucoma. Br J Ophthalmol. 2004;88(5):708-713.
  5. Jampel H. Position statement on marijuana and the treatment of glaucoma. American Glaucoma Society website. http://www.americanglaucomasociety.net/patients/position_statements/marijuana_glaucoma. Published August 10, 2009. Accessed April 30, 2014.
  6. Heplar RS, Frank IR. Marihuana smoking and intraocular pressure. JAMA. 1971;217:1392.
  7. Dawson WW, Jiménez-Antillon CF, Perez JM, Zeskind JA. Marijuana and vision—after ten years’ use in Costa Rica. Invest Ophthalmol Visual Sci. 1997;16:689-699.
  8. Pinar-Sueiro S, Rodríguez-Puertas R, Vecino E. Cannabinoid applications in glaucoma. Arch Soc Esp Oftalmol. 2011;86(1):16-23.
  9. Mohamed N, Meyer D. Intraocular pressure-lowering effect of oral paracetamol and its in vitro corneal penetration properties. Clin Ophthalmol. 2013;7:219-327.
  10. Robson PJ. Therapeutic potential of cannabinoid medicines. Drug Test Anal. 2014;6(1-2):24-30.
  11. Marsicano G, Moosmann B, Hermann H, et al. Neuroprotective properties of cannabinoids against oxidative stress: role of cannabinoids receptors CB1. J Neurochem. 2002;80:448-456.
  12. Perwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci. 2012;367(1607):3353-3363.
  13. Merritt JC. Glaucoma, hypertenstion, and marijuana. J Natl Med Assoc. 1982;74(8):715-716.
  14. Royal College of Physicians. Cannabis and cannabis-based medicines. Potential benefits and risks to health. http://www.rcplondon.ac.uk/sites/default/files/documents/cannabis_report_web.pdf. Published 2005. Accessed May 9, 2014.
 

Contact Info

Bryn Mawr Communications LLC
1008 Upper Gulph Road, Suite 200
Wayne, PA 19087

Phone: 484-581-1800
Fax: 484-581-1818

About Glaucoma Today

Glaucoma Today is mailed bimonthly (six times a year) to 11,519 glaucoma specialists, general ophthalmologists, and clinical optometrists who treat patients with glaucoma. Glaucoma Today delivers important information on recent research, surgical techniques, clinical strategies, and technology.