CBD-infused eye drops are considered favorable in treating neuropathic ocular pain or diabetic retinopathy (eye complications due to diabetes).
But, What are the merits and demerits of CBD eye drops over prescription eye drops?
We are familiar with CBD products in the form of oils, pastes, crystals, creams, balms, patches, edibles, and more. And users are left with a wide variety of choices to deliver these formulations through different administration routes such as oral, sublingual, topical, rectal, nasal, etc.
In this lineup, the ocular route delivers desired cannabinoids through the eyes.
Although scientific references signify that smoking cannabis with a high THC potent lowers intraocular pressure of glaucoma, developing eye drops with cannabis compounds has been a challenge because of its lipophilic nature.
Comparatively, prescription eye drops also have some challenges about targeting the drug to the back of the eye and providing relief for pain and inflammation for eye conditions. For example, in glaucoma, the second leading cause of blindness in the United States, studies report that topical treatments with pharmaceutical eye drops come with adverse effects.
In such a case, do cannabinoids infused eye drops meet these expectations? What novelties are adopted in drug delivery to improve efficacy and relief in affected populations?
Therefore, consider this post as a brief introduction to simplify our understanding of CBD eye drops, let us review the role of cannabinoids in ocular applications.
What Are CBD Eye drops?
Eye drops infused with cannabis extracted cannabidiol (CBD) and dissolved in mineral oil are CBD eye drops. Although it seems simple, research points out the complexities of this type of CBD formulation due to its lipid profile.
The 2019 study1 contends that cannabidiol is a lipophilic molecule, so its topical delivery to the back of the eye is challenging.
An ophthalmic formula must penetrate the watery tear layer and pass through the cornea to reach the eye. Since cannabis solutions may not dissolve in water, it is difficult for natural and synthetic cannabinoids to be effective topical eye application.
But, contradicting the above reference, a 2017 study2 points out that lipophilic drugs are absorbed well through the cornea, whereas both lipophilic and hydrophilic compounds are well able to penetrate through the conjunctiva and sclera.
Cannabinoids and Glaucoma
Glaucoma Research Foundation (GRF) defines glaucoma as a complex disease where the optic nerve is damaged and leads to permanent vision loss.
Most importantly, this condition displays itself by a rise in intraocular pressure (IOP). IOP depends on the balance between the amount of fluid produced and drained, thereby maintaining the appropriate eye pressure. And this is an active continuous process responsible for the health of the eye.
- Initial studies in 1971, observed that smoking marijuana displayed a considerable decrease in intraocular pressure in a large percentage of participants in a clinical study.
- A 2017 study3 compiles from several other studies that cannabinoids can potentially lower IOP through multiple mechanisms besides the currently available anti-glaucoma medications. One of the key inferences of this study is that THC showed beneficial effects in treating glaucoma and neuroprotective actions to treat ocular diseases.
- Bearing in mind that cannabinoids are not water-soluble, researchers from the University of British Columbia have derived an eye drop using nanoparticle technology.
- The study has produced nanoparticles loaded with CBGA to penetrate the cornea. This new formula forms a lens in the eye once administered and then slowly begins to release cannabinoids.
When the drop is administered into the eye, it stays in a liquid state, until it balances with the temperature of the ocular surface. Then transforms to a gel state, taking the form of a lens. This lens slowly releases the CBGA taking eight hours to dissolve in the eye.
- Two conclusions from the 2016 study4 is noteworthy here:
- Exogenous cannabinoids, THC, and CBD together contain properties capable of bringing structural and functional changes in the retina.
- The study favors the use of synthetic cannabinoids in therapeutic applications for curing and preventing retinal diseases.
- Similarly, 2019 animal model study1 on analog derivatives of CBD proved that CBD analogs displayed higher penetration into ocular tissues.
Additional reading: CBD for Glaucoma
Does CBD lower eye pressure?
According to The American Academy of Ophthalmology (AAO) studies proposes that CBD does not lower IOP but increases it.
Additionally, reference from two studies is mention-worthy here.
1.The 2018 study5 tested and compared the results of IOP on rats after independently administering eye drops containing THC and CBD.
The following observations were reported.
Results of THC
- When eye drops containing THC were applied, IOP declined by 30% within eight hours.
- The effect of THC was sex-dependent. Female rats showed no effect in IOP at the end of eight hours, but they showed a moderate drop in IOP at the end of four hours.
- Male rats retained the effects of THC for 8 hours, whereas female rats for 4 hours.
Results of CBD
- IOP considerably increased in male and female mice at the 1st and 4th hour after administering CBD eye drops.
Results of THC & CBD
- Combined administration of THC and CBD showed no reduction in IOP in male rats.
2. A 2006 randomized study6 examined six glaucoma patients for IOP levels after sublingual administration of THC and CBD. Here too, similar results as the above study are reported. They are:
- IOP substantially reduced in two hours after sublingual administration of 5mg THC and was well tolerated by patients.
- Sublingual administration of 20 mg CBD did not decline IOP.
- A higher dose of 40mg CBD displayed a short time elevation of IOP at 4 hours.
Are CBD Eye Drops Safe?
From the above discussions, we can perceive that research so far shows mixed results on the effect of CBD eye drops. Also, research in this area is complicated, expensive, and time-consuming. Therefore, it is hardly possible to arrive at any conclusion if CBD as eye drops are safe to use.
Furthermore, a 2019 study7 points out that while the use of CBD for several diseases is growing, it lacks sufficient scientific evidence to prove its efficacy.
In general, although CBD has a good safety profile, some adverse effects of CBD intake may be CBD-induced drug-drug interactions, diarrhea, fatigue, vomiting, hypersomnia or excess sleepiness, and abnormalities in the liver.
CBD drops and eye dryness
There are quite a few aspects to take into consideration before addressing CBD and eye dryness.
- Firstly, determining the cause of eye dryness is essential. Is the condition the result of consumption of CBD, THC, or both?
- Dry eye syndrome is typical in glaucoma. 40-50% of glaucoma patients experience eye dryness.
- Immune system disorders such as Sjogren’s syndrome are associated with dry eyes and dry mouth symptoms. The most common causes being rheumatoid arthritis and lupus.
- Xerostomia or dry mouth also referred to as cottonmouth, is an adverse side effect for people using marijuana.
- Prolonged use of glaucoma eye drops, prescription medication such as antihistamines and antidepressants.
Can you use CBD oil as eye drops?
There is little to no reference about the use of CBD in its oil formulation for topical eye applications. The above reference from several studies that we have discussed has highlighted the implications of the use of CBD on eye pressure. But there is no specific mention of CBD oil.
Moreover, concerning the lipophilic nature of CBD oil and its compatibility with the eyes, there is a need for more qualitative evidence.
A textual reference8discusses that a non-randomized study in healthy volunteers compared with glaucoma patients showed temporary reductions in IOP with oral, topical eye drops, and intravenous administration of cannabinoids. And, it also points out that systematic reviews concluded that the trial was unclear.
Again, in the above reference, none of the trials have mentioned the use of CBD oil as eye drops.
CBD Eye drops for macular degeneration
Another potential application of cannabinoids in ocular health is Macular Degeneration. (MD) Yet another leading cause for vision loss in the USA.
‘Macula’ is the central region of the retina, which controls our sharp focus. All of our activities, reading, recognizing, image capturing, involves macular functioning. Deterioration in this region results in macular degeneration leading to loss of central vision.
According to a 2008 study9 abundant growth of vascular endothelial growth factor (VEGF) proteins is the major cause of abnormal blood vessel growth in the retina.
Reference from anecdotal evidence from a patient suffering from MD reports that after administering CBD oil sublingually, the severity of MD went down. The patient observed improvements in her condition from Intermediate MD to an early stage of MD.
The Ocular Endocannabinoid system
Briefly summarising key points from the 2016 study4:
- The retina is an extension of the Central Nervous System (CNS)
- The study identifies the presence of cannabinoid systems in ocular tissues.
- The receptors, ligands, and enzymes that constitute the endocannabinoid system are expressed in the retina.
Additionally, a recent study10 confirms that the endocannabinoid system (ECS) plays a crucial role in regulating inflammation, tissue repair, and pain perception in the conjunctiva and the cornea in humans.
In short, we can generalize that the ECS has a significant role in the ocular immune response. In the same lines the 2016 study11 proposes the need for additional studies focussing on the therapeutic potential of ECS modulating drugs in ocular diseases.
- Treating ocular conditions with cannabinoids is complex. There are a lot of unknowns concerning dosage, frequency, routes of administration, formulation, etc. There is a need for more research that focuses on the anti-inflammatory and neuroprotective properties of cannabinoids.
- Nanotechnology shows promising potential in delivering lipophilic drugs into the human body with improved bio-availability.
- People affected with glaucoma, macular degeneration, pain, and inflammation experience severe side effects due to prolonged intake of prescription drugs. Despite the side effects, the medications fail to provide relief from pain. The application of nanotechnology and novel drug delivery in plant extracts could provide improved bioavailability and benefit affected populations.
- Synthetic cannabinoids show encouraging results for the use and prevention of retinal diseases.
- CBD products have flooded the market, and users seeking alternatives from prescription drugs are enthusiastic to try them for managing their lifestyle. But from a practical point of view, medical practitioners show inhibitions for recommending cannabinoid therapy due to quality problems. Some of the major concerns affecting the regulation of CBD-based products are the presence of high levels of pesticides, heavy metals and incorrect amounts of CBD stated in labels.
- Therefore, users need to exercise caution while purchasing CBD products. Manufacturers need to pursue ethical business standards and practices to ensure the supply of high-quality products to the market.
- Taskar P, Adelli G, Patil A, Lakhani P, Ashour E, Gul W, ElSohly M, Majumdar S. Analog Derivatization of Cannabidiol for Improved Ocular Permeation. J Ocul Pharmacol Ther. 2019 Jun;35(5):301-310. doi: 10.1089/jop.2018.0141. Epub 2019 Apr 18. PMID: 30998110
- Vaajanen A, Vapetalo H. A Single Drop in the Eye – Effects on the Whole Body?. Open Ophthalmol J. 2017;11:305-314. Published 2017 Oct 31. doi:10.2174/1874364101711010305
- Adelli, Goutham & Bhagav, Prakash & Repka, M.A. & Gul, Waseem & Elsohly, Mahmoud & Majumdar, S.. (2017). Chapter 78. Ocular Delivery of Tetrahydrocannabinol.10.1016/B978-0-12-800756-3.00089-2
- Thomas Schwitzer, Raymund Schwan, Karine Angioi-Duprez, Anne Giersch, Vincent Laprevote, “The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications“, Neural Plasticity, vol. 2016, Article ID 2916732, 10 pages, 2016
- Sally Miller, Laura Daily, Emma Leishman, Heather Bradshaw, Alex Striker; Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2018;59(15):5904-5911
- Tomida I, Azuara-Blanco A, House H, Flint M, Pertwee RG, Robson PJ. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study.JGlaucoma.2006Oct;15(5):349-53
- Huestis MA, Solimini R, Pichini S, Pacifici R, Carlier J, Busardò FP. Cannabidiol Adverse Effects and Toxicity. Curr Neuropharmacol. 2019;17(10):974-989
- National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017 Jan 12. 4, Therapeutic Effects of Cannabis and Cannabinoids
- Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res. 2008;27(4):331-371. doi:10.1016/j.preteyeres.2008.05.001
- Aiello F, Gallo Afflitto G, Li JO, Martucci A, Cesareo M, Nucci C. CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization, and Wound Healing. J Clin Med. 2020;9(12):4036. Published 2020 Dec 14. doi:10.3390/jcm9124036
- Cairns, E., Toguri, J., Porter, R., Szczesniak, A. & Kelly, M. (2016). Seeing over the horizon – targeting the endocannabinoid system for the treatment of ocular disease. Journal of Basic and Clinical Physiology and Pharmacology, 27(3), 253-265