Introduction

Glaucoma is an eye condition that affects around 80 million people worldwide.¹ It is typically caused by an increased inner fluid pressure in the eyes, also known as intraocular pressure (IOP), which causes damage to the optic nerve, leading to visual impairment.^2-4 Currently, the available treatment consists of eye drops, laser therapy and in some cases, surgery, which aim to lower the IOP.^2-4 

Increasingly, there has been growing interest in the use of cannabis and its active compounds to treat glaucoma by targeting the IOP.⁵ Its potential benefits and drawbacks will be discussed in more detail in this article.

What is Glaucoma?

Inside the front of the eye, there are some cell tissues called the ciliary body that produce clear fluid, known as the aqueous humor, which fills the eye structure.⁶ In normal physiology, there is a constant balance of fluid production and drainage, where the fluid leaves the inside of the eye through the pupil.⁶ The purpose of the fluid is:

• To supply essential nutrients to the eyes
• Remove waste from the eyes
• Maintain the shape of the eye structure 
• Maintain the IOP⁶

When that balance is disrupted, glaucoma can occur.³ This is when the IOP is raised, causing visual impairment from damage to the optic nerve, and so visual information cannot be optimally relayed to the brain.³ This eye condition has been recorded to affect around 2% of the UK population over 40 years of age, and becomes more common as we age.⁷ 

As it is a gradual progressive disease, you may not notice it at first, until years later, and it is more frequently detected in routine eye tests.⁴ Sometimes, the symptoms may occur very suddenly.⁴ They include:^3,4

• Blurry peripheral vision
• Multi-coloured circles around bright lights
• A red eye
• Headaches
• Intense eye pain
• Tenderness around the eye area
• Nausea and vomiting^3,4

There are several types of glaucoma.^3,4 Primary open angle glaucoma is the most typical form where the drainage system for the aqueous humor gets blocked over time.^3,4 

When the drainage system is suddenly blocked and the IOP is elevated over a short period of time, this is called acute angle closure glaucoma, where symptoms present very quickly, though this is less common.^3,4 

Other times, there may be another condition causing glaucoma, in which case it is categorised as secondary glaucoma.^3,4 Congenital or childhood glaucoma may also be a possibility if there is abnormal development of the eyes.^3,4

What is the current treatment for glaucoma?

Current approaches to treat glaucoma are dependent on the type and severity that you may have. This allows a personalised management strategy specific for your condition.⁴ Unfortunately, there is no cure for the loss of vision.^3,4 However, there are medications and therapies that can alleviate the elevated IOP and improve the drainage system in the eye. 

First line of treatment will usually be an eye drop solution containing a fatty compound called prostaglandin, with different derivatives such as latanoprost, bimatoprost, tafluprost, and travoprost.^3,8 They work by widening the channels and connective tissues that allow increased outflow of fluid in the eyes.⁸ They are generally considered more preferable compared to other medications such as beta-blockers and carbonic anhydrase inhibitors, as prostaglandin solutions are applied topically once a day and have a low likelihood of systemic side effects.⁸ 

There are also options for laser treatment where the laser focuses on the drainage channels or the iris to improve fluid outflow.^3,9 In some laser procedures, the ciliary body is targeted instead, to decrease the production of aqueous humour.⁹ These processes will allow the IOP to be lowered to halt optical damage.⁹ Sometimes retreatment may be needed.³ 

If medication and laser therapy are not able to provide sufficient results, surgery may be suggested.³ Minimally invasive glaucoma surgery, commonly known as MIGS, may be suitable for those with a mild to moderate severity of the eye condition.^3,10 For more advanced disease, a trabeculectomy may be required, where a new channel to drain the aqueous fluid is created under the eye to relieve the elevated IOP.^3,11

As glaucoma is a progressive disease, it is important to have follow-up and regular check-up with a specialist doctor in the ophthalmology department.^3,4

How does cannabis affect eye pressure?

Cannabis has been increasingly investigated in modern medicine for the treatment of various illnesses such as chronic pain, insomnia, epilepsy and multiple sclerosis for muscle spasms.^5,12 The two main therapeutic components in cannabis are delta(9)-tetrahydrocannabinol, also known as THC, and cannabidiol which is more commonly known as CBD.⁵ THC is a psychoactive compound, meaning the mind is affected after administration, whilst CBD is not.⁵ There are 2 types of receptors in the body that interact with THC and CBD.⁵ They have been found in the nervous system, cells involved in the immune system, and some in the eye.⁵ 

THC particularly, has been shown to lower IOP in previous studies.^5,13 Different administration methods were tested, including inhalation through smoking, intravenous through injecting THC into the veins, oral consumption and sublingual, in which the medication was placed under the tongue where it was absorbed.^5,13 

Although the exact mechanism of how THC in cannabis is able to lower IOP has not been explicitly demonstrated, it has been suggested from previous research that interactions between THC and its receptors in the eyes can reduce the amount of aqueous humor created and increase fluid outflow through the drainage channels, as well as lowering overall blood pressure in the body which consequently lowers the pressure of the fluid that is supplied into the eyes.^5,13

What are the downsides and risks from using cannabis to treat glaucoma?

Even though THC has been shown to reduce IOP, the effect is usually transient, lasting only a few hours.⁵ Even with increased doses of THC, it does not seem to be able to prolong the decrease in IOP.¹³ This poses a practical difficulty for patients to have to administer multiple times a day compared to once daily of prostaglandin eye drops, and so THC use would not seem as a suitable option for consistent pressure control.^5,8,13 

Also, the methods of administration in many research studies use systemic delivery of THC, which means a greater likelihood and frequency of side effects from the psychoactive component of cannabis.^5,13 

Development of topical formulations have been investigated but THC has poor aqueous solubility, meaning that it does not dissolve in liquid well.^5,13 Solubility is important in the body because of the different membranes and phases that the drug has to pass to be able to have an effect. Results from topical administrations have not shown conclusive benefits to reducing IOP.¹³ Some of the adverse events from the use of THC in treating glaucoma have been shown to include:

• Dizziness 
• Low blood pressure
• Anxiety
• Panic
• Euphoria
• Increased heart rate, known as tachycardia
• Drowsiness
• Disorientation
• Distortion of perception^5,13

Although these side effects have not been shown in all participants of these studies, some have highlighted how the benefits from lowered IOP were overshadowed and may go under-appreciated due to the adverse effects.¹³ 

There are also concerns of long-term use of cannabinoids, as some studies have shown to negatively impact visual information being relayed from the retina to the brain, causing colour and precision to be affected.⁵ Therefore, more research with a long period of follow-up would be optimal to fully understand the advantages and disadvantages of using cannabinoids to treat glaucoma for the majority of patients.^5,13 

Moreover, research needs to be done on patients for the use of cannabinoids as a possible add-on to existing regimens to ensure there are sufficient benefits to justify their use, and that the side effects do not overlap or get worse from the interactions of the different chemical compounds.^5,13

What Do Experts and Guidelines Say?

At the moment, medical cannabis is not recommended as a treatment for glaucoma.¹⁴ Therefore, the key to effective management is to continue the treatment plan, such as using eye drops and going to regular check-ups as requested under the guidance of healthcare professionals.⁴ Future research may be able to develop and allow better understanding of cannabis-derived medications but current evidence encourages the use of prostaglandin eye drop solution as first line treatment.⁸

If you are considering using cannabinoids to treat glaucoma, it is important to speak to healthcare professionals, who will provide more information on the effects of cannabis compounds in the body and what the possible drawbacks are.^5,13 You may also see other specialists who can discuss the management of the side effects of using cannabis.⁵

Summary

Glaucoma is a significant global health complication. Although cannabis has shown promising results in research studies, it is not able to replace current first or second line treatment, which have proven evidence in lowering IOP, providing relief from the associated discomfort and has a better safety profile with fewer side effects. More research is still required to ensure better understanding of whether cannabis derivatives can be a beneficial alternative or adjunct to existing treatment.