The use of cannabis for the treatment of glaucoma has been around for several decades. In fact, glaucoma was among the top reasons for the granting of compassionate use of medical marijuana when the project was still active. Even today, states that have legalized medical marijuana have glaucoma as a top reason for use.
About Glaucoma
Glaucoma is a blanket term for a group is eye diseases in which the optic nerve is damaged and vision is lost. If it’s caught early, it is possible to slow or even stop the progression of the disease. It is known as the “silent thief of sight” as vision loss occurs slowly over a long person of time. Among the accepted treatments for glaucoma are:
- Medication
- Laser treatment
- Surgery
In the case of each treatment, the goal is to reduce the pressure on the eye. And while these treatments can stop or slow the progression of the disease, there’s no way to reverse the damage that has been already done and it, therefore, permanent.
Nearly 60 million people worldwide suffer from some form of glaucoma and 2 million in the United States alone.
Glaucomas fall into one of these 4 categories:
- Primary Open Angle Glaucoma (POAG) – The drainage canal of the eye becomes blocked and the fluid build-up causes pressure to build in the eye. The pressure can cause damage to the optic nerve.
- Angle Closure Glaucoma – The eye cannot drain properly due to the drainage canal being too narrow or closed completely. As a result, eye pressure rises quickly and be triggered by pupil dilation.
- Normal Tension Glaucoma – Also known as low-pressure glaucoma, the optic nerve is damaged even though there is no elevation in eye pressure. Risks for this type of glaucoma include family history and cardiovascular disease.
- Secondary Glaucomas – Glaucomas that develop as the result of another event or disease. This can include trauma, cataracts, diabetes, eye surgery, or tumors. This type of glaucoma often requires surgery to correct the damage to the fluid drainage canal.
Causes and Predispositions of Glaucoma
The greatest cause of glaucoma is pressure within the eye. This presents with only 50% of people with open-angle glaucoma. In the US, 90% of the cases of glaucoma are open angle, in East Asia and other countries, half of all cases are closed-angle glaucoma.
Among the predispositions for glaucoma are:
- Genetics – Any person with a family member who has had glaucoma is at risk for glaucoma. The risk of having POAG is up to 4 times more likely for a person if their sibling had been diagnosed with glaucoma. This is due to some types of POAG being traced to genetic mutations.
- Ethnicity – Studies have shown that persons of Asian descent and the Inuit population of Canada and Greenland are the most susceptible to angle closure glaucoma.
- Dietary – Dietary habits don’t generally affect primary glaucomas. However, they can play a role in secondary glaucomas. For those who are diagnosed with diabetes or high blood pressure who fail to follow dietary recommendations and proper medications to manage their conditions can increase their possibility of developing secondary glaucoma. In addition, those who already have started developing glaucoma or who have cataracts are susceptible to glaucoma by consuming caffeine in excess as it increases the ocular pressure.
- Drugs – In particular prolonged use of steroids and growth hormones can severely restrict blood flow to the eyes causing steroid-induced glaucoma.
CBD and Glaucoma
Since the 1970s, many have touted the use of cannabis to treat the symptoms of glaucoma. Several studies have been done to further this belief, but until recently, no studies have been done on the use of the cannabinoid CBD.
CBD or cannabidiol is one of 113 different cannabinoids (cannabis related chemical compounds) that are naturally produced in cannabis plants and in humans.
Cannabinoids such as CBD and its sibling THC, tetrahydrocannabinol, works with the body’s endocannabinoid system (ECS) to create homeostasis within the body.
The ECS is comprised of neurotransmitters and neuroreceptors throughout the brain, the central nervous system, and the peripheral nervous system.
The primary receptors of the ECS are known as CB1 (cannabinoid receptor type 1) and CB2 (cannabinoid receptor type 2).
The more common of the 2 receptors is the CB1 receptor. The CB1 receptor is found throughout the body in such locations as:
- Adrenal glands
- Brain
- Digestive tract
- Fat cells
- Kidneys
- Liver cells
- Lungs
- Muscle cells
- Ovaries
- Pituitary gland
- Placenta
- Retinas
- Spine
- Thyroid gland
C1 receptors are responsible for regulating the effects of activities including anxiety, cardiovascular activity, drug, and behavioral addictions, gastrointestinal activity, motor control, sense of smell, and adaptation to change.
CB2 receptors are primarily found in the brain, gastrointestinal system, immune system, and the peripheral nervous system.
The CB2 receptors are responsible for:
- Autoimmunity
- Bone health
- Cancer inhibition
- Cardiovascular processes
- Gastrointestinal processes
- Inflammation
- Kidney function
- Liver function
- Lung function
- Neuroprotection
- Pain responses
- Skin reactions
As the CB1 and CB2 are receptors, that means they receive some sort of signal. In their case, they receive signals specifically from neurotransmitters. Neurotransmitters are chemical messengers which transmits signals across chemical synapses, from one nerve cell to another nerve cell, muscle cell, or gland cell.
The CB1 and CB2 bind to neurotransmitters in the body. Examples of major neurotransmitters include:
- Adenosine
- Adenosine triphosphate
- Adrenaline
- Anandamide
- Aspartate
- Carbon monoxide
- CART (cocaine and amphetamine regulated transcript)
- Dopamine
- Epinephrine
- Glutamate
- Glycine
- Histamine
- Hydrogen sulfide
- Nitric oxide
- Noradrenaline
- Norepinephrine
- Octopamine
- Opioid peptides
- Oxytocin
- Phenethylamine
- Serotonin
- Somatostatin
When exposed to CBD, the CB1 and CB2 receptors act differently. When CBD comes in contact with a CB1 receptor, CBD acts as an antagonist by activating, but not binding to the receptor. This allows the CBD to inhibit (but not prevent) the absorption of neurotransmitters such as serotonin. Because CBD inhibits the neurotransmitter, it can regulate the flow of it thus preventing rapid absorption and depletion of the neurotransmitter. When a neurotransmitter is depleted too quickly, it throws the body out of balance.
In the case of CB2, it acts as an agonist, allowing CBD to bind with the neuroreceptor and allowing neurotransmitters to pass through. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219532/)
CBD has a direct effect on the retinas via the CB1 receptors. This means that CBD inhibits and can regulate the neurotransmitters located in the retina.
However, that may not be the best situation for the retina.
Case Studies
There have been a lack of cases studies on the effect of CBD on the different types of glaucoma, but so far, the case studies aren’t promising.
One recent study, conducted in late 2018 looked at how THC and CBD regulate intraocular pressure. For the study,” topically applied THC and CBD were tested in living mice by using tonometry (tests for eye pressure) and measurements of messenger ribonucleic acid (mRNA levels). In addition, the lipidomic consequences of CBD treatment were tested by using lipid analysis.”
The results found a stunning revelation about CBD. The study noted that “CBD was found to have two opposing effects on ocular pressure, one of which involved antagonism of tonic signaling. CBD prevents THC from lowering ocular pressure.”
In a further explanation the study stated “When tested in our model, we found that CBD (5 mM) in male mice substantially raised IOP at 1 and 4 hours. Female mice saw a similar rise at both time points. Strikingly, the same experiment in CB1 knockout (mice) resulted in a decrease in ocular pressure at 1 hour but no effect at 4 hours. This indicates that CBD has two opposing effects on IOP. The first and dominant effect of raising IOP is likely CB1-dependent since the effect is absent in CB1 knockout mice and may be a consequence of cannabinoid receptor antagonism. We tested whether the IOP reduction was due to activity at GPR18 receptors since GPR18 activation can lower IOP. CBD had no effect on IOP in animals pretreated with the GPR18 antagonist O1918.” So in these cases, CBD either raised or had no effect on intraocular eye pressure. (https://iovs.arvojournals.org/article.aspx?articleid=2718702)
Another study that dates back to 2006, found similar results. The purpose of the study was to “assess the effect on intraocular pressure (IOP) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD).”
When CBD was used in the study, the results found that “CBD administration did not reduce the IOP at any time. However, the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours after administration, from 23.2 to 25.9 mm Hg. Vital signs and visual acuity were not significantly changed. Sublingual administration of 20 mg CBD did not reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise.” (https://www.ncbi.nlm.nih.gov/pubmed/16988594)
A study from 1983 took a look at several cannabinoids in the treatment of intraocular pressure. It found that “comparison of l-delta 9-, delta 8-, 11-OH-delta 9- and 11-OH- delta 8-THC indicates that minor configurational changes have only a small influence on activity with regard to induction of a fall in intraocular pressure, although 11-OH-delta 8-THC has increased activity. 8 alpha-OH-, 8 alpha-diOH- and 8 beta-diOH-delta 9-THC have little or no activity but 8 beta-OH-delta 9-THC is as active as delta 9-THC indicating that the hydroxyl group in the beta-position does not influence activity. Modification of the C5H11 alkyl side chain (3′-OH-delta 9-THC) reduced activity to 20% relative to delta 9-THC. Cannabidiol (CBD), cannabichromene, cannabigerol, and olivetol had no activity, but 10-OH-CBD had some activity at 2 mg/animal.” In other words, THC was effective, other cannabinoids, including CBD, was not and had no activity. An exception was a CBD derivative called 10-OH-CBD which has minor activity. (https://www.ncbi.nlm.nih.gov/pubmed/6295702)
THC and Glaucoma
Many studies have been done on the efficacy of THC and glaucoma. In the 1970s the studies were convincing enough to convince the United States government to grate a “compassionate use” program that allowed certain glaucoma sufferers to not only use but receive medical-grade marijuana from the government.
One of these studies from 1975 looked at THC and euphoria and intraocular pressure. The results of the study found “The peak effect of THC on the central nervous system coincided well with the reduction of intraocular pressure induced by the drug; hypotony, however, outlasted euphoria. The results indicate that THC may have value as a hypotonizing ocular medicant.” (https://www.ncbi.nlm.nih.gov/pubmed/1147519)
The Federal Compassionate Investigational New Drug (IND) Program started in 1978. It was the result of the case of United States v. Randall, which was the first successful medical necessity defense in the history and the first case to extend the necessity defense to the crimes of possession or cultivation of marijuana. Between 1978 and the end of the program in 1992, 48 people applied to the program and 15 people received pre-rolled marijuana cigarettes each month from the National Institute on Drug Abuse at the University of Mississippi, which had been allowed by the government to grow and experiment with marijuana. While the program stopped accepting new applicants in 1992, existing patients continued to receive their marijuana each month. To this date, only 3 of the 15 are still alive and receiving prescription marijuana and are the only people fully eligible to legally consume marijuana in the US.
The American Glaucoma Society Position on Marijuana
The American Glaucoma Society (AGS) is an organization of ophthalmologists that promotes education and research about glaucoma among physicians and scientists. The group has put forth a position paper on the use of marijuana. It says in part “Although marijuana does lower the IOP temporarily, IOP lowering is only one consideration in slowing the optic nerve damage of glaucoma. For instance, there is a growing body of evidence that inadequate blood supply to the optic nerve may contribute to glaucoma damage. As marijuana given systemically is known to lower blood pressure, it is possible that such an effect could be deleterious to the optic nerve in glaucoma, possibly reducing or eliminating whatever beneficial effect that is conferred by lowering IOP. For this reason, marijuana, or its components administered systemically, cannot be recommended without a long-term trial which evaluates the health of the optic nerve.” It further concludes “Although marijuana can lower the IOP, its side effects and short duration of action, coupled with a lack of evidence that its use alters the course of glaucoma, preclude recommending this drug in any form for the treatment of glaucoma at the present time.” (http://www.eyestucson.com/storage/app/media/AGS_marijuana.pdf)
Conclusion
While CBD can be great for a number of ailments, studies point to it not being beneficial for glaucoma and in fact, may aggravate the condition.
Whole cannabis and THC however, seem to be beneficial to the reduction of intraocular pressure and pain associated with the disease.
In either case, further studies of CBD, THC, and cannabis needs to be performed to get a definitive determination of their benefits.
