It’s been 50 years since researchers first identified marijuana as a potential therapeutic agent for the treatment of glaucoma. Proof that smoked cannabis could reduce certain deleterious symptoms of glaucoma is often cited as the benchmark of the modern medical marijuana movement. In the decades since, cannabis and cannabis derivatives have proven effective for addressing a number of additional conditions ranging from anxiety, PTSD, and pain relief to Crohn’s disease, multiple sclerosis, cancer, Parkinson’s disease and more.
In the state of Florida and most other states that have legalized medical marijuana, glaucoma remains a qualifying condition for cannabis-based treatments. But despite this history of acceptance, the use of marijuana for the treatment of glaucoma remains a divided subject within the medical and research communities.
Marijuana Lowers IOP
Glaucoma is a degenerative disease that damages the eye’s optic nerve, leading to loss of vision and in some cases blindness. This condition is often linked to an increase in fluid pressure within the eye. Reducing this interocular pressure (IOP) has been shown to significantly delay the progression of the disease. The 1971 reporting that smoked marijuana could lower IOP by 25 to 30% added a degree of scientific validity to anecdotal reports and traditional medical use of marijuana for glaucoma relief.
Later studies yielded similar results. In the book Marijuana as Medicine? The Science Beyond the Controversy the authors state that:
The first such reports [of marijuana’s potential to reduce IOP] generated considerable interest because at the time conventional medications for glaucoma caused a variety of adverse side effects.
But also went on to say that:
Other treatments for the disorder have since eclipsed marijuana-based medicines.
This second statement is not universally accepted, however. The case for medical marijuana therapies for the treatment of glaucoma is still considered a viable option by many (and for reasons more complex than the simple lowering of IOP).
Pros, Cons & Unknowns
A position statement from the American Glaucoma Society acknowledges:
It has been definitively demonstrated, and widely appreciated, that smoking marijuana lowers IOP in both normal individuals and in those with glaucoma, and therefore might be a treatment for glaucoma.
But also notes that:
Less often appreciated is marijuana’s short duration of action (only 3-4 hours), meaning that to lower the IOP around the clock it would have to be smoked every three hours.
The time/dose nature of marijuana-based glaucoma therapy has caused some within the medical community to discount it as a primary solution for slowing the progression of glaucoma. What is more widely acknowledged is the potential benefits of nausea mitigation and pain relief that marijuana can provide for patients during late-stage and end-stage glaucoma.
Another potential source of controversy has to do with blood pressure. As we have previously reported, critics of marijuana therapies for glaucoma point out that its use not only lowers IOP, but also systolic blood pressure, resulting in reduced blood flow to the optic nerve and a lowing of ocular perfusion pressure (OPP) in parts of the eye that control lens shape and the production of protective liquids. A lowering of OPP is generally considered to be a risk factor for the development of glaucoma. However, in recent years, some researchers have asserted that the lowering of systolic blood pressure may not play a direct role in OPP levels, which may instead be related solely to elevated IOP levels and additional factors not fully understood at this time.
The research community also remains somewhat divided as to whether it is marijuana’s ability to lower blood pressure that results in a reduction of IOP, or whether this reduction occurs due to a decrease in fluid production triggered by by marijuana’s interactions with cannabinoid receptors in the eye.
Glaucoma Treatment: THC vs CBD
As early as 1981, THC was identified as the primary cannabinoid in marijuana that was responsible for lowering IOP.
Recent research has revealed that the CBD component of marijuana can actually prevent THC from lowering IOP. The researchers who identified this phenomenon wrote that:
We conclude that THC lowers IOP by activating two receptors — CB1 and GPR18.
CBD, contrary to expectation, has two opposing effects on IOP and can interfere with the effects of THC.
Science Daily has reported that:
CBD — a major chemical component in marijuana — appears to increase pressure inside the eye of mice, suggesting the use of the substance in the treatment of glaucoma may actually worsen the condition. A study comparing the effects of a sublingual application of THC or CBD extracts showed a significant lowering of IOP with the THC formulation, no change in IOP with lower-dose CBD formulations, and a measurable but transient increase in IOP with higher dosages of CBD.
Such findings have caused the American Academy of Ophthalmology and other bodies to warn against the use of topical or oral CBD for the treatment of glaucoma. By the same token, individuals who choose to use smoked or oral marijuana for glaucoma therapy might want to select strains or products with a higher THC/low CBD component.
While marijuana’s role in lowering IOP will likely remain a subject for discussion, there are other and perhaps even more compelling reasons why cannabis and cannabis derivatives might be an appropriate addition to glaucoma therapies. A number of studies detail the anti-inflammatory and neuroprotective properties of marijuana, which include the suppression of apoptosis (cellular death) and a decrease in the production of free radicals.
A review published in the Journal of Clinical Medicine states:
Another interesting aspect of cannabinoid usage in glaucoma is connected with the neuroprotective capabilities of these molecules.
The study’s authors note that there have been few human studies to date assessing these potential neuroprotective effects, but the literature includes a wide range of animal-based studies to support that support this assertion. They go on to list three ways in which cannabinoids may provide protection:
Glutamate inhibition: Glutamate is known to increase retinal ganglion cell death via activation of nitric oxide synthase and the consequent increase in oxidative damage.
Endothelin inhibition: The vasoconstrictor endothelin-1 is higher in patients affected by normal tension glaucoma than in normal controls and may therefore contribute to disease progression.
Inhibition of nitric oxide release: Activation of CB1 and CB2 receptors in the retina and central nervous system inhibits the production of nitric oxide and inflammatory cytokines that are responsible for oxidative stress and retinal ganglion cell death.
What is sometimes overlooked in academic assessments of marijuana’s role in glaucoma therapies are the ways in which patients may use it to mitigate some of the additional physical and psychological effects associated with the disease such as pain, anxiety, and depression.
In a recent article in the Yale Journal of Biology and Medicine, the authors reviewed the potential efficacy of a number of herbal medicines for the treatment of glaucoma, and stated:
With the steady legalization of marijuana and a positive shift in its social acceptability, glaucoma patients are more likely to use marijuana as a therapeutic alternative.
A 2019 paper published in Current Ophthalmology Reports notes that:
[Marijuana’s] broad side effect profile, short half-life, and limited corneal penetration have prevented its development into a commercial ocular anti-hypertensive.
Then adds that:
Several techniques for retaining the therapeutic effect and minimizing or eliminating the side effects of delta-9-tetrahydrocannabinol are being investigated, but these are still in the early stages.
The American Academy of Ophthalmology states:
Scientists are exploring whether the active ingredients in marijuana may yet offer a glaucoma treatment. If the effects of cannabis compounds can be isolated, made to be long-acting, and the side effects eliminated, they may lead to new treatments in the future.
One such product now in development was announced by Emerald Bioscience in a December 2020 press release. The company’s novel THC product, known as THCVHS, “appears to not only be more effective at reducing IOP, but also has a longer duration of response when compared to standard of care treatment for glaucoma.”
In addition to lowering IOP, the formulation appears to provide additional benefits for glaucoma patients. The authors of the study cited in the release comment that:
A large percentage of glaucoma patients do not experience increased IOP but nevertheless experience vision loss believed to result from other neurodegenerative effects on the cells of the optical nerve.
THC is also known to have neuroprotective properties. If our drug can protect against vision loss in patients with normal IOP as well, we would have an extraordinary new solution to offer for the prevention of glaucoma-related vision loss.
As new research on THC’s potential therapeutic benefits for the treatment of glaucoma emerge, CannaMD will continue to provide updates.