Unlike THC, CBD May Increase Glaucoma-Related Eye Pressure

The Investigative Ophthalmology & Visual Science journal just published a new study looking at the effects of THC and CBD on eye pressure in mice.

This study comes almost 50 years after researchers first showed the positive effect of cannabis on glaucoma-related eye pressure.

Now, researchers are finally beginning to understand the underlying mechanisms responsible for this effect and that not all cannabinoids are created equal when it comes to eye pressure.

The History of Glaucoma and Cannabis

Glaucoma refers to a family of diseases that are associated with increased pressure in the eye. This causes damage to the optic nerve and, if left untreated, eventually leads to blindness.

Researchers first discovered the medical value of cannabis for treating glaucoma in 1971. That year Hepler and Frank published a groundbreaking study where they showed inhalation of cannabis lowers eye pressure by up to 30%.

Unfortunately, ocular research exploring the use of cannabis became completely stalled by the 1980s. As a result, researchers never discovered the mechanism of action by which cannabis affects pressure in the eye.

New Research Brings New Insights

Luckily, continued research has given us great insight into the nature of our own cannabinoid receptors.

Cannabinoid receptors are located throughout our nervous system, including our eyes. They respond to cannabinoids, which can be made by our bodies, synthesized in a lab, or derived from cannabis.

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prominent cannabinoid compounds found in cannabis.

The first cannabinoid receptor, CB1, was discovered by researchers in 1990.

Since the discovery of CB1, three other cannabinoid receptors have been identified—CB2, GPR18, and GPR119. Ocular researchers have found that CB1, GPR18, and GPR119 all play a role in regulating vertebrate eye pressure.

THC vs. CBD

THC can activate all three of the cannabinoid receptors (CB1, GPR18, and GPR119) that regulates eye pressure.

What about CBD?

While THC is the primary psychoactive cannabinoid compound in cannabis, the non-psychoactive CBD is present in levels comparable to THC.

With its approval by the FDA for the treatment of epileptic seizures, CBD has received increasing amounts of funding and attention as a potential therapeutic drug.

CBD can activate one of the cannabinoid receptors (GPR18) that regulate eye pressure. But unlike THC, CBD actually dampens the activity of CB1, one of the other eye pressure-regulating cannabinoid receptors.

This means that CBD could be directly opposing THC when it comes to regulating eye pressure. In fact, several studies have shown that CBD either has no effect on eye pressure or, in one case, actually increases eye pressure.

The Latest Study

Researchers at Indiana University decided to dive deeper. They designed a set of experiments to test the effects of THC and CBD on eye pressure and investigate which cannabinoid receptors are involved in the process.

The researchers used mice as a model system for the vertebrate eye. THC and CBD formulations were applied topically. They analyzed their results in a blinded fashion to avoid researcher bias.

The Results

THC Lowers Eye Pressure in Males More than Females

As expected, the researchers found that THC reduced eye pressure. Interestingly the effect was much more significant in male mice than female mice.

Male mice experienced a significant drop in eye pressure at both 4 and 8 hours after THC application.

The 8-hour time point, in particular, showed a nearly 30% reduction in eye pressure. This is similar to the effect seen in the original 1971 study that first looked at cannabis and glaucoma-associated eye pressure.

Female mice, however, showed only a modest reduction in eye pressure at 4 hours and no effect at 8 hours after THC application.

THC Lowers Eye Pressure by Activating Cannabinoid Receptors

Finally identifying a mechanism of action, the researchers found that THC requires the CB1 and GPR18 cannabinoid receptors to lower eye pressure.

They also found that the levels of these two receptors are lower in female mice than male mice. This could explain the surprising sex-dependent effect of THC on eye pressure.

CBD Interferes with the Effects of THC on Eye Pressure

The effect of CBD on eye pressure is complex but intriguing.

When the researchers treated mice with CBD, their eye pressure went up. This result is similar to another previously published study.

Remember: CBD can activate one eye pressure-regulating cannabinoid receptor (GPR18), but it inhibits another (CB1). As we just learned, both of these receptors regulate eye pressure via THC.

When the researchers treated mice with CBD but mutated the CB1 receptor, eye pressure actually went DOWN.

When they got rid of both CB1 and GPR18, eye pressure stayed the same.

This means that CBD has a complex, dual role in regulating eye pressure. But under normal conditions, it acts to increase eye pressure—the opposite effect of THC.

When both THC and CBD were applied, there was no effect on eye pressure. So when applied together, CBD opposes the eye pressure-lowering effect of THC.

Closing Thoughts

In one swoop, this study accomplished quite a few feats.

First, it managed to identify a mechanism for the long known positive effect of cannabis on glaucoma-related eye pressure.

Second, this study uncovered a completely unknown sex-dependent effect of THC on eye pressure. Several early studies tested the efficacy of topical THC in male and female glaucoma patients but failed to show significant effects. In light of the results of this new study, the topic deserves to be revisited.

Third, it managed to tease apart the subtle differences that THC and CBD have on eye pressure.

Interestingly, this is not the first time that THC and CBD have been shown to have opposing actions. One prime example is anxiety—CBD can alleviate anxiety while THC can exacerbate it. It will be interesting to see what further research reveals about the yin and yang relationship of THC and CBD.

If there is one thing to take away from this study it would be in regards to CBD. Cannabidiol has been considered favorably at best and harmless at worst. However, it’s important to realize that its effects may not always be benign, especially for those with pre-existing conditions like glaucoma. As more studies are done, more symptomatic conflicts may arise.

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