THC lowered eye pressure by 28% in male mice, but CBD counteracted this effect and showed sex-dependent differences | Research

The takeaway

A mouse study found that topical THC lowered intraocular pressure by about 28% for 8 hours via CB1 and GPR18 receptors, with stronger effects in males. CBD had two opposing effects on eye pressure and prevented THC from lowering it.

Ophthalmologists treating glaucoma; cannabis researchers studying cannabinoid receptor pharmacology; patients considering cannabis for glaucoma.

CBD prevented THC from lowering eye pressure, challenging cannabis-for-glaucoma assumptions

What the researchers found

Researchers tested topical THC and CBD on intraocular pressure (IOP) in mice.

A single topical application of THC lowered IOP by approximately 28% for 8 hours in male mice. This effect was mediated by combined activation of two receptors: CB1 and GPR18.

The effect was sex-dependent: THC lowered IOP more in males than females. mRNA levels of both CB1 and GPR18 receptors were higher in male mouse eyes, potentially explaining the sex difference.

CBD was not simply inactive as previously assumed. It had two opposing effects on eye pressure: one that could lower it and one that could raise it.

Most importantly, CBD prevented THC from lowering IOP. This has significant implications for cannabis-based glaucoma treatments, as products containing both THC and CBD (which includes most whole-plant cannabis) may be less effective than THC alone.

Why it matters

Cannabis has been used for glaucoma for decades, but this study reveals that CBD may actually counteract THC's beneficial IOP-lowering effect. This means whole-plant cannabis or CBD-rich products could be counterproductive for glaucoma, and sex differences may affect treatment response.

The numbers in context

THC lowered IOP by ~28% for 8 hours in male mice. Effect mediated by CB1 and GPR18 receptors. Stronger in males (higher CB1 and GPR18 mRNA in male eyes). CBD prevented THC from lowering IOP.

How the study worked

Mouse study using tonometry to measure IOP after topical application of THC and CBD. mRNA expression analysis of cannabinoid receptors. Lipid analysis of CBD treatment effects. Tested in both male and female mice.

What this study cannot tell us

Mouse study may not translate directly to human eyes. Topical application in mice differs from how humans typically use cannabis. The sex difference needs confirmation in humans. The mechanism by which CBD blocks THC's IOP effect is not fully characterized.

How to read the evidence

Moderate. Well-designed mechanistic study with receptor identification and sex-difference characterization, but mouse model needs human confirmation.

When this study was published

Published in 2018. The finding that CBD opposes THC's IOP effects was a significant contribution to understanding cannabis-glaucoma interactions.

The bigger picture

The finding that CBD blocks THC's IOP-lowering effect challenges the popular notion that whole-plant cannabis is always superior to isolated compounds. For glaucoma specifically, pure THC may be more effective than THC/CBD combinations.

Questions still open

Do human eyes show the same sex-dependent response to THC? Could topical THC eye drops be developed without CBD? Does the CBD-THC interaction apply to IOP effects in humans?

Common questions

Should people use cannabis for glaucoma?

This study suggests that whole-plant cannabis containing both THC and CBD may not effectively lower eye pressure because CBD blocks THC's beneficial effect. THC alone lowered pressure significantly, but practical challenges (short duration of effect, psychoactive properties) remain barriers to cannabis-based glaucoma treatment.

Why does sex matter for this effect?

Male mouse eyes had higher levels of both CB1 and GPR18 receptors, which are the targets through which THC lowers eye pressure. This meant THC worked better in males. If this translates to humans, cannabis-based glaucoma treatments might work differently in men versus women.

Read the original research

Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.

Investigative ophthalmology & visual science, 59(15), 5904-5911

View on PubMed ↗Publisher’s paper ↗

Citation

Miller, Sally; Daily, Laura; Leishman, Emma; Bradshaw, Heather; Straiker, Alex. (2018). Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.. Investigative ophthalmology & visual science, 59(15), 5904-5911. https://doi.org/10.1167/iovs.18-24838