Plasma THC Levels Associated With Reduced Intraocular Pressure in Healthy Adults

Inhaled cannabis and intravenous delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, have been shown to lower intraocular pressure (IOP) in past research — although THC has not yet been adopted as a treatment for elevated IOP in clinical practice. A study published in Frontiers in Medicine aimed to define the relationship between plasma THC levels and IOP in healthy adults.

One reason for the lack of clinical adoption is the poor corneal penetration of available topically administered, pharmaceutical formulations of THC. In a recent double-blind, randomized study, inhaled THC reduced IOP by 16%. A new analysis of the same study group assessed the correlation between plasma THC levels and IOP, and it is the first to do so to the authors’ knowledge.

In total, 300 people were screened and 11 were enrolled in the IOP portion of the study. Eligible participants included healthy adults older than 21 years who were licensed drivers, had driven 1000 miles in the previous year, and were regular cannabis smokers, having used it at least 4 times in the previous month. Participants also had to abstain from cannabis for 2 days before the baseline screening visit and the experimental visit.

During the experimental visit, participants received a cannabis cigarette to smoke “the way they do at home to get high,” with a minimum of 4 puffs required over 10 minutes. Participants had their IOP measured and completed driving simulations, iPad-based performance assessments, and bodily fluid draws both before smoking and in the 6 hours after smoking during the experimental visit.

Plasma levels of THC were measured before smoking, then approximately 12, 40, 80, and 120 minutes and every hour for 3 hours after smoking. At each time point, 3 IOP readings were averaged for each eye using the FDA-approved noncontact Reichert Ocular Response Analyzer.

Twenty-two eyes from the 11 participants were included in the final analysis. The average peak plasma THC level, 45 ng/mL, occurred at approximately 12 minutes post smoking and rapidly declined afterward. By 55 minutes after smoking, levels declined to less than 10 ng/mL on average.

There was a strong negative correlation between plasma THC levels and IOP. The average IOP before participants smoked cannabis was 17.5 mm Hg. Afterward, IOP levels dropped 7% to 16%, with the greatest drop seen at 60 minutes after smoking. As plasma THC levels decreased over time, IOP levels increased. Overall, IOP levels remained significantly lowered for 4 hours after cannabis inhalation even as THC levels dropped.

Notably, increasing plasma levels up to 20 ng/mL were strongly correlated with decreased IOP, but plasma THC levels above 20 ng/mL did not correlate with further reduction in IOP.

Although a strong negative correlation between plasma THC levels and IOP was identified in this study, the mechanism behind the effect of THC on IOP is still being investigated. The systemic and psychoactive effects of smoking cannabis are also a limiting factor of adoption in clinical practice, according to the study authors.

“Given the wide range of systemic considerations, the routine use of inhaled or ingested cannabis for glaucoma treatment has not been clinically practical,” they wrote. “However, novel compounds with improved corneal penetration are being developed for topical administration, thereby mitigating systemic side effects.”

This study is limited by the exclusion of patients with glaucoma or ocular hypertension or those on IOP-lowering medications. Defining the effects of cannabis on IOP in such patients requires further research, the authors concluded.

Reference

Mosaed S, Smith AK, Liu JHK, et al. The Relationship Between Plasma Tetrahydrocannabinol Levels and Intraocular Pressure in Healthy Adult Subjects. Front Med (Lausanne). Published online January 17, 2022. doi:10.3389/fmed.2021.736792