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Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.
Invest Ophthalmol Vis Sci 2018; 59(15):5904-5911IO

Abstract

Purpose

It has been known for nearly 50 years that cannabis and the psychoactive constituent Δ9-tetrahydrocannabinol (THC) reduce intraocular pressure (IOP). Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a major cause of blindness. THC likely acts via one of the known cannabinoid-related receptors (CB1, CB2, GPR18, GPR119, GPR55) but this has never been determined explicitly. Cannabidiol (CBD) is a second major constituent of cannabis that has been found to be without effect on IOP in most studies.

Methods

Effects of topically applied THC and CBD were tested in living mice by using tonometry and measurements of mRNA levels. In addition the lipidomic consequences of CBD treatment were tested by using lipid analysis.

Results

We now report that a single topical application of THC lowered IOP substantially (∼28%) for 8 hours in male mice. This effect is due to combined activation of CB1 and GPR18 receptors each of which has been shown to lower ocular pressure when activated. We also found that the effect was sex-dependent, being stronger in male mice, and that mRNA levels of CB1 and GPR18 were higher in males. Far from inactive, 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.

Conclusions

We conclude that THC lowers IOP by activating two receptors-CB1 and GPR18-but in a sex-dependent manner. CBD, contrary to expectation, has two opposing effects on IOP and can interfere with the effects of THC.

Authors+Show Affiliations

The Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States.The Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States.The Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States.The Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States.The Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30550613

Citation

Miller, Sally, et al. "Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure." Investigative Ophthalmology & Visual Science, vol. 59, no. 15, 2018, pp. 5904-5911.
Miller S, Daily L, Leishman E, et al. Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest Ophthalmol Vis Sci. 2018;59(15):5904-5911.
Miller, S., Daily, L., Leishman, E., Bradshaw, H., & Straiker, A. (2018). Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Investigative Ophthalmology & Visual Science, 59(15), pp. 5904-5911. doi:10.1167/iovs.18-24838.
Miller S, et al. Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest Ophthalmol Vis Sci. 2018 12 3;59(15):5904-5911. PubMed PMID: 30550613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. AU - Miller,Sally, AU - Daily,Laura, AU - Leishman,Emma, AU - Bradshaw,Heather, AU - Straiker,Alex, PY - 2018/12/15/entrez PY - 2018/12/15/pubmed PY - 2018/12/15/medline SP - 5904 EP - 5911 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 59 IS - 15 N2 - Purpose: It has been known for nearly 50 years that cannabis and the psychoactive constituent Δ9-tetrahydrocannabinol (THC) reduce intraocular pressure (IOP). Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a major cause of blindness. THC likely acts via one of the known cannabinoid-related receptors (CB1, CB2, GPR18, GPR119, GPR55) but this has never been determined explicitly. Cannabidiol (CBD) is a second major constituent of cannabis that has been found to be without effect on IOP in most studies. Methods: Effects of topically applied THC and CBD were tested in living mice by using tonometry and measurements of mRNA levels. In addition the lipidomic consequences of CBD treatment were tested by using lipid analysis. Results: We now report that a single topical application of THC lowered IOP substantially (∼28%) for 8 hours in male mice. This effect is due to combined activation of CB1 and GPR18 receptors each of which has been shown to lower ocular pressure when activated. We also found that the effect was sex-dependent, being stronger in male mice, and that mRNA levels of CB1 and GPR18 were higher in males. Far from inactive, 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. Conclusions: We conclude that THC lowers IOP by activating two receptors-CB1 and GPR18-but in a sex-dependent manner. CBD, contrary to expectation, has two opposing effects on IOP and can interfere with the effects of THC. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/30550613/Δ9_Tetrahydrocannabinol_and_Cannabidiol_Differentially_Regulate_Intraocular_Pressure_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.18-24838 DB - PRIME DP - Unbound Medicine ER -