ArticleThe Journal of pharmacology and experimental therapeutics2011
Indirect sympatholytic actions at β-adrenoceptors account for the ocular hypotensive actions of cannabinoid receptor agonists.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- The endocannabinoid system and ophthalmic pathologies: a review of molecular mechanisms and its implications for clinical practice.Frontiers in medicine · 2025Review
- The Relationship Between Plasma Tetrahydrocannabinol Levels and Intraocular Pressure in Healthy Adult Subjects.Frontiers in medicine · 2021Article
- Endocannabinoid metabolism and transport as targets to regulate intraocular pressure.Experimental eye research · 2020Article
- Application of Fluorine- and Nitrogen-Walk Approaches: Defining the Structural and Functional Diversity of 2-Phenylindole Class of Cannabinoid 1 Receptor Positive Allosteric Modulators.Journal of medicinal chemistry · 2020Article
- Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.Investigative ophthalmology & visual science · 2018Article
- Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options.Neuronal signaling · 2018Review
- Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure.Pharmaceuticals (Basel, Switzerland) · 2018Article
- Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative Diseases.Current neuropharmacology · 2018Review
- The In Vivo Effects of the CBJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2017Article
- A GPR119 Signaling System in the Murine Eye Regulates Intraocular Pressure in a Sex-Dependent Manner.Investigative ophthalmology & visual science · 2017Article
- Evidence for a GPR18 Role in Diurnal Regulation of Intraocular Pressure.Investigative ophthalmology & visual science · 2016Article
- Harnessing the Endocannabinoid 2-Arachidonoylglycerol to Lower Intraocular Pressure in a Murine Model.Investigative ophthalmology & visual science · 2016Article
- The Endocannabinoid System as a Therapeutic Target in Glaucoma.Neural plasticity · 2016Review
- Turning Down the Thermostat: Modulating the Endocannabinoid System in Ocular Inflammation and Pain.Frontiers in pharmacology · 2016Review
- The intraocular pressure-lowering properties of intravenous paracetamol.Clinical ophthalmology (Auckland, N.Z.) · 2016Article
- Cannabinoid-induced chemotaxis in bovine corneal epithelial cells.Investigative ophthalmology & visual science · 2015Article
- A GPR18-based signalling system regulates IOP in murine eye.British journal of pharmacology · 2013Article
- New therapeutic targets for intraocular pressure lowering.ISRN ophthalmology · 2013Review
- Role of Endocannabinoids in Glaucoma: A Review.Journal of current glaucoma practiceReview
- Marijuana for glaucoma treatment: a recipe for disaster.Arquivos brasileiros de oftalmologiaArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Intraocular pressure (IOP) is the primary risk factor for glaucoma, a blinding eye disease. Cannabinoid agonists have long been known to decrease IOP, suggesting they may be useful in glaucoma treatment. However, the specific mechanism by which cannabinoids generate this ocular hypotensive effect remains unknown. The current evidence suggests the cannabinoids reduce IOP through actions at cannabinoid 1 (CB(1)) receptors within the eye, and adrenergic receptors (ARs) may also contribute to this action of cannabinoids. Considering this, the present study aimed to elucidate the mechanism behind the ocular hypotensive properties of cannabinoids through the use of mice genetically lacking either cannabinoid receptors or βARs. Cannabinoid agonists, βAR antagonists, and βAR agonists decreased IOP in wild-type mice and CB(2)(-/-) mice. In contrast, none of these compounds were found to reduce IOP in βAR(-/-) or CB(1)(-/-) mice. Desensitization of the βARs and depletion of catecholamines in wild-type mice also eliminated the ability of the cannabinoid agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) to reduce IOP, strongly implicating a role for both βARs and catecholamines in the ocular hypotensive properties of cannabinoids. Finally, CB(1) receptors were shown to colocalize with tyrosine hydroxylase, a marker for adrenergic neurons. Taken together, these findings suggest that βARs are required for the ocular hypotensive properties of cannabinoids, and cannabinoids reduce IOP by acting as indirect sympatholytics and inhibiting norepinephrine release within the eye.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.