The search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB₁) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB₁ receptor agonist, WIN 55212–2, applied topically at doses of 25 or 50 µg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 ± 0.5% and 23 ± 0.9%, respectively). A maximal reduction of 20 ± 0.7% and 31 ± 0.6%, respectively, is reached in the first 60 min. These data confirm that CB₁ receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB₁ receptor agonists should deserve further research and clinical development.

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