The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure inhuman glaucoma resistant to conventional therapies

The search for new ocular hypotensive agents represents a frontier of curre nt eye research because blindness due to optic neuropathy occurs insidiousl y in 10% of all patients affected by glaucoma. Cannabinoids have been propo sed to lower intraocular pressure by either central or peripheral effects b ut a specific mechanism for this action has never been elucidated. We recen tly demonstrated the presence of the central cannabinoid receptor (CB1) mRN A 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 mug (n = 8), decreases the intraocular pressure of human glauc oma 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 intr aocular pressure, and suggest that, among various classes of promising anti glaucoma agents, synthetic CB1 receptor agonists should deserve further res earch and clinical development.