Palmitoylethanolamide (PeaPure, PeaVera, Visimast) reduces high ocular pressure (glaucoma)

Glaucoma is the second most prevalent cause of blindness worldwide. Although several factors are involved in the pathogenesis of glaucoma, the main therapeutic strategy is actually based on intraocular pressure (IOP) reduction.

Treatment with PEA (PeaPure, Visimasr) can reduce intraocular pressure without side effects. This was the result of a clinical placebo-controlled trial. The researchers ivestigated the effect of systemic administration of PEA on IOP in patients with ocular hypertension and primary open glaucoma (POAG).

Forty-two patients were enrolled in a prospective, randomized, double-blind, crossover clinical trial held at the Institute of Ophthalmology of the University of Catania, Italy.

PEA is synthesized during inflammation and tissue damage, and it shares with AEA anti-inflammatory, analgesic, and antioxidant properties. PEA is a component of the tissue-protective mechanisms acting through the downregulation of mediator release from mast cells. It prevents mast cell degranulation, through an autocoid local injury antagonism mechanism; the anti-inflammatory effect is mediated by the action on mast cells and by its binding to peroxisome proliferator-activated receptor alpha. It is also a ligand for the orphan GPR55 receptor. The relief of neuropathic pain could be mediated through action on receptors located on the nociceptive pathway and on mast cells.


Of the 42 patients enrolled in this trial, 21 received first PEA and 21 received placebo. All patients concluded the study. At baseline, no significant difference was seen between the two groups in age, sex, best-corrected visual acuity, CCT, vertical C/D ratio, MD, PSD, or mean circadian IOP value.

PEA treatment reduced IOP significantly (ANOVA, P < 0.001). At baseline, the mean IOP ± SD was 21.6 ± 1.7 mm Hg; at 1 and 2 months, respectively, the mean IOP was 18.4 ± 1.8 mm Hg and 18.1 ± 1.4 mm Hg (both Tukey-Kramer, P < 0.01 vs. baseline), and the mean IOP reduction was 3.2 ± 1.3 mm Hg (14.7% ± 6.1%) and 3.5 ± 1.2 mm Hg (15.9% ± 5.1%)

Treatment with placebo did not significantly change the IOP (ANOVA, ns) (mean IOP ± SD at baseline, 21.5 ± 1.5 mm Hg). At 1 and 2 months, respectively, the mean IOP was 21.1 ± 1.6 mm Hg and 21.2 ± 1.7 mm Hg, and the mean IOP reduction was 0.4 ± 1.2 mm Hg (1.8% ± 5.5%) and 0.3 ± 1.3 mm Hg (1.2% ± 6.2%).

IOP was significantly lower in PEA-treated subjects than in placebo-treated subjects at all time points (t-test P < 0.001). No statistically significant changes were seen in best-corrected visual acuity, CCT, vertical C/D ratio, MD, or PSD. No severe adverse events were recorded; adverse events included influenza (two subjects). One subject had dyspepsia that regressed with regular assumption of the tablets after meals; no changes were found in answers on the MDQ questionnaire.


In conclusion, systemic administration of PEA reduces IOP in patients with glaucoma and ocular hypertension; mild adverse events were recorded. The decrease in IOP was 16% of baseline IOP, not much different from that of some ocular hypotensive drugs currently used (topical CAI, alpha agonists). This suggests that PEA, a drug of a class that has been proposed for the treatment of glaucoma but that is not used because of concerns about side effects, could be a valuable tool in the treatment of such disease.

Source: Gagliano C, Ortisi E, Pulvirenti L, Reibaldi M, Scollo D, Amato R, Avitabile T, Longo A. Ocular hypotensive effect of oral palmitoyl-ethanolamide: a clinical trial. Invest Ophthalmol Vis Sci. 2011 Aug 3;52(9):6096-100. doi: 10.1167/iovs.10-7057.

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