GAT229 is a positive allosteric modulator of cannabinoid receptor 1 (CB) and the S-(–) enantiomer of the CB modulator GAT211. It does not activate the receptor on its own but enhances the binding and activity of CB agonists. GAT229 (1 µM) enhances the binding of the CB full agonist CP 55,940 to CHO cells expressing human recombinant CB (hCB), as well as the activity of 2-arachidonoyl glycerol (2-AG; ), arachidonoyl ethanolamide (AEA; ), and CP 55,940 in arrestin2 recruitment assays and increases ERK1/2 and PLCβ3 phosphorylation in HEK293 cells expressing hCB GAT229 (1 μM) enhances depolarization-induced suppression of excitation but does not inhibit excitatory postsynaptic currents (EPSCs) in murine autaptic hippocampal neurons. GAT229 (0.2%, topical) reduces intraocular pressure by 5.8 and 7.7 mm Hg after 6 and 12 hours, respectively, in a transgenic mouse model of ocular hypertension using nose, ear, eye mutation (nee) mice.