Oleamide is an amide of oleic acid and an agonist of cannabinoid 1 (CB1) receptors (Ki = 8.13 µM in a radioligand binding assay).¹ It is selective for CB1 over CB2 receptors, where it inhibits binding of the CB receptor full agonist CP 55,940 by only 42.5% in HEK-293T cells expressing human CB2 receptors when used at a concentration of 100 µM. Oleamide (10 µM) inhibits cAMP accumulation induced by forskolin in N1E 115 mouse neuroblastoma cells, an effect that is reversed by the CB1 antagonist SR141716A. Oleamide was first identified in the cerebrospinal fluid of sleep-deprived cats, and it has also been detected in the cerebrospinal fluid of rats and humans.² In rats, it induces physiological sleep when administered at doses ranging from 5 to 50 mg and increases food intake when administered into the nucleus accumbens shell, and in group-housed and socially isolated mice, it has anxiolytic-like effects.^2,3,4 Oleamide also induces transactivation of PPARα, PPARβ, and PPARγ and inhibits activity of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) at concentrations in the low micromolar range.⁵