Cannabinoids inhibit hypocretin neuron activity. A, In a typical cell, WIN55,212,2 (5 μm) blocked spike frequency and hyperpolarized the membrane potential. Resting membrane potential, −57.2 mV. B, The cannabinoid antagonist AM251 (5 μm) increased spike frequency and blocked WIN55,212,2-induced inhibition of spike frequency. C, Bar graph showing the effect of WIN55,212,2, anandamide, and AM251 on spike frequency. D, The CB1R antagonist AM251 reversed the effect of WIN55,212,2 on spike frequency. *p < 0.05, statistical significance. The number of cells is shown in parentheses. Error bars indicate SEM. Win, WIN55,212,2; Ctrl, control; ANA, anandamide; n.s., nonsignificant.