The pineal gland has a functional endocannabinoid system. Both CB1 and CB2 receptors, as well as the endogenous ligands that bind them, anandamide, and 2-AG, are present. The activity of the CB1 receptors varies according to a daily cycle. The lowest activity occurs at the end of the daylight period. The enzyme responsible for synthesizing new endocannabinoid molecules, NAPE-PLD, gets reduced during the middle of the dark period.