Opiates derived from the opium poppy, Papaver somniferum, have been used in for millenia for their anti-diarrheal, analgesic and euphoric properties. More recently, endogenous peptides, enkephalins, dynorphins, and endorphins, were found to bind to the same sites as opiate alkaloids. The receptors for the classical opioids are three related GPCRs, delta, kappa, and mu, also known as OP1, OP2 and OP3, resepctively, that activate Gi/o to reduce intracellular cAMP levels. Although most clinically used opioids function by activation of the mu opioid receptor, agonits of spinal opioid receptors have antinociceptive activity that is independent of mu. In addition, activation of increases locomotor activity, inhibits gastrointestinal motility, and decreases respiratory frequency. Agonists for opioid receptors also exhibit antidepressant-like activity in animal models.