Is the cannabinoid system critical for newborn development? Ester Fride, Yoav Ginsburg and Raphael Mechoulam Hebrew University of Jerusalem and the College of Judea and Samaria, Israel Since endogenous cannabinoids (endocannabinoids) have been detected in milk, we hypothesized that endocannabinoids may play a role in development of the newborn. Thus, we blocked cannabinoid receptors in newborn mice by daily administration of the cannabinoid-1 (CB1) receptor antagonist SR141716A. Pups were assessed for weight gain, developmental "ear flap detachment" and the presence of "milkbands" in their stomachs. Pups injected with SR141716A did not gain weight and died within 6-8 days after birth. Development of ear-flap detachment was delayed. Co-administration of the CB1 receptor agonist THC (delta9-tetrahydrocannabinol) prevented SR141716A-induced effects. The endocannabinoid 2-AG (2-arachidonoyl glycerol) increased weight gain on day 9 of life but did not reverse the growth-inhibiting effects of SR141716A. The synthetic 2-AG analog (HU-313), having a longer half life than 2-AG, increased weight gain more dramatically than 2-AG. Maternal behavior of the dams was not different towards SR141716A-treated newborns compared to controls. However, milkbands were detected only in 15% of the SR141716A-treated pups (compared to 100% in controls), indicating that experimental pups obtained far less maternal milk than normal. We conclude that endocannabinoids in maternal milk may play a critical role in the physical growth of newborns. Keywords: cannabinoids, development, ontogeny, behavioral pharmacology, feeding

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