Biphasic effects of anandamide

Pharmacol Biochem Behav. 1998 Feb;59(2):347-52. doi: 10.1016/s0091-3057(97)00422-x.


Effects of the endogenous cannabimimetic anandamide were assessed over a wide dose range in a series of physiological and behavioral assays. These included the tetrad of tests in mice commonly used to assess cannabinoid-induced effects (motor activity, ring catalepsy, hypothermia, and analgesia tests), as well as a model for agonistic behavior on dyadic interactions of singly housed males with nonaggressive group-housed partners. Anandamide-induced effects on leukocyte phagocytosis were measured in a chemiluminescence assay. Results indicated that the higher doses tested (10-100 mg/kg) produced the well-known inhibitory effects in all of the above parameters as well as inhibition of phagocytosis. The lowest dose of anandamide tested (0.01 mg/kg) stimulated behavioral activities in the open field, on the ring and aggressive behavior in timid singly housed mice. This dose of 0.01 mg/kg, also stimulated phagocytosis. We suggest several possible mechanisms to explain these findings such as a differential involvement of a Gs and a Gi protein activated at low and high doses, respectively, allosteric modulation of the cannabinoid, and activation of presynaptic cannabinoid receptors by low doses of anandamide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aggression / drug effects
  • Animals
  • Arachidonic Acids / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Cannabinoids / pharmacology*
  • Catalepsy / chemically induced
  • Defecation / drug effects
  • Dose-Response Relationship, Drug
  • Endocannabinoids
  • Female
  • Leukocytes / drug effects
  • Luminescent Measurements
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Motor Activity / drug effects
  • Pain Measurement / drug effects
  • Phagocytosis / drug effects
  • Polyunsaturated Alkamides


  • Arachidonic Acids
  • Calcium Channel Blockers
  • Cannabinoids
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • anandamide