Attenuation of spontaneous opiate withdrawal in mice by the anandamide transport inhibitor AM404

Eur J Pharmacol. 2002 Nov 1;454(1):103-4. doi: 10.1016/s0014-2999(02)02483-4.


The endogenous cannabinoid, anandamide, has been shown to attenuate naloxone-precipitated opiate withdrawal in rodents. Here we show that the spontaneous, but not the naloxone-precipitated withdrawal syndrome in morphine-dependent mice is attenuated by the inhibitor of carrier-mediated anandamide transport N-(4-hydroxyphenyl) arachidonylethanolamide (AM404) (2 and 10 mg/kg, i.p.). These results suggest that spontaneous but not opioid antagonist-precipitated withdrawal is associated with dynamic changes in endogenous cannabinoid signaling.

Publication types

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

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism*
  • Arachidonic Acids / pharmacology*
  • Biological Transport / drug effects
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Endocannabinoids
  • Mice
  • Morphine Dependence / metabolism*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Polyunsaturated Alkamides
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / metabolism


  • Arachidonic Acids
  • Endocannabinoids
  • Narcotic Antagonists
  • Polyunsaturated Alkamides
  • Naloxone
  • anandamide
  • N-(4-hydroxyphenyl)arachidonylamide