Endogenous cannabinoid, 2-arachidonoylglycerol, attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice

Taku Yamaguchi, Yumi Hagiwara, Hiroyuki Tanaka, Takayuki Sugiura, Keizo Waku, Yukihiro Shoyama, Shigenori Watanabe, Tsuneyuki Yamamoto

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88 Citations (Scopus)


In the present study, we examined the effects of endogenous ligand 2-arachidonoylglycerol (2-AG) on naloxone-precipitated withdrawal in morphine-dependent mice, in comparison with that of two cannabinoid agonists, an ingredient of Cannabis sativa Δ8-tetrahydrocannabinol (Δ8-THC) and the synthetic cannabinoid CB1 receptor agonist HU-210. 2-AG at a dose of 10 μg per mouse (i.c.v.) significantly inhibited both jumping and forepaw tremor as signs of withdrawal following naloxone challenge in morphine-dependent mice. Furthermore, both Δ8-THC and HU-210 significantly attenuated these symptoms of withdrawal in morphine-dependent mice. Therefore, it is suggested that inactivation of the endogenous cannabinoid system is related to the induction of withdrawal syndrome in morphine-dependent mice. Moreover, hyperlocomotor activity in morphine-dependent mice was markedly increased by Δ8-THC 10 mg/kg, which had no effect in naive mice. This finding suggested that in morphine dependence, upregulation of cannabinoid CB1 receptors occurred. Non-psychoactive CB1 receptor agonists or accelerators of endocannabinoid synthesis may be potential as therapeutic drugs for opiate withdrawal symptoms.

Original languageEnglish
Pages (from-to)121-126
Number of pages6
JournalBrain Research
Issue number1-2
Publication statusPublished - Aug 3 2001

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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