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Anandamide may mediate sleep induction

Nature volume 389, pages 25–26 (1997)Cite this article

We report here that oleamide, a putative sleep factor1, and anandamide, an endogenous cannabinoid ligand2,3, cause similar pharmacological effects in mice. Only anandamide binds to the cannabinoid CB1receptor but by inhibiting the enzyme which inactivates anandamide (thus increasingits concentration), oleamide potentiates anandamide binding to CB1enhancing anandamide effects in mice. Our observations raise the possibility that some oleamide effects (including induction of sleep) may be mediated by anandamide.

Cravatt et al. identified and reported the sleep-inducing properties of oleamide, a lipid found in the cerebrospinal fluid of sleep-deprived cats1; and we have isolated and characterized anandamide, a lipid from the brain which is an agonist for the cannabinoid receptor2,3. Drowsiness or sleepiness are well-known effects in the later stages of intoxication by marijuana, whose active constituent, Δ9-tetrahydrocannabinol (Δ9-THC), and anandamide have a close biochemical and behavioural profile. Both substances bind to the brain cannabinoid receptor, CB1 (2–4).

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Figure 1: Dose-dependent inhibition of [14C]anandamide hydrolysis by N18TG2 cell 10,000g particulate fractions.

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Authors and Affiliations

  1. Department of Natural Products, David Bloom Centre for Pharmacy, Faculty of Medicine, Hebrew University, Jerusalem, 91120, Israel

    Raphael Mechoulam, Ester Fride, Lumir Hanu & Tzviel Sheskin

  2. Istituto per la Chimica di Molecole di Interesse Biologico, Via Toiano 6, Arco Felice, 80072, Naples, Italy

    Tiziana Bisogno & Vincenzo Di Marzo

  3. Department of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Michael Bayewitch & Zvi Vogel

Authors
  1. Raphael Mechoulam
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  2. Ester Fride
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  3. Lumir Hanu
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  4. Tzviel Sheskin
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  5. Tiziana Bisogno
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  6. Vincenzo Di Marzo
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  7. Michael Bayewitch
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  8. Zvi Vogel
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Mechoulam, R., Fride, E., Hanu, L. et al. Anandamide may mediate sleep induction. Nature 389, 25–26 (1997). https://doi.org/10.1038/37891

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