Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Scientific Correspondence
  • Published:

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).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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

References

  1. Cravatt, B. F. et al. Science 268, 1506–1509(1995).

    Google Scholar 

  2. Devane, W. A. et al. Science 258, 1946–1949(1992).

    Google Scholar 

  3. Fride, E. & Mechoulam, R. Eur. J. Pharmacol. 231, 313–314(1993).

    Google Scholar 

  4. Piomelli, D. Arachidonic Acid in Cell Signaling 167–195 (Landes Co., Austin, 1996).

    Book  Google Scholar 

  5. Santucci, V., Storme, J. J., Soubrie, P. & Le Fur, G. Life Sci. 58, 103–110(1996).

    Google Scholar 

  6. Martin, B. R. et al. Pharmacol. Biochem. Behav. 40, 471–478(1991).

    Google Scholar 

  7. Boring, D. L., Berglund, B. A. & Howlett, A. C. Prostaglandins Leukot. Essent. Fatty Acids 55, 207–210(1996).

    Google Scholar 

  8. Maurelli, S. et al. FEBS Lett. 277, 82(1995).

    Google Scholar 

  9. Cravatt, B. F. et al. Nature 384, 83–87(1996).

    Google Scholar 

  10. Di Marzo, V. et al. Nature 372, 686–691(1994).

    Google Scholar 

  11. Vogel, Z. et al. J. Neurochem. 61, 352–355(1993).

    Google Scholar 

  12. di Tomaso, E., Beltramo, M. & Piomelli, D. Nature 382, 677–678(1996).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ester Fride
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lumir Hanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tzviel Sheskin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tiziana Bisogno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vincenzo Di Marzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael Bayewitch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zvi Vogel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mechoulam, R., Fride, E., Hanu, L. et al. Anandamide may mediate sleep induction. Nature 389, 25–26 (1997). https://doi.org/10.1038/37891

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/37891

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing