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.

Part I: The Endocannabinoid System, Mechanisms of Action and Functions

Endocannabinoids, feeding and suckling – from our perspective

Abstract

In this overview we have summarized some aspects of our published work related to the effects of the endocannabinoid system on appetite and suckling. As noted also by several other groups we have found that anandamide, a major endocannabinoid, enhances appetite in mice. On partial or full food deprivation over 24 h the levels of 2-arachidonoyl glycerol (2-AG), a second major cannabinoid, are initially elevated in mouse brain; however, partial food deprivation over a longer period causes reduction of 2-AG levels. Blocking the endocannabinoid system with a CB1 antagonist on the 1st day after birth leads to inhibition of suckling; later administration also affects suckling, but does not fully block it.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

References

  1. Mechoulam R . The Pharmacohistory of Cannabis sativa. In: Mechoulam R (ed), The Cannabinoids as Therapeutic Agents. CRC Press Inc.: Boca Raton, FL, 1986, pp 1–19.

    Google Scholar 

  2. Gaoni Y, Mechoulam R . Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646–1647.

    Article  CAS  Google Scholar 

  3. Di Tomaso E, Beltramo M, Piomelli D . Brain cannabinoids in chocolate. Nature 1996; 382: 677–678.

    Article  CAS  Google Scholar 

  4. Di Marzo V, Sepe N, De Petrocellis L, Berger A, Crozier G, Fride E et al. Trick or treat from food endocannabinoids? Nature 1998; 396: 636.

    Article  CAS  Google Scholar 

  5. Fride E, Ginzburg Y, Breuer A, Bisogno T, Di Marzo V, Mechoulam R . Critical role of the endogenous cannabinoid system in mouse pup suckling and growth. Eur J Pharmacol 2001; 419: 207–214.

    Article  CAS  Google Scholar 

  6. Zimmer A, Zimmer AM, Hohmann AG, Herkenhanm M, Bonner TI . Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 1999; 96: 5780–5785.

    Article  CAS  Google Scholar 

  7. Petrov ES, Varlinskaya EI, Smotherman WP . Endogenous opioids and the first suckling episode in the rat. Dev Psychobiol 1998; 33: 175–183.

    Article  CAS  Google Scholar 

  8. Contos JJ, Fukushima N, Weiner JA, Kaushal D, Chun J . Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc Natl Acad Sci USA 2000; 97: 13384–13389.

    Article  CAS  Google Scholar 

  9. Moolenaar WH . Development of our current understanding of bioactive lysophospholipids. Ann NY Acad Sci 2000; 905: 1–10.

    Article  CAS  Google Scholar 

  10. Fride E, Foox A, Rosenberg E, Faigenboim M, Cohen V, Barda L et al. Milk intake and survival in newborn cannabinoid CB1 receptor knockout mice: evidence for a ‘CB3’ receptor. Eur J Pharmacol 2003; 461: 27–34.

    Article  CAS  Google Scholar 

  11. Breivogel CS, Griffin G, Di Marzo V, Martin BR . Evidence for a new G protein-coupled cannabinoids receptor in mouse brain. Mol Pharmacol 2001; 60: 155–163.

    Article  CAS  Google Scholar 

  12. Berry EM, Mechoulam R . Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacol Ther 2002; 95: 185–190.

    Article  CAS  Google Scholar 

  13. Kirkham TC, Williams CM . Endogenous cannabinoids and appetite. Nutr Res Rev 2001; 14: 65–86.

    Article  CAS  Google Scholar 

  14. Williams CM, Kirkham TC . Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacol 1999; 143: 315–317.

    Article  CAS  Google Scholar 

  15. Hao S, Avraham Y, Mechoulam R, Berry EM . Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice. Eur J Pharmacol 2002; 392: 147–156.

    Article  Google Scholar 

  16. Šulcová E, Mechoulam R, Fride E . Biphasic effects of anandamide. Pharmacol Biochem Behav 1998; 59: 347–352.

    Article  Google Scholar 

  17. Paton WDM, Pertwee RG . The pharmacology of cannabis in animals. In: Mechoulam R (ed). Marijuana, Chemistry, Pharmacology, Metabolism and Clinical Effects. Academic Press: New York, 1973, pp 191–285.

    Google Scholar 

  18. McLaughlin CL, Baile CA, Bender PE . Cannabinols and feeding in sheep. Psychopharmacol 1979; 64: 321–323.

    Article  CAS  Google Scholar 

  19. Berrendero F, Sepe N, Ramos JA, Di Marzo V, Fernandez-Ruiz JJ . Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period. Synapse 1999; 33: 181–191.

    Article  CAS  Google Scholar 

  20. Mechoulam R, Ben-Shabat S, Hanuš L, Kaminski NE, Schatz AR, Gopher A et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50: 83–90.

    Article  CAS  Google Scholar 

  21. Mechoulam R, Fride E, Ben-Shabat S, Meiri U, Horowitz M . Carbachol, an acetylcholine receptor agonist, enhances production in rat aorta of 2-arachidonoyl glycerol, a hypotensive endocannabinoid. Eur J Pharmacol 1998; 362: R1–R3.

    Article  CAS  Google Scholar 

  22. Panikashvili D, Simeonidou C, Ben-Shabat S, Hanuš L, Breuer A, Mechoulam R et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001; 413: 527–531.

    Article  CAS  Google Scholar 

  23. Kirkham TC, Williams CM, Fezza F, Di Marzo V . Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol 2002; 136: 550–557.

    Article  CAS  Google Scholar 

  24. Hanuš L, Avraham Y, Ben-Shushan D, Zolotarev O, Berry EM, Mechoulam R . Short term fasting and prolonged semistarvation have opposite effect on 2-AG levels in mouse brain. Brain Res 2003; 983: 144–151.

    Article  Google Scholar 

  25. Berger A, Crozier G, Bisogno T, Cavaliere P, Innis S, Di Marzo V . Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets. Proc Natl Acad Sci USA 2001; 98: 6402–6406.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R Mechoulam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mechoulam, R., Berry, E., Avraham, Y. et al. Endocannabinoids, feeding and suckling – from our perspective. Int J Obes 30 (Suppl 1), S24–S28 (2006). https://doi.org/10.1038/sj.ijo.0803274

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803274

Keywords

This article is cited by

Search

Quick links