Annual Update in Intensive Care and Emergency Medicine 2011

Conclusion
Taken together, the evidence suggests that release of endocannabinoids and activation
of cannabinoid receptors occurs during intestinal inflammation and sepsis
and that manipulation of the endocannabinoid system may represent an important
therapeutic target in managing sepsis and microcirculatory disturbances.
However, it remains essential to resolve whether activation of cannabinoid receptors
is pro- or anti-inflammatory in sepsis and which receptor subtypes (CB2R
and/or CB1R or non-CB1R/CB2R) are individually or collectively involved in
mediating these actions.
References
The Endocannabinoid System 23
1. Hanus LO (2008) Pharmacological and therapeutic secrets of plant and brain (endo) cannabinoids.
Med Res Rev 29: 213–271
2. Gaoni Y, Mechoulam R (1964) Isolation, structure and partial synthesis of an active constituent
of hashish. J Am Chem Soc 86: 1646–1647
3. Mechoulam R, Gaoni Y (1967) The absolute configuration of delta-1-tetrahydrocannabinol,
the major active constituent of hashish. Tetrahedron Lett 12: 1109–1111
4. Jones G, Pertwee RG, Gill EW, et al (1974) Relative pharmacological potency in mice of
optical isomers of delta 1-tetrahydrocannabinol. Biochem Pharmacol 23: 439–446
5. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid
receptor and functional expression of the cloned cDNA. Nature 346: 561–564
6. Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral
receptor for cannabinoids. Nature 365: 61–65
7. Van Sickle MD, Duncan M, Kingsley PJ, et al (2005) Identification and functional characterization
of brainstem cannabinoid CB2 receptors. Science 310: 329–332
8. Julien B, Grenard P, Teixeira-Clerc F, et al (2005) Antifibrogenic role of the cannabinoid
receptor CB2 in the liver. Gastroenterology 128: 742–755
9. Juan-Pico P, Fuentes E, Bermudez-Silva FJ, et al (2006) Cannabinoid receptors regulate
Ca(2+) signals and insulin secretion in pancreatic beta-cell. Cell Calcium 39: 155–162
10. Ofek O, Karsak M, Leclerc N, et al (2006) Peripheral cannabinoid receptor, CB2, regulates
bone mass. Proc Natl Acad Sci USA 103: 696–701
11. Di Marzo V (2009) The endocannabinoid system: its general strategy of action, tools for
its pharmacological manipulation and potential therapeutic exploitation. Pharmacol Res
60: 77–84
12. Stella N (2010) Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and
astrocytomas. Glia 58: 1017–1030
13. O’Sullivan SE (2007) Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated
receptors. Br J Pharmacol 152: 576–582
14. Maccarrone M, Gasperi V, Catani MV, et al (2010) The endocannabinoid system and its
relevance for nutrition. Ann Rev Nutr 30: 423–440
15. Kinsey SG, Long JZ, O’Neal ST, et al (2009) Blockade of endocannabinoid-degrading
enzymes attenuates neuropathic pain. J Pharmacol Exp Ther 330: 902–910
16. Bisogno T, Howell F, Williams G, et al (2003) Cloning of the first sn1-DAG lipases points
to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell
Biol 163: 463–468
17. De Petrocellis L, Di Marzo V (2009) An introduction to the endocannabinoid system:
from the early to the latest concepts. Best Pract Res Clin Endocrinol Metab 23: 1–15
18. Di Pasquale E, Chahinian H, Sanchez P, Fantini J (2009) The insertion and transport of
anandamide in synthetic lipid membranes are both cholesterol-dependent. PloS ONE
4:e4989
19. Massi P, Valenti M, Vaccani A, et al (2008) 5-Lipoxygenase and anandamide hydrolase
(FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid.
J Neurochem 104: 1091–100
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