Regular Article
Oxidative metabolism of endocannabinoids

https://doi.org/10.1054/plef.2001.0359Get rights and content

Abstract

There is increasing evidence that endocannabinoids play roles in a number of physiological and pathological processes ranging from the regulation of food intake to the inhibition of cancer cell proliferation. Consequently, multiple investigations into endocannabinoid metabolic disposition have been initiated. Such studies have begun to shed light on the mechanisms that regulate the endogenous cannabinoid system. In addition, they have identified a number of novel, endocannabinoid-derived lipids. In the future, these studies may form the foundation of efforts designed to subtly manipulate endocannabinoid tone in vivo to achieve therapeutic benefits without the profound side-effects observed with synthetic cannabinoid treatment.

In addition to the well-studied hydrolytic mode of endocannabinoid metabolism, accumulating data suggest that these lipids are also susceptible to oxidative metabolism by a number of fatty acid oxygenases. These include the cyclooxygenases, lipoxygenases, and cytochrome P450s known to be involved in eicosanoid production from arachidonic acid. The available evidence concerning endocannabinoid oxidation is reviewed and the potential biological significance of this mode of metabolism is considered.

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    This work was supported by grants from the National Foundation for Cancer Research and the National Institutes of Health (CA89450 and GM15431).

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    Correspondence to: Lawrence J. Marnett, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. Tel.: +615-343-7328; Fax: +615-343-7534; E-mail: [email protected]

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