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Cited by 104Cannabis and Cannabinoid ResearchEicosanoids and Hypertension PharmacologyFatty Acid Research and Health

Fatty Acid Amide Hydrolase: A Gate-Keeper of the Endocannabinoid System

Fezza, Filomena, De Simone, Chiara, Amadio, Daniele, Maccarrone, Mauro·2008·Subcellular Biochemistry
DOI 10.1007/978-1-4020-8831-5_4
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Abstract

The family of endocannabinoids contains several polyunsaturated fatty acid amides such as anandamide (AEA), but also esters such as 2-arachidonoylglycerol (2-AG). These compounds are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta9-tetrahydrocannabinol (Delta9-THC), the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA at its receptors is limited by cellular uptake, through a putative membrane transporter, followed by intracellular degradation by fatty acid amide hydrolase (FAAH). Growing evidence demonstrates that FAAH is the critical regulator of the endogenous levels of AEA, suggesting that it may serve as an attractive therapeutic target for the treatment of human disorders. In particular, FAAH inhibitors may be next generation therapeutics of potential value for the treatment of pathologies of the central nervous system, and of peripheral tissues. Investigations into the structure and function of FAAH, its biological and therapeutic implications, as well as a description of different families of FAAH inhibitors, are the topic of this chapter.

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Crossref · 10.1007/978-1-4020-8831-5_4

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  • FAAH hydrolyzes PEA, which does not bind cannabinoid receptors but functions as an endogenous ligand for PPAR-α.

    “Besides serving as the major catabolic enzyme of AEA, FAAH hydrolyzes other bioactive lipids, such as N-palmitoylethanolamine (PEA) (Fezza et al, 2008), which does not bind cannabinoid receptors, but functions as an endogenous ligand for peroxisome proliferator receptor-α (PPAR-α) (Lo Verme et al, 2005).”

    From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Fezza et al, 2008

  • FAAH is the principal catabolic enzyme for fatty-acid amides including anandamide and N-palmitoylethanolamine.

    “Fatty-acid amide hydrolase (FAAH) is the principle catabolic enzyme for fatty-acid amides including AEA and N-palmitoylethanolamine (PEA).25”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [25]

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Authors
Fezza, F., De Simone, C., Amadio, D., & Maccarrone, M.
Affiliations
University of Rome Tor Vergata (IT)
ORCID
Venue
Subcellular Biochemistry
Publisher
Springer Netherlands
Published
2008
Volume
49
Pages
101-132
ISSN
0306-0225 (ISSN-L)
DOI
10.1007/978-1-4020-8831-5_4
OpenAlex
W97923480
Cited by
99
References
156
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 7 · 2014: 8 · 2013: 7 · 2012: 8
FWCI
44.84
Type
book chapter
Language
en
Open access
closed
Locations
  • Sub-cellular biochemistry/Subcellular biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
fatty acid amide hydrolase, endocannabinoid system, anandamide, 2-arachidonoylglycerol, FAAH inhibitors, cannabinoid receptors, delta-9-tetrahydrocannabinol, membrane transporters, intracellular degradation, therapeutic target, central nervous system disorders
MeSH terms
Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Gene Expression Regulation, Humans, Models, Molecular, Receptors, Cannabinoid, Cannabinoid Receptor Modulators, Endocannabinoids

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