In Silico and In Vitro Analysis of Major Cannabis-Derived Compounds as Fatty Acid Amide Hydrolase Inhibitors

Emanuele Criscuolo, Maria Laura De Sciscio, Filomena Fezza, Mauro Maccarrone

Research output: Contribution to journalArticlepeer-review

Abstract

Accumulated evidence suggests that enhancing the endocannabinoid (eCB) tone, in particular of anandamide (N-arachidonoylethanolamine, AEA), has therapeutic potential in many human diseases. Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme principally responsible for the degradation of AEA, and thus it represents a relevant target to increase signaling thereof. In recent years, different synthetic and natural compounds have been developed and tested on rat FAAH, but little is known of their effect on the human enzyme. Here, we sought to investigate six major cannabis-derived compounds to compare their action on rat and human FAAHs. To this aim, we combined an in silico analysis of their binding mode and affinity, with in vitro assays of their effect on enzyme activity. This integrated approach allowed to disclose differences in efficacy towards rat and human FAAHs, and to highlight the role of key residues involved in the inhibition of both enzymes. This study suggests that the therapeutic efficacy of compounds targeted towards FAAH should be always tested in vitro on both rat and human enzymes.

Original languageEnglish
JournalMolecules (Basel, Switzerland)
Volume26
Issue number1
DOIs
Publication statusPublished - Dec 24 2020

Keywords

  • cannabinoids
  • docking
  • endocannabinoids
  • FAAH
  • inhibition
  • modeling

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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