Affinage

FAAH

Fatty-acid amide hydrolase 1 · UniProt O00519

Length
579 aa
Mass
63.1 kDa
Annotated
2026-04-28
100 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FAAH is an integral membrane serine hydrolase that degrades anandamide and related fatty acid amides, serving as the primary catabolic enzyme controlling endocannabinoid tone in the nervous system and peripheral tissues (PMID:11106785, PMID:19389627). It functions as an allosteric homodimer in which occupation of a single active-site serine nucleophile is sufficient to block catalysis across both subunits, with tryptophan 445 at the dimer interface mediating inter-subunit communication (PMID:32041998). FAAH activity is modulated by membrane cholesterol content, which enhances substrate accessibility and enzymatic activity (PMID:24215562), and its transcription is induced by progesterone (via Ikaros), estrogen (via ERβ/LSD1-mediated epigenetic remodeling), and leptin (via a CRE-like element) (PMID:12799380, PMID:22802127, PMID:29967158). The common human C385A polymorphism reduces FAAH expression and elevates anandamide levels, enhancing fronto-amygdala connectivity, facilitating fear extinction, decreasing anxiety, and attenuating leptin-mediated hypophagia, establishing FAAH as a critical determinant of endocannabinoid signaling in pain, anxiety, metabolic regulation, and neuroinflammation (PMID:25731744, PMID:29967158, PMID:21506952, PMID:34587978).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Identification of FAAH as a serine hydrolase with an amidase catalytic domain responsible for anandamide degradation established the molecular identity and enzymatic mechanism of the primary endocannabinoid-degrading enzyme.

    Evidence cDNA cloning from rat, mouse, human, and pig with recombinant protein purification and domain analysis

    PMID:11106785

    Open questions at the time
    • No high-resolution structure yet available
    • Membrane topology and oligomeric state not resolved
    • Physiological substrate hierarchy not defined
  2. 2003 High

    Discovery that progesterone activates FAAH transcription through Ikaros binding to ERE2/3 sites, and leptin acts additively via a CRE-like element, revealed how hormonal signals control endocannabinoid tone by regulating FAAH expression.

    Evidence Promoter-reporter assays, EMSA/supershift, site-directed mutagenesis in human T lymphocytes

    PMID:12799380

    Open questions at the time
    • Physiological relevance of Ikaros-mediated regulation in non-immune cells not tested
    • Leptin-FAAH transcriptional pathway intermediates not fully mapped
  3. 2008 High

    The crystal structure of humanized rat FAAH with an inhibitor revealed the structural basis for species-selective inhibitor binding and enabled rational drug design by interconverting rat and human active sites through mutagenesis.

    Evidence X-ray crystallography at 2.75 Å resolution with site-directed mutagenesis

    PMID:18753625

    Open questions at the time
    • Full-length human FAAH structure not yet solved
    • Membrane-embedded dimer structure unknown
  4. 2009 High

    Demonstration that PF-3845 covalently carbamylates the FAAH active-site serine, selectively raises brain anandamide for 24 hours, and produces CB1-dependent analgesia established the in vivo proof-of-concept that selective FAAH inhibition modulates endocannabinoid signaling to reduce pain.

    Evidence Structural/mechanistic studies, activity-based protein profiling, in vivo pharmacology with CB1 antagonist

    PMID:19389627

    Open questions at the time
    • Contribution of non-anandamide FAAH substrates to analgesic effect unclear
    • Long-term consequences of sustained FAAH inhibition not assessed
  5. 2012 High

    Estrogen was shown to induce FAAH transcription via ERβ binding to proximal ERE sites with recruitment of the histone demethylase LSD1, causing epigenetic remodeling that protects Sertoli cells from anandamide-induced apoptosis, broadening the hormonal control of FAAH to include estrogen-dependent epigenetic mechanisms.

    Evidence ChIP, luciferase reporters, promoter mutagenesis, bisulfite methylation, FAAH siRNA knockdown, apoptosis assays in mouse Sertoli cells

    PMID:22802127

    Open questions at the time
    • Whether ERβ/LSD1-mediated regulation operates in neural tissues not tested
    • Interplay between progesterone/Ikaros and estrogen/ERβ pathways not examined
  6. 2012 High

    Tissue-specific FAAH rescue experiments showed that non-neuronal FAAH is required for anti-allodynic effects of FAAH inhibitors in inflammatory pain, acting through both CB1 and CB2 receptors, clarifying that peripheral endocannabinoid metabolism is a key analgesic site.

    Evidence Neuron-specific FAAH rescue mouse model, pharmacological inhibition, CB1/CB2 antagonists, endocannabinoid mass spectrometry

    PMID:21506952

    Open questions at the time
    • Specific peripheral cell type(s) responsible not identified
    • Relative contribution of peripheral vs. central FAAH in chronic pain models unknown
  7. 2014 Medium

    Cholesterol was found to enhance FAAH membrane binding affinity, dimer stability, and enzymatic activity, with co-localization of cholesterol, anandamide, and FAAH in neuroblastoma cells, establishing membrane lipid composition as a regulator of FAAH catalysis.

    Evidence Combined enzyme activity assays, co-localization imaging, and molecular dynamics simulation in mouse neuroblastoma cells

    PMID:24215562

    Open questions at the time
    • In vivo validation of cholesterol-dependent activity modulation not performed
    • Whether cholesterol acts by altering substrate presentation vs. direct protein interaction not resolved
  8. 2015 High

    The human FAAH C385A polymorphism was shown via knock-in mice to reduce FAAH expression and activity, elevate anandamide, enhance fronto-amygdala connectivity, and facilitate fear extinction, directly linking FAAH genetic variation to anxiety and emotional learning circuits.

    Evidence Knock-in mouse generation, FAAH activity assays, behavioral testing, fMRI connectivity, parallel human genotype-phenotype analysis

    PMID:25731744

    Open questions at the time
    • Downstream signaling mediators of enhanced fear extinction not identified
    • Whether effects are fully CB1-dependent not tested
  9. 2017 High

    Proteome-wide activity profiling revealed that the clinical FAAH inhibitor BIA 10-2474 inhibited multiple off-target lipases, causing lipid network dysregulation in human cortical neurons, while the selective inhibitor PF04457845 did not—clarifying that toxicity in the BIA 10-2474 trial arose from off-target effects rather than FAAH inhibition per se.

    Evidence Activity-based protein profiling in human cells and tissues, lipidomics in human cortical neurons

    PMID:28596366

    Open questions at the time
    • Complete target list of BIA 10-2474 metabolites not characterized
    • Whether any FAAH-dependent lipid changes contribute to neurotoxicity not excluded
  10. 2018 High

    FAAH was established as a required effector of leptin's hypophagic action: leptin increases hypothalamic FAAH activity to reduce anandamide, and C385A knock-in mice or pharmacological FAAH inhibition abolished leptin-induced reductions in food intake and body weight.

    Evidence Leptin administration in WT/ob/ob mice, endocannabinoid mass spectrometry, FAAH C385A knock-in mice, FAAH inhibitor pharmacology

    PMID:29967158

    Open questions at the time
    • Transcriptional vs. post-translational mechanism of leptin-induced FAAH activation not distinguished in vivo
    • Whether other FAAH substrates beyond AEA contribute to metabolic effects unknown
  11. 2020 High

    Kinetic analysis revealed FAAH operates as an allosteric homodimer where occupation of one active site blocks both subunits, with W445 at the dimer interface mediating inter-subunit communication, fundamentally redefining the stoichiometry of FAAH inhibition.

    Evidence Hill coefficient analysis, stoichiometric inhibitor titration, site-directed mutagenesis (W445Y, F432A) of human and rat FAAH

    PMID:32041998

    Open questions at the time
    • Structural basis for allosteric communication not determined at atomic level
    • Whether allostery is substrate-dependent not tested
    • In vivo relevance of half-site inhibition not demonstrated
  12. 2021 Medium

    FAAH genetic deletion rescued hippocampal synaptic plasticity and dendritic spine density in an Alzheimer's model via a CB1R/TRPV1-independent mechanism involving upregulation of microglial phagocytic and amyloid-clearance pathways, extending FAAH function to neuroinflammation and neurodegeneration.

    Evidence Electrophysiology, dendritic spine morphometry, flow cytometry, and molecular analysis in 5xFAD/FAAH−/− mice

    PMID:34587978

    Open questions at the time
    • Identity of the FAAH-derived lipid mediator(s) responsible for microglial activation unknown
    • CB1R/TRPV1-independent mechanism not molecularly defined
    • Replication in independent AD models needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for FAAH allosteric communication across the dimer interface, the identity of FAAH substrates beyond anandamide that drive its metabolic and neuroinflammatory functions, and the mechanism by which FAAH loss activates microglial phagocytic programs remain unresolved.
  • Full-length membrane-embedded human FAAH dimer structure not solved
  • Substrate hierarchy in vivo not systematically defined
  • Mechanism of FAAH-dependent microglial reprogramming unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3
Partners
CNR1CNR2ESR2IKZF1KDM1A
Complex memberships
FAAH homodimer

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 PF-3845 is a covalent FAAH inhibitor that carbamylates the active-site serine nucleophile of FAAH, as confirmed by mechanistic and structural studies. It selectively inhibits FAAH in vivo (verified by activity-based protein profiling), raises brain anandamide levels for up to 24 hours, and produces CB1 receptor-dependent reductions in inflammatory pain. Mechanistic studies (active-site carbamylation), structural studies, activity-based protein profiling, in vivo pharmacology with CB1 antagonist Chemistry & biology High 19389627
2008 Crystal structure of humanized rat FAAH (h/rFAAH) complexed with inhibitor PF-750 at 2.75-Å resolution revealed the structural basis for species selectivity of FAAH inhibitors. The active sites of rat and human FAAH were interconverted by site-directed mutagenesis, producing a protein with human FAAH inhibitor-sensitivity but rat FAAH expression yield. X-ray crystallography, site-directed mutagenesis, inhibitor profiling Proceedings of the National Academy of Sciences of the United States of America High 18753625
2011 PF-04457845 inhibits FAAH by a covalent, irreversible mechanism involving carbamylation of the active-site serine nucleophile (kinact/Ki = 40,300 M⁻¹s⁻¹; IC50 = 7.2 nM for human FAAH), with exquisite selectivity over other serine hydrolases as demonstrated by competitive activity-based protein profiling. In vitro enzyme kinetics, active-site carbamylation mechanism, competitive activity-based protein profiling ACS medicinal chemistry letters High 21666860
2000 FAAH is a serine hydrolase containing an amidase domain with a serine catalytic nucleophile responsible for hydrolysis of anandamide and related fatty acid amides. Conserved domains include a hydrophobic domain important for self-association and a proline-rich domain potentially important for subcellular localization. Recombinant FAAH was purified and characterized following cloning from rat, mouse, human, and pig. cDNA cloning, recombinant protein purification, domain mutagenesis/sequence analysis, enzyme activity assays Chemistry and physics of lipids High 11106785
2011 A catalytically silent splice variant of FAAH-1 (termed FLAT, FAAH-like anandamide transporter) lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells, identifying it as a molecular component of anandamide transport in neural cells. Known anandamide transport inhibitors (AM404, OMDM-1) blocked these effects. Molecular cloning, binding assays, cellular uptake assays, pharmacological inhibition, in vivo antinociceptive studies Nature neuroscience Medium 22101642
2013 A follow-up study found that FLAT displayed residual catalytic activity sensitive to FAAH inhibitors and abolished by mutation of its catalytic serine; overexpression of FLAT potentiated AEA cellular uptake in a manner dependent on its catalytic activity rather than transport function. FLAT was not detected in multiple tissues examined, suggesting it does not serve as a global intracellular AEA carrier. PCR-based generation of FLAT construct, mutagenesis of catalytic serine, cellular uptake assays in FAAH-expressing and FAAH-deficient cells, immunofluorescence localization PloS one Medium 24223930
2014 Membrane lipid composition modulates FAAH structure, subcellular localization, and activity. The FAAH dimer is stabilized by the lipid bilayer, shows higher membrane-binding affinity and enzymatic activity in membranes containing both cholesterol and the substrate anandamide (AEA). Co-localization of cholesterol, AEA, and FAAH in mouse neuroblastoma cells suggests cholesterol increases FAAH substrate accessibility. Combined experimental (enzyme activity assays, co-localization imaging) and computational (molecular dynamics simulation) approach The Biochemical journal Medium 24215562
2020 FAAH is an allosteric homodimeric enzyme: occupation of only one of the two active sites is sufficient to fully block catalysis. A single W445Y substitution eliminated allostery (Hill coefficient ~1.0) without reducing activity, while F432A reduced specific activity but retained allostery. Human FAAH also showed allosteric AEA hydrolysis (Hill coefficient ~1.9), implicating W445 at the dimer interface as a key allosteric residue. Site-directed mutagenesis, enzyme kinetics (Hill coefficient analysis), stoichiometric inhibitor titration of human and rat FAAH Scientific reports High 32041998
2003 Progesterone activates the FAAH promoter in human T lymphocytes through the transcription factor Ikaros. Mutation of Ikaros binding sites (ERE2/3) in the FAAH promoter prevented progesterone-induced FAAH transcription. Leptin additively activates FAAH expression via a cAMP response element-like site. Progesterone-induced FAAH upregulation decreased cellular anandamide levels. Transient expression/reporter assays, EMSA and supershift assays, site-directed mutagenesis of promoter, enzyme activity assays The Journal of biological chemistry High 12799380
2012 Estrogen (E2) directly induces FAAH transcription in mouse Sertoli cells via estrogen receptor β binding to two proximal ERE sequences (ERE2/3) in the faah promoter. The histone demethylase LSD1 is associated with these sites and mediates E2 induction of FAAH expression. E2 induced epigenetic modifications (decreased DNA methylation at CpG and H3K9 methylation) compatible with transcriptional activation. FAAH silencing abolished E2-mediated protection against anandamide-induced apoptosis. Luciferase reporter assays, promoter mutagenesis, ChIP, bisulfite methylation analysis, FAAH siRNA knockdown, apoptosis assays Cellular and molecular life sciences : CMLS High 22802127
2017 Activity-based proteomic profiling of the FAAH inhibitor BIA 10-2474 in human cells and tissues revealed that it inhibits several lipases beyond FAAH that are not targeted by the selective inhibitor PF04457845. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, indicating that promiscuous lipase inhibition causes metabolic dysregulation in the nervous system. Activity-based protein profiling (ABPP) in human cells/tissues, lipid network analysis in human cortical neurons Science (New York, N.Y.) High 28596366
2015 The common human FAAH C385A polymorphism (rs324420) reduces FAAH expression and activity, thereby increasing anandamide levels. Knock-in mice recapitulating this variant showed selectively enhanced fronto-amygdala connectivity, facilitated fear extinction learning, and decreased anxiety-like behaviors, paralleling effects in human A-allele carriers. Knock-in mouse generation, FAAH activity and expression assays, behavioral testing, neuroimaging (fMRI connectivity), parallel human genetics analysis Nature communications High 25731744
2018 FAAH activity is required for leptin's hypophagic effects. Leptin-deficient mice showed elevated hypothalamic anandamide and reduced FAAH activity; leptin administration to WT mice reduced AEA and increased FAAH activity. FAAH C385A knock-in mice with reduced FAAH activity were unresponsive to leptin-induced reductions in food intake and body weight. Pharmacological FAAH inhibition was sufficient to prevent leptin-mediated changes in body weight and food intake. Leptin administration to WT/ob/ob mice (endocannabinoid measurement by mass spectrometry), FAAH C385A knock-in mice, FAAH inhibitor pharmacology, high-fat diet challenge Proceedings of the National Academy of Sciences of the United States of America High 29967158
2012 FAAH anti-allodynic effects in LPS-induced tactile allodynia are mediated specifically by neuronal FAAH: mice expressing FAAH exclusively in the nervous system (under neural specific enolase promoter) did not show the anti-allodynic phenotype of wild-type mice treated with FAAH inhibitors. The anti-allodynic effects required activation of both CB1 and CB2 receptors. Neuron-specific FAAH rescue mouse model, pharmacological inhibition (URB597, OL-135, PF-3845), endocannabinoid mass spectrometry, CB1/CB2 antagonist pharmacology British journal of pharmacology High 21506952
2014 In the periaqueductal grey (PAG), anandamide (but not 2-AG) produced reduction of inhibitory GABAergic transmission via disinhibition. This AEA-induced suppression was enhanced by the FAAH inhibitor URB597, while 2-AG-induced suppression was unmasked only by the MAGL inhibitor JZL184. Combined FAAH/MAGL inhibition enhanced tonic disinhibition, consistent with analgesic action. In vitro electrophysiological recordings from rat midbrain PAG slices, cannabinoid receptor antagonist pharmacology British journal of pharmacology High 25041240
2008 FAAH was unexpectedly localized to the nucleus of invasive extravillous trophoblasts in recurrent miscarriage cases (verified by western blotting of subcellular fractions and confocal microscopy), as opposed to cytoplasmic localization in normal pregnancies. FAAH was overexpressed in trophoblasts that had invaded the decidua in 67% of recurrent miscarriage cases but not in normal pregnancies. Immunohistochemistry, subcellular fractionation with western blotting, confocal microscopy Placenta Medium 18805581
2021 FAAH genetic inactivation in the 5xFAD Alzheimer's disease mouse model rescued hippocampal synaptic plasticity (basal synaptic transmission and LTP at CA3-CA1 synapses) and restored dendritic spine density in CA1 pyramidal neurons. The LTP rescue was independent of CB1R and TRPV1 receptors. FAAH deletion upregulated microglial phagocytic factors (TREM2, CTSD) and amyloid beta clearance factors (complement C3, C3AR), potentiating amyloid beta phagocytosis. Electrophysiology (LTP recording), flow cytometry, dendritic spine morphometry, molecular analysis of microglial markers in 5xFAD/FAAH⁻/⁻ mice Journal of neuroinflammation Medium 34587978
2012 Hyperglycemia downregulates FAAH-1 expression in retinal pigment epithelial cells, leading to elevated anandamide and upregulated CB1 receptor expression. Overexpression of FAAH-1 blocked high-glucose-induced CB1R internalization, ROS generation, and apoptosis (reduced Bax/Bcl-2 ratio and caspase activation), establishing FAAH-1 as a regulator of CB1R-mediated apoptosis in diabetic retinopathy. Overexpression of FAAH-1, siRNA knockdown of CB1R, CB1R antagonist (AM251), ROS measurement, apoptosis assays (caspase-3/9, PARP cleavage, cell viability) Journal of cellular physiology Medium 21442624

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chemistry & biology 373 19389627
2006 Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS drug reviews 345 16834756
2009 Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo. Proceedings of the National Academy of Sciences of the United States of America 310 19918051
2017 Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474. Science (New York, N.Y.) 242 28596366
2006 Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. British journal of pharmacology 236 16331291
2007 Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors. Neuropharmacology 227 17709120
2015 FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nature communications 225 25731744
2002 The fatty acid amide hydrolase (FAAH). Prostaglandins, leukotrienes, and essential fatty acids 173 12052036
2013 Amygdala FAAH and anandamide: mediating protection and recovery from stress. Trends in pharmacological sciences 172 24325918
2006 Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in rats. Journal of neurochemistry 170 16805835
2000 The fatty acid amide hydrolase (FAAH). Chemistry and physics of lipids 168 11106785
2011 Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor. ACS medicinal chemistry letters 145 21666860
2009 Targeting fatty acid amide hydrolase (FAAH) to treat pain and inflammation. The AAPS journal 135 19184452
2008 Structure-guided inhibitor design for human FAAH by interspecies active site conversion. Proceedings of the National Academy of Sciences of the United States of America 133 18753625
2011 A catalytically silent FAAH-1 variant drives anandamide transport in neurons. Nature neuroscience 129 22101642
2007 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. Journal of neurochemistry 114 18028339
2009 Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors. Learning & memory (Cold Spring Harbor, N.Y.) 113 19403796
2009 Individual and additive effects of the CNR1 and FAAH genes on brain response to marijuana cues. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 98 20010552
2006 Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice. Neuropharmacology 94 16448676
2012 The fatty acid amide hydrolase (FAAH) inhibitor PF-3845 acts in the nervous system to reverse LPS-induced tactile allodynia in mice. British journal of pharmacology 92 21506952
2020 Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors. Annual review of pharmacology and toxicology 89 32867595
2003 Progesterone activates fatty acid amide hydrolase (FAAH) promoter in human T lymphocytes through the transcription factor Ikaros. Evidence for a synergistic effect of leptin. The Journal of biological chemistry 89 12799380
2013 Inhibition of FAAH and activation of PPAR: new approaches to the treatment of cognitive dysfunction and drug addiction. Pharmacology & therapeutics 87 23333350
2009 Endocannabinoid system in first trimester placenta: low FAAH and high CB1 expression characterize spontaneous miscarriage. Placenta 86 19419760
2003 Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH) in the human placenta. Placenta 77 14580383
2009 FAAH deficiency promotes energy storage and enhances the motivation for food. International journal of obesity (2005) 74 20029375
2019 A perspective review on fatty acid amide hydrolase (FAAH) inhibitors as potential therapeutic agents. European journal of medicinal chemistry 68 31945644
2014 FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway. Oncotarget 61 24811863
2020 Potential application of endocannabinoid system agents in neuropsychiatric and neurodegenerative diseases-focusing on FAAH/MAGL inhibitors. Acta pharmacologica Sinica 60 32203086
2016 Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 59 27005594
2011 Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition. PloS one 58 22140525
2012 The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1. Cellular and molecular life sciences : CMLS 55 22802127
2007 The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites. Journal of molecular medicine (Berlin, Germany) 54 17216208
2017 Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration. Redox biology 53 29197803
2013 Macamides and their synthetic analogs: evaluation of in vitro FAAH inhibition. Bioorganic & medicinal chemistry 53 23891163
2013 Selective inhibition of FAAH produces antidiarrheal and antinociceptive effect mediated by endocannabinoids and cannabinoid-like fatty acid amides. Neurogastroenterology and motility 52 24460851
2009 The FAAH inhibitor URB-597 interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus (house musk shrew). Physiology & behavior 52 19239915
2008 Intermediate cannabis dependence phenotypes and the FAAH C385A variant: an exploratory analysis. Psychopharmacology 52 19002671
2015 Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model. British journal of pharmacology 51 26398331
2013 Chiral 1,3,4-oxadiazol-2-ones as highly selective FAAH inhibitors. Journal of medicinal chemistry 50 24083878
2013 Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine inflammatory pain model. Neuropharmacology 50 24384256
2006 Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat. Psychopharmacology 49 17111174
2015 Preclinical Characterization of the FAAH Inhibitor JNJ-42165279. ACS medicinal chemistry letters 48 26713105
2019 A New Use for an Old Drug: Carmofur Attenuates Lipopolysaccharide (LPS)-Induced Acute Lung Injury via Inhibition of FAAH and NAAA Activities. Frontiers in pharmacology 44 31379583
2017 Blockade of alcohol escalation and "relapse" drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice. Psychopharmacology 43 28730283
2016 Fatty acid amide hydrolase (FAAH) blockade ameliorates experimental colitis by altering microRNA expression and suppressing inflammation. Brain, behavior, and immunity 43 27327245
2015 Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context. Frontiers in cellular neuroscience 40 25870539
2014 Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models. Pharmacology, biochemistry, and behavior 40 25058512
2003 Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH) in the human placenta. Placenta 40 12744923
2020 Characterization of the peripheral FAAH inhibitor, URB937, in animal models of acute and chronic migraine. Neurobiology of disease 39 33129939
2019 OPRM1 rs1799971, COMT rs4680, and FAAH rs324420 genes interact with placebo procedures to induce hypoalgesia. Pain 39 31335650
2015 Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 39 25910421
2017 The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synaptic plasticity. Scientific reports 38 28894217
2018 Inhibitions of anandamide transport and FAAH synthesis decrease apoptosis and oxidative stress through inhibition of TRPV1 channel in an in vitro seizure model. Molecular and cellular biochemistry 37 30159798
2014 Membrane lipids are key modulators of the endocannabinoid-hydrolase FAAH. The Biochemical journal 36 24215562
2020 The endocannabinoid hydrolase FAAH is an allosteric enzyme. Scientific reports 35 32041998
2009 Association of polymorphisms of the cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes with heroin addiction: impact of long repeats of CNR1. The pharmacogenomics journal 35 20010914
2018 Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on feeding and energy balance. Proceedings of the National Academy of Sciences of the United States of America 33 29967158
2018 Pharmacological blockade of fatty acid amide hydrolase (FAAH) by URB597 improves memory and changes the phenotype of hippocampal microglia despite ethanol exposure. Biochemical pharmacology 33 30098312
2021 Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine. Cells 32 34685523
2015 Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH) Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture. PloS one 32 26561012
2021 Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer's disease. Journal of neuroinflammation 31 34587978
2010 Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. Journal of clinical psychopharmacology 31 20631561
2009 Variants in the CNR1 and the FAAH genes and adiposity traits in the community. Obesity (Silver Spring, Md.) 31 19165169
2021 Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization. International journal of molecular sciences 30 34299330
2021 Role of PI3K/Akt axis in mitigating hippocampal ischemia-reperfusion injury via CB1 receptor stimulation by paracetamol and FAAH inhibitor in rat. Neuropharmacology 30 34968475
2020 Impacts of epidural electrical stimulation on Wnt signaling, FAAH, and BDNF following thoracic spinal cord injury in rat. Journal of cellular physiology 30 32488870
2012 Aryl Piperazinyl Ureas as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) in Rat, Dog, and Primate. ACS medicinal chemistry letters 30 24900385
2017 Fatty acid amide hydrolase (FAAH) inhibitor PF-3845 reduces viability, migration and invasiveness of human colon adenocarcinoma Colo-205 cell line: an in vitro study. Acta biochimica Polonica 29 28850633
2015 Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety. PloS one 29 26360704
2013 Inhibition of fatty acid amide hydrolase (FAAH) as a novel therapeutic strategy in the treatment of pain and inflammatory diseases in the gastrointestinal tract. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 29 24275607
2014 Inhibition of peripheral FAAH depresses activities of bladder mechanosensitive nerve fibers of the rat. The Journal of urology 28 24746881
2012 Hyperglycemia induces apoptosis via CB1 activation through the decrease of FAAH 1 in retinal pigment epithelial cells. Journal of cellular physiology 28 21442624
2021 Distinct Activity of Endocannabinoid-Hydrolyzing Enzymes MAGL and FAAH in Key Regions of Peripheral and Central Nervous System Implicated in Migraine. International journal of molecular sciences 27 33530477
2017 Pharmacological inhibition of FAAH modulates TLR-induced neuroinflammation, but not sickness behaviour: An effect partially mediated by central TRPV1. Brain, behavior, and immunity 27 28237711
2017 N-arachidonoyl-serotonin, a dual FAAH and TRPV1 blocker, inhibits the retrieval of contextual fear memory: Role of the cannabinoid CB1 receptor in the dorsal hippocampus. Journal of psychopharmacology (Oxford, England) 27 28583049
2013 The macamide N-3-methoxybenzyl-linoleamide is a time-dependent fatty acid amide hydrolase (FAAH) inhibitor. Molecular neurobiology 27 23853040
2012 Peripheral effects of FAAH deficiency on fuel and energy homeostasis: role of dysregulated lysine acetylation. PloS one 27 22442717
2018 FAAH inhibition attenuates TLR3-mediated hyperthermia, nociceptive- and anxiety-like behaviour in female rats. Behavioural brain research 26 29953903
2015 Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects. The pharmacogenomics journal 26 25558980
2015 Effects of fatty acid amide hydrolase (FAAH) inhibitors on working memory in rats. Psychopharmacology 26 26558620
2014 Endocannabinoid modulation by FAAH and monoacylglycerol lipase within the analgesic circuitry of the periaqueductal grey. British journal of pharmacology 26 25041240
2007 Vanilloid receptor 1 (TRPV1/VR1) co-localizes with fatty acid amide hydrolase (FAAH) in retinal amacrine cells. Visual neuroscience 26 17686199
2018 Impact of FAAH genetic variation on fronto-amygdala function during emotional processing. European archives of psychiatry and clinical neuroscience 25 30291441
2016 A dual inhibitor of FAAH and TRPV1 channels shows dose-dependent effect on depression-like behaviour in rats. Acta neuropsychiatrica 25 27938441
2014 Correlating FAAH and anandamide cellular uptake inhibition using N-alkylcarbamate inhibitors: from ultrapotent to hyperpotent. Biochemical pharmacology 25 25283614
2013 (4-Phenoxyphenyl)tetrazolecarboxamides and related compounds as dual inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). European journal of medicinal chemistry 25 23455058
2008 Nuclear localisation of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) in invasive trophoblasts and an association with recurrent miscarriage. Placenta 25 18805581
2020 Antidepressant-like effects of pharmacological inhibition of FAAH activity in socially isolated female rats. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 24 31948828
2013 Role of FAAH-like anandamide transporter in anandamide inactivation. PloS one 23 24223930
2021 GPR18 drives FAAH inhibition-induced neuroprotection against HIV-1 Tat-induced neurodegeneration. Experimental neurology 22 33736974
2010 C358A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) and insulin resistance in patients with diabetes mellitus type 2. Diabetes research and clinical practice 22 20056290
2008 Evaluating the association of FAAH common gene variation with childhood, adult severe obesity and type 2 diabetes in the French population. Obesity facts 22 20054193
2022 Activity-based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity. Angewandte Chemie (International ed. in English) 21 36083191
2022 FAAH Inhibition Restores Early Life Stress-Induced Alterations in PFC microRNAs Associated with Depressive-Like Behavior in Male and Female Rats. International journal of molecular sciences 21 36555739
2021 Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen-Glucose Deprivation-Induced Ischemic Neuronal Injury. International journal of nanomedicine 21 34093011
2021 The role of endocannabinoid pathway in the neuropathology of Alzheimer's disease: Can the inhibitors of MAGL and FAAH prove to be potential therapeutic targets against the cognitive impairment associated with Alzheimer's disease? Brain research bulletin 21 34217798
2018 Inhibition of Fatty Acid Amide Hydrolase (FAAH) by Macamides. Molecular neurobiology 21 29926378
2018 Analgesic effects of FAAH inhibitor in the insular cortex of nerve-injured rats. Molecular pain 21 30380982
2014 Prostamide F(2) α receptor antagonism combined with inhibition of FAAH may block the pro-inflammatory mediators formed following selective FAAH inhibition. British journal of pharmacology 20 24102214