Peripheral FAAH inhibition causes profound antinociception and protects against indomethacin-induced gastric lesions
Open accessAbstract
Fatty-acid amide hydrolase (FAAH) catalyzes the intracellular hydrolysis of the endocannabinoid anandamide and other bioactive lipid amides. In the present study, we conducted a comparative characterization of the effects of the newly identified brain-impermeant FAAH inhibitor, URB937 ([3-(3-carbamoylphenyl)-4-hydroxy-phenyl] N-cyclohexylcarbamate), in various rodent models of acute and persistent pain. When administered by the oral route in mice, URB937 was highly active (median effective dose, ED(50), to inhibit liver FAAH activity: 0.3mgkg(-1)) and had a bioavailability of 5.3%. The antinociceptive effects of oral URB937 were investigated in mouse models of acute inflammation (carrageenan), peripheral nerve injury (chronic sciatic nerve ligation) and arthritis (complete Freund's adjuvant). In all models, URB937 was as effective or more effective than standard analgesic and anti-inflammatory drugs (indomethacin, gabapentin, dexamethasone) and reversed pain-related responses (mechanical hyperalgesia, thermal hyperalgesia, and mechanical allodynia) in a dose-dependent manner. ED(50) values ranged from 0.2 to 10mgkg(-1), depending on model and readout. Importantly, URB937 was significantly more effective than two global FAAH inhibitors, URB597 and PF-04457845, in the complete Freund's adjuvant model. The effects of a combination of URB937 with the non-steroidal anti-inflammatory agent, indomethacin, were examined in the carrageenan and chronic sciatic nerve ligation models. Isobolographic analyses showed that the two compounds interacted synergistically to attenuate pain-related behaviors. Furthermore, URB937 reduced the number and severity of gastric lesions produced by indomethacin, while exerting no ulcerogenic effect when administered alone. The results indicate that the peripheral FAAH inhibitor URB937 is more effective than globally active FAAH inhibitors at inhibiting inflammatory pain. Our findings further suggest that FAAH and cyclooxygenase inhibitors interact functionally in peripheral tissues, to either enhance or hinder each other's actions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dual administration of URB937 and the nonsteroidal anti-inflammatory drug indomethacin synergistically attenuates hyperalgesia, allodynia, and edema induced by intraplantar carrageenan injection.
“Similarly, dual administration of URB937 and the nonsteroidal anti-inflammatory drug (NSAID) indomethacin synergistically attenuates hyperalgesia, allodynia, and edema induced by intraplantar carrageenan injection (Sasso et al, 2012).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Sasso et al, 2012
FAAH inhibition attenuates mechanically-induced pain in the CFA model of inflammatory pain.
“FAAH inhibition attenuates mechanically-induced pain in the CFA model of inflammatory pain (Ahn et al, 2009(Ahn et al, , 2011;;Jayamanne et al, 2006;Sasso et al, 2012).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Sasso et al, 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633 · see citing works
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Bennett, G. J., & Xie, Y.-K. (1988) · Pain · doi:10.1016/0304-3959(88)90209-6 · Cited by 5,376 · see citing works
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Hargreaves, K., Dubner, R. A., Brown, F. J., Flores, C., & Joris, J. L. (1988) · Pain · doi:10.1016/0304-3959(88)90026-7 · Cited by 5,155 · see citing works
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957 · see citing works
Self-citationModulation of anxiety through blockade of anandamide hydrolysis
Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Rana, G. L., Calignano, A., et al. (2003) · Nature Medicine · doi:10.1038/nm803 · Cited by 1,293 · see citing works
Self-citationFu, J., Gaetani, S., Oveisi, F., Verme, J., Serrano, A., de Fonseca, F. D., Rosengarth, A., Luecke, H., Giacomo, B. D., Tarzia, G., et al. (2003) · Nature · doi:10.1038/nature01921 · Cited by 1,113 · see citing works
Self-citationControl of pain initiation by endogenous cannabinoids
Calignano, A., Rana, G. L., Giuffrida, A., & Piomelli, D. (1998) · Nature · doi:10.1038/28393 · Cited by 1,055 · see citing works
Self-citationLo Verme, J., Fu, J., Astarita, G., La Rana, G., Russo, R., Calignano, A., & Piomelli, D. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.006353 · Cited by 882 · see citing works
Self-citationSostres, C., Gargallo, C. J., Arroyo, M., & Lanas, Á. (2010) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2009.11.005 · Cited by 689 · see citing works
Structure and function of fatty acid amide hydrolase
McKinney, M. K., & Cravatt, B. F. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133450 · Cited by 680 · see citing works
Gobbi, G., Bambico, F. R., Mangieri, R. A., Bortolato, M., Campolongo, P., Solinas, M., Cassano, T., Morgese, M. G., Debonnel, G., Duranti, A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509591102 · Cited by 676 · see citing works
Self-citationCannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors
Agarwal, N., Pacher, P., Tegeder, I., Amaya, F., Constantin, C. E., Brenner, G. J., Rubino, T., Michalski, C. W., Marsicano, G., Monory, K., et al. (2007) · Nature Neuroscience · doi:10.1038/nn1916 · Cited by 571 · see citing works
Drug Synergism and Dose-Effect Data Analysis
Tallarida, R. J. (2000) · Chapman & Hall/CRC eBooks · doi:10.1201/9781420036107 · Cited by 567 · see citing works
Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors
Richardson, J. D., Kilo, S., & Hargreaves, K. (1998) · Pain · doi:10.1016/s0304-3959(97)00213-3 · Cited by 498 · see citing works
The Endocannabinoid System and Pain
Guindon, J., & Hohmann, A. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709789824660 · Cited by 476 · see citing works
Pharmacological Profile of the Selective FAAH Inhibitor KDS-4103 (URB597)
Piomelli, D., Tarzia, G., Duranti, A., Tontini, A., Mor, M., Compton, T. R., Dasse, O. A., Monaghan, E. P., Parrott, J. A., & Putman, D. (2006) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2006.00021.x · Cited by 445 · see citing works
Self-citationAnandamide suppresses pain initiation through a peripheral endocannabinoid mechanism
Clapper, J. R., Moreno-Sanz, G., Russo, R., Guijarro, A., Vacondio, F., Duranti, A., Tontini, A., Sanchini, S., Sciolino, N. R., Spradley, J. M., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2632 · Cited by 346 · cited 6× · see citing works
“This effect is likely mediated by activation of CB1 receptors because it is blocked by the CB1 antagonist AM251, but not by the CB2 antagonist AM630 [15].”
BackgroundMethodInfluentialSelf-citationChan, C., Boyce, S., Brideau, C., Ford‐Hutchinson, A. W., Gordon, R. J., Guay, D., Hill, R. G., Li, C. S., Mancini, J. A., & Penneton, M. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10713-1 · Cited by 313 · see citing works
Richardson, D., Pearson, R. G., Kurian, N., Latif, M. L., Garle, M. J., Barrett, D. A., Kendall, D. A., Scammell, B. E., Reeve, A. J., & Chapman, V. (2008) · Arthritis Research & Therapy · doi:10.1186/ar2401 · Cited by 303 · see citing works
Mor, M., Rivara, S., Lodola, A., Plazzi, P. V., Tarzia, G., Duranti, A., Tontini, A., Piersanti, G., Kathuria, S., & Piomelli, D. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm031140x · Cited by 276 · see citing works
Self-citationMast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation
Boyce, J. A. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00512.x · Cited by 255 · see citing works
Ahn, K., Smith, S. E., Liimatta, M. B., Beidler, D. R., Sadagopan, N., Dudley, D. T., Young, T., Wren, P. B., Zhang, Y., Swaney, S. M., et al. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.180257 · Cited by 229 · see citing works
Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor
Johnson, D. S., Stiff, C. M., Lazerwith, S. E., Kesten, S. R., Fay, L. K., Morris, M. J., Beidler, D. R., Liimatta, M. B., Smith, S. E., Dudley, D. T., et al. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100190t · Cited by 200 · see citing works
Spinal Endocannabinoids and CB 1 Receptors Mediate C-Fiber–Induced Heterosynaptic Pain Sensitization
Pernía‐Andrade, A. J., Kato, A., Witschi, R., Nyilas, R., Katona, I., Freund, T. F., Watanabe, M., Filitz, J., Koppert, W., Schüttler, J., et al. (2009) · Science · doi:10.1126/science.1171870 · Cited by 186 · see citing works
Russo, R., LoVerme, J., La Rana, G., Compton, T. R., Parrott, J., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Calignano, A., et al. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.119941 · Cited by 182 · see citing works
Self-citationDiscovery and Development of Fatty Acid Amide Hydrolase (FAAH) Inhibitors
Seierstad, M. J., & Breitenbucher, J. G. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm800311k · Cited by 179 · see citing works
Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain
Hansen, H. S. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.03.022 · Cited by 136 · see citing works
A role for endocannabinoids in indomethacin-induced spinal antinociception
Gühring, H., Hamza, M., Sergejeva, M., Ateş, M., Kotalla, C., Ledent, C. A., & Brune, K. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)02485-8 · Cited by 121 · see citing works
Naidu, P. S., Booker, L., Cravatt, B. F., & Lichtman, A. H. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.143487 · Cited by 114 · see citing works
Telleria-Diaz, A., Schmidt, M., Kreusch, S., Neubert, A.-K., Schache, F., Vazquez, E., Vanegas, H., Schaible, H.-G., & Ebersberger, A. (2010) · Pain · doi:10.1016/j.pain.2009.08.013 · Cited by 109 · see citing works
Stein, C., & Zöllner, C. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-79090-7_14 · Cited by 104 · see citing works
Qin, C. X., Chen, X., Hughes, R. A., Williams, S. J., & Woodman, O. L. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm070352h · Cited by 99 · see citing works
Flanagan, J. M., Gerber, A. L., Cadet, J. L., Beutler, E., & Sipe, J. C. (2006) · Human Genetics · doi:10.1007/s00439-006-0250-x · Cited by 85 · see citing works
Lambert, D. M., & Muccioli, G. G. (2007) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e3282f00061 · Cited by 61 · see citing works
Jain, N., Kulkarni, S. K., & Singh, À. (2002) · Life Sciences · doi:10.1016/s0024-3205(02)01549-7 · Cited by 60 · see citing works
Proudnikov, D., Kroslak, T., Sipe, J. C., Randesi, M., Li, D., Hamon, S., Ho, A., Ott, J., & Kreek, M. J. (2009) · The Pharmacogenomics Journal · doi:10.1038/tpj.2009.59 · Cited by 46 · see citing works
Kaufmann, I., Hauer, D., Huge, V., Vogeser, M., Campolongo, P., Choukèr, A., Thiel, M., & Schelling, G. (2009) · European Surgical Research · doi:10.1159/000235870 · Cited by 43 · see citing works
Role of sensory nerves in gastroprotective effect of anandamide in rats.
Warzecha, Z., DEMBINSKI, A. B., Ceranowicz, P., Dembiński, M., Cieszkowski, J., Kownacki, P., & Konturek, P. C. (2011) · PubMed · Cited by 41 · see citing works
Effects of COX-2 inhibition on spinal nociception: the role of endocannabinoids.
Staniaszek, L., Norris, L., Kendall, D., Barrett, D., & Chapman, V (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00703.x · Cited by 36 · see citing works
Moreno‐Sanz, G., Barrera, B., Guijarro, A. I., D’Elia, I., Otero, J. A., Álvarez, A. I., Bandiera, T., Merino, G., & Piomelli, D. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.07.001 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [16]Moreno-Sanz G Barrera B Guijarro A d’Elia I Otero JA Alvarez AI Bandiera T Merino G Piomelli D ABCG2 (BCRP) restricts access of FAAH inhibitor URB937 to the central nervous system Pharmacol Res 2011 64 359 63 21767647 PMC3729352
Cited by
Sorted by citations
Endocannabinoid signaling at the periphery: 50 years after THC
Maccarrone, M., Bab, I., Bı́ró, T., Cabral, G. A., Dey, S. K., Marzo, V. D., Konje, J. C., Kunos, G., Mechoulam, R., Pacher, P., et al. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.02.008 · Cited by 648 · see citing works
Chemical Probes of Endocannabinoid Metabolism
Blankman, J. L., & Cravatt, B. F. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.006387 · Cited by 327 · see citing works
Donvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301 · see citing works
Turcotte, C., Chouinard, F., Lefebvre, J. S., & Flamand, N. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ru0115-021r · Cited by 249 · see citing works
Peripheral gating of pain signals by endogenous lipid mediators
Piomelli, D., & Sasso, O. (2014) · Nature Neuroscience · doi:10.1038/nn.3612 · Cited by 236 · see citing works
Self-citationModel-Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development
Milligan, P. A., Brown, M. J., Marchant, B., Martin, S. W., van der Graaf, P. H., Benson, N., Nucci, G., Nichols, D. J., Boyd, R. A., Mandema, J. W., et al. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2013.54 · Cited by 238 · see citing works
Kinsey, S. G., Wise, L. E., Ramesh, D., Abdullah, R., Selley, D. E., Cravatt, B. F., & Lichtman, A. H. (2013) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.201426 · Cited by 169 · see citing works
McPartland, J. M., Guy, G. W., & Marzo, V. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089566 · Cited by 161 · see citing works
Sasso, O., Moreno‐Sanz, G., Martucci, C., Realini, N., Dionisi, M., Mengatto, L., Duranti, A., Tarozzo, G., Tarzia, G., Mor, M., et al. (2012) · Pain · doi:10.1016/j.pain.2012.10.018 · Cited by 105 · see citing works
Self-citationEnhanced endocannabinoid tone as a potential target of pharmacotherapy
Toczek, M., & Malinowska, B. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.04.054 · Cited by 104 · see citing works
Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications
Pertwee, R. G. (2013) · Proceedings of The Nutrition Society · doi:10.1017/s0029665113003649 · Cited by 98 · see citing works
Favia, A. D., Habrant, D., Scarpelli, R., Migliore, M., Albani, C., Bertozzi, S. M., Dionisi, M., Tarozzo, G., Piomelli, D., Cavalli, A., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3011146 · Cited by 82 · see citing works
Self-citationWilkerson, J. L., Ghosh, S., Mustafa, M., Abdullah, R. A., Niphakis, M. J., Cabrera, R., Maldonado, R. L., Cravatt, B. F., & Lichtman, A. H. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.11.015 · Cited by 78 · see citing works
Peripheral FAAH and soluble epoxide hydrolase inhibitors are synergistically antinociceptive
Sasso, O., Wagner, K., Morisseau, C., Inceoglu, B., Hammock, B. D., & Piomelli, D. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.04.001 · Cited by 68 · see citing works
Self-citationA Binding Site for Nonsteroidal Anti-inflammatory Drugs in Fatty Acid Amide Hydrolase
Bertolacci, L., Romeo, E., Veronesi, M., Magotti, P., Albani, C., Dionisi, M., Lambruschini, C., Scarpelli, R., Cavalli, A., Vivo, M. D., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja308733u · Cited by 64 · see citing works
Self-citationA Lipid Gate for the Peripheral Control of Pain
Piomelli, D., Hohmann, A. G., Seybold, V. S., & Hammock, B. D. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3475-14.2014 · Cited by 65 · see citing works
Self-citationTargeting Fatty-Acid Amide Hydrolase with Prodrugs for CNS-Selective Therapy
Meinig, J. M., Ferrara, S. J., Banerji, T., Banerji, T., Sanford-Crane, H. S., BOURDETTE, D. N., & Scanlan, T. S. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00239 · Cited by 64 · see citing works
Fichna, J., Sałaga, M., Stuart, J. M., Saur, D., Sobczak, M., Zatorski, H., Timmermans, J., Bradshaw, H. B., Ahn, K., & Storr, M. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12272 · Cited by 64 · see citing works
Greco, R., Bandiera, T., Mangione, A., Demartini, C., Siani, F., Nappi, G., Sandrini, G., Guijarro, A., Armirotti, A., Piomelli, D., et al. (2015) · Cephalalgia · doi:10.1177/0333102414566862 · Cited by 63 · see citing works
Self-citationSasso, O., Migliore, M., Habrant, D., Armirotti, A., Albani, C., Summa, M., Moreno‐Sanz, G., Scarpelli, R., & Piomelli, D. (2015) · The FASEB Journal · doi:10.1096/fj.15-270637 · Cited by 63 · see citing works
Self-citationTargeting the cannabinoid system for pain relief?
Chiou, L., Hu, S. S., & Ho, Y. (2013) · Acta anaesthesiologica Taiwanica · doi:10.1016/j.aat.2013.10.004 · Cited by 57 · see citing works
Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation
Gyires, K., & Zádori, Z. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160303110150 · Cited by 57 · see citing works
O’Sullivan, S. E., Yates, A. S., & Porter, R. K. (2021) · Molecules · doi:10.3390/molecules26206178 · Cited by 52 · see citing works
Falchi, F., Bertozzi, S. M., Ottonello, G., Ruda, G. F., Colombano, G., Fiorelli, C., Martucci, C., Bertorelli, R., Scarpelli, R., Cavalli, A., et al. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b02075 · Cited by 51 · see citing works
Self-citationHossain, M. Z., Ando, H., Unno, S., & Kitagawa, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041423 · Cited by 52 · see citing works
Grim, T. W., Ghosh, S., Hsu, K.-L., Cravatt, B. F., Kinsey, S. G., & Lichtman, A. H. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.07.008 · Cited by 50 · see citing works
Endogenous N -acyl taurines regulate skin wound healing
Sasso, O., Pontis, S., Armirotti, A., Cardinali, G., Kovacs, D., Migliore, M., Summa, M., Moreno‐Sanz, G., Picardo, M., & Piomelli, D. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1605578113 · Cited by 50 · see citing works
Self-citationFAAH inhibition as a preventive treatment for migraine: A pre-clinical study
Greco, R., Demartini, C., Zanaboni, A. M., Tumelero, E., Reggiani, A. M., Misto, A., Piomelli, D., & Tassorelli, C. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104624 · Cited by 49 · see citing works
Self-citationGreco, R., Demartini, C., Zanaboni, A., Casini, I., Icco, R. D., Reggiani, A. M., Misto, A., Piomelli, D., & Tassorelli, C. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105157 · Cited by 44 · see citing works
Self-citationThe Potential of Inhibitors of Endocannabinoid Metabolism for Drug Development: A Critical Review
Fowler, C. J. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-20825-1_4 · Cited by 45 · see citing works
Slivicki, R. A., Saberi, S. A., Iyer, V., Vemuri, K. V., Makriyannis, A., & Hohmann, A. G. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.252288 · Cited by 45 · see citing works
Crowe, M. S., Leishman, E., Banks, M. L., Gujjar, R., Mahadevan, A., Bradshaw, H. B., & Kinsey, S. G. (2014) · British Journal of Pharmacology · doi:10.1111/bph.13012 · Cited by 45 · see citing works
COX inhibitors: a patent review (2011 – 2014)
Consalvi, S., Biava, M., & Poce, G. (2015) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2015.1090973 · Cited by 44 · see citing works
Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies
Migliore, M., Habrant, D., Sasso, O., Albani, C., Bertozzi, S. M., Armirotti, A., Piomelli, D., & Scarpelli, R. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.12.036 · Cited by 44 · see citing works
Self-citationBonezzi, F., Sasso, O., Pontis, S., Realini, N., Romeo, E., Ponzano, S., Nuzzi, A., Fiasella, A., Bertozzi, F., & Piomelli, D. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.230516 · Cited by 43 · see citing works
Self-citationPember, S. O., Mejia, G. L., Price, T. J., & Pasteris, R. J. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.02.061 · Cited by 43 · see citing works
Bryk, M., & Starowicz, K. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00270-y · Cited by 40 · see citing works
The endocannabinoid system – current implications for drug development
Fowler, C. J. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13229 · Cited by 38 · see citing works
Development of multitarget agents possessing soluble epoxide hydrolase inhibitory activity
Hiesinger, K., Wagner, K. M., Hammock, B. D., Proschak, E., & Hwang, S. H. (2018) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2018.12.003 · Cited by 37 · see citing works
Cipriano, M., Björklund, E., Wilson, A. A., Congiu, C., Onnis, V., & Fowler, C. J. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.09.065 · Cited by 33 · see citing works
NSAIDs: eNdocannabinoid stimulating anti-inflammatory drugs?
Fowler, C. J. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.05.003 · Cited by 33 · see citing works
Supra-spinal FAAH is required for the analgesic action of paracetamol in an inflammatory context
Dalmann, R., Daulhac, L., Antri, M., Eschalier, A., & Mallet, C. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.006 · Cited by 32 · see citing works
Kinsey, S. G., & Cole, E. C. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.06.001 · Cited by 32 · see citing works
Slivicki, R. A., Xu, Z., Mali, S. S., & Hohmann, A. G. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.02.002 · Cited by 31 · see citing works
Burston, J. J., Mapp, P. I., Sarmad, S., Barrett, D. A., Niphakis, M. J., Cravatt, B. F., Walsh, D. A., & Chapman, V. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13574 · Cited by 30 · see citing works
Endocannabinoid and Prostanoid Crosstalk in Pain
Buisseret, B., Alhouayek, M., Guillemot‐Legris, O., & Muccioli, G. G. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.04.009 · Cited by 30 · see citing works
Moreno‐Sanz, G., Duranti, A., Melzig, L., Fiorelli, C., Ruda, G. F., Colombano, G., Mestichelli, P., Sanchini, S., Tontini, A., Mor, M., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4007017 · Cited by 30 · see citing works
Self-citationLi, G., Ma, X., Abais, J. M., Boini, K. M., Li, P.-L., & Ritter, J. K. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.233239 · Cited by 27 · see citing works
Moreno‐Sanz, G., Sasso, O., Guijarro, A. I., Oluyemi, O., Bertorelli, R., Reggiani, A. M., & Piomelli, D. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02098.x · Cited by 26 · see citing works
Self-citationNon-Phytocannabinoid Constituents of Cannabis and Herbal Synergy
McPartland, J. M., & Russo, E. B. (2014) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199662685.003.0015 · Cited by 25 · see citing works
Trexler, K. R., Eckard, M. L., & Kinsey, S. G. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2018.12.009 · Cited by 25 · see citing works
Gastric acid inhibitory and gastric protective effects of Cannabis and cannabinoids
Abdel‐Salam, O. M. E. (2016) · Asian Pacific Journal of Tropical Medicine · doi:10.1016/j.apjtm.2016.04.021 · Cited by 24 · see citing works
Goswami, S. K., İnceoğlu, B., Yang, J., Wan, D., Kodani, S. D., Trindade‐da‐Silva, C. A., Morisseau, C. H. P., & Hammock, B. D. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.10.018 · Cited by 22 · see citing works
Scarpelli, R., Sasso, O., & Piomelli, D. (2015) · ChemMedChem · doi:10.1002/cmdc.201500395 · Cited by 21 · see citing works
Self-citationAnandamide in primary sensory neurons: too much of a good thing?
Valente, J. D. S., Varga, A., Ananthan, K., Khajuria, A., & Nagy, I. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12467 · Cited by 20 · see citing works
Fotio, Y., Palese, F., Tipan, P. G., Ahmed, F., & Piomelli, D. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15031 · Cited by 19 · see citing works
Self-citationDeplano, A., Karlsson, J., Svensson, M. V., Moraca, F., Catalanotti, B., Fowler, C. J., & Onnis, V. (2020) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2020.1743283 · Cited by 19 · see citing works
Investigation of the Involvement of the Endocannabinoid System in TENS-Induced Antinociception
de Oliveira, H. U., dos Santos, R. S., Malta, I., Pinho, J. P., Almeida, A. F. S., Sorgi, C. A., Peti, A. P. F., Xavier, G. S., dos Reis, L. M., Faccioli, L. H., et al. (2019) · Journal of Pain · doi:10.1016/j.jpain.2019.11.009 · Cited by 16 · see citing works
Vozella, V., Ahmed, F., Choobchian, P., Merrill, C. B., Zibardi, C., Tarzia, G., Mor, M., Duranti, A., Tontini, A., Rivara, S., et al. (2019) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.13166 · Cited by 14 · see citing works
Self-citationNo more pain upon G q‐protein‐coupled receptor activation: role of endocannabinoids
Hu, S. S., Ho, Y., & Chiou, L. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12475 · Cited by 14 · see citing works
RetractedTerkawi, A. S., Jackson, W. M., Hansoti, S., Tabassum, R., & Flood, P. D. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000258 · Cited by 11 · see citing works
Synergistic antinociceptive effects of concomitant NAAA and peripheral FAAH inhibition
Tagne, A. M., Fotio, Y., Uppal, P. S., & Piomelli, D. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114194 · Cited by 10 · see citing works
Self-citationMetabolic reprogramming in the spinal cord drives the transition to pain chronicity
Tagne, A. M., Fotio, Y., Lee, H.-L., Jung, K., Katz, J., Ahmed, F., Le, J., Bazinet, R. P., Jang, C., & Piomelli, D. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116261 · Cited by 9 · see citing works
Self-citationCannabis, Cannabinoids, and Visceral Pain
Abalo, R., & Martín‐Fontelles, M. I. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-800756-3.00051-x · Cited by 9 · see citing works
Dongdem, J. T., Helegbe, G. K., Opare-Asamoah, K., Wezena, C. A., & Ocloo, A. (2022) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-021-00539-1 · Cited by 9 · see citing works
Deplano, A., Karlsson, J., Fowler, C. J., & Onnis, V. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104034 · Cited by 9 · see citing works
Deplano, A., Karlsson, J., Moraca, F., Svensson, M. V., Cristiano, C., Morgillo, C. M., Fowler, C. J., Russo, R., Catalanotti, B., & Onnis, V. (2021) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2021.1875459 · Cited by 8 · see citing works
Thompson, J. M., Blanton, H. L., Pietrzak, A., Little, W., Sherfey, C., & Guindon, J. (2019) · Molecular Pain · doi:10.1177/1744806919874192 · Cited by 8 · see citing works
Development of a Multigram Synthesis of URB937, a Peripherally Restricted FAAH Inhibitor
Fiorelli, C., Scarpelli, R., Piomelli, D., & Bandiera, T. (2013) · Organic Process Research & Development · doi:10.1021/op300301u · Cited by 7 · see citing works
Self-citationURB937 Prevents the Development of Mechanical Allodynia in Male Rats with Trigeminal Neuralgia
Demartini, C., Greco, R., Zanaboni, A. M., Francavilla, M., Facchetti, S., & Tassorelli, C. (2023) · Pharmaceuticals · doi:10.3390/ph16111626 · Cited by 6 · see citing works
Berg, B. B., Linhares, A. F. S., Martins, D. M., Rachid, M. A., Cáu, S. B. D. A., Galdino, G. S., de Carvalho, J. C. S., Sorgi, C. A., Romero, T. R. L., Pinho, V., et al. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175932 · Cited by 5 · see citing works
Possible Therapeutic Options for Complex Regional Pain Syndrome
Cha, M., Lee, K. H., Kwon, M., & Lee, B. H. (2021) · Biomedicines · doi:10.3390/biomedicines9060596 · Cited by 5 · see citing works
Synthesis Methods and Therapeutic Journey of Carprofen and Its Derivatives: A Review
Limban, C., Nuță, D. C., Căproiu, M. T., Dumitrescu, D. E., Papacocea, S., TELEHOIU, A. T. B., & Dumitraşcu, F. (2025) · Chemical Biology & Drug Design · doi:10.1111/cbdd.70122 · Cited by 4 · see citing works
Cannabinoids and Endocannabinoids
Jung, K., & Piomelli, D. (2015) · Springer eBooks · doi:10.1007/978-1-4614-6434-1_136-1 · Cited by 4 · see citing works
Self-citationModulation of central endocannabinoid system results in gastric mucosal protection in the rat
Tóth, V. É., Fehér, Á., Németh, J., Gyertyán, I., Zádori, Z., & Gyires, K. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.02.012 · Cited by 4 · see citing works
Cannabinoids and Endocannabinoids
Jung, K., & Piomelli, D. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3474-4_136 · Cited by 4 · see citing works
Self-citationFatemi, S. A., Abssy, S. S., Bourke, S. L., Murray, K., Kyeremaa-Adjei, C., Honigman, L., Mohabir, N., Sexton, C. A., Cormie, M. A., Tomin, R., et al. (2025) · Pain · doi:10.1097/j.pain.0000000000003850 · Cited by 3 · see citing works
Combined Endocannabinoid and Cyclooxygenase Inhibition Additively Attenuates Post-Surgical Pain
Rodriguez, C. E. B., Vanegas, S. O., Reck, A. M., Schrom, Y., & Kinsey, S. G. (2025) · Cannabis and Cannabinoid Research · doi:10.1089/can.2024.0088 · Cited by 2 · see citing works
Have the Genetics of Cannabis Involvement Gone to Pot?
Arpana Agrawal, A., & Lynskey, M. T. (2014) · Nebraska Symposium on Motivation/The Nebraska symposium on motivation · doi:10.1007/978-1-4939-0653-6_5 · Cited by 2 · see citing works
Caraceni, P., Borrelli, F., Giannone, F. A., & Izzo, A. A. (2014) · Wiley eBooks · doi:10.1002/9781118451281.ch7 · Cited by 2 · see citing works
The role of anandamide in digestive and defensive functions of the gut
Sharkey, K. A., & Tsang, D. K. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19081-0.00001-9 · Cited by 1 · see citing works
Couttas, T. A., Hoffmann, A., Jieu, B., Golla, F. R., Shepherd, C. E., Leweke, F. M., & Rohleder, C. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-04120-4 · Cited by 1 · see citing works
Woyach, V. L., Sherman, K., Hillard, C. J., Hopp, F. A., Hogan, Q. H., & Dean, C. (2022) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00073.2022 · Cited by 1 · see citing works
Reitz, F., Salm, D. C., Lüdtke, D. D., dos Santos, Á., Traebert, J. L., & Martins, D. F. (2018) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2018.08.010 · Cited by 1 · see citing works
The endocannabinoid system : a translational study from Achilles tendinosis to cyclooxygenase
Björklund, E. (2014) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
New Pain Management Vistas in Palliative Care
Merritt, C. K., Tran, L. B., Shah, R. V., & Kaye, A. D. (2012) · Springer eBooks · doi:10.1007/978-1-4614-5164-8_26
Endocannabinoid metabolism : the impact of inflammatory factors and pharmacological inhibitors
Karlsson, J. (2018) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Cuesta, B. B. (2014) · doi:10.18002/10612/3262
Finn, D. P. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718030800.793480342
Dongdem, J. T., Helegbe, G. K., Opare-Asamoah, K., Wezena, C. A., & Ocloo, A. (2022) · Figshare · doi:10.6084/m9.figshare.17870454
Elgohary, R., & Baraka, S. M. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01862-4
Limban, C., Marinaș, I. C., Chifiriuc, M. C., Căproiu, M. T., Dumitraşcu, F., Kapronczai, E.-E., Zarafu, I., Nuță, D. C., Ioniță, P., Avram, S., et al. (2026) · ChemistryOpen · doi:10.1002/open.70258
Raabe, R. (2014) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/r9rc-gz34
- Authors
- Sasso, O., Bertorelli, R., Bandiera, T., Scarpelli, R., Colombano, G., Armirotti, A., Moreno-Sanz, G., Reggiani, A., & Piomelli, D.
- Affiliations
- Italian Institute of Technology (IT)
- University of California, Irvine (US)
- Corresponding author
- Piomelli, Daniele
- ORCID
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 65
- Issue
- 5
- Pages
- 553-563
- ISSN
- 1043-6618 (ISSN-L)
- PMC
- PMC3738192
- OpenAlex
- W2026469610
- Cited by
- 96
- References
- 41
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 11 · 2015: 11 · 2014: 16 · 2013: 11 · 2012: 6
- FWCI
- 10.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute on Drug Abuse (R01DA012413, DP1DA031387)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- fatty acid amide hydrolase, endocannabinoids, anandamide, antinociception, inflammatory pain, peripheral nerve injury, carrageenan, complete Freund's adjuvant, sciatic nerve ligation, indomethacin, gastric lesions, cyclooxygenase inhibitors, drug synergy, oral bioavailability, hyperalgesia, allodynia
- MeSH terms
- Fatty Acid Amide Hydrolases, Amidohydrolases, Analgesics, Animals, Anti-Inflammatory Agents, Non-Steroidal, Arthritis, Experimental, Benzamides, Cannabinoids, Carbamates, Disease Models, Animal, Enzyme Inhibitors, Hyperalgesia, Indomethacin, Male, Pain, Pyridazines, Sciatic Nerve, Stomach Ulcer, Urea, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
