The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.
Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism
Open accessAbstract
Peripheral cannabinoid receptors exert a powerful inhibitory control over pain initiation, but the endocannabinoid signal that normally engages this intrinsic analgesic mechanism is unknown. To address this question, we developed a peripherally restricted inhibitor (URB937) of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of the endocannabinoid anandamide. URB937 suppressed FAAH activity and increased anandamide levels outside the rodent CNS. Despite its inability to access brain and spinal cord, URB937 attenuated behavioral responses indicative of persistent pain in rodent models of peripheral nerve injury and inflammation and prevented noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CB₁ cannabinoid receptor blockade prevented these effects. These results suggest that anandamide-mediated signaling at peripheral CB₁ receptors controls the access of pain-related inputs to the CNS. Brain-impenetrant FAAH inhibitors, which strengthen this gating mechanism, might offer a new approach to pain therapy.
Overview
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
Verification
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?
In the citing paper
“Similarly, the peripherally restricted FAAH inhibitor URB937 attenuates carrageenaninduced allodynia and hyperalgesia through a CB 1 mechanism of action.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Clapper et al, 2010
In the citing paper
“However, unlike brain-permeating FAAH inhibitors, the anti-edematous effects of URB937 are mediated by both CB 1 and CB 2 receptors (Clapper et al, 2010).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Clapper et al, 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Ahluwalia, J., Yaqoob, M., Urbán, L., Bevan, S., & Nagy, I. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01550.x · Cited by 82
RetractedA 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
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
The formalin test: an evaluation of the method
Tjølsen, A., Berge, O., Hunskaar, S., Rosland, J. H., & Hole, K. (1992) · Pain · doi:10.1016/0304-3959(92)90003-t · Cited by 2,434
SYNTHETIC ANALGESICS. II. DITHIENYLBUTENYL- AND DITHIENYLBUTYLAMINES
Eddy, N. B., & Leimbach, D. G. (1953) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)05180-8 · Cited by 1,765
Cravatt, B. F., Demarest, K., Patricelli, M. P., Bracey, M. H., Giang, D. K., Martin, B. R., & Lichtman, A. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161191698 · Cited by 1,310
Modulation 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
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 1,069
Self-citationBlood-brain barrier active efflux transporters: ATP-binding cassette gene family
Löscher, W., & Potschka, H. (2004) · NeuroRx · doi:10.1602/neurorx.2.1.86 · Cited by 873
Attacking pain at its source: new perspectives on opioids
Stein, C., Schäfer, M., & Machelska, H. (2003) · Nature Medicine · doi:10.1038/nm908 · Cited by 603
Cited by
Sorted by citations
Items 201–300 of 361
Lafreniere, J. D., & Kelly, M. E. M. (2018) · Neuronal Signaling · doi:10.1042/ns20170144 · Cited by 16
β–Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models
Martín-Escura, C., Medina-Peris, A., Spear, L. A., de la Torre‐Martínez, R., Olivos-Oré, L. A., Barahona, M. V., González‐Rodríguez, S., Fernandez-Ballester, G. J., Fernández-Carvajal, A. M., Artalejo, A. R., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052692 · Cited by 15
Charrua, A., Matos, R., Oliveira, R., Marczylo, T. H., Nagy, I., & Cruz, F. (2019) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-019-01729-9 · Cited by 15
Colombano, G., Albani, C., Ottonello, G., Ribeiro, A., Scarpelli, R., Tarozzo, G., Daglian, J. M., Jung, K., Piomelli, D., & Bandiera, T. (2014) · ChemMedChem · doi:10.1002/cmdc.201402374 · Cited by 15
Self-citationBouchet, C. A., McPherson, K. B., Coutens, B., Janowsky, A. J., & Ingram, S. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0037-23.2023 · Cited by 15
Cannabis constituents for chronic neuropathic pain; reconciling the clinical and animal evidence
Sokolaj, E. E., Assareh, N., Anderson, K. E., Aubrey, K. R., & Vaughan, C. W. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15964 · Cited by 16
“It is known that while the cannabis-like side effects of cannabinoids are mediated by the brain, its analgesic effects are also mediated by the spine and even the periphery (Clapper et al., 2010; Jhaveri et al., 2006; Martin et al., 1999; Smith & Martin, 1992).”
Yue, Y., Zhang, Q., & Wang, J. (2019) · Marine Drugs · doi:10.3390/md17070395 · Cited by 15
“The arachidonoyl amide had a similar effect but its binding activity to CB1 receptor was weaker than AEA [36,37].”
BackgroundVozella, 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 15
“Finally, FAAH activity measurements in brain tissue showed, as expected from prior studies,([9,10]) that a substantial level of enzyme inhibition was achieved in CNS with high subchronic dosing (Figure 8).”
BackgroundResultInfluentialSelf-citationGreco, R., Demartini, C., Zanaboni, A. M., Francavilla, M., Reggiani, A. M., Realini, N., Scarpelli, R., Piomelli, D., & Tassorelli, C. (2022) · The Journal of Headache and Pain · doi:10.1186/s10194-022-01449-1 · Cited by 16
“AEA, PEA, OEA and 2‐AG levels For the evaluation of lipid concentrations in central and peripheral areas related to trigeminal pain, rats were given ARN14633, ARN14280 or vehicle and were sacrificed by decapitation after exposure to carbon dioxide [29].”
MethodSelf-citationDevesa, I., & Ferrer-Montiel, A. V. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12455 · Cited by 14
“Indeed, endocannabinoids produced under inflammation, such as anandamide and 2-arachidonyl glycerol, may act as activators of TRPV1 channels (Singh et al., 2005; Clapper et al., 2010; Schreiber et al., 2012; Khasabova et al., 2013).”
BackgroundDönertaş, B., Ünel, Ç. Ç., & Erol, K. (2018) · Journal of Experimental Pharmacology · doi:10.2147/jep.s162059 · Cited by 14
Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders
Kumar, U. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms26010152 · Cited by 15
Aguiar, D. D., Gonzaga, A. C. R., Teófilo, A. L. H., Miranda, F. A., Perez, A. C., Duarte, I. D. G., & Romero, T. R. L. (2022) · Life Sciences · doi:10.1016/j.lfs.2021.120279 · Cited by 13
Carnevali, L., Barbetti, M., Fotio, Y., Ferlenghi, F., Vacondio, F., Mor, M., Piomelli, D., & Sgoifo, A. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06473-w · Cited by 14
“Further, confirming prior work (Clapper et al. 2010; Moreno-Sanz et al. 2011), URB937 increased the levels of three functionally significant FAEs – the endo-cannabinoid anandamide and the endogenous PPAR-α agonists OEA and PEA – in plasma and not in the brain.”
InfluentialSelf-citationShin, M.-C., Yukihira, T., Ito, Y., & Akaike, N. (2012) · Toxicon · doi:10.1016/j.toxicon.2012.12.011 · Cited by 13
Veloso, C. C., Ferreira, R. C. M., Rodrigues, V. G., Duarte, L. P., Klein, A., Duarte, I. D. G., Romero, T. R. L., & Perez, A. C. (2017) · Inflammopharmacology · doi:10.1007/s10787-017-0391-7 · Cited by 13
“In literature, FAAH and MAGL inhibitors, given systemically, may result in antinociception (Kinsey C. C. Veloso et al. et al. 2009; Clapper et al. 2010; Kinsey et al. 2011a; Kinsey et al. 2011b).”
BackgroundKeimpema, E., Hökfelt, T. G. M., Harkany, T., & Doherty, P. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12431 · Cited by 13
“FAAH manipulation either genetically or pharmacologically increases peripheral and central AEA levels, and promotes analgesia in a CB1R-mediated manner (Clapper et al., 2010).”
BackgroundAbdollahi, M., Castaño, J. D., Salem, J. B., & Beaudry, F. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04186-w · Cited by 14
“AEA plays a crucial role in modulating pain perception in mammals [37], which is likely related to its ability to bind with and without exposure to AEA.”
Yuan, C., Tsang, A., Berumen, M., Rodríguez, A., Yun, F., Mesic, A., Olivares, A., Dubon, L., Nguyen, A., Pavana, L., et al. (2025) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2025.118112 · Cited by 12
Moreno‐Sanz, G., Barrera, B., Armirotti, A., Bertozzi, S. M., Scarpelli, R., Bandiera, T., Prieto, J. G., Duranti, A., Tarzia, G., Merino, G., et al. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.06.004 · Cited by 12
“Compound 8 (cyclohexylcarbamic acid 3′carbamoyl-6-methylbiphenyl-3-yl ester) was prepared as reported [12].”
BackgroundMethodInfluentialSelf-citationMenthol reduces phototoxicity pain in a mouse model of photodynamic therapy
Wright, L., Baptista‐Hon, D. T., Bull, F. A., Dalgaty, F., Gallacher, M., Ibbotson, S. H., & Hales, T. G. (2017) · Pain · doi:10.1097/j.pain.0000000000001096 · Cited by 12
“Furthermore, FAAH inhibitors, which inhibit the metabolism of the endocannabinoid, anandamide, to arachidonic acid, are analgesic [10].”
BackgroundFluorine NMR‐Based Screening on Cell Membrane Extracts
Veronesi, M., Romeo, E., Lambruschini, C., Piomelli, D., Bandiera, T., Scarpelli, R., Garau, G., & Dalvit, C. (2013) · ChemMedChem · doi:10.1002/cmdc.201300438 · Cited by 12
Self-citationSchaffler, K., Yassen, A., Reeh, P. W., & Passier, P. C. C. M. (2017) · Pain Medicine · doi:10.1093/pm/pnx281 · Cited by 12
Kościelniak-Merak, B., Batko, I., Fleszar, M. G., Kocot-Kępska, M., Gamian, A., Kobylarz, K., Sztefko, K., & Tomasik, P. (2020) · Minerva Anestesiologica · doi:10.23736/s0375-9393.19.13703-0 · Cited by 12
Christie, S., & Zagorodnyuk, V. P. (2021) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00065.2021 · Cited by 12
Yan, L., Pan, M., Fu, M., Wang, J., Huang, W., & Qian, H. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.01.009 · Cited by 12
CB1 receptor-mediated respiratory depression by endocannabinoids
Iring, A., Hricisák, L., & Benyó, Z. (2017) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2017.02.011 · Cited by 12
Paracetamol: Update on its Analgesic Mechanism of Action
Mallet, C., Eschalier, A., & Daulhac, L. (2017) · Pain Relief - From Analgesics to Alternative Therapies · doi:10.5772/66649 · Cited by 11
“The fact that the analgesic action of paracetamol is maintained after URB937 administration and lost after URB597 treatment [10] shows that only brain and not peripheral, FAAH is involved and thereby confirms the central action of paracetamol.”
BackgroundInfluentialSilva, H.-H., Tavares, V., Neto, B. V., Cerqueira, F., Medeiros, R., & Silva, R. (2023) · Genes · doi:10.3390/genes14101946 · Cited by 12
“It is involved in nociception, inflammatory reactions and a variety of other processes [108–111].”
BackgroundBorgonetti, V., Vozella, V., Ware, T., Cruz, B., Bullard, R., Cravatt, B. F., Galeotti, N., & Roberto, M. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107462 · Cited by 12
Roa‐Coria, J. E., Navarrete‐Vázquez, G., Fowler, C. J., Flores‐Murrieta, F. J., Déciga‐Campos, M., & Granados‐Soto, V. (2012) · Life Sciences · doi:10.1016/j.lfs.2012.09.024 · Cited by 11
“, 2006, 2007), and that FAAH inhibitors reduce the behavioral and biochemical consequences of formalin in this test (Lichtman et al., 2004; Sit et al., 2007; Clapper et al., 2010; Thors et al., 2010), inhibition of FAAH could in theory be involved in the action of HD.”
BackgroundWright, N. J. D. (2024) · AIMS neuroscience · doi:10.3934/neuroscience.2024009 · Cited by 11
“…[4,5,22–24] together with 3 isoforms that exhibit high levels of expression [25] throughout the CNS in areas such as the olfactory bulb, hippocampus, basal ganglia, and cerebellum and peripherally in sympathetic terminals, trigeminal ganglion, dorsal root ganglia, and nociceptive terminals [26–29].”
BackgroundLodola, A., Rivara, S., & Mor, M. (2011) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-386485-7.00001-6 · Cited by 11
Self-citationZoerner, A. A., Rakers, C., Engeli, S., Bátkai, S., May, M., Jordan, J., & Tsikas, D. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-5729-9 · Cited by 11
Argueta, D. A., Avalos, B., Goel, Y., Tran, H., Fotio, Y., Piomelli, D., DiPatrizio, N. V., & Gupta, K. (2025) · Blood Advances · doi:10.1182/bloodadvances.2024015439 · Cited by 10
“13 The antinociceptive effects of AEA are enhanced in a synergistic manner by palmitoylethanolamide (PEA), 14 a member of the paracannabinoid family of lipid mediators; these agents share biogenetic and degradative pathways with AEA but do not productively interact with CBRs. 15 PEA produces marked…”
Self-citationThe endocannabinoid system and emotional processing: pathophysiology and therapeutic potential
Finn, D. P., Viveros, M., & Marco, E. M. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881111428526 · Cited by 10
“However, research in this field continues, with the focus shifting to drugs that do not cross the blood–brain barrier or that reduce endocannabinoid tone by decreasing the availability of cannabinoid precursors (Clapper et al., 2010; Minkkila et al., 2010; Petrosino and Di Marzo, 2010).”
BackgroundSynergistic 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
Self-citationGruen, M., Laux‐Biehlmann, A., Zollner, T. M., & Nagel, J. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.05.017 · Cited by 9
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
“Fatty acid amide hydrolase I (FAAH-1) has been proposed as a promising target for the discovery of drugs to treat pain, inflammation and other pathologies [3, 4].”
BackgroundThe biosynthesis and roles of N-acylethanolamines in plants
Arias‐Gaguancela, O., & Chapman, K. D. (2022) · Advances in botanical research · doi:10.1016/bs.abr.2021.07.002 · Cited by 9
Arias‐Gaguancela, O., Aziz, M., & Chapman, K. D. (2022) · PLANT PHYSIOLOGY · doi:10.1093/plphys/kiac556 · Cited by 9
“, 2003) and neurological and cognitive functions in vertebrates in general (Kathuria et al., 2003; Clapper et al., 2010; Servadio et al., 2016).”
BackgroundTurnbull, J., Jha, R. R., Gowler, P. R. W., Ferrands-Bentley, R., Kim, D., Barrett, D. A., Sarmanova, A., Fernandes, G., Doherty, M., Zhang, W., et al. (2024) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2024.04.006 · Cited by 8
Cannabinoids For the Treatment of Neuropathic Pain: Are They Safe and Effective?
Gutierrez, T., & Hohmann, A. G. (2011) · Future Neurology · doi:10.2217/fnl.11.6 · Cited by 8
Self-citationMangiatordi, G. F., Cavalluzzi, M. M., Delre, P., Lamanna, G., Lumuscio, M. C., Saviano, M., Majoral, J., Mignani, S. M., Duranti, A., & Lentini, G. (2023) · Biomedicines · doi:10.3390/biomedicines11020469 · Cited by 8
Self-citationReceptor and Channel Heteromers as Pain Targets
Berg, K. A., Patwardhan, A. M., & Akopian, A. N. (2012) · Pharmaceuticals · doi:10.3390/ph5030249 · Cited by 8
“Activation of either subtype of cannabinoid receptor, CB1 or CB2, which are found in areas of the brain and in the periphery involved in pain processing, can have profound antinociceptive effects (for review see [93,94]).”
BackgroundChen, Y., Wang, Y., Jin, Q., Wang, X., Hu, J., & Wang, X. (2017) · Process Biochemistry · doi:10.1016/j.procbio.2017.10.022 · Cited by 8
Thompson, J. M., Blanton, H. L., Pietrzak, A., Little, W., Sherfey, C., & Guindon, J. (2019) · Molecular Pain · doi:10.1177/1744806919874192 · Cited by 8
“URB937 inhibited writhing responses to acetic acid-induced visceral pain, mechanical, and thermal sensitivity induced by sciatic nerve ligation (SNL) and intraplantar carrageenan injection, respectively, and pain-related Fos activation in the spinal cord comparable to centrally acting FAAH inhibitors in a cannabinoid…”
BackgroundAnandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level
Spicarova, D., & Paleček, J. (2024) · Physiological Research · doi:10.33549/physiolres.935371 · Cited by 7
“The great hope of clinicians was to test peripherally restricted cannabinoid agonists based on preclinical research clearly showing the analgesic effects of peripheral cannabinoid receptor activation [2,3,81].”
Zhang, H., Zhao, L., Lu, X., Peng, W., Zhang, L., Zhang, Z., Hu, L., Cao, J., & Tu, Y. (2023) · Pain · doi:10.1097/j.pain.0000000000003103 · Cited by 8
Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase
Qiu, Y., Zhang, Y., Li, Y., & Ren, J. (2016) · Molecules · doi:10.3390/molecules21020229 · Cited by 7
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
Self-citationLarauche, M. H., Mulak, A., Ha, C., Million, M., Arnett, S. D., Germano, P., Pearson, J. P., Currie, M. G., & Taché, Y. (2024) · Neurogastroenterology & Motility · doi:10.1111/nmo.14927 · Cited by 6
“40,64 CB 2 receptors have been involved mainly in modulating post-inflammatory visceral hypersensitivity to CRD in colitis models 79–82 in keeping with their expression primarily on various immune cell populations.”
URB937 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
“…neuropathy [29–31], and diabetic peripheral neuropathy [32]. confirm the anti-allodynic effect of URB937, as previously reported in other neuropathic pain models, namely, sciatic nerve CCI [22,27,28], chemotherapy-induced neuropathy [29–31 and diabetic peripheral neuropathy [32].”
BackgroundMethodInfluentialDual effect of anandamide on spinal nociceptive transmission in control and inflammatory conditions
Pontearso, M., Slepicka, J., Bhattacharya, A., Spicarova, D., & Paleček, J. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116369 · Cited by 6
Non-endocannabinoid N-Acylethanolamines and Monoacylglycerols: Old Molecules New Targets
Hansen, H. S., Kleberg, K., & Hassing, H. A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-420126-2.00001-8 · Cited by 6
Effect of Fatty Acid Amide Hydrolase Inhibitor URB597 on Orofacial Pain Perception in Rats
Zubrzycki, M., Zubrzycka, M., Wysiadecki, G., Szemraj, J., Jerczyńska, H., & Stasiołek, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094665 · Cited by 6
“Previous studies have shown that FAAH inhibitors that act by increasing endocannabinoid levels and extending their duration of action without eliciting the psychoactive effects related to direct CB1 receptor activation may offer a promising treatment option for headaches [21,22,25,31,34].”
BackgroundDifferential inhibitory effects of endocannabinoids on neuronal firing of mouse meningeal afferents
Krivoshein, G., Pietra, A. D., Savinainen, J. R., van den Maagdenberg, A. M. J. M., & Giniatullin, R. A. (2025) · The Journal of Headache and Pain · doi:10.1186/s10194-025-02041-z · Cited by 5
“In the presence of CB1 activity, nociceptive signals originating from the peripheral TGVS are blocked and do not reach the central nervous system [8–10] and CB2 receptor activation was shown to counteract acute migraine-like pain in a rat model [11].”
Warren, W. G., Osborn, M., David-Pereira, A., Tsantoulas, C., Xue, W., Yates, A., & O’Sullivan, S. E. (2024) · European Journal of Pain · doi:10.1002/ejp.4718 · Cited by 5
Modulation of Pain by Endocannabinoids in the Periphery
Uhelski, M. L., Khasabova, I. A., & Simone, D. A. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.79673 · Cited by 5
“neuropathic pain) and carrageenan-induced inflammation in the affected hind paw, but did not alter responses on the non-affected hind paw [81, 82].”
BackgroundA review of the patent literature surrounding TRPV1 modulators
Devesa, I., Fernandez-Ballester, G. J., Fernández-Carvajal, A. M., & Ferrer-Montiel, A. V. (2025) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2025.2467698 · Cited by 4
“Genetic or pharmacological inactivation of FAAH produces analgesic, anti-inflammatory, anxio-lytic and antidepressant phenotypes, suggesting that FAAH is a promising therapeutic target [69].”
Characterization of URB Series Synthetic Cannabinoids by HRMS and UHPLC–MS/MS
Agostini, M., Favretto, D., Renzoni, C., Vogliardi, S., & Duranti, A. (2023) · Pharmaceuticals · doi:10.3390/ph16020201 · Cited by 4
“Data regarding mp, NMR, and IR are present in [41,44,45,51,52].”
BackgroundInfluentialSelf-citationRamsay, S. D., Spencer, N. J., & Zagorodnyuk, V. P. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175624 · Cited by 4
Endocannabinoids rein in pain outside the brain
Lovinger, D. M. (2010) · Nature Neuroscience · doi:10.1038/nn1010-1155 · Cited by 4
Involvement of cannabinoid type 1 receptor in fasting-induced analgesia
Lee, J.-Y., Lee, G. J., Nakamura, A., Lee, P. R., Kim, Y., Won, C. H., Furue, H., & Oh, S. B. (2020) · Molecular Pain · doi:10.1177/1744806920969476 · Cited by 4
“16 In addition, sensory neuron-specific CB1 knockout mice showed increased basal pain sensitivity.”
Complementary and Alternative Medicine
Price, K. N., Thompson, A. M., & Shi, V. Y. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-77724-7.00028-0 · Cited by 4
Arias‐Gaguancela, O., Herrell, E., Aziz, M., & Chapman, K. D. (2023) · Scientific Reports · doi:10.1038/s41598-023-34754-z · Cited by 4
Heiliczer, S., Yanko, R., Sharav, Y., Aframian, D., Klutstein, M., Wilensky, A., & Haviv, Y. (2023) · The Journal of the American Dental Association (1939) · doi:10.1016/j.adaj.2023.08.014 · Cited by 4
Cannabinoids and Endocannabinoids
Jung, K., & Piomelli, D. (2015) · Springer eBooks · doi:10.1007/978-1-4614-6434-1_136-1 · Cited by 4
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
Cannabinoids and Endocannabinoids
Jung, K., & Piomelli, D. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3474-4_136 · Cited by 4
Self-citationNanì, M. F., Rinaldi, M. M., Miraglia, M., Amico, K. R., Cicco, P. D., & Romano, B. (2025) · Progress in Lipid Research · doi:10.1016/j.plipres.2025.101358 · Cited by 3
Bruijnzeel, A. W., Behnood‐Rod, A., Chellian, R., Malphurs, W. L., Caudle, R. M., Febo, M., Setlow, B., Murphy, N. P., & Neubert, J. K. (2026) · Scientific Reports · doi:10.1038/s41598-025-31828-y · Cited by 3
Greco, R., & Tassorelli, C. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-417041-4.00007-2 · Cited by 3
The Endocannabinoid System in Local and Systemic Inflammation
Kelly, M. E. M., Lehmann, C., & Zhou, J. (2017) · Colloquium Series on Integrated Systems Physiology From Molecule to Function · doi:10.4199/c00151ed1v01y201702isp074 · Cited by 4
Kumar, R., Prasoon, P., Gautam, M., & Ray, S. B. (2016) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_1402_15 · Cited by 3
Endocannabinoid biochemistry: What do we know after 50 years?
Fezza, F., & Maccarrone, M. (2014) · Wiley eBooks · doi:10.1002/9781118451281.ch3 · Cited by 3
Lai, M., Rocca, V. L., Amato, R., Iacono, E., Filipponi, C., Catelli, E., Bogani, L., Fonnesu, R., Lottini, G., Carli, A. D., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.08.479661 · Cited by 3
Self-citationDistinct endocannabinoids specifically signal to astrocytes and neuronsPreprint
Noriega‐Prieto, J. A., Falcón‐Moya, R., Eraso‐Pichot, A., Fundazuri, U. B., Guttipatti, P., Belisle, L., Moreno, A. R., van der Stelt, M., Cheer, J. F., Marsicano, G., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.13.544877 · Cited by 3
“, 2009), AEA has also been shown to act through CB1 receptors in various neurobiological contexts (Clapper et al., 2010; Kinsey et al., 2009; Straiker et al., 2011).”
BackgroundState of the Art Review: Thiazide Diuretics Exploit the Endocannabinoid System via NAPE-PLD
Garau, G. (2025) · American Journal of Hypertension · doi:10.1093/ajh/hpaf174 · Cited by 2
Understanding and Targeting the Endocannabinoid System with Activity‐Based Protein Profiling
Zhu, N., Janssen, A. P. A., & van der Stelt, M. (2023) · Israel Journal of Chemistry · doi:10.1002/ijch.202200115 · Cited by 2
Kingwell, K. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3300 · Cited by 2
- Simple Lipids with Two Different Components
Leray, C. (2012) · CRC Press eBooks · doi:10.1201/b12894-8 · Cited by 2
Neural Secretions and Regulation of Gut Functions
Welcome, M. O. (2018) · Springer eBooks · doi:10.1007/978-3-319-91056-7_9 · Cited by 3
Takizawa, M., Cerneus, D. P., Michon, I. N., Rijnders, S., van der Heide, D., Meijer, J., Stoelzel, M., & Sato, Y. Z. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01402-1 · Cited by 2
Lifestyle modifications and complementary treatments for hidradenitis suppurativa
De, D. R., Rick, J. W., Shih, T., Alavi, A., Hsiao, J. L., & Shi, V. Y. (2022) · Dermatological Reviews · doi:10.1002/der2.117 · Cited by 2
“Anandamide is a CB1 agonist that interacts with vanilloid receptors to regulate nociceptive signals, pain, and itch, to the peripheral nervous system.(86,87) Cannabinoids may have an analgesic effect through inhibition of the release of calcitonin gene‐related peptide, which is stored in sensory neurons and involved i…”
Background‘’The Science Behind Raj Yoga Meditation-A Narrative Review’’
(2023) · Advancement in Yoga and Physical Therapy · doi:10.33140/aypt.01.02.01 · Cited by 2
Promising Inhibitors of Endocannabinoid Degrading Enzymes Sharing a Carbamate Scaffold
Jaiswal, S., & Ayyannan, S. R. (2024) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/0113895575328120241107061303 · Cited by 1
Bhattacharya, A., Vasconcelos, D., Spicarova, D., & Paleček, J. (2025) · Scientific Reports · doi:10.1038/s41598-025-98567-y · Cited by 1
“The AEA-induced analgesia was recognized to be underlined by a peripheral mechanism via CB 1 receptor activation in the animal model of neuropathic pain, while increased AEA levels were achieved with a peripherally restricted FAAH inhibitor (URB937) 2 .”
The day anandamide almost died, and other endocannabinoid stories
Piomelli, D. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-13908-6.00004-9 · Cited by 1
Self-citationEvaluating FABP5 as a Therapeutic Target for Pain Management
Warren, W. G., Osborn, M., Kaczocha, M., Yates, A. S., & O’Sullivan, S. E. (2026) · European Journal of Pain · doi:10.1002/ejp.70267 · Cited by 1
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
“URB937 ([3-(3-carbamoylphenyl)-4-hydroxy-phenyl] N-cyclohexyl-carbamate), a derivative of URB597, is a peripherally restricted FAAH inhibitor that selectively increases AEA outside the CNS [115].”
Kingwell, K. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2939 · Cited by 1
Effects of URB937 on an animal model of migraine pain
Greco, R., Mangione, A. S., Icco, R. D., Bandiera, T., Sandrini, G., Nappi, G., Piomelli, D., & Tassorelli, C. (2013) · The Journal of Headache and Pain · doi:10.1186/1129-2377-14-s1-p68 · Cited by 1
Self-citationSimple Lipids with Two Different Components
(2012) · CRC Press eBooks · doi:10.1201/b12894-4 · Cited by 1
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
Implication of the endocannabidiome and metabolic pathways in fragile X syndrome pathophysiology
Dionne, O., Abolghasemi, A., Corbin, F., & Çaku, A. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.115962 · Cited by 1
“The CB1 receptor is also expressed in the peripheral nervous system and some peripheral tissues, such as gastrointestinal tract (neuronal and non-neuronal cells), liver, adipocytes, muscle, skin, and reproductive system (Clapper et al., 2010; Izzo and Sharkey, 2010; Maccarrone et al., 2015).”
The Endocannabinoid System and the Early Development of the Brain
Thapa, S., & Bukiya, A. N. (2025) · Springer eBooks · doi:10.1007/978-3-031-87990-6_4 · Cited by 1
Katz, P. S., Edwards, S., & Molina, P. E. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1071-7_23 · Cited by 1
Control of analgesic and anti-inflammatory pathways by fatty acid amide hydrolase
Long, J. H. (2012) · Cited by 1
Metadata
- Authors
- Clapper, J. R., Moreno-Sanz, G., Russo, R., Guijarro, A., Vacondio, F., Duranti, A., Tontini, A., Sanchini, S., Sciolino, N. R., Spradley, J. M., Hohmann, A. G., Calignano, A., Mor, M., Tarzia, G., & Piomelli, D.
- Affiliations
- University of California, Irvine (US)
- University of Naples Federico II (IT)
- University of Parma (IT)
- University of Urbino (IT)
- University of Georgia (US)
- Corresponding author
- Piomelli, Daniele
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2010-09-19
- Volume
- 13
- Issue
- 10
- Pages
- 1265-1270
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3260554
- OpenAlex
- W2143684129
- Cited by
- 346
- References
- 52
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 13 · 2023: 21 · 2022: 23 · 2021: 17 · 2020: 21 · 2019: 18 · 2018: 14 · 2017: 23 · 2016: 24 · 2015: 27 · 2014: 32 · 2013: 31 · 2012: 34
- FWCI
- 22.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Funders
- National Institute on Drug Abuse (R01DA012413)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- anandamide, CB1 receptor, fatty acid amide hydrolase, FAAH inhibitors, chronic pain, peripheral nerve injury, inflammation, spinal cord nociception, analgesia, blood-brain barrier
- MeSH terms
- Rimonabant, Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonic Acids, Cannabinoids, Carrageenan, Chlorobenzenes, Chromatography, Liquid, Disease Models, Animal, Drug Administration Routes, Drug Administration Schedule, Enzyme Inhibitors, Escape Reaction, Ethylene Glycols, Feeding Behavior, Formaldehyde, Gene Expression Regulation, Hyperalgesia, Indoles, Male, Mice, Inbred C57BL, Monoacylglycerol Lipases, Motor Activity, Pain, Pain Measurement, Peripheral Nervous System Diseases, Piperidines, Pyrazoles, Sciatica, Mass Spectrometry, Spinal Cord, Time Factors, Tissue Distribution, Tritium, Oncogene Proteins v-fos, Rats, Sprague-Dawley, Pain Threshold, Mice, Knockout, Statistics, Nonparametric, PPAR alpha, Mice, Rats, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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
