Cited by 795Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsNeuropeptides and Animal Physiology

The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.

An endocannabinoid mechanism for stress-induced analgesia

Open access

Hohmann, Andrea G., Suplita, Richard L., Bolton, Nathan M., Neely, Mark H., Fegley, Darren, Mangieri, Regina, Krey, Jocelyn F., Michael Walker, J., Holmes, Philip V., Crystal, Jonathon D., Duranti, Andrea, Tontini, Andrea, Mor, Marco, Tarzia, Giorgio, Piomelli, Daniele·2005·Nature

DOI 10.1038/nature03658

Open this paper in CoChat — free account

Abstract

Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

Integrity signals

Registry

Crossref · 10.1038/nature03658

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

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
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N. E., Schatz, A. R., Gopher, A., Almog, S., Martin, B. R., Compton, D. R., et al. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00109-d · Cited by 2,913
Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study
Herkenham, M., Lynn, A., Johnson, M., Melvin, L., de Costa, B., & Rice, K. (1991) · The Journal of Neuroscience · doi:10.1523/jneurosci.11-02-00563.1991 · Cited by 2,159
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957
Self-citation
Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system
Tsou, K., Brown, S., Sañudo-Peña, M. C., Mackie, K., & Walker, J. M. (1998) · Neuroscience · doi:10.1016/s0306-4522(97)00436-3 · Cited by 1,586
A second endogenous cannabinoid that modulates long-term potentiation
Stella, N., Schweitzer, P., & Piomelli, D. (1997) · Nature · doi:10.1038/42015 · Cited by 1,496
Self-citation
Brain monoglyceride lipase participating in endocannabinoid inactivation
Dinh, T. P., Carpenter, D., Leslie, F. M., Freund, T. F., Katona, I., Sensi, S. L., Kathuria, S., & Piomelli, D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152334899 · Cited by 1,373
Self-citation
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-citation
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
Zimmer, A., Zimmer, A. M., Hohmann, A. G., Herkenham, M. A., & Bonner, T. I. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5780 · Cited by 1,078
Self-citation

Show all 30 references

Research works printed but not linked: 1

Walker, J. M. & Hohmann, A. G. in Cannabinoids—Handbook of Experimental Pharmacology (ed. Pertwee, R.) 509–554 (Springer, Berlin, 2005)

Sorted by citations

The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077
Polyunsaturated fatty acids and their metabolites in brain function and disease
Bazinet, R. P., & Layé, S. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3820 · Cited by 1,703
Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.
Russo, E. B. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01238.x · Cited by 1,535
Endocannabinoid-Mediated Control of Synaptic Transmission
Kano, M., Ohno‐Shosaku, T., Hashimotodani, Y., Uchigashima, M., & Watanabe, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00019.2008 · Cited by 1,595
A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol
Blankman, J. L., Simon, G. M., & Cravatt, B. F. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.11.006 · Cited by 1,177
Central modulation of pain
Ossipov, M. H., Dussor, G. O., & Porreca, F. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43766 · Cited by 1,234
Descending control of nociception: Specificity, recruitment and plasticity
Heinricher, M. M., Tavares, I., Leith, J. L., & Lumb, B. M. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.12.009 · Cited by 953
Effects of cannabinoids and cannabinoid‐enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
De Petrocellis, L., Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., Stott, C. G., & Di Marzo, V. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01166.x · Cited by 946
Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
Long, J. Z., Li, W., Booker, L., Burston, J. J., Kinsey, S. G., Schlosburg, J. E., Pavón, F. J., Serrano, A., Selley, D. E., Parsons, L. H., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.129 · Cited by 954
Olfactory exposure to males, including men, causes stress and related analgesia in rodents
Sorge, R. E., Martin, L. J., Isbester, K. A., Sotocinal, S. G., Rosen, S., Tuttle, A. H., Wieskopf, J. S., Acland, E. L., Dokova, A., Kadoura, B., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2935 · Cited by 905
Targeting the endocannabinoid system: to enhance or reduce?
Marzo, V. D. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2553 · Cited by 822
Stress-induced analgesia
Butler, R. K., & Finn, D. P. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.04.003 · Cited by 768
Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis
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 692
Self-citation
Neurobiological Interactions Between Stress and the Endocannabinoid System
Morena, M., Patel, S., Bains, J. S., & Hill, M. N. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.166 · Cited by 698
Multiple Functions of Endocannabinoid Signaling in the Brain
Katona, I., & Freund, T. F. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150420 · Cited by 630
Endocannabinoid signaling as a synaptic circuit breaker in neurological disease
Katona, I., & Freund, T. F. (2008) · Nature Medicine · doi:10.1038/nm.f.1869 · Cited by 579
Enzymatic pathways that regulate endocannabinoid signaling in the nervous system
Ahn, K., McKinney, M. K., & Cravatt, B. F. (2008) · Chemical Reviews · doi:10.1021/cr0782067 · Cited by 529
From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology
Ligresti, A., PETROCELLIS, L. D., & Marzo, V. D. (2016) · Physiological Reviews · doi:10.1152/physrev.00002.2016 · Cited by 505
The Endocannabinoid System and Pain
Guindon, J., & Hohmann, A. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709789824660 · Cited by 476
Self-citation
When does acute pain become chronic?
Voscopoulos, C., & Lema, M. (2010) · British Journal of Anaesthesia · doi:10.1093/bja/aeq323 · Cited by 473
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 451
Self-citation
The transition of acute postoperative pain to chronic pain: an integrative overview of research on mechanisms
Chapman, C. R., & Vierck, C. J. (2017) · The Journal of Pain · doi:10.1016/j.jpain.2016.11.004 · Cited by 423
Neurobiology of addiction
Goodman, A. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.030 · Cited by 445
A neuroscientist's guide to lipidomics
Piomelli, D., Astarita, G., & Rapaka, R. S. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2233 · Cited by 399
Self-citation
Enzyme Inhibitor Discovery by Activity-Based Protein Profiling
Niphakis, M. J., & Cravatt, B. F. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035708 · Cited by 374
Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats
Campos, A. C., & Guimarães, F. S. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1168-x · Cited by 364
Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand
SUGIURA, T., KISHIMOTO, S., OKA, S., & Gokoh, M. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2006.03.003 · Cited by 374
Inactivation of N-Acyl Phosphatidylethanolamine Phospholipase D Reveals Multiple Mechanisms for the Biosynthesis of Endocannabinoids
Leung, D., Saghatelian, A., Simon, G. M., & Cravatt, B. F. (2006) · Biochemistry · doi:10.1021/bi060163l · Cited by 354
Relations between nonsuicidal self-injury and suicidal behavior in adolescence: a systematic review
Grandclerc, S., De Labrouhe, D., Spodenkiewicz, M., Lachal, J., & Moro, M.-R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153760 · Cited by 332
Blockade of Endocannabinoid-Degrading Enzymes Attenuates Neuropathic Pain
Kinsey, S. G., Long, J. Z., O’Neal, S. T., Abdullah, R. A., Poklis, J. L., Boger, D. L., Cravatt, B. F., & Lichtman, A. H. (2009) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.155465 · Cited by 330
Chemical Probes of Endocannabinoid Metabolism
Blankman, J. L., & Cravatt, B. F. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.006387 · Cited by 327
Cannabis, the mind and society: the hash realities
Murray, R. M., Morrison, P. D., Henquet, C., & Forti, M. D. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2253 · Cited by 329
Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond
Pertwee, R. G. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00108.x · Cited by 326
Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
Rahn, E. J., & Hohmann, A. G. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.08.002 · Cited by 305
Self-citation
Cannabinoids in the management of difficult to treat pain
Russo, E. B. (2008) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s1928 · Cited by 300
Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory
Campolongo, P., Roozendaal, B., Trezza, V., Hauer, D., Schelling, G., McGaugh, J. L., & Cuomo, V. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900835106 · Cited by 294
Descending modulation of pain: the GABA disinhibition hypothesis of analgesia
Lau, B. K., & Vaughan, C. W. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.07.010 · Cited by 294
Elevation of Endocannabinoid Levels in the Ventrolateral Periaqueductal Grey through Inhibition of Fatty Acid Amide Hydrolase Affects Descending Nociceptive Pathways via Both Cannabinoid Receptor Type 1 and Transient Receptor Potential Vanilloid Type-1 Receptors
Maione, S., Bisogno, T., de Novellis, V., Palazzo, E., Cristino, L., Valenti, M., Petrosino, S., Guglielmotti, V., Rossi, F., & Marzo, V. D. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.093286 · Cited by 299
Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models
Jayamanne, A., Greenwood, R., Mitchell, V. A., Aslan, S., Piomelli, D., & Vaughan, C. W. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706510 · Cited by 287
Self-citation
Cannabis and Pain: A Clinical Review
Hill, K. P., Palastro, M. D., Johnson, B., & Ditre, J. W. (2017) · Cannabis and Cannabinoid Research · doi:10.1089/can.2017.0017 · Cited by 282
Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses
Busquets-Garcia, A., Puighermanal, E., Pastor, A., de la Torre, R., Maldonado, R., & Ozaita, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.022 · Cited by 273
Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease
Chen, R., Zhang, J., Wu, Y., Wang, D., Feng, G., Tang, Y., Teng, Z., & Chen, C. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.09.030 · Cited by 277
Endocannabinoid signaling in microglial cells
Stella, N. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.037 · Cited by 278
The cannabinoid system and pain
Woodhams, S. G., Chapman, V., Finn, D. P., Hohmann, A. G., & Neugebauer, V. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.06.015 · Cited by 285
Self-citation
Supply and demand for endocannabinoids
Alger, B. E., & Kim, J. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.03.003 · Cited by 284
Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats
de Bitencourt, R. M., Pamplona, F. A., & Takahashi, R. N. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2008.07.001 · Cited by 277
Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies
Finn, D. P., Haroutounian, S., Hohmann, A. G., Krane, E. J., Soliman, N., & Rice, A. S. C. (2021) · Pain · doi:10.1097/j.pain.0000000000002268 · Cited by 280
Self-citation
Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites
Turcotte, C., Chouinard, F., Lefebvre, J. S., & Flamand, N. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ru0115-021r · Cited by 258
Presynaptic Modulation by Endocannabinoids
Lovinger, D. M. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-74805-2_14 · Cited by 247
Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice
Monory, K., Blaudzun, H., Massa, F., Kaiser, N., Lemberger, T., Schütz, G., Wotjak, C. T., Lutz, B., & Marsicano, G. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050269 · Cited by 261
Peripheral gating of pain signals by endogenous lipid mediators
Piomelli, D., & Sasso, O. (2014) · Nature Neuroscience · doi:10.1038/nn.3612 · Cited by 240
Self-citation
Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids
Hill, M. N., & McEwen, B. S. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.11.001 · Cited by 235
Effects of acute and repeated restraint stress on endocannabinoid content in the amygdala, ventral striatum, and medial prefrontal cortex in mice
Rademacher, D. J., Meier, S. E., Shi, L., Vanessa Ho, W.-S., Jarrahian, A., & Hillard, C. J. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.06.012 · Cited by 233
Anxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404
Bortolato, M., Campolongo, P., Mangieri, R. A., Scattoni, M. L., Frau, R., Trezza, V., Rana, G. L., Russo, R., Calignano, A., Gessa, G. L., et al. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301061 · Cited by 236
Self-citation
Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus
Makara, J. K., Mor, M., Fegley, D., Szabó, S. I., Kathuria, S., Astarita, G., Duranti, A., Tontini, A., Tarzia, G., Rivara, S., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1521 · Cited by 235
Self-citation
Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex®, a Cannabis‐Based Medicine
Russo, E. B., Guy, G. W., & Robson, P. (2007) · Chemistry & Biodiversity · doi:10.1002/cbdv.200790150 · Cited by 228
Monoacylglycerol Lipase Activity Is a Critical Modulator of the Tone and Integrity of the Endocannabinoid System
Chanda, P. K., Gao, Y., Mark, L., Btesh, J., Strassle, B. W., Lu, P., Piesla, M. J., Zhang, M.-Y., Bingham, B., Uveges, A. J., et al. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.068304 · Cited by 236
Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats
Petrosino, S., Palazzo, E., de Novellis, V., Bisogno, T., Rossi, F., Maione, S., & Di Marzo, V. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.08.011 · Cited by 227
Mechanism of Carbamate Inactivation of FAAH: Implications for the Design of Covalent Inhibitors and In Vivo Functional Probes for Enzymes
Alexander, J. P., & Cravatt, B. F. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.08.011 · Cited by 227
2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain
Baggelaar, M. P., Maccarrone, M., & van der Stelt, M. (2018) · Progress in Lipid Research · doi:10.1016/j.plipres.2018.05.002 · Cited by 224
The endocannabinoid system: emotion, learning and addiction
Moreira, F. A., & Lutz, B. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00104.x · Cited by 233
Novel Mechanistic Class of Fatty Acid Amide Hydrolase Inhibitors with Remarkable Selectivity
Ahn, K., Johnson, D. S., Fitzgerald, L. R., Liimatta, M. B., Arendse, A., Stevenson, T. I., Lund, E. T., Nugent, R. A., Nomanbhoy, T. K., Alexander, J. P., et al. (2007) · Biochemistry · doi:10.1021/bi701378g · Cited by 217
Targeting CB2 receptors and the endocannabinoid system for the treatment of pain
Anand, P., Whiteside, G. T., Fowler, C. J., & Hohmann, A. G. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.12.003 · Cited by 220
Self-citation
Effects of endocannabinoid system modulation on cognitive and emotional behavior
Zanettini, C. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00057 · Cited by 214
The role of corticosteroids and stress in chronic pain conditions
McEwen, B. S., & Kalia, M. (2010) · Metabolism · doi:10.1016/j.metabol.2010.07.012 · Cited by 213
Endocannabinoid mechanisms of pain modulation
Hohmann, A. G., & Suplita, R. L. (2006) · The AAPS Journal · doi:10.1208/aapsj080479 · Cited by 217
Self-citation
A FAAH-Regulated Class of N- Acyl Taurines That Activates TRP Ion Channels
Saghatelian, A., McKinney, M. K., Bandell, M., Patapoutian, A., & Cravatt, B. F. (2006) · Biochemistry · doi:10.1021/bi0608008 · Cited by 216
Regulation of endocannabinoid signaling by stress: Implications for stress-related affective disorders
Gorzalka, B. B., Hill, M. N., & Hillard, C. J. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.03.004 · Cited by 211
The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats
Pamplona, F. A., Prediger, R. D. S., Pandolfo, P., & Takahashi, R. N. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0514-0 · Cited by 211
The Role of the Endocannabinoid System in Pain
Woodhams, S. G., Sagar, D. R., Burston, J. J., & Chapman, V. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-662-46450-2_7 · Cited by 216
The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids
Pertwee, R. G. (2005) · The AAPS Journal · doi:10.1208/aapsj070364 · Cited by 218
Sex and hormonal cycle differences in rat brain levels of pain-related cannabimimetic lipid mediators.
Bradshaw, H. B., Rimmerman, N., Krey, J. F., & Walker, J. M. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00933.2005 · Cited by 202
Self-citation
European Pain Federation ( EFIC ) position paper on appropriate use of cannabis‐based medicines and medical cannabis for chronic pain management
Häuser, W., Finn, D. P., Kalso, E. A., Krcevski‐Škvarč, N., Kress, H. G., Morlion, B. J., Perrot, S., Schäfer, M., Wells, C., & Brill, S. (2018) · European Journal of Pain · doi:10.1002/ejp.1297 · Cited by 211
Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders
Ahn, K., Johnson, D. S., & Cravatt, B. F. (2009) · Expert Opinion on Drug Discovery · doi:10.1517/17460440903018857 · Cited by 205
Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain
Roques, B. P., Fournié‐Zaluski, M., & Wurm, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3673 · Cited by 198
Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes
Russo, E. B. (2016) · Cannabis and Cannabinoid Research · doi:10.1089/can.2016.0009 · Cited by 193
Cannabinoids and Pain: Sites and Mechanisms of Action
Starowicz, K., & Finn, D. P. (2017) · Advances in pharmacology · doi:10.1016/bs.apha.2017.05.003 · Cited by 203
Endocannabinoid system, stress and HPA axis
Micale, V., & Drago, F. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.07.039 · Cited by 189
Cannabinoids potentiate emotional learning plasticity in neurons of the medial prefrontal cortex through basolateral amygdala inputs
Laviolette, S. R., & Grace, A. A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0707-06.2006 · Cited by 189
Crystal Structure of the Human Monoacylglycerol Lipase, a Key Actor in Endocannabinoid Signaling
Labar, G., Bauvois, C., Borel, F., Ferrer, J.-L., Wouters, J., & Lambert, D. M. (2009) · ChemBioChem · doi:10.1002/cbic.200900621 · Cited by 195
Pain, decisions, and actions: a motivational perspective
Wiech, K., & Tracey, I. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00046 · Cited by 188
Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways
İnceoğlu, B., Jinks, S. L., Ulu, A., Hegedus, C. M., Georgi, K., Schmelzer, K. R., Wagner, K. M., Jones, P. D., Morisseau, C. H. P., & Hammock, B. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809765105 · Cited by 188
Divergent Modulation of Nociception by Glutamatergic and GABAergic Neuronal Subpopulations in the Periaqueductal Gray
Samineni, V. K., Grajales‐Reyes, J. G., Copits, B. A., O’Brien, D. E., Trigg, S. L., Gomez, A. M., Bruchas, M. R., & Gereau, R. W. (2017) · eNeuro · doi:10.1523/eneuro.0129-16.2017 · Cited by 188
The major central endocannabinoid directly acts at GABA A receptors
Sigel, E., Baur, R., Rácz, I., Marazzi, J., Smart, T. G., Zimmer, A., & Gertsch, J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113444108 · Cited by 187
ChemDB: a public database of small molecules and related chemoinformatics resources
Chen, J. H., Swamidass, S. J., Dou, Y., Bruand, J., & Baldi, P. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti683 · Cited by 187
Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years
Maccarrone, M., Di Marzo, V., Gertsch, J., Grether, U., Howlett, A. C., Hua, T., Makriyannis, A., Piomelli, D., Ueda, N., & van der Stelt, M. (2023) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000600 · Cited by 183
Self-citation
Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders
Deng, H., & Li, W. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.10.006 · Cited by 189
Exercise-induced endocannabinoid signaling is modulated by intensity
Raichlen, D. A., Foster, A. D., Seillier, A., Giuffrida, A., & Gerdeman, G. L. (2013) · European Journal of Applied Physiology · doi:10.1007/s00421-012-2495-5 · Cited by 181
Activation of Orexin 1 Receptors in the Periaqueductal Gray of Male Rats Leads to Antinociception via Retrograde Endocannabinoid (2-Arachidonoylglycerol)-Induced Disinhibition
Ho, Y., Lee, H., Tung, L.-W., Liao, Y.-Y., Fu, S.-Y., Teng, S.-F., Liao, H.-T., Mackie, K., & Chiou, L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2671-11.2011 · Cited by 180
Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors
Serrano, A., & Parsons, L. H. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.06.005 · Cited by 188
Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in rats
Sciolino, N. R., Zhou, W., & Hohmann, A. G. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.04.010 · Cited by 179
Self-citation
Distribution of the Endocannabinoid System in the Central Nervous System
Hu, S. S., & Mackie, K. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-20825-1_3 · Cited by 187
Identification of a Novel Endocannabinoid-Hydrolyzing Enzyme Expressed by Microglial Cells
Muccioli, G. G., Xu, C., Odah, E., Cudaback, E., Cisneros, J. A., Lambert, D. M., López-Rodríguez, M. L., Bajjalieh, S., & Stella, N. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4830-06.2007 · Cited by 175
Extended Swimming Exercise Reduces Inflammatory and Peripheral Neuropathic Pain in Rodents
Kuphal, K. E., Fibuch, E. E., & Taylor, B. K. (2007) · Journal of Pain · doi:10.1016/j.jpain.2007.08.001 · Cited by 170
Structural Basis for Human Monoglyceride Lipase Inhibition
Bertrand, T., Augé, F., Houtmann, J., Rak, A., Vallée, F., Mikol, V., Berne, P., Michot, N., Cheuret, D., Hoornaert, C., et al. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.11.060 · Cited by 176
Role of the endocannabinoid system in regulation of the hypothalamic-pituitary-adrenocortical axis
Steiner, M. S., & Wotjak, C. T. (2008) · Progress in brain research · doi:10.1016/s0079-6123(08)00433-0 · Cited by 174
Endogenous Cannabinoids: Structure and Metabolism
Bisogno, T. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01676.x · Cited by 170
Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System
McPartland, J. M., Guy, G. W., & Marzo, V. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089566 · Cited by 168
Quantification of brain endocannabinoid levels: methods, interpretations and pitfalls
Buczynski, M. W., & Parsons, L. H. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00787.x · Cited by 171
Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain
Jhaveri, M. D., Richardson, D., Kendall, D. A., Barrett, D. A., & Chapman, V. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3326-06.2006 · Cited by 159

Authors: Hohmann, A. G., Suplita, R. L., Bolton, N. M., Neely, M. H., Fegley, D., Mangieri, R., Krey, J. F., Michael Walker, J., Holmes, P. V., Crystal, J. D., Duranti, A., Tontini, A., Mor, M., Tarzia, G., & Piomelli, D.
Affiliations: University of Georgia (US)
University of California, Irvine (US)
Brown University (US)
University of Urbino (IT)
University of Parma (IT)
Corresponding author: Hohmann, Andrea G.
Piomelli, Daniele
ORCID: Hohmann, Andrea G.
Bolton, Nathan M.
Mangieri, Regina
Krey, Jocelyn F.
Holmes, Philip V.
Crystal, Jonathon D.
Duranti, Andrea
Tontini, Andrea
Mor, Marco
Piomelli, Daniele
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-06
Volume: 435
Issue: 7045
Pages: 1108-1112
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature03658
OpenAlex: W2030777873
Cited by: 778
References: 30
Citations by year: 2026: 14 · 2025: 24 · 2024: 22 · 2023: 22 · 2022: 28 · 2021: 26 · 2020: 22 · 2019: 20 · 2018: 29 · 2017: 53 · 2016: 34 · 2015: 38 · 2014: 40 · 2013: 33 · 2012: 45
FWCI: 39.98
Type: journal article
Language: en
Open access: green
escholarship.org
Licence: cc-by
www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: stress-induced analgesia, endocannabinoid system, CB1 receptor, periaqueductal gray, 2-arachidonoylglycerol, anandamide, monoacylglycerol lipase, fatty acid amide hydrolase, opioid-independent analgesia, pain inhibition, stress-related disorders, therapeutic target
MeSH terms: Analgesia, Animals, Arachidonic Acids, Biological Transport, Biphenyl Compounds, Glycerides, Hydrolysis, Male, Mesencephalon, Monoacylglycerol Lipases, Stress, Physiological, Rats, Sprague-Dawley, Rats, Wistar, Receptor, Cannabinoid, CB1, Rats, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids, In Vitro Techniques

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

An endocannabinoid mechanism for stress-induced analgesia

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks