The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase
Open accessAbstract
The medicinal properties of marijuana have been recognized for centuries, but clinical and societal acceptance of this drug of abuse as a potential therapeutic agent remains fiercely debated. An attractive alternative to marijuana-based therapeutics would be to target the molecular pathways that mediate the effects of this drug. To date, these neural signaling pathways have been shown to comprise a cannabinoid receptor (CB 1 ) that binds the active constituent of marijuana, tetrahydrocannabinol (THC), and a postulated endogenous CB 1 ligand anandamide. Although anandamide binds and activates the CB 1 receptor in vitro , this compound induces only weak and transient cannabinoid behavioral effects in vivo , possibly a result of its rapid catabolism. Here we show that mice lacking the enzyme fatty acid amide hydrolase (FAAH −/− ) are severely impaired in their ability to degrade anandamide and when treated with this compound, exhibit an array of intense CB 1 -dependent behavioral responses, including hypomotility, analgesia, catalepsy, and hypothermia. FAAH −/− -mice possess 15-fold augmented endogenous brain levels of anandamide and display reduced pain sensation that is reversed by the CB 1 antagonist SR141716A. Collectively, these results indicate that FAAH is a key regulator of anandamide signaling in vivo , setting an endogenous cannabinoid tone that modulates pain perception. FAAH may therefore represent an attractive pharmaceutical target for the treatment of pain and neuropsychiatric disorders.
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In the citing paper
“AEA and 2-AG are rapidly hydrolyzed by fatty acid amide hydrolase (FAAH) (Cravatt et al, 1996(Cravatt et al, , 2001)), and monoacylglycerol lipase (MAGL) (Dinh et al, 2002), respectively.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Cravatt et al, 2001
In the citing paper
“FAAH-/- mice are hypoalgesic in models of acute and inflammatory pain; these effects are blocked by a CB1 antagonist.29, 30”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [29]
Citations
Cites
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909
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
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
Self-citation2-Arachidonoylgylcerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain
Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., & Waku, K. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2437 · Cited by 2,196
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
Zygmunt, P. M., Petersson, J., Andersson, D. A., Chuang, H.-H., Sørgård, M., Di Marzo, V., Julius, D., & Högestätt, E. D. (1999) · Nature · doi:10.1038/22761 · Cited by 2,142
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
Self-citationSR141716A, a potent and selective antagonist of the brain cannabinoid receptor
Rinaldi, M. L., Barth, F., Héaulme, M., Shire, D. J., Calandra, B., Congy, C., Martinez, S., Maruani, J., Neliat, G., Caput, D., et al. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00773-x · Cited by 1,762
Formation and inactivation of endogenous cannabinoid anandamide in central neurons
Marzo, V. D., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.-C., & Piomelli, D. (1994) · Nature · doi:10.1038/372686a0 · Cited by 1,585
Pharmacology of cannabinoid CB1 and CB2 receptors
Pertwee, R. G. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(97)82001-3 · Cited by 1,526
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Research works printed but not linked: 3
- P B Smith, D R Compton, S P Welch, R K Razdan, R Mechoulam, B R Martin J Pharmacol Exp Ther 270, 219–227 (1994).
- I B Adams, D R Compton, B R Martin J Pharmacol Exp Ther 284, 1209–1217 (1998).
- K A Willoughby, S F Moore, B R Martin, E F Ellis J Pharmacol Exp Ther 282, 243–247 (1997).
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Items 101–103 of 103
p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus
Xia, S., Zhou, Z., Leung, C., Zhu, Y., Pan, X., Qi, J., Morena, M., Hill, M. N., Xie, W., & Jia, Z. (2016) · eLife · doi:10.7554/elife.14653 · Cited by 21
URB597, an inhibitor of fatty acid amide hydrolase, reduces hyperalgesia in diabetic rats
Hasanein, P., Parviz, M., Keshavarz, M., & Roohbakhsh, A. (2009) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y09-026 · Cited by 14
Cannabinoid Type-1 Receptor Reduces Pain and Neurotoxicity Produced by Chemotherapy
Khasabova, I. A., Khasabov, S., Paz, J., Harding-Rose, C., Simone, D. A., & Seybold, V. S. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0403-12.2012 · Cited by 129
Metadata
- Authors
- Cravatt, B. F., Demarest, K., Patricelli, M. P., Bracey, M. H., Giang, D. K., Martin, B. R., & Lichtman, A. H.
- Affiliations
- Scripps Research Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-07-24
- Volume
- 98
- Issue
- 16
- Pages
- 9371-9376
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC55427
- OpenAlex
- W2043033522
- Cited by
- 1,310
- References
- 42
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 28 · 2023: 30 · 2022: 45 · 2021: 33 · 2020: 32 · 2019: 32 · 2018: 43 · 2017: 54 · 2016: 50 · 2015: 49 · 2014: 72 · 2013: 61 · 2012: 68
- FWCI
- 34.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH58542, R01MH058542)
- National Institute on Drug Abuse (R01DA013173, P01DA009789, DA‐03672, DA 09789, DA 131173)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- anandamide, fatty acid amide hydrolase, CB1 receptor, endocannabinoid system, cannabinoid receptor signaling, pain perception, analgesia, catalepsy, hypothermia, hypomotility, SR141716A, cannabinoid receptor antagonists, pharmacological pain management
- MeSH terms
- Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonic Acids, Behavior, Animal, Brain, Cannabinoids, Ethanolamines, Receptors, Drug, Signal Transduction, Pain Threshold, Mice, Knockout, Receptors, Cannabinoid, Mice, Polyunsaturated Alkamides, Endocannabinoids
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