Cited by 1,310Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsEicosanoids and Hypertension Pharmacology

Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase

Open access
Cravatt, Benjamin F., Demarest, Kristin, Patricelli, Matthew P., Bracey, Michael H., Giang, Dan K., Martin, Billy R., Lichtman, Aron H.·2001·Proceedings of the National Academy of Sciences

Abstract

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.

Integrity signals

Registry

Crossref · 10.1073/pnas.161191698

Cites

42 of 42 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?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
Published
2001-07-24
Volume
98
Issue
16
Pages
9371-9376
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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 › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › 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

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