Cited by 159Cannabis and Cannabinoid ResearchEicosanoids and Hypertension PharmacologyFatty Acid Research and Health

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The Biodisposition and Metabolism of Anandamide in Mice

Willoughby, Karen A., Moore, Sandra F., Martin, Billy R., Ellis, Earl F.·1997·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(24)36812-0

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Abstract

The endogenous cannabinoid anandamide (AN) has been reported to produce pharmacological effects similar to those of delta9-tetrahydrocannabinol but with a shorter duration of action. Also, AN is known to be metabolized to arachidonic acid. The purpose of this study was to examine the time course of distribution and metabolism of AN. Male mice were each administered 20 microCi 3H-AN and 50 mg/kg AN (i.v.). At 1, 5, 15 and 30 min after administration, the animals were sacrificed, and various tissues were removed, solubilized and counted to determine the distribution of 3H. Also, samples from brain, adrenal gland and plasma were extracted with ethyl acetate and analyzed by HPLC to separate 3H-labeled AN, arachidonic acid and other metabolites. AN was detectable in brain by 1 min after injection. At 1 min after injection, the rank order of radioactivity per milligram or microliter of tissue was adrenal > lung > kidney > plasma > heart > liver > diaphragm > brain > fat. Although the 1 and 5 min metabolic profiles of brain 3H showed that AN was clearly present, most AN had already been transformed to arachidonic acid and other polar metabolites, and there were almost no detectable brain levels of AN at 15 and 30 min. In plasma and adrenal gland, AN was the predominant form at 1 and 5 min. Our experiments confirm that AN quickly reaches the brain and suggest that rapid metabolism of AN plays a key role in the time course of the pharmacological activity of this naturally occurring cannabinoid receptor ligand.

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Authors: Willoughby, K. A., Moore, S. F., Martin, B. R., & Ellis, E. F.
Affiliations: Virginia Commonwealth University (US)
Corresponding author: Ellis, Earl F.
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 1997-07
Volume: 282
Issue: 1
Pages: 243-247
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1016/s0022-3565(24)36812-0
OpenAlex: W2259059236
Cited by: 159
References: 16
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 5 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 8
FWCI: 6.19
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed
Funders: National Institutes of Health (5r01da008677-03)
National Institute on Drug Abuse (DA-08677)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords: anandamide, endocannabinoids, tissue distribution, metabolism, arachidonic acid, brain, adrenal gland, plasma, polar metabolites, cannabinoid receptor ligands, pharmacokinetics
MeSH terms: Animals, Arachidonic Acids, Brain, Cannabinoids, Male, Mice, Inbred ICR, Motor Activity, Tissue Distribution, Mice, Polyunsaturated Alkamides, Endocannabinoids

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The Biodisposition and Metabolism of Anandamide in Mice

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