Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Abstract
Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.
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The most studied endogenous ligands that bind cannabinoid receptors are AEA and 2-AG.
“The most studied endogenous ligands that bind cannabinoid receptors are AEA (Devane et al, 1992) and 2arachidonoylglycerol (2-AG) (Mechoulam et al, 1995;Sugiura et al, 1995).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Devane et al, 1992
Cannabinoids act on brain reward pathways; CB1 receptors are co-localized with opioid receptors on dopaminergic cells of the nucleus accumbens.
“Cannabinoids, like many analgesics and recreational drugs, act on the brain’s reward pathways. Cannabinoid-1 receptors (CB1R) are co-localized with the opioid receptors on the dopaminergic cells of the nucleus accumbens, probably the most important structure in human reward pathways, which partly overlaps the antinociceptive pathways [30–32].”
From Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial (2012) · cites this paper as [31]
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- Authors
- Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R.
- Affiliations
- Hebrew University of Jerusalem (IL)
- University of Aberdeen (GB)
- Technion – Israel Institute of Technology (IL)
- Venue
- Science
- Published
- 1992-12-18
- Volume
- 258
- Issue
- 5090
- Pages
- 1946-1949
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1989073099
- Cited by
- 5,633
- References
- 21
- Citations by year
- 2026: 58 · 2025: 122 · 2024: 137 · 2023: 161 · 2022: 163 · 2021: 232 · 2020: 235 · 2019: 184 · 2018: 166 · 2017: 170 · 2016: 173 · 2015: 161 · 2014: 190 · 2013: 173 · 2012: 232
- FWCI
- 50.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (5r01da006481-03)
- National Institute on Drug Abuse (DA 6481)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- anandamide, cannabinoid receptors, competitive receptor binding, synaptosomal membranes, vas deferens contraction, porcine brain, structure elucidation
- MeSH terms
- Amides, Animals, Arachidonic Acids, Binding, Competitive, Brain, Brain Chemistry, Cannabinoids, Chromatography, Thin Layer, Fatty Acids, Unsaturated, Kinetics, Gas Chromatography-Mass Spectrometry, Receptors, Drug, Swine, Receptors, Cannabinoid, Polyunsaturated Alkamides, Endocannabinoids
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