ABSTRACT Cannabinoid receptors are molecular targets for marijuana and hashish, the widespread drugs of abuse. These receptors are expressed in areas of the central nervous system that

contribute in important ways to the control of memory, cognition, movement and pain perception1. Indeed, such functions can be strongly influenced by cannabinoid drugs, with consequences

that include euphoria, analgesia, sedation and memory impairment2. Although the pharmacology of cannabinoid drugs is now beginning to be understood, we still lack essential information on

the endogenous signalling system(s) by which cannabinoid receptors are normally engaged. An endogenous ligand for cannabinoid receptors, anandamide, has been described3. Here we report that

phospholipase C and diacylglycerol lipase. 2-AG activates neuronal cannabinoid receptors as a full agonist, and prevents the induction of long-term potentiation at CA3–CA1 synapses. Our

results indicate that 2-AG is a second endogenous cannabinoid ligand in the central nervous system. Access through your institution Buy or subscribe This is a preview of subscription

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE IMPACT OF CANNABINOID TYPE 2

RECEPTORS (CB2RS) IN NEUROPROTECTION AGAINST NEUROLOGICAL DISORDERS Article 06 October 2020 _CANNABIS SATIVA_ TERPENES ARE CANNABIMIMETIC AND SELECTIVELY ENHANCE CANNABINOID ACTIVITY Article

Open access 15 April 2021 ENDOCANNABINOID SIGNALING REGULATES THE REINFORCING AND PSYCHOSTIMULANT EFFECTS OF KETAMINE IN MICE Article Open access 24 November 2020 REFERENCES * Herkenham,

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neurons: mediation by arachidonic acid and its metabolites. _J. Neurosci._ 13, 2033–2049 (1993). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank G. R. Siggins for

use of equipment (funded by NIMH), S. Madamba for technical help, and P. Magistretti, M. Beltramo and A. Giuffrida for reading the manuscript critically. This research was supported by the

Neurosciences Research Foundation, which receives major support from Novartis, and by a scientist development award from the National Institute of Drug Abuse (to P.S.). AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * The Neurosciences Institute, San Diego, 92121, California, USA Nephi Stella & Daniele Piomelli * Department of Neuropharmacology, The Scripps Research

Institute, La Jolla, 92037, California, USA Paul Schweitzer Authors * Nephi Stella View author publications You can also search for this author inPubMed Google Scholar * Paul Schweitzer View

author publications You can also search for this author inPubMed Google Scholar * Daniele Piomelli View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to Daniele Piomelli. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Stella, N., Schweitzer, P. & Piomelli, D. A

second endogenous cannabinoid that modulates long-term potentiation . _Nature_ 388, 773–778 (1997). https://doi.org/10.1038/42015 Download citation * Received: 10 April 1997 * Accepted: 18

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