Evidence map›Paper›PMID 26504214›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Endocannabinoid signaling mediates oxytocin-driven social reward.

Don Wei, DaYeon Lee, Conor D Cox, Carley A Karsten, Olga Peñagarikano, Daniel H Geschwind, Christine M Gall, Daniele Piomelli

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 1 pooled it
15.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

119 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.

  1. Pooled it
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  4. Endocannabinoid contributions to the perception of socially relevant, affective touch in humans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
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  7. The Neurochemical Orchestra of the Runner's High: A Narrative Review of Neuromodulatory Mechanisms with a Focus on Endocannabinoids.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026
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59 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Don WeiDepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697;ORCID http://orcid.org/0000-0003-2198-5921
DaYeon LeeDepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697;
Conor D CoxDepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697;
Carley A KarstenDepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697;
Olga PeñagarikanoDepartment of Pharmacology, School of Medicine, University of the Basque Country, Barrio Sarriena s/n, Leioa 48940, Spain;
Daniel H GeschwindProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095;
Christine M GallDepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697;
Daniele PiomelliDepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697; Unit of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genova 16163, Italy piomelli@uci.edu.
University of California, Irvine · USUniversity of California, Los Angeles · USUniversity of the Basque Country · ES

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008620 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GOLDIN, ALAN L · 1999 to 2023
$8.1M
Characterization of Anandamide Transport in BrainR01DA012413 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI PIOMELLI, DANIELE · 1998 to 2016
$4.7M
NIDA NIH HHS DA012413NIDA NIH HHS R01 DA012413NIGMS NIH HHS T32 GM008620
6 · The paper itself

Abstract

Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. Pharmacological and genetic experiments show that anandamide mobilization and consequent activation of CB1 cannabinoid receptors are necessary and sufficient to express the rewarding properties of social interactions, assessed using a socially conditioned place preference test. We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc. Pharmacological blockade of oxytocin receptors stops this response, whereas chemogenetic, site-selective activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus stimulates it. Genetic or pharmacological interruption of anandamide degradation offsets the effects of oxytocin receptor blockade on both social place preference and cFos expression in the NAc. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.

Indexed as

RewardSocial BehaviorAnalysis of VarianceAnimalsArachidonic AcidsAutism Spectrum DisorderBenzamidesBenzodiazepinesCamphanesCarbamatesClozapineCocaineEndocannabinoidsImmunohistochemistryInfusions, IntraventricularLipids4-(3,5-dihydroxybenzyl)-N-(2-methyl-4-((1-methyl-4,10-dihydropyrazolo(3,4-b)(1,5)benzodiazepin-5(1H)-yl)carbonyl)benzyl)piperazine-1-carboxamideAM 251anandamideArachidonic AcidsBenzamidesBenzodiazepinesCamphanesCarbamatesClozapineclozapine N-oxideCocainecyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl esterEndocannabinoidsL 368899LipidsOxytocinPiperazinesPiperidinesPolyunsaturated AlkamidesPyrazolesReceptors, Cannabinoidanandamideendocannabinoidoxytocinrewardsocial behavior

Identifiers

PMID26504214
PMCPMC4653148
OpenAlexW2162507318

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.