ArticleCell reports2014
Genetic disruption of 2-arachidonoylglycerol synthesis reveals a key role for endocannabinoid signaling in anxiety modulation.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05142267 (Stress and Opioid Misuse Risk), which is not on this map. Cited by 91 papers.
What it found
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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.
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.
Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms
Who cites it
91 citing papers in PubMed, 151 citations in OpenAlex.
- Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.European archives of psychiatry and clinical neuroscience · 2026Trial
- Sterol carrier protein 2 loss reduces anxiety and enhances fear extinction.Journal of affective disorders · 2026Article
- Cannabidiol and neural correlates of threat anticipation in alcohol use disorder.Psychopharmacology · 2026Article
- Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Behavioral Decoding Reveals Cortical Endocannabinoid Potentiation during ΔbioRxiv : the preprint server for biology · 2025Article
- Article
- Prefrontal correlates of fear generalization during endocannabinoid depletion.The Journal of clinical investigation · 2025Article
- Endocannabinoid signaling in stress, nausea, and vomiting.Neurogastroenterology and motility · 2025Review
- The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibition of diacylglycerol lipase α induced blood-brain barrier breach in female Sprague-Dawley rats.The Journal of physiology · 2025Article
- Identification of DAGLA as an autoantibody target in cerebellar ataxia.Journal of neurology, neurosurgery, and psychiatry · 2024Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Pharmacological diacylglycerol lipase inhibition impairs contextual fear extinction in mice.Psychopharmacology · 2024Article
- Peripheral Endocannabinoid Components and Lipid Plasma Levels in Patients with Resistant Migraine and Co-Morbid Personality and Psychological Disorders: A Cross-Sectional Study.International journal of molecular sciences · 2024Article
- AstrocyticCannabis and cannabinoid research · 2024Article
- PREFRONTAL CORRELATES OF FEAR GENERALIZATION DURING ENDOCANNABINOID DEPLETION.bioRxiv : the preprint server for biology · 2024Article
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
- Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Gene expression in the primate orbitofrontal cortex related to anxious temperament.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Endocannabinoid (eCB) signaling has been heavily implicated in the modulation of anxiety and depressive behaviors and emotional learning. However, the role of the most-abundant endocannabinoid 2-arachidonoylglycerol (2-AG) in the physiological regulation of affective behaviors is not well understood. Here, we show that genetic deletion of the 2-AG synthetic enzyme diacylglycerol lipase α (DAGLα) in mice reduces brain, but not circulating, 2-AG levels. DAGLα deletion also results in anxiety-like and sex-specific anhedonic phenotypes associated with impaired activity-dependent eCB retrograde signaling at amygdala glutamatergic synapses. Importantly, acute pharmacological normalization of 2-AG levels reverses both phenotypes of DAGLα-deficient mice. These data suggest 2-AG deficiency could contribute to the pathogenesis of affective disorders and that pharmacological normalization of 2-AG signaling could represent an approach for the treatment of mood and anxiety disorders.
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Registered trials
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.