ArticleThe Journal of clinical investigation2021
Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Modulating the endocannabinoid system in alcohol use disorder: A translational systematic review and meta-analysis of preclinical and human studies.Molecular psychiatry · 2026Pooled it
- Association of stress-sensitive mid-insula activity with alcohol drinking and negative affect-like behavior during abstinence in mice.Neuropharmacology · 2026Article
- Endocannabinoid modulation of defensive state transitions to innate and learned threat.Psychopharmacology · 2026Article
- Individual and additive effects of childhood maltreatment and substance use disorder histories on baseline and stress-induced changes in peripheral stress biomarkers.Psychopharmacology · 2026Article
- Cannabinoid-based Pharmacology for the Management of Substance Use Disorders.Current topics in behavioral neurosciences · 2026Review
- An Amygdala-hippocampus Circuit for Endocannabinoid Modulation of Anxiety Avoidance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking.International journal of molecular sciences · 2025Article
- Sex Differences in Mouse Models of Voluntary Alcohol Drinking and Abstinence-Induced Negative Emotion.Alcohol (Fayetteville, N.Y.) · 2024Review
- A Novel Mouse Home Cage Lickometer System Reveals Sex- and Housing-Based Influences on Alcohol Drinking.eNeuro · 2024Article
- Coordinated action of a gut-liver pathway drives alcohol detoxification and consumption.Nature metabolism · 2024Article
- A novel mouse home cage lickometer system reveals sex- and housing-based influences on alcohol drinking.bioRxiv : the preprint server for biology · 2024Article
- Striatonigral direct pathway 2-arachidonoylglycerol contributes to ethanol effects on synaptic transmission and behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Differential roles of diacylglycerol lipase (DAGL) enzymes in nicotine withdrawal.Brain research · 2023Article
- Article
- Opposing retrograde and astrocyte-dependent endocannabinoid signaling mechanisms regulate lateral habenula synaptic transmission.Cell reports · 2023Article
- Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption.Frontiers in psychiatry · 2023Article
- 2-Arachidonoylglycerol-mediated endocannabinoid signaling modulates mechanical hypersensitivity associated with alcohol withdrawal in mice.Alcoholism, clinical and experimental research · 2022Article
- New insights into the mechanism of alcohol-mediated organ damage via its impact on immunity, metabolism, and repair pathways: A summary of the 2021 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2022Review
- Alcohol-Endocannabinoid Interactions: Implications for Addiction-Related Behavioral Processes.Alcohol research : current reviews · 2022Review
- Effects of Cannabinoid Exposure during Neurodevelopment on Future Effects of Drugs of Abuse: A Preclinical Perspective.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 3 countries.
Funding
Abstract
Alcohol use disorder (AUD) is associated with substantial morbidity, mortality, and societal cost, and pharmacological treatment options for AUD are limited. The endogenous cannabinoid (eCB) signaling system is critically involved in reward processing and alcohol intake is positively correlated with release of the eCB ligand 2-Arachidonoylglycerol (2-AG) within reward neurocircuitry. Here we show that genetic and pharmacological inhibition of diacylglycerol lipase (DAGL), the rate limiting enzyme in the synthesis of 2-AG, reduces alcohol consumption in a variety of preclinical models ranging from a voluntary free-access model to aversion resistant-drinking and dependence-like drinking induced via chronic intermittent ethanol vapor exposure in mice. DAGL inhibition during either chronic alcohol consumption or protracted withdrawal was devoid of anxiogenic and depressive-like behavioral effects. Lastly, DAGL inhibition also prevented ethanol-induced suppression of GABAergic transmission onto midbrain dopamine neurons, providing mechanistic insight into how DAGL inhibition could affect alcohol reward. These data suggest reducing 2-AG signaling via inhibition of DAGL could represent an effective approach to reduce alcohol consumption across the spectrum of AUD severity.
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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.