ArticlePharmacological research2016
Broad impact of deleting endogenous cannabinoid hydrolyzing enzymes and the CB1 cannabinoid receptor on the endogenous cannabinoid-related lipidome in eight regions of the mouse brain.
Article in Pharmacological research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
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- Sex differences in plasma endocannabinoids and related lipids before and after single and repeated mTBI: an exploratory study of endolipid plasma biomarkers.Frontiers in molecular neuroscience · 2026Article
- Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.Molecular psychiatry · 2025Article
- Dysregulated glycerophospholipid metabolism in amygdala may mediate favipiravir-induced anxiety-like behaviors in mice.Frontiers in pharmacology · 2025Article
- Palmitoylethanolamide causes dose-dependent changes in brain function and the lipidome.Frontiers in neuroscience · 2024Article
- High-performance liquid chromatography-tandem mass spectrometry method for the analysis of N-oleoyl glycine and N-oleoyl alanine in brain and plasma.Journal of separation science · 2023Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Anxiety Modulation by Cannabinoids-The Role of Stress Responses and Coping.International journal of molecular sciences · 2023Review
- Cannabinoid CB1 receptors regulate salivation.Scientific reports · 2022Article
- Differential Expression of CBCannabis and cannabinoid research · 2022Article
- N-Acylethanolamine-Hydrolyzing Acid Amidase Inhibition, but Not Fatty Acid Amide Hydrolase Inhibition, Prevents the Development of Experimental Autoimmune Encephalomyelitis in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in gastroparesis: A sex- and subtype-dependent observation.Neurogastroenterology and motility · 2021Article
- Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective.Frontiers in neurology · 2020Review
- Review
- Cannabinoid receptor-mediated modulation of inhibitory inputs to mitral cells in the main olfactory bulb.Journal of neurophysiology · 2019Article
- Article
- 2-Linoleoylglycerol Is a Partial Agonist of the Human Cannabinoid Type 1 Receptor that Can Suppress 2-Arachidonolyglycerol and Anandamide Activity.Cannabis and cannabinoid research · 2019Article
- Elevated Levels of Arachidonic Acid-Derived Lipids Including Prostaglandins and Endocannabinoids Are Present Throughout ABHD12 Knockout Brains: Novel Insights Into the Neurodegenerative Phenotype.Frontiers in molecular neuroscience · 2019Article
- The neuroprotective mechanism of 2-arachidonoylglycerol 2-AG against non-caspase-dependent apoptosis in mice hippocampal neurons following MCAO.Neuropsychiatric disease and treatment · 2019Article
- Positive Allosteric Modulation of Cannabinoid Receptor Type 1 Suppresses Pathological Pain Without Producing Tolerance or Dependence.Biological psychiatry · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeThe enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) hydrolyze endogenous cannabinoids (eCBs), N-arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG), respectively. These enzymes also metabolize eCB analogs such as lipoamines and 2-acyl glycerols, most of which are not ligands at CB1. To test the hypothesis that deleting eCB hydrolyzing enzymes and CB1 shifts lipid metabolism more broadly and impacts more families of eCB structural analogs, targeted lipidomics analyses were performed on FAAH KO, MAGL KO, and CB1 KO mice and compared to WT controls in 8 brain regions. EXPERIMENTAL APPROACH: Methanolic extracts of discrete brain regions (brainstem, cerebellum, cortex, hippocampus, hypothalamus, midbrain, striatum and thalamus) were partially purified on C-18 solid-phase extraction columns. Over 70 lipids per sample were then analyzed with HPLC/MS/MS. KEY
resultsAEA and 2-AG were unaffected throughout the brain in CB1 KO mice; however, there was an increase in the arachidonic acid (AA) metabolite, PGE2 in the majority of brain areas. By contrast, PGE2 and AA levels were significantly reduced throughout the brain in the MAGL KO corresponding to significant increases in 2-AG. No changes in AA or PGE2 were seen throughout in the FAAH KO brain, despite significant increases in AEA, suggesting AA liberated by FAAH does not contribute to steady state levels of AA or PGE2. Changes in the lipidome were not confined to the AA derivatives and showed regional variation in each of the eCB KO models. CONCLUSIONS AND IMPLICATIONS: AEA and 2-AG hydrolyzing enzymes and the CB1 receptor link the eCB system to broader lipid signaling networks in contrasting ways, potentially altering neurotransmission and behavior independently of cannabinoid receptor signaling.
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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.