ArticleInternational journal of molecular sciences2021
Distinct Activity of Endocannabinoid-Hydrolyzing Enzymes MAGL and FAAH in Key Regions of Peripheral and Central Nervous System Implicated in Migraine.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- FAAH as a Molecular Regulator of Endocannabinoid Signaling: Mechanistic Insights into Reproductive, Metabolic, and Inflammatory Dysfunctions in Polycystic Ovary Syndrome.Molecules (Basel, Switzerland) · 2026Review
- The Endocannabinoid System in Neuropsychiatric Disorders: Mechanisms, Dysregulation and Therapeutic Potential.Biomedicines · 2026Review
- Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Ex vivo stimulation of the trigeminal nucleus caudalis induces peripheral CGRP release in the trigeminal ganglion and reveals a distinct dopamine-endocannabinoid mechanism relevant to migraine.The journal of headache and pain · 2025Article
- Differential inhibitory effects of endocannabinoids on neuronal firing of mouse meningeal afferents.The journal of headache and pain · 2025Article
- Inhibition of endocannabinoid hydrolases MAGL, FAAH and ABHD6 by AKU-005 reduces ex vivo cortical spreading depression.The journal of headache and pain · 2025Article
- Enhancement of the endocannabinoid system through monoacylglycerol lipase inhibition relieves migraine-associated pain in mice.The journal of headache and pain · 2025Article
- Combined effects of cannabidiol and Δ9-tetrahydrocannabinol alleviate migraine-like symptoms in mice.Cephalalgia : an international journal of headache · 2025Article
- Formoterol dynamically alters endocannabinoid tone in the periaqueductal gray inducing headache.The journal of headache and pain · 2024Article
- Interplay between cannabinoids and the neuroimmune system in migraine.The journal of headache and pain · 2024Review
- Inhibition of 2-AG hydrolysis alleviates posttraumatic headache attributed to mild traumatic brain injury.The journal of headache and pain · 2024Article
- Effects of the Dual FAAH/MAGL Inhibitor AKU-005 on Trigeminal Hyperalgesia in Male Rats.Cells · 2024Article
- Hemp Seed Oil Inhibits the Adipogenicity of the Differentiation-Induced Human Mesenchymal Stem Cells through Suppressing the Cannabinoid Type 1 (CB1).Molecules (Basel, Switzerland) · 2024Article
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
- Activity of FAAH-Inhibitor JZP327A in an Experimental Rat Model of Migraine.International journal of molecular sciences · 2023Article
- Potent dual MAGL/FAAH inhibitor AKU-005 engages endocannabinoids to diminish meningeal nociception implicated in migraine pain.The journal of headache and pain · 2023Article
- Cannabinoid Receptor 2 Blockade Prevents Anti-Depressive-like Effect of Cannabidiol Acid Methyl Ester in Female WKY Rats.International journal of molecular sciences · 2023Article
- ABHD6 and MAGL control 2-AG levels in the PAG and allodynia in a CSD-induced periorbital model of headache.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Review
- Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats.Current issues in molecular biology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
In migraine pain, cannabis has a promising analgesic action, which, however, is associated with side psychotropic effects. To overcome these adverse effects of exogenous cannabinoids, we propose migraine pain relief via activation of the endogenous cannabinoid system (ECS) by inhibiting enzymes degrading endocannabinoids. To provide a functional platform for such purpose in the peripheral and central parts of the rat nociceptive system relevant to migraine, we measured by activity-based protein profiling (ABPP) the activity of the main endocannabinoid-hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH). We found that in trigeminal ganglia, the MAGL activity was nine-fold higher than that of FAAH. MAGL activity exceeded FAAH activity also in DRG, spinal cord and brainstem. However, activities of MAGL and FAAH were comparably high in the cerebellum and cerebral cortex implicated in migraine aura. MAGL and FAAH activities were identified and blocked by the selective and potent inhibitors JJKK-048/KML29 and JZP327A, respectively. The high MAGL activity in trigeminal ganglia implicated in the generation of nociceptive signals suggests this part of ECS as a priority target for blocking peripheral mechanisms of migraine pain. In the CNS, both MAGL and FAAH represent potential targets for attenuation of migraine-related enhanced cortical excitability and pain transmission.
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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.