ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Corticotropin-releasing hormone drives anandamide hydrolysis in the amygdala to promote anxiety.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 2 of them syntheses that pooled it.
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Who cites it
143 citing papers in PubMed, 2 syntheses or guidelines pooled it, 239 citations in OpenAlex.
- Endocannabinoids and Stress-Related Neurospsychiatric Disorders: A Systematic Review and Meta-Analysis of Basal Concentrations and Response to Acute Psychosocial Stress.Cannabis and cannabinoid research · 2024Pooled it
- Individual differences in glucocorticoid regulation: Does it relate to disease risk and resilience?Frontiers in neuroendocrinology · 2020Pooled it
- Intrathecal morphine administration reduces postoperative pain and peripheral endocannabinoid levels in total knee arthroplasty patients: a randomized clinical trial.BMC anesthesiology · 2018Trial
- Sterol carrier protein 2 loss reduces anxiety and enhances fear extinction.Journal of affective disorders · 2026Article
- PET imaging of FAAH in chronic Cannabis users: longitudinal assessment during short-term abstinence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Longitudinal changes in endocannabinoids and clinical course of adolescent non-suicidal self-injury.Translational psychiatry · 2026Article
- Psilocybin improves novel object recognition in a rat model of Fragile X Syndrome through the modulation of the BDNF/TrkB signaling pathway.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Towards Mechanism-Informed Treatments for Mental Health.Journal of neurochemistry · 2026Review
- Endocannabinoid response to social stress in chronic non-medical prescription opioid users.Psychopharmacology · 2026Article
- Involvement of the central amygdaloid nucleus in the regulation of sex differences in the stress relief response in mice.Biology of sex differences · 2026Article
- Genetic deletion of NAPE-PLD alters stress responsiveness and HPA-axis functionality in a context-dependent manner in mice.Neuropharmacology · 2025Article
- A network of basolateral amygdala projection neurons contributes to stress-induced activation of the hypothalamic-pituitary-adrenal axis.Science advances · 2025Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- The endocannabinoidome-gut microbiome-brain axis as a novel therapeutic target for autism spectrum disorder.Journal of biomedical science · 2025Review
- Understanding the Role of Endocannabinoids in Posttraumatic Stress Disorder.International journal of molecular sciences · 2025Review
- Effects of pharmacological inhibition of fatty acid amide hydrolase on corticosterone release: a systematic review of preclinical studies.Discover mental health · 2025Review
- Endocannabinoid signaling in stress, nausea, and vomiting.Neurogastroenterology and motility · 2025Review
- Alterations of the endocannabinoid system in adolescents with non-suicidal self-injury as a function of childhood maltreatment.Translational psychiatry · 2024Article
- Identification of a stress-responsive subregion of the basolateral amygdala in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Emotional comorbidities in epilepsy result from seizure-induced corticosterone activity.Neurobiology of stress · 2024Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 5 countries.
Funding
Abstract
Corticotropin-releasing hormone (CRH) is a central integrator in the brain of endocrine and behavioral stress responses, whereas activation of the endocannabinoid CB1 receptor suppresses these responses. Although these systems regulate overlapping functions, few studies have investigated whether these systems interact. Here we demonstrate a novel mechanism of CRH-induced anxiety that relies on modulation of endocannabinoids. Specifically, we found that CRH, through activation of the CRH receptor type 1 (CRHR1), evokes a rapid induction of the enzyme fatty acid amide hydrolase (FAAH), which causes a reduction in the endocannabinoid anandamide (AEA), within the amygdala. Similarly, the ability of acute stress to modulate amygdala FAAH and AEA in both rats and mice is also mediated through CRHR1 activation. This interaction occurs specifically in amygdala pyramidal neurons and represents a novel mechanism of endocannabinoid-CRH interactions in regulating amygdala output. Functionally, we found that CRH signaling in the amygdala promotes an anxious phenotype that is prevented by FAAH inhibition. Together, this work suggests that rapid reductions in amygdala AEA signaling following stress may prime the amygdala and facilitate the generation of downstream stress-linked behaviors. Given that endocannabinoid signaling is thought to exert "tonic" regulation on stress and anxiety responses, these data suggest that CRH signaling coordinates a disruption of tonic AEA activity to promote a state of anxiety, which in turn may represent an endogenous mechanism by which stress enhances anxiety. These data suggest that FAAH inhibitors may represent a novel class of anxiolytics that specifically target stress-induced anxiety.
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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.