ArticleMolecular psychiatry2020
Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice.
Article in Molecular psychiatry, 2020. 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 93 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.
Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms
Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 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
- Functional neuroimaging of fatty acid amide hydrolase inhibition in posttraumatic stress disorder: a randomized clinical trial.Translational psychiatry · 2026Trial
- Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study.Psychopharmacology · 2026Trial
- Effects of acute alcohol administration on endocannabinoids and relation to subjective effects.Psychopharmacology · 2026Trial
- Circulating endocannabinoids in children and adolescents: associations with anxiety and the impact of selective serotonin reuptake inhibitors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder - associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment.Translational psychiatry · 2025Trial
- Endocannabinoid contributions to the perception of socially relevant, affective touch in humans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Cannabinoid modulation of corticolimbic activation during extinction learning and fear renewal in adults with posttraumatic stress disorder.Neurobiology of learning and memory · 2023Trial
- Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer.Translational psychiatry · 2022Trial
- Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial.Psychoneuroendocrinology · 2021Trial
- Longitudinal changes in endocannabinoids and clinical course of adolescent non-suicidal self-injury.Translational psychiatry · 2026Article
- Endocannabinoid dysregulation and PTSD in urban adolescents: Associations with anandamide concentrations and FAAH genotype.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
- Endocannabinoid response to social stress in chronic non-medical prescription opioid users.Psychopharmacology · 2026Article
- FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- A systematic review of spontaneous recovery in human fear conditioning.Frontiers in behavioral neuroscience · 2026Review
- Genetic deletion of NAPE-PLD alters stress responsiveness and HPA-axis functionality in a context-dependent manner in mice.Neuropharmacology · 2025Article
- Research Review: What we have learned about the endocannabinoid system in developmental psychopathology.Journal of child psychology and psychiatry, and allied disciplines · 2025Review
- Comment on Zabik et al. (2024): timing and dosage effects of THC in fear extinction: challenges and feasibility in a clinical setting.Psychopharmacology · 2025Article
- The Contribution of Baseline Circulating Endocannabinoids to Individual Differences in Human Pain Sensitivity: A Quantitative Sensory Testing Study.bioRxiv : the preprint server for biology · 2025Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C->A substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.
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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.