ArticleMolecular psychiatry2013
Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity.
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 1 of them a synthesis that pooled it.
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Who cites it
201 citing papers in PubMed, 1 synthesis or guideline pooled it, 300 citations in OpenAlex.
- Evidence of CNIH3 involvement in opioid dependence.Molecular psychiatry · 2016Pooled 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
- The efficacy of elevating anandamide via inhibition of fatty acid amide hydrolase (FAAH) combined with internet-delivered cognitive behavioral therapy in the treatment of post-traumatic stress disorder: a randomized, placebo-controlled clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- 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
- The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Trial
- Cannabinoid treatment for autism: a proof-of-concept randomized trial.Molecular autism · 2021Trial
- A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis.Translational psychiatry · 2020Trial
- Trial
- Early intervention following trauma may mitigate genetic risk for PTSD in civilians: a pilot prospective emergency department study.The Journal of clinical psychiatry · 2014Trial
- Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans.Neurobiology of learning and memory · 2014Trial
- Sterol carrier protein 2 loss reduces anxiety and enhances fear extinction.Journal of affective disorders · 2026Article
- Cannabidiol and neural correlates of threat anticipation in alcohol use disorder.Psychopharmacology · 2026Article
- Endocannabinoid modulation of defensive state transitions to innate and learned threat.Psychopharmacology · 2026Article
- Exercise-induced anandamide-CB1R signaling and prefrontal-amygdala stress circuits in adolescent depression: a critical hypothesis-driven narrative review.Frontiers in psychiatry · 2026Review
- Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026Review
- Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Personality-based intergenerational effects of prenatal THC exposure in an inherited mouse model of social dominance and submissiveness.Scientific reports · 2025Article
- Fatty acid amide hydrolase inhibition alleviates anxiety-like symptoms in a rat model used to study post-traumatic stress disorder.Psychopharmacology · 2025Article
141 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Endocannabinoids are released 'on-demand' on the basis of physiological need, and can be pharmacologically augmented by inhibiting their catabolic degradation. The endocannabinoid anandamide is degraded by the catabolic enzyme fatty acid amide hydrolase (FAAH). Anandamide is implicated in the mediation of fear behaviors, including fear extinction, suggesting that selectively elevating brain anandamide could modulate plastic changes in fear. Here we first tested this hypothesis with preclinical experiments employing a novel, potent and selective FAAH inhibitor, AM3506 (5-(4-hydroxyphenyl)pentanesulfonyl fluoride). Systemic AM3506 administration before extinction decreased fear during a retrieval test in a mouse model of impaired extinction. AM3506 had no effects on fear in the absence of extinction training, or on various non-fear-related measures. Anandamide levels in the basolateral amygdala were increased by extinction training and augmented by systemic AM3506, whereas application of AM3506 to amygdala slices promoted long-term depression of inhibitory transmission, a form of synaptic plasticity linked to extinction. Further supporting the amygdala as effect-locus, the fear-reducing effects of systemic AM3506 were blocked by intra-amygdala infusion of a CB1 receptor antagonist and were fully recapitulated by intra-amygdala infusion of AM3506. On the basis of these preclinical findings, we hypothesized that variation in the human FAAH gene would predict individual differences in amygdala threat-processing and stress-coping traits. Consistent with this, carriers of a low-expressing FAAH variant (385A allele; rs324420) exhibited quicker habituation of amygdala reactivity to threat, and had lower scores on the personality trait of stress-reactivity. Our findings show that augmenting amygdala anandamide enables extinction-driven reductions in fear in mouse and may promote stress-coping in humans.
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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.