Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity.

paper Cited Public

Authors: Gunduz-Cinar, O; MacPherson, K P; Cinar, R; Gamble-George, J; Sugden, K; Williams, B; Godlewski, G; Ramikie, T S; Gorka, A X; Alapafuja, S O; Nikas, S P; Makriyannis, A; Poulton, R; Patel, S; Hariri, A R; Caspi, A; Moffitt, T E; Kunos, G; Holmes, A
Year: 2013
Journal: Molecular psychiatry
PMID: 22688188
DOI: 10.1038/mp.2012.72
PMCID: PMC3549323

Figure 1

The fatty acid amide hydrolase (FAAH) inhibitor AM3506 (5-(4-hydroxyphenyl)pentanesulfonyl fluoride) facilitates fear extinction. Systemic treatment with AM3506 (n = 3 per time point) produced profound and lasting brain FAAH inhibition, as measured by [3H]ethanolamine activity (a), but not monoacylglycerol lipase, as assayed via [3H]glycerol activity (b) (*P<0.05 vs 1 mg/kg/time point 0). (c) Systemic AM3506 treatment before extinction training reduced fear on a retrieval test (n = 10–11 per treatment). Systemic AM3506 did not affect fear during a retrieval test when administered before conditioning (n = 8 per treatment) (d), after extinction training (n = 12 per treatment) (e) or before fear memory reactivation (n = 8 per treatment) (f). Systemic AM3506 did not affect fear open field locomotor activity (n = 8 per treatment) (g), forced swim ‘depression-related’ behavior (n = 8 per treatment) (h) or fasting-induced feeding (n = 8 per treatment) (i). Cond = conditioning; Ext = extinction; Rect = reactivation; Ret = retrieval. *P<0.05. Data are means±s.e.m.

Figure 2

Extinction training and AM3506 (5-(4-hydroxyphenyl)pentanesulfonyl fluoride) increase anandamide levels in the basolateral amygdala. (a) Schematic of testing and tissue collection procedure. (b) Systemic AM3506 treatment and extinction training increased anandamide levels in the basolateral amygdala in fear-conditioned (CS–US) mice, as compared to non-conditioned (CS) controls (n = 10–11 per treatment). (c) Systemic AM3506 treatment and extinction training increased anandamide levels in the cortex and striatum, as compared to vehicle treated controls (n = 10–11 per treatment). (d) Low-frequency stimulation (LFS) of the external capsule was used to induce endocannabinoid-mediated long-term depression of inhibitory, GABAergic, transmission (LTDi) in the basolateral amygdala. (e) In slices treated with 2 μm AM3506, but not vehicle, there was a marked and lasting reduction in evoked inhibitory postsynaptic currents (eIPSCs) amplitude following LFS, relative to baseline (n = 7–8 per treatment). Example traces of eIPSC amplitudes are shown on the right. (f) Paired pulse ratio (PPR), measuring the peak change in eIPSC amplitude over two consecutive stimulations, was higher in AM3506-treated slices after stimulation, relative to pre-stimulation baseline. CS = conditioned stimulus; US = unconditioned stimulus. *P<0.05. Data are means±s.e.m.

Figure 3

AM3506 (5-(4-hydroxyphenyl)pentanesulfonyl fluoride) facilitates fear extinction via CB1 receptor (CB1R) in the basolateral amygdala. (a) The ability of systemic AM3506 treatment before extinction to reduce fear on a retrieval test was blocked by systemic treatment with the CB1R antagonist SR141716 (n = 9–12 per treatment). (b) The ability of pre-extinction systemic AM3506 treatment to reduce fear on a retrieval test was blocked by intra-amygdala infusion of SR141716 (n = 7 per treatment). (c) Cannula tip localization. (d) Pre-extinction infusion of AM3506 into the amygdala was sufficient to reduce fear on a retrieval test (n = 8–11 per treatment). (e) Cannula tip localization. VEH = vehicle; SR = SR141716; AM = AM3506. *P<0.05. Data are means±s.e.m.

Figure 4

The lesser-expressing human fatty acid amide hydrolase (FAAH) gene 385A variant is associated with fear-related endophenotypes and traits. (a) Both the right and left amygdala exhibited significant habituation to repeated viewing of threatening faces. (b) Individuals carrying at least one lesser-expressing FAAH 385A variant showed greater amygdala-mediated habituation to threatening stimuli in all three clusters from (a). Given the low occurrence of homozygous AA carriers (n = 3) in this sample, A/A and C/A carriers (n = 31) were combined and compared with C/C homozygotes (n = 50). Data are means±s.e.m. (c, d) AA homozygotes scored significantly lower on a personality endophenotype of Stress Reactivity, measured by the Multidimensional Personality Questionnaire.47 *P<0.05. Data are means±s.e.m.

#	Section	Preview
60	Results and Discussion — AM3506 and extinction training boost amygdala anandamide	Ex vivo levels of anandamide in the BLA were significantly elevated in mice that had received…
61	Results and Discussion — AM3506 and extinction training boost amygdala anandamide	Our results are consistent with prior data showing that extinction training selectively increases…
62	Results and Discussion — AM3506 enhances amygdala synaptic plasticity	To determine the consequences of these elevated anandamide levels for plasticity within amygdala…
63	Results and Discussion — AM3506 enhances amygdala synaptic plasticity	In slices treated with vehicle, this stimulation protocol did not produce a change in eIPSC…
64	Results and Discussion — AM3506 enhances amygdala synaptic plasticity	The effect of AM3506 on glutamatergic transmission in the BLA was tested by measuring fEPSP.…
65	Results and Discussion — AM3506 enhances amygdala synaptic plasticity	Collectively, these data show that AM3506-induced elevation of anandamide in the BLA is associated…
66	Results and Discussion — AM3506 facilitates fear extinction via the amygdala	The most likely receptor target of the effects of augmented anandamide in the BLA is CB1R, which is…
67	Results and Discussion — AM3506 facilitates fear extinction via the amygdala	Next, to isolate the extinction-facilitating action of AM3506 to CB1Rs within the BLA, we…
68	Results and Discussion — AM3506 facilitates fear extinction via the amygdala	Our final step was to determine whether direct amygdala administration of AM3506 itself produced…
69	Results and Discussion — FAAH gene variation modulates human amygdala habituation to threat	Our rodent experiments suggest that inhibiting FAAH, via AM3506 administration, facilitates…
70	Results and Discussion — FAAH gene variation modulates human amygdala habituation to threat	In the first study, we used imaging genetics in a sample of middle-aged adults (N = 81) who…
71	Results and Discussion — FAAH gene variation modulates human amygdala habituation to threat	demonstrating significantly greater habituation compared with C385 homozygotes in all three clusters…
72	Results and Discussion — FAAH gene variation modulates human amygdala habituation to threat	FAAH gene variation associates with low human stress reactivity We next tested the influence of FAAH…
73	Results and Discussion — FAAH gene variation modulates human amygdala habituation to threat	= −0.08, t = 239, P<0.05) (Figures 4c and d), but did not differ from other cohort members on…
74	Results and Discussion — Conclusions	The endocannabinoid system has emerged as an important regulator of stress and emotional processing,…

Name	Type
129S1/Sv1mJ local	cohort
129S1/Sv1mJ mice local	cohort
129S1/SvImJ (S1) local	cohort
2-AG	drug
2-arachidonoylglycerol	drug
[2H4] anandamide local	drug
2-oleoyl-[3H]glycerol local	drug
2-oleoyl-glycerol local	drug
[3H]anandamide local	drug
[3H]ethanolamine local	drug
AA genotype	variant
acetic acid	drug
AC genotype local	variant
Achievement local	phenotype
aCSF	drug
Adult Health and Behavior Study local	cohort
aggression	phenotype
alienation	phenotype
AM3056 local	drug
AM3506 local	drug
AM404 local	drug
amygdala	anatomy
amygdala fear-plasticity endophenotype local	phenotype
amygdala habituation	phenotype
Amygdala reactivity	phenotype
anandamide	drug
animal models	cohort
Antiarrhythmic local	drug
antidepressant-related activity local	phenotype
Antihypertensive local	drug
anxiety	phenotype
assay buffer local	drug
basolateral amygdala	anatomy
BLA	anatomy
brain	anatomy
C385A local	variant
Cardiovascular medication local	drug
Caucasian participants	cohort
CB1R desensitization local	phenotype
CB1 receptor	drug
CB1R knockout mice local	cohort
CC genotype local	variant
cerebellum	anatomy
cerebral blood flow	phenotype
cerebrum	anatomy
CNQX	drug
Cnr1	gene
Constraint vs Disinhibition local	phenotype
coronal slice local	anatomy
cortex	anatomy
Corticolimbic circuits local	anatomy
Cresyl violet	drug
CS-alone training local	phenotype
CS group local	cohort
CsMeSO3 local	drug
CS–US group local	cohort
CS–US training local	phenotype
depression-related immobility local	phenotype
diet‑induced obese mice local	cohort
dimethyl sulfoxide	drug
d/l AP-5	drug
dorsal striatum	anatomy
drug	drug
drug treatment	drug
DSM-IV	phenotype
Dunedin Multidisciplinary Health and Development Study local	cohort
EDTA	drug
EGTA	drug
eIPSC	phenotype
Emotion	phenotype
Endocannabinoid-mediated LTD local	phenotype
endocannabinoid system	drug
Excitatory LTD local	phenotype
Exposure therapy local	phenotype
external capsule	anatomy
extinction	phenotype
extinction consolidation local	phenotype
extinction-facilitating effect local	phenotype
extinction memories local	phenotype
extinction-resistant model local	phenotype
Extinction testing local	phenotype
extinguished mice local	cohort
FAAH	gene
FAAH C385A local	variant
FAAH C385A polymorphism local	variant
FAAH inhibitor local	drug
FAAH loss-of-function variant local	variant
Fasting-induced feeding local	phenotype
fatty acid free bovine serum albumin local	drug
fear	phenotype
fear acquisition local	phenotype
Fear after extinction local	phenotype
fear conditioning	phenotype
fear extinction	phenotype
fear memory local	phenotype
fear memory learning local	phenotype
fear-related disorders local	phenotype
fear-related endophenotypes local	phenotype
Fear-related traits local	phenotype
fear retrieval local	phenotype
fEPSP	phenotype
field recordings local	phenotype
fluoxetine	drug
food intake	phenotype
forced swim test	phenotype
forebrain	anatomy
freezing local	phenotype
Freezing local	phenotype
GABA	phenotype
glucocorticoid	drug
glucose intolerance	phenotype
glutamate	drug
harm avoidance	phenotype
Hepatic effects local	phenotype
HEPES	drug
human	cohort
humans	cohort
hyperglycemia	phenotype
Illumina Human 610-Quad BeadChip local	drug
immobility	phenotype
impaired fear extinction local	phenotype
impaired fear extinction learning local	phenotype
impaired fear extinction retrieval local	phenotype
insulin resistance	phenotype
iPSCs	cohort
isoflurane	drug
lateral amygdala	anatomy
locomotor activity	phenotype
long-term extinction local	phenotype
long-term fear local	phenotype
Low-frequency stimulation (LFS) local	drug
LTDi local	phenotype
MAGL	gene
mice	cohort
Middle-aged adult cohort local	cohort
Na-ATP	drug
Na-GTP	drug
Naïve cohorts of mice local	cohort
normal fear local	phenotype
nucleus accumbens	anatomy
obese mice local	cohort
obesity	phenotype
P129T local	variant
paraformaldehyde	drug
participants	cohort
personality data local	phenotype
personality traits	phenotype
physical dependence	phenotype
picrotoxin	drug
post-extinction fear local	phenotype
Post-Traumatic Stress Disorder	phenotype
PPR local	phenotype
Problem drug/alcohol abuse local	phenotype
psychotropic medication	drug
Puregene kit local	drug
pyramidal neurons	anatomy
QX-314	drug
rats	cohort
retrieval test local	phenotype
retrieval_test local	phenotype
rimonabant	drug
rodent experiments local	cohort
rodents	cohort
rs324420 local	variant
S1 local	cohort
S1 mice local	cohort
saline	drug
self-control	phenotype
Siemens 3T MAGNETOM Allegra local	drug
Social Closeness local	phenotype
Social Potency local	phenotype
spatial reference memory local	phenotype
spontaneous locomotion local	phenotype
SR141716	drug
Street drug use local	phenotype
Stress Reaction local	phenotype
Stress-reactive personality local	phenotype
stress response	phenotype
Study members local	cohort
synaptic plasticity	phenotype
TEA-Cl local	drug
threat-related amygdala reactivity	phenotype
threat-related reactivity local	phenotype
Threat response local	phenotype
time spent in center square local	phenotype
tissue homogenate local	drug
Traditionalism local	phenotype
trait extinction local	phenotype
trait stress reactivity local	phenotype
traumatic fear memories local	phenotype
Tris-HCl buffer	drug
Tween local	drug
unconditioned fear local	phenotype
unconditioned group local	cohort
unconditioned mice local	cohort
URB597	drug
Vanilla-extract solution local	drug
ventromedial prefrontal cortex	anatomy
Well Being local	phenotype
whole brain	anatomy
WIN55212 local	drug
within-session extinction local	phenotype
yohimbine	drug
Young Adult Birth Cohort local	cohort
zinc depletion local	drug

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In this knowledge base

Title	Year	PMID
Evidence of CNIH3 involvement in opioid dependence.	2016	26239289
Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.	2015	26595473
Amygdala FAAH and anandamide: mediating protection and recovery from stress.	2013	24325918

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Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder.	Singewald N et al.	—	2023	→
Anxiety Modulation by Cannabinoids-The Role of Stress Responses and Coping.	Haller J	—	2023	→
Association of anandamide and 2-arachidonoylglycerol concentrations with clinical features and body mass index in eating disorders and obesity.	Baenas I et al.	—	2023	→
Association of <i>FAAH</i> rs324420 (C385A) Polymorphism with High-Level Performance in Volleyball Players.	Silva HH et al.	—	2023	→
Challenges and considerations for treating PTSD with medicinal cannabis: the Australian clinician's perspective.	Ney LJ et al.	—	2023	→
Childbirth-related posttraumatic stress symptoms - examining associations with hair endocannabinoid concentrations during pregnancy and lifetime trauma.	Bergunde L et al.	—	2023	→
Circulating endocannabinoids and psychological outcomes in women with PTSD.	Botsford C et al.	—	2023	→
Disruption of tonic endocannabinoid signalling triggers cellular, behavioural and neuroendocrine responses consistent with a stress response.	Petrie GN et al.	—	2023	→
Endocannabinoids modulate fear extinction controlled by a cortical-amygdala projection.	Adhikari A	—	2023	→
Enhancing Psychological Interventions for Post-Traumatic Stress Disorder (PTSD) Treatment with Memory Influencing Drugs.	Marchetta E et al.	—	2023	→
Fatty acid amide hydrolase C385A polymorphism affects susceptibility to various diseases.	Hosseinzadeh Anvar L et al.	—	2023	→
Fatty Acid-Binding Protein 5 Gene Deletion Enhances Nicotine-Conditioned Place Preference: Illuminating the Putative Gateway Mechanisms.	Roeder N et al.	—	2023	→
Identification of a novel fatty acid binding protein-5-CB2 receptor-dependent mechanism regulating anxiety behaviors in the prefrontal cortex.	Uzuneser TC et al.	—	2023	→
<i>FAAH</i> rs324420 Polymorphism: Biological Pathways, Impact on Elite Athletic Performance and Insights for Sport Medicine.	Silva HH et al.	—	2023	→
Neuropharmacological Modulation of N-methyl-D-aspartate, Noradrenaline and Endocannabinoid Receptors in Fear Extinction Learning: Synaptic Transmission and Plasticity.	Battaglia S et al.	—	2023	→
Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace.	Gao B et al.	—	2023	→
Plasma Endocannabinoid Levels in Patients with Borderline Personality Disorder and Healthy Controls.	Spohrs J et al.	—	2023	→
Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation.	Perini I et al.	—	2023	→
The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.	Hill MN et al.	—	2023	→
Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders.	Li Y et al.	—	2023	→
A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults.	Zabik NL et al.	—	2022	→
Acquisition of threat responses are associated with elevated plasma concentration of endocannabinoids in male humans.	Weisser S et al.	—	2022	→
CB2 cannabinoid receptor expression is increased in 129S1/SvImJ mice: behavioral consequences.	Ten-Blanco M et al.	—	2022	→
Circulating endocannabinoids and genetic polymorphisms as predictors of posttraumatic stress disorder symptom severity: heterogeneity in a community-based cohort.	deRoon-Cassini TA et al.	—	2022	→
Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction.	Liu Z et al.	—	2022	→
Effects of endocannabinoid system modulation on social behaviour: A systematic review of animal studies.	Ahmed M et al.	—	2022	→
Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats.	Warren WG et al.	—	2022	→
FAAH polymorphism (rs324420) modulates extinction recall in healthy humans: an fMRI study.	Spohrs J et al.	—	2022	→
Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation.	Green DG et al.	—	2022	→
Genetic variation in endocannabinoid signaling is associated with differential network-level functional connectivity in youth.	Sisk LM et al.	—	2022	→
<i>FAAH</i> rs324420 Polymorphism Is Associated with Performance in Elite Rink-Hockey Players.	Silva HH et al.	—	2022	→
In it together? The case for endocannabinoid-noradrenergic interactions in fear extinction.	Warren WG et al.	—	2022	→
Local modulation by presynaptic receptors controls neuronal communication and behaviour.	Lovinger DM et al.	—	2022	→
Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders.	Navarro D et al.	—	2022	→
Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats.	Vecchiarelli HA et al.	—	2022	→
Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder: A Promising Case of Preclinical-Clinical Translation?	Mayo LM et al.	—	2022	→
The endocannabinoid system in social anxiety disorder: from pathophysiology to novel therapeutics.	Ahmed M et al.	—	2022	→
The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD.	Crombie KM et al.	—	2022	→
The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer's disease.	Jain S et al.	—	2022	→
The role of the cannabinoid system in fear memory and extinction in male and female mice.	Mizuno I et al.	—	2022	→
The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD.	Leen NA et al.	—	2022	→
Translation of animal endocannabinoid models of PTSD mechanisms to humans: Where to next?	Ney LJ et al.	—	2022	→
Amygdalar endocannabinoids are affected by predator odor stress in a sex-specific manner and modulate acoustic startle reactivity in female rats.	Albrechet-Souza L et al.	—	2021	→
Cannabidiol and the corticoraphe circuit in post-traumatic stress disorder.	Alexander C et al.	—	2021	→
Cannabinoid polymorphisms interact with plasma endocannabinoid levels to predict fear extinction learning.	Ney LJ et al.	—	2021	→
Cannabinoid treatment for autism: a proof-of-concept randomized trial.	Aran A et al.	—	2021	→
Cannabis use and posttraumatic stress disorder comorbidity: Epidemiology, biology and the potential for novel treatment approaches.	Kondev V et al.	—	2021	→
Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking.	Martin EL et al.	—	2021	→
Deficiency in endocannabinoid synthase <i>DAGLB</i> contributes to Parkinson’s disease and dopaminergic neuron dysfunction	Liu Z et al.	—	2021	—
Endocannabinoid modulation of dopamine release during reward seeking, interval timing, and avoidance.	Everett TJ et al.	—	2021	→
Endocannabinoids, cannabinoids and the regulation of anxiety.	Petrie GN et al.	—	2021	→
Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial.	Crombie KM et al.	—	2021	→
Fatty acid amide hydrolase binding is inversely correlated with amygdalar functional connectivity: a combined positron emission tomography and magnetic resonance imaging study in healthy individuals.	Green DGJ et al.	—	2021	→
Fear extinction learning and anandamide: an fMRI study in healthy humans.	Spohrs J et al.	—	2021	→
Investigating the role of CB1 endocannabinoid transmission in the anti-fear and anxiolytic-like effects of ventromedial prefrontal cortex deep brain stimulation.	Gidyk DC et al.	—	2021	→
Resilience to fear: The role of individual factors in amygdala response to stressors.	Fonseca R et al.	—	2021	→
Selective inhibition of monoacylglycerol lipase is associated with passive coping behavior and attenuation of stress-induced dopamine release in the medial prefrontal cortex.	Pavón FJ et al.	—	2021	→
Sex-dependent effects of endocannabinoid modulation of conditioned fear extinction in rats.	Morena M et al.	—	2021	→
Sex differences in anxiety and depression: circuits and mechanisms.	Bangasser DA et al.	—	2021	→
The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial.	Paulus MP et al.	—	2021	→
The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: a double-blind, randomized, placebo-controlled proof-of-concept study.	Schmidt ME et al.	—	2021	→
The endocannabinoid system in the amygdala and modulation of fear.	Gunduz-Cinar O	—	2021	→
Understanding the dynamic and destiny of memories.	de Oliveira Alvares L et al.	—	2021	→
Use of cannabinoids for the treatment of patients with post-traumatic stress disorder.	Forsythe ML et al.	—	2021	→
2-Arachidonoylglycerol Modulation of Anxiety and Stress Adaptation: From Grass Roots to Novel Therapeutics.	Bedse G et al.	—	2020	→
A Molecular Collapse and the Mental "Falling Down".	Katona I	—	2020	→
A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis.	Davies C et al.	—	2020	→
Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice.	Bouter Y et al.	—	2020	→
Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice.	Mock ED et al.	—	2020	→
Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial.	Mayo LM et al.	—	2020	→
Endocannabinoid modulating drugs improve anxiety but not the expression of conditioned fear in a rodent model of post-traumatic stress disorder.	Vimalanathan A et al.	—	2020	→
Endocannabinoid System Components as Potential Biomarkers in Psychiatry.	Navarrete F et al.	—	2020	→
Kaempferol Facilitated Extinction Learning in Contextual Fear Conditioned Rats via Inhibition of Fatty-Acid Amide Hydrolase.	Ahmad H et al.	—	2020	→
Lights on Endocannabinoid-Mediated Synaptic Potentiation.	Piette C et al.	—	2020	→
Medical Cannabis in Children.	Aran A et al.	—	2020	→
Meet Your Stress Management Professionals: The Endocannabinoids.	deRoon-Cassini TA et al.	—	2020	→
Predicting Brain Functional Connectivity Using Mobile Sensing.	Obuchi M et al.	—	2020	→
The endocannabinoid system in modulating fear, anxiety, and stress .	Maldonado R et al.	—	2020	→
The role of catecholamines in modulating responses to stress: Sex-specific patterns, implications, and therapeutic potential for post-traumatic stress disorder and opiate withdrawal.	Ross JA et al.	—	2020	→
Cannabinoid interventions for PTSD: Where to next?	Ney LJ et al.	—	2019	→
Cannabinoid Regulation of Fear and Anxiety: an Update.	Papagianni EP et al.	—	2019	→
Endocannabinoid signaling in psychiatric disorders: a review of positron emission tomography studies.	Sloan ME et al.	—	2019	→
Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Accumulative Effects of Trauma.	Bassir Nia A et al.	—	2019	→
Excitation of Diverse Classes of Cholecystokinin Interneurons in the Basal Amygdala Facilitates Fear Extinction.	Rovira-Esteban L et al.	—	2019	→
<i>CNR1</i> and <i>FAAH</i> variation and affective states induced by marijuana smoking.	Palmer RHC et al.	—	2019	→
Identification of a novel gene regulating amygdala-mediated fear extinction.	Gunduz-Cinar O et al.	—	2019	→
Impact of FAAH genetic variation on fronto-amygdala function during emotional processing.	Gärtner A et al.	—	2019	→
Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses.	Zimmermann T et al.	—	2019	→
Influence of Δ9-tetrahydrocannabinol on long-term neural correlates of threat extinction memory retention in humans.	Hammoud MZ et al.	—	2019	→
In the face of stress: Interpreting individual differences in stress-induced facial expressions.	Mayo LM et al.	—	2019	→
Lower circulating endocannabinoid levels in children with autism spectrum disorder.	Aran A et al.	—	2019	→
Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity.	Habib AM et al.	—	2019	→
Resilience as a translational endpoint in the treatment of PTSD.	Rakesh G et al.	—	2019	→
Selective neural sensitivity to familial threat in adolescents with weak family bonds.	Sharp PB et al.	—	2019	→
Stress and glucocorticoid modulation of feeding and metabolism.	Balsevich G et al.	—	2019	→
Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.	Lisboa SF et al.	—	2019	→
The Endocannabinoid System: A New Treatment Target for Obsessive Compulsive Disorder?	Kayser RR et al.	—	2019	→
Upregulation of Anandamide Hydrolysis in the Basolateral Complex of Amygdala Reduces Fear Memory Expression and Indices of Stress and Anxiety.	Morena M et al.	—	2019	→
Changes in Gene Expression in the Locus Coeruleus-Amygdala Circuitry in Inhibitory Avoidance PTSD Model.	Sabban EL et al.	—	2018	→
Chronic treatment with URB597 ameliorates post-stress symptoms in a rat model of PTSD.	Fidelman S et al.	—	2018	→
Effects of Cannabinoid Drugs on Aversive or Rewarding Drug-Associated Memory Extinction and Reconsolidation.	Stern CAJ et al.	—	2018	→
Effects of fatty acid amide hydrolase inhibitor URB597 in a rat model of trauma-induced long-term anxiety.	Danandeh A et al.	—	2018	→
Elucidating the mechanisms of fear extinction in developing animals: a special case of NMDA receptor-independent extinction in adolescent rats.	Bisby MA et al.	—	2018	→
Enhancing Endocannabinoid Neurotransmission Augments The Efficacy of Extinction Training and Ameliorates Traumatic Stress-Induced Behavioral Alterations in Rats.	Morena M et al.	—	2018	→
FAAH variant Pro129Thr modulates subjective effects produced by cocaine administration.	Patel MM et al.	—	2018	→
Functional Relevance of Endocannabinoid-Dependent Synaptic Plasticity in the Central Nervous System.	Augustin SM et al.	—	2018	→
Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice.	Cavener VS et al.	—	2018	→
Inhibition of fatty acid amide hydrolase in the central amygdala alleviates co-morbid expression of innate anxiety and excessive alcohol intake.	Stopponi S et al.	—	2018	→
Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder.	Hill MN et al.	—	2018	→
Involvement of Activated Brain Stress Responsive Systems in Excessive and "Relapse" Alcohol Drinking in Rodent Models: Implications for Therapeutics.	Zhou Y et al.	—	2018	→
Lost in translation: how to upgrade fear memory research.	Flores Á et al.	—	2018	→
Modulation of the endocannabinoid system by sex hormones: Implications for posttraumatic stress disorder.	Ney LJ et al.	—	2018	→
Severity of alcohol dependence is associated with the fatty acid amide hydrolase Pro129Thr missense variant.	Sloan ME et al.	—	2018	→
The Role of the Endocannabinoid System and Genetic Variation in Adolescent Brain Development.	Meyer HC et al.	—	2018	→
The selective reversible FAAH inhibitor, SSR411298, restores the development of maladaptive behaviors to acute and chronic stress in rodents.	Griebel G et al.	—	2018	→
Anxiety disorders.	Craske MG et al.	—	2017	→
Blockade of alcohol escalation and "relapse" drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice.	Zhou Y et al.	—	2017	→
Cannabidiol in medical marijuana: Research vistas and potential opportunities.	Rong C et al.	—	2017	→
Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.	Shoshan N et al.	—	2017	→
Constitutive Increases in Amygdalar Corticotropin-Releasing Factor and Fatty Acid Amide Hydrolase Drive an Anxious Phenotype.	Natividad LA et al.	—	2017	→
Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward.	Volkow ND et al.	—	2017	→
Endocannabinoids: Effectors of glucocorticoid signaling.	Balsevich G et al.	—	2017	→
Genetic variants associated with physical and mental characteristics of the elite athletes in the Polish population.	Peplonska B et al.	—	2017	→
Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders.	Lester KJ et al.	—	2017	→
Imaging Genetics and Genomics in Psychiatry: A Critical Review of Progress and Potential.	Bogdan R et al.	—	2017	→
Regulation of fear extinction by long-term depression: The roles of endocannabinoids and brain derived neurotrophic factor.	Bennett MR et al.	—	2017	→
Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.	Silveira MM et al.	—	2017	→
The effects of cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala and hippocampus on the consolidation of a traumatic event.	Shoshan N et al.	—	2017	→
The effects of enhancing endocannabinoid signaling and blocking corticotrophin releasing factor receptor in the amygdala and hippocampus on the consolidation of a stressful event.	Aisenberg N et al.	—	2017	→
The Endocannabinoid System and Anxiety.	Lisboa SF et al.	—	2017	→
The endocannabinoid system as a target for addiction treatment: Trials and tribulations.	Sloan ME et al.	—	2017	→
The endocannabinoid system as a target for novel anxiolytic drugs.	Patel S et al.	—	2017	→
The genetics of anxiety-related negative valence system traits.	Savage JE et al.	—	2017	→
2-arachidonoylglycerol signaling impairs short-term fear extinction.	Hartley ND et al.	—	2016	→
Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.	Robinson SL et al.	—	2016	→
Cannabinoids and post-traumatic stress disorder: clinical and preclinical evidence for treatment and prevention.	Mizrachi Zer-Aviv T et al.	—	2016	→
Circumspectives: Cannabis and Psychiatric Illness: Blunt Thoughts.	Heilig M et al.	—	2016	→
Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches.	Sartori SB et al.	—	2016	→
Common Polymorphisms in the Age of Research Domain Criteria (RDoC): Integration and Translation.	Glatt CE et al.	—	2016	→
Developmental regulation of fear learning and anxiety behavior by endocannabinoids.	Lee TT et al.	—	2016	→
Does Cannabis Cause, Exacerbate or Ameliorate Psychiatric Disorders? An Oversimplified Debate Discussed.	Haney M et al.	—	2016	→
Emotional arousal state influences the ability of amygdalar endocannabinoid signaling to modulate anxiety.	Morena M et al.	—	2016	→
Endocannabinoid concentrations in hair are associated with PTSD symptom severity.	Wilker S et al.	—	2016	→
Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats.	Lim J et al.	—	2016	→
Endocannabinoids and Stress Resilience: Is Deficiency Sufficient to Promote Vulnerability?	Hill MN et al.	—	2016	→
Endocannabinoid Signaling Regulates Sleep Stability.	Pava MJ et al.	—	2016	→
Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.	Whittle N et al.	—	2016	→
Evidence of CNIH3 involvement in opioid dependence.	Nelson EC et al.	—	2016	→
FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence.	Spagnolo PA et al.	—	2016	→
Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.	Gunduz-Cinar O et al.	—	2016	→
Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma.	Lazary J et al.	—	2016	→
Genetic and Environmental Factors Associated with Cannabis Involvement.	Bogdan R et al.	—	2016	→
Genetic influences on the neural and physiological bases of acute threat: A research domain criteria (RDoC) perspective.	Sumner JA et al.	—	2016	→
Genetic Moderation of Stress Effects on Corticolimbic Circuitry.	Bogdan R et al.	—	2016	→
Genetics as a molecular window into recovery, its treatment, and stress responses after stroke.	Juth V et al.	—	2016	→
Impaired Ethanol-Induced Sensitization and Decreased Cannabinoid Receptor-1 in a Model of Posttraumatic Stress Disorder.	Matchynski-Franks JJ et al.	—	2016	→
Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species.	Gee DG et al.	—	2016	→
Inhibition of PARP-1 participates in the mechanisms of propofol-induced amnesia in mice and human.	Jia L et al.	—	2016	→
Interactions Between Anandamide and Corticotropin-Releasing Factor Signaling Modulate Human Amygdala Function and Risk for Anxiety Disorders: An Imaging Genetics Strategy for Modeling Molecular Interactions.	Demers CH et al.	—	2016	→
Maintenance of aversive memories shown by fear extinction-impaired phenotypes is associated with increased activity in the amygdaloid-prefrontal circuit.	Laricchiuta D et al.	—	2016	→
Neurobiological Interactions Between Stress and the Endocannabinoid System.	Morena M et al.	—	2016	→
Neurobiology of addiction: a neurocircuitry analysis.	Koob GF et al.	—	2016	→
Neuroimaging of Fear-Associated Learning.	Greco JA et al.	—	2016	→
Plasma Biomarkers for Monitoring Brain Pathophysiology in FMR1 Premutation Carriers.	Giulivi C et al.	—	2016	→
PTSD: from neurobiology to pharmacological treatments.	Kelmendi B et al.	—	2016	→
Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.	Yi B et al.	—	2016	→
Stress and Fear Extinction.	Maren S et al.	—	2016	→
The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats.	Aliczki M et al.	—	2016	→
The endocannabinoid system and Post Traumatic Stress Disorder (PTSD): From preclinical findings to innovative therapeutic approaches in clinical settings.	Berardi A et al.	—	2016	→
2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons.	Llorente-Berzal A et al.	—	2015	→
An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials.	Bowers ME et al.	—	2015	→
Behavioral genetics: of mice, men, and internal bliss.	Schiller D	—	2015	→
Corticotropin-releasing hormone drives anandamide hydrolysis in the amygdala to promote anxiety.	Gray JM et al.	—	2015	→
Endocannabinoids and Mental Disorders.	Rubino T et al.	—	2015	→
Endocannabinoid signaling mediates oxytocin-driven social reward.	Wei D et al.	—	2015	→
Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation.	Atsak P et al.	—	2015	→
FAAH genetic variation enhances fronto-amygdala function in mouse and human.	Dincheva I et al.	—	2015	→
Finding translation in stress research.	Hariri AR et al.	—	2015	→
Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants.	Ogawa S et al.	—	2015	→
Interaction between the cholecystokinin and endogenous cannabinoid systems in cued fear expression and extinction retention.	Bowers ME et al.	—	2015	→
Investigational drugs under development for the treatment of PTSD.	Ragen BJ et al.	—	2015	→
Modulation of Fear Extinction by Stress, Stress Hormones and Estradiol: A Review.	Stockhorst U et al.	—	2015	→
Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.	Carey CE et al.	—	2015	→
NMDA receptor subunits and associated signaling molecules mediating antidepressant-related effects of NMDA-GluN2B antagonism.	Kiselycznyk C et al.	—	2015	→
Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders.	Singewald N et al.	—	2015	→
Sulfonyl fluorides as privileged warheads in chemical biology.	Narayanan A et al.	—	2015	→
The endocannabinoid system in guarding against fear, anxiety and stress.	Lutz B et al.	—	2015	→
Toward a translational approach to targeting the endocannabinoid system in posttraumatic stress disorder: a critical review of preclinical research.	Papini S et al.	—	2015	→
Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder.	Neumeister A et al.	—	2015	→
Blockade of CB1 receptors prevents retention of extinction but does not increase low preincubated conditioned fear in the fear incubation procedure.	Pickens CL et al.	—	2014	→
Can fear extinction be enhanced? A review of pharmacological and behavioral findings.	Fitzgerald PJ et al.	—	2014	→
Cannabinoid modulation of fear extinction brain circuits: a novel target to advance anxiety treatment.	Rabinak CA et al.	—	2014	→
Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans.	Rabinak CA et al.	—	2014	→
Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors.	Pietrzak RH et al.	—	2014	→
Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation.	Bluett RJ et al.	—	2014	→
Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors.	Briscione MA et al.	—	2014	→
Early intervention following trauma may mitigate genetic risk for PTSD in civilians: a pilot prospective emergency department study.	Rothbaum BO et al.	—	2014	→
Glutamatergic mechanisms associated with stress-induced amygdala excitability and anxiety-related behavior.	Masneuf S et al.	—	2014	→
HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand?	Whittle N et al.	—	2014	→
Individual differences in response to positive and negative stimuli: endocannabinoid-based insight on approach and avoidance behaviors.	Laricchiuta D et al.	—	2014	→
Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders.	Bukalo O et al.	—	2014	→
More surprises lying ahead. The endocannabinoids keep us guessing.	Piomelli D	—	2014	→
Prefrontal single-unit firing associated with deficient extinction in mice.	Fitzgerald PJ et al.	—	2014	→
Risky alcohol consumption in young people is associated with the fatty acid amide hydrolase gene polymorphism C385A and affective rating of drug pictures.	Bühler KM et al.	—	2014	→
Tales from the dark side: do neuromodulators of drug withdrawal require changes in endocannabinoid tone?	Oleson EB et al.	—	2014	→
The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury.	Tchantchou F et al.	—	2014	→
The hypocretin/orexin system mediates the extinction of fear memories.	Flores Á et al.	—	2014	→
The role of stress and fear in the development of mental disorders.	Gonzalez P et al.	—	2014	→
50 years of hurdles and hope in anxiolytic drug discovery.	Griebel G et al.	—	2013	→
Amygdala FAAH and anandamide: mediating protection and recovery from stress.	Gunduz-Cinar O et al.	—	2013	→
Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study.	Neumeister A et al.	—	2013	→
Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses.	Trouche S et al.	—	2013	→
Individual differences in recovery from traumatic fear.	Holmes A et al.	—	2013	→
Inhibition of FAAH and activation of PPAR: new approaches to the treatment of cognitive dysfunction and drug addiction.	Panlilio LV et al.	—	2013	→
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