Cannabinoid facilitation of fear extinction memory recall in humans.

paper Cited Public

Authors: Rabinak, Christine A; Angstadt, Mike; Sripada, Chandra S; Abelson, James L; Liberzon, Israel; Milad, Mohammed R; Phan, K Luan
Year: 2013
Journal: Neuropharmacology
PMID: 22796109
DOI: 10.1016/j.neuropharm.2012.06.063
PMCID: PMC3445738

Figure 1

Schematic of the experimental protocol.

LLM interpretation

This figure is a schematic diagram illustrating a three-day experimental protocol for fear acquisition, extinction learning, and memory recall. Day 1 shows fear acquisition using colored squares (blue, yellow, red) paired with auditory stimuli; Day 2 depicts extinction learning following the administration of 7.5 mg THC or PBO with a 120-minute delay; Day 3 shows the extinction memory recall test. Each day includes boxes detailing the number of trials for various stimulus conditions (e.g., CS+E, CS+U, CS-).

Figure 2

Skin conductance responses (SCRs) to the CS+E during extinction learning. Mean SCRs to the CS+E during early (average first four trials) and late (average last four trials) extinction learning. PBO (green bars) and THC (red bars).

LLM interpretation

This bar chart displays mean skin conductance responses (SCR [$\mu\text{S}^{1/2}$]) for PBO (green) and THC (red) groups during early and late extinction learning. SCR values are higher during early extinction compared to late extinction for both groups. In the early phase, the THC group shows a higher mean SCR than the PBO group, whereas the values are nearly identical during the late phase.

Figure 3

Skin conductance responses (SCRs) during the extinction memory recall test. Mean differential SCRs during the first two trials of the CS+E minus the first two trials of the CS+U during the extinction memory recall test. Difference scores greater than zero reflect greater responding to the CS+E, difference scores equal to zero reflect no difference in responding between the CS+E and CS+U, and scores less than zero reflect greater responding to the CS+U (LaBar et al., 1998; LaBar et al., 1995). PBO (green bars) and THC (red bars).

LLM interpretation

This bar chart displays the mean difference in skin conductance responses (SCR) between the CS+E and CS+U conditions during an extinction memory recall test. The PBO group (green bar) shows a positive mean difference, while the THC group (red bar) shows a negative mean difference. The y-axis is labeled "Mean Difference SCR (SC+E - CS+U) [$\mu$S$^{1/2}$]" and ranges from -0.3 to 0.3.

#	Section	Preview
0	1. Introduction	The inability to suppress inappropriate fear responses is the hallmark of anxiety disorders, such as…
1	1. Introduction	Unfortunately, a major limitation of extinction is that it is a temporary phenomenon and…
2	1. Introduction	Exciting new evidence has shown that pharmacological agents known as “cognitive enhancers” can…
3	1. Introduction	Emerging studies in rodents suggest that activation of the cannabinoid (CB) system within the brain…
4	1. Introduction	In humans, however, the role of cannabinoids on fear extinction learning remains unknown. The…
5	2. Materials and Methods — 2.1 Subjects	Twenty-nine healthy, right-handed volunteers (twelve males; aged 21–45 years; Caucasian = 21;…
6	2. Materials and Methods — 2.1 Subjects	All female subjects completed study sessions about 1 week prior to menses onset (based on…
7	2. Materials and Methods — 2.2 Fear conditioning, extinction, and testing procedures	Participants were studied over 3 consecutive days (see Figure 1). On Day 1, all participants…
8	2. Materials and Methods — 2.2 Fear conditioning, extinction, and testing procedures	The next day (Day 2) all participants underwent an extinction session in which one of the CS+s…
9	2. Materials and Methods — 2.2 Fear conditioning, extinction, and testing procedures	To assess extinction retention, we conducted an extinction memory recall test approximately 24 hours…
10	2. Materials and Methods — 2.2 Fear conditioning, extinction, and testing procedures	At the beginning of each session participants were told that they may or may not hear a loud noise…
11	2. Materials and Methods — 2.3 Psychophysiological measures and data analysis	SCRs were measured by two disposable carbon fiber electrodes attached between the first and second…
12	2. Materials and Methods — 2.3 Psychophysiological measures and data analysis	SCR for each CS trial was calculated by subtracting the mean skin conductance level during the 2 sec…
13	2. Materials and Methods — 2.3 Psychophysiological measures and data analysis	SCRs and US expectancy ratings were analyzed using analysis of variance (ANOVA). Post-hoc…
14	3. Results — 3.1 Fear Acquisition	An ANOVA of SCR during fear acquisition revealed a significant main effect of stimulus [F(1,27) =…
15	3. Results — 3.1 Fear Acquisition	± 0.24] during the last trial of fear acquisition [main effect of stimulus [F(1,27) = 80.76, p <…
16	3. Results — 3.2 Extinction Learning	An ANOVA of SCR and of US expectancy ratings with three, two-level factors – drug (THC, PBO),…
17	3. Results — 3.2 Extinction Learning	shown)] compared to late extinction [SCR: THC = 0.13 ± 0.05; PBO = 0.13 ± 0.04 (Figure 2); US…
18	3. Results — 3.2 Extinction Learning	Of note, elevated SCRs and greater US expectancy ratings to the CS+E during early extinction…
19	3. Results — 3.3 Extinction Memory Recall Test	An ANOVA of SCR during the extinction memory recall test (first two CS+E vs. first two CS+U trials)…

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The endocannabinoid system in the amygdala and modulation of fear.	Gunduz-Cinar O	—	2021	→
The role of endocannabinoids in consolidation, retrieval, reconsolidation, and extinction of fear memory.	Mizuno I et al.	—	2021	→
The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial.	Bonn-Miller MO et al.	—	2021	→
Use of cannabinoids for the treatment of patients with post-traumatic stress disorder.	Forsythe ML et al.	—	2021	→
Acute effects of cannabinoids on symptoms of obsessive-compulsive disorder: A human laboratory study.	Kayser RR et al.	—	2020	→
Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.	Haspula D et al.	—	2020	→
Cannabinoids as therapeutics for PTSD.	Sbarski B et al.	—	2020	→
Effects of ∆<sup>9</sup>-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies.	Raymundi AM 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	→
Failure of fear extinction in insomnia: An evolutionary perspective.	Perogamvros L et al.	—	2020	→
Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice.	Mayo LM et al.	—	2020	→
Reviewing the Potential of Psychedelics for the Treatment of PTSD.	Krediet E et al.	—	2020	→
The Effectiveness of Cannabinoids in the Treatment of Posttraumatic Stress Disorder (PTSD): A Systematic Review.	Hindocha C 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	→
Cannabidiol and the Remainder of the Plant Extract Modulate the Effects of Δ9-Tetrahydrocannabinol on Fear Memory Reconsolidation.	Murkar A et al.	—	2019	→
Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: study protocol of a randomized controlled trial.	van der Flier FE et al.	—	2019	→
Cannabinoid interventions for PTSD: Where to next?	Ney LJ et al.	—	2019	→
Current understanding of fear learning and memory in humans and animal models and the value of a linguistic approach for analyzing fear learning and memory in humans.	Raber J et al.	—	2019	→
Impaired inhibition as an intermediate phenotype for PTSD risk and treatment response.	van Rooij SJH et al.	—	2019	→
Influence of Δ9-tetrahydrocannabinol on long-term neural correlates of threat extinction memory retention in humans.	Hammoud MZ et al.	—	2019	→
Navigating Blind in the Green Rush: Clinical Considerations and Harm Reduction Practices for Cannabis.	Meffert BN et al.	—	2019	→
Sex differences in fear extinction.	Velasco ER 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	→
Alcohol, cannabis, and other drug use: Engagement and outcome in PTSD treatment.	Bedard-Gilligan M et al.	—	2018	→
Amygdala Inhibitory Circuits Regulate Associative Fear Conditioning.	Krabbe S et al.	—	2018	→
Cannabis regulatory science: risk-benefit considerations for mental disorders.	Borodovsky JT et al.	—	2018	→
Critical evaluation of current data analysis strategies for psychophysiological measures of fear conditioning and extinction in humans.	Ney LJ et al.	—	2018	→
Effects of acute Δ9-tetrahydrocannabinol on next-day extinction recall is mediated by post-extinction resting-state brain dynamics.	Rabinak CA et al.	—	2018	→
Effects of Cannabinoid Drugs on Aversive or Rewarding Drug-Associated Memory Extinction and Reconsolidation.	Stern CAJ et al.	—	2018	→
Fear as a translational mechanism in the psychopathology of anorexia nervosa.	Murray SB et al.	—	2018	→
Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder.	Hill MN et al.	—	2018	→
Modulation of the endocannabinoid system by sex hormones: Implications for posttraumatic stress disorder.	Ney LJ et al.	—	2018	→
Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine.	Fattore L et al.	—	2018	→
Review of the neurological benefits of phytocannabinoids.	Maroon J et al.	—	2018	→
Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder.	Lisieski MJ et al.	—	2018	→
Attentional Control and Fear Extinction in Subclinical Fear: An Exploratory Study.	Forcadell E et al.	—	2017	→
Cannabinoid Modulation of the Stressed Hippocampus.	Scarante FF et al.	—	2017	→
Does fear extinction in the laboratory predict outcomes of exposure therapy? A treatment analog study.	Forcadell E et al.	—	2017	→
Emotional Modulation of Learning and Memory: Pharmacological Implications.	LaLumiere RT et al.	—	2017	→
Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study.	Ganella DE et al.	—	2017	→
Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders.	Lester KJ et al.	—	2017	→
Is cannabis treatment for anxiety, mood, and related disorders ready for prime time?	Turna J et al.	—	2017	→
Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review.	Steenkamp MM et al.	—	2017	→
Precondition of right frontal region with anodal tDCS can restore the fear memory impairment induced by ACPA in male mice.	Manteghi F et al.	—	2017	→
The Endocannabinoid System and Anxiety.	Lisboa SF et al.	—	2017	→
Cannabinoid Modulation of Frontolimbic Activation and Connectivity During Volitional Regulation of Negative Affect.	Gorka SM 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	→
Endocannabinoid concentrations in hair are associated with PTSD symptom severity.	Wilker S et al.	—	2016	→
From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology.	Ligresti A et al.	—	2016	→
Marijuana Legalization: Impact on Physicians and Public Health.	Wilkinson ST et al.	—	2016	→
Modulation of fear extinction processes using transcranial electrical stimulation.	Abend R et al.	—	2016	→
Neural signals of vicarious extinction learning.	Golkar A et al.	—	2016	→
On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development.	Risbrough VB et al.	—	2016	→
Stress and Fear Extinction.	Maren S 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	→
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	→
Augmentation of Evidence-Based Psychotherapy for PTSD With Cognitive Enhancers.	Marin MF et al.	—	2015	→
Brain sites involved in fear memory reconsolidation and extinction of rodents.	Baldi E et al.	—	2015	→
Drug discovery strategies that focus on the endocannabinoid signaling system in psychiatric disease.	Wyrofsky R et al.	—	2015	→
Intranasal oxytocin administration prior to exposure therapy for arachnophobia impedes treatment response.	Acheson DT 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	→
Novelty-facilitated extinction: providing a novel outcome in place of an expected threat diminishes recovery of defensive responses.	Dunsmoor JE et al.	—	2015	→
Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders.	Singewald N 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	→
Can fear extinction be enhanced? A review of pharmacological and behavioral findings.	Fitzgerald PJ et al.	—	2014	→
Cannabinoid modulation of amygdala subregion functional connectivity to social signals of threat.	Gorka SM 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	→
Endogenous cortisol levels influence exposure therapy in spider phobia.	Lass-Hennemann J et al.	—	2014	→
Enhance, delete, incept: manipulating hippocampus-dependent memories.	Spiers HJ et al.	—	2014	→
From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.	VanElzakker MB et al.	—	2014	→
Looking beyond Fear and Extinction Learning: Considering Novel Treatment Targets for Anxiety.	Britton JC 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	→
Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder.	Roitman P et al.	—	2014	→
Psychophysiology in the study of psychological trauma: where are we now and where do we need to be?	Acheson DT et al.	—	2014	→
The neurobiological bases of memory formation: from physiological conditions to psychopathology.	Bisaz R et al.	—	2014	→
Amygdala FAAH and anandamide: mediating protection and recovery from stress.	Gunduz-Cinar O et al.	—	2013	→
Cannabis therapy.	Müller-Vahl K et al.	—	2013	→
Endocannabinoid system and mood disorders: priming a target for new therapies.	Micale V et al.	—	2013	→
Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses.	Trouche S et al.	—	2013	→
Infusion of cannabidiol into infralimbic cortex facilitates fear extinction via CB1 receptors.	Do Monte FH et al.	—	2013	→
Risk for anxiety and implications for treatment: developmental, environmental, and genetic factors governing fear regulation.	Hartley CA et al.	—	2013	→
Stress enhances the consolidation of extinction memory in a predictive learning task.	Hamacher-Dang TC et al.	—	2013	→
Targeting the endocannabinoid system to treat haunting traumatic memories.	Akirav I	—	2013	→