ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Enhancing Endocannabinoid Neurotransmission Augments The Efficacy of Extinction Training and Ameliorates Traumatic Stress-Induced Behavioral Alterations in Rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 94 citations in OpenAlex.
- Functional neuroimaging of fatty acid amide hydrolase inhibition in posttraumatic stress disorder: a randomized clinical trial.Translational psychiatry · 2026Trial
- Cannabinoid modulation of corticolimbic activation during extinction learning and fear renewal in adults with posttraumatic stress disorder.Neurobiology of learning and memory · 2023Trial
- 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
- Investigational drugs in PTSD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Radical Revelations: The Interplay of Nitrosative Stress, the Endocannabinoid System, and Treatment of Age-Related Disorders.International journal of molecular sciences · 2026Review
- Differential effects of adolescent fatty acid amide hydrolase and monoacylglycerol lipase inhibition on adolescent and adult behaviors in male rats.Psychopharmacology · 2026Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 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
- Differential Effects of Adolescent Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Inhibition on Adolescent and Adult Behaviors in Male Rats.Research square · 2025Article
- Endocannabinoids inhibit contextual fear memory generalization via hippocampal GABAergic synaptic transmission.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Interindividual and sex differences in resilience and vulnerability to post-traumatic stress disorder (PTSD): insights from animal models.Biology of sex differences · 2025Review
- Understanding the Role of Endocannabinoids in Posttraumatic Stress Disorder.International journal of molecular sciences · 2025Review
- Social buffering during fear extinction rescues long-term trauma-induced memory and emotional behavioral alterations in rats.Translational psychiatry · 2025Article
- Rat Models in Post-Traumatic Stress Disorder Research: Strengths, Limitations, and Implications for Translational Studies.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Endocannabinoid and neuroplasticity-related changes as susceptibility factors in a rat model of posttraumatic stress disorder.Neurobiology of stress · 2024Article
- Cannabinoids in the Treatment of Selected Mental Illnesses: Practical Approach and Overview of the Literature.Pharmacopsychiatry · 2024Review
- Predator odor stress reactivity, alcohol drinking and the endocannabinoid system.Neurobiology of stress · 2024Article
- Australian clinical feasibility considerations for treatment of PTSD with cannabinoid-augmented exposure therapy.The Australian and New Zealand journal of psychiatry · 2024Article
- Biomarkers of stress resilience: A review.Neuroscience applied · 2024Article
- The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.Psychological medicine · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure to a traumatic event may result in the development of post-traumatic stress disorder (PTSD). Endocannabinoids are crucial modulators of the stress response, interfere with excessive retrieval and facilitate the extinction of traumatic memories. Exposure therapy, combined with pharmacotherapy, represents a promising tool for PTSD treatment. We investigated whether pharmacological manipulations of the endocannabinoid system during extinction learning ameliorates the behavioral changes induced by trauma exposure. Rats were exposed to inescapable footshocks paired with social isolation, a risk factor for PTSD. One week after trauma, rats were subjected to three spaced extinction sessions, mimicking human exposure therapy. The anandamide hydrolysis inhibitor URB597, the 2-arachidonoylglycerol hydrolysis inhibitor JZL184 or the cannabinoid agonist WIN55,212-2 were administered before or after the extinction sessions. Rats were tested for extinction retention 16 or 36 days after trauma and 24-h later for social interaction. Extinction training alone reduced fear of the trauma-associated context but did not restore normal social interaction. Traumatized animals not exposed to extinction sessions exhibited reductions in hippocampal anandamide content with respect to home-cage controls. Noteworthy, all drugs exerted beneficial effects, but URB597 (0.1 mg/kg) induced the best improvements by enhancing extinction consolidation and restoring normal social behavior in traumatized rats through indirect activation of CB1 receptors. The ameliorating effects remained stable long after treatment and trauma exposure. Our findings suggest that drugs potentiating endocannabinoid neurotransmission may represent promising tools when combined to exposure-based psychotherapies in the treatment of 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.