Cited by 54Cannabis and Cannabinoid ResearchMemory and Neural MechanismsPosttraumatic Stress Disorder Research

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Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies

Lisboa, Sabrina F., Vila-Verde, C., Rosa, J., Uliana, D. L., Stern, C. A. J., Bertoglio, L. J., Resstel, L. B., Guimaraes, F. S.·2019·Psychopharmacology

DOI 10.1007/s00213-018-5127-x

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Abstract

Rationale Aversive learning and memory are essential to cope with dangerous and stressful stimuli present in an ever-changing environment. When this process is dysfunctional, however, it is associated with posttraumatic stress disorder (PTSD). The endocannabinoid (eCB) system has been implicated in synaptic plasticity associated with physiological and pathological aversive learning and memory.Objective and methods The objective of this study was to review and discuss evidence on how and where in the brain genetic or pharmacological interventions targeting the eCB system would attenuate aversive/traumatic memories through extinction facilitation in laboratory animals and humans. The effect size of the experimental intervention under investigation was also calculated.Results Currently available data indicate that direct or indirect activation of cannabinoid type-1 (CB1) receptor facilitates the extinction of aversive/traumatic memories. Activating CB1 receptors around the formation of aversive/traumatic memories or their reminders can potentiate their subsequent extinction. In most cases, the effect size has been large (Cohen's d ≥ 1.0). The brain areas responsible for the abovementioned effects include the medial prefrontal cortex, amygdala, and/or hippocampus. The potential role of cannabinoid type-2 (CB2) receptors in extinction learning is now under investigation.Conclusion Drugs augmenting the brain eCB activity can temper the impact of aversive/traumatic experiences by diverse mechanisms depending on the moment of their administration. Considering the pivotal role the extinction process plays in PTSD, the therapeutic potential of these drugs is evident. The sparse number of clinical trials testing these compounds in stress-related disorders is a gap in the literature that needs to be addressed.

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Authors: Lisboa, S. F., Vila-Verde, C., Rosa, J., Uliana, D. L., Stern, C. A. J., Bertoglio, L. J., Resstel, L. B., & Guimaraes, F. S.
Affiliations: Universidade de São Paulo (BR)
Universidade Federal do Paraná (BR)
Universidade Federal de Santa Catarina (BR)
Corresponding author: Lisboa, Sabrina F.
ORCID: Lisboa, Sabrina F.
Rosa, J.
Uliana, D. L.
Stern, C. A. J.
Bertoglio, L. J.
Resstel, L. B.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2019-01
Volume: 236
Issue: 1
Pages: 201-226
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-018-5127-x
OpenAlex: W2907417472
Cited by: 54
References: 268
Citations by year: 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 16 · 2020: 10 · 2019: 4
FWCI: 1.28
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo (2012/17626-7)
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (465458/2014-9)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Keywords: endocannabinoid system, cannabinoid type 1 receptor, cannabinoid type 2 receptor, post-traumatic stress disorder, aversive memory, traumatic memory, memory extinction, medial prefrontal cortex, amygdala, hippocampus, synaptic plasticity, stress-related disorders, cannabinoid receptor agonists
MeSH terms: Amygdala, Animals, Avoidance Learning, Cannabinoids, Extinction, Psychological, Fear, Hippocampus, Humans, Neuronal Plasticity, Stress Disorders, Post-Traumatic, Prefrontal Cortex

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Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies

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