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Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies
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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“Enhanced eCB signallingfor example, induced by blocking the serine hydrolase enzyme FAAHreduces stress and anxiety responses and promotes fear-extinction learning (Gunduz-Cinar, Hill, McEwen, & Holmes, 2013;Lisboa et al., 2019;Mayo et al., 2019;Patel et al., 2017).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Lisboa et al., 2019
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Metadata
- 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.
- Venue
- Psychopharmacology
- Published
- 2019-01
- Volume
- 236
- Issue
- 1
- Pages
- 201-226
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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