On disruption of fear memory by reconsolidation blockade: evidence from cannabidiol treatment
Open accessAbstract
The search for reconsolidation blockers may uncover clinically relevant drugs for disrupting memories of significant stressful life experiences, such as those underlying the posttraumatic stress disorder. Considering the safety of systemically administered cannabidiol (CBD), the major non-psychotomimetic component of Cannabis sativa, to animals and humans, the present study sought to investigate whether and how this phytocannabinoid (3-30 mg/kg intraperitoneally; i.p.) could mitigate an established memory, by blockade of its reconsolidation, evaluated in a contextual fear-conditioning paradigm in rats. We report that CBD is able to disrupt 1- and 7-days-old memories when administered immediately, but not 6 h, after their retrieval for 3 min, with the dose of 10 mg/kg being the most effective. This effect persists in either case for at least 1 week, but is prevented when memory reactivation was omitted, or when the cannabinoid type-1 receptors were antagonized selectively with AM251 (1.0 mg/kg). Pretreatment with the serotonin type-1A receptor antagonist WAY100635, however, failed to block CBD effects. These results highlight that recent and older fear memories are equally vulnerable to disruption induced by CBD through reconsolidation blockade, with a consequent long-lasting relief in contextual fear-induced freezing. Importantly, this CBD effect is dependent on memory reactivation, restricted to time window of <6 h, and is possibly dependent on cannabinoid type-1 receptor-mediated signaling mechanisms. We also observed that the fear memories disrupted by CBD treatment do not show reinstatement or spontaneous recovery over 22 days. These findings support the view that reconsolidation blockade, rather than facilitated extinction, accounts for the aforementioned CBD results in our experimental conditions.
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The acute effects of CBD in the marble burying test and aversive memory reconsolidation were prevented by CB1-receptor antagonists.
“Indeed, the acute effects of CBD in the marble burying test and aversive memory reconsolidation were prevented by CB1-receptor antagonists (24, 26).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [24]
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- Authors
- Stern, C. A. J., Gazarini, L., Takahashi, R. N., Guimarães, F. S., & Bertoglio, L. J.
- Affiliations
- Universidade Federal de Santa Catarina (BR)
- Universidade de São Paulo (BR)
- Corresponding author
- Gazarini, Lucas
- Bertoglio, Leandro J
- Venue
- Neuropsychopharmacology
- Published
- 2012-05-02
- Volume
- 37
- Issue
- 9
- Pages
- 2132-2142
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3398715
- OpenAlex
- W1966133745
- Cited by
- 156
- References
- 58
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 13 · 2023: 8 · 2022: 15 · 2021: 12 · 2020: 15 · 2019: 17 · 2018: 9 · 2017: 13 · 2016: 14 · 2015: 8 · 2014: 6 · 2013: 12 · 2012: 4
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Universidade Federal de Santa Catarina
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- cannabidiol, memory reconsolidation blockade, fear memory, post-traumatic stress disorder, contextual fear conditioning, cannabinoid type 1 receptor, AM251, memory reactivation, memory extinction, reinstatement, spontaneous recovery, phytocannabinoids
- MeSH terms
- Animals, Cannabidiol, Conditioning, Psychological, Extinction, Psychological, Fear, Male, Memory, Random Allocation, Rats, Wistar, Evidence-Based Medicine, Receptor, Cannabinoid, CB1, Rats
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