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Cannabidiol regulation of learned fear: implications for treating anxiety-related disorders

Jurkus, Regimantas; Day, Harriet L.; Guimaraes, Francisco S.; Lee, Jonathan L.; Bertoglio, Leandro J.; Stevenson, Carl W.

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Regimantas Jurkus

Harriet L. Day

Francisco S. Guimaraes

Jonathan L. Lee

Leandro J. Bertoglio


Anxiety and trauma-related disorders are psychiatric diseases with a lifetime prevalence of up to 25%. Phobias and post-traumatic stress disorder (PTSD) are characterized by abnormal and persistent memories of fear-related contexts and cues. The effects of psychological treatments such as exposure therapy are often only temporary and medications can be ineffective and have adverse side effects. Growing evidence from human and animal studies indicates that cannabidiol, the main non-psychotomimetic phytocannabinoid present in Cannabis sativa, alleviates anxiety in paradigms assessing innate fear. More recently, the effects of cannabidiol on learned fear have been investigated in preclinical studies with translational relevance for phobias and PTSD. Here we review the findings from these studies, with an emphasis on cannabidiol regulation of contextual fear. The evidence indicates that cannabidiol reduces learned fear in different ways: (1) cannabidiol decreases fear expression acutely, (2) cannabidiol disrupts memory reconsolidation, leading to sustained fear attenuation upon memory retrieval, and (3) cannabidiol enhances extinction, the psychological process by which exposure therapy inhibits learned fear. We also present novel data on cannabidiol regulation of learned fear related to explicit cues, which indicates that auditory fear expression is also reduced acutely by cannabidiol. We conclude by outlining future directions for research to elucidate the neural circuit, psychological, cellular, and molecular mechanisms underlying the regulation of fear memory processing by cannabidiol. This line of investigation may lead to the development of cannabidiol as a novel therapeutic approach for treating anxiety and trauma-related disorders such as phobias and PTSD in the future.

Journal Article Type Article
Acceptance Date Nov 11, 2016
Publication Date Nov 24, 2016
Deposit Date Nov 14, 2016
Publicly Available Date Nov 24, 2016
Journal Frontiers in Pharmacology
Electronic ISSN 1663-9812
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 7
Issue 454
Keywords Anxiety, Cannabidiol, extinction, Fear conditioning, reconsolidation, phobia, Post-traumatic stress disorder
Public URL
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Additional Information This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.


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