P.1.j.006 Involvement of the prelimbic cortex in the disruptive effect of cannabidiol on fear memory reconsolidation

Stern, Cristina Aparecida Jark; Gazarmi, L.; Vanvossen, Ana Carolina; Zuardi, Antônio Waldo; Guimarães, Francisco Silveira; Takahashi, Reinaldo Ν.; Bertoglio, Leandro J.

doi:10.1016/s0924-977x(14)70511-5

Cited by 9 publications

(3 citation statements)

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“…CBD was shown to act in the IL cortex to facilitate fear extinction as infusing CBD into this region enhanced extinction, an effect which also depended on CB 1 receptors (Do Monte et al , ). The disruptive effect of CBD on fear memory reconsolidation was blocked by pretreatment with a CB 1 receptor antagonist given systemically or infused into the PL cortex, whereas prior 5‐HT 1A receptor antagonism had no effect on the disruption of reconsolidation by CBD (Stern et al , ; ).…”

Section: Pharmacological Mechanisms and Brain Sites Involved In The Ementioning

confidence: 99%

Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety‐related and substance abuse disorders

Lee

Bertoglio

Guimarães

et al. 2017

British J Pharmacology

124

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Learning to associate cues or contexts with potential threats or rewards is adaptive and enhances survival. Both aversive and appetitive memories are therefore powerful drivers of behaviour, but the inappropriate expression of conditioned responding to fear-and drug-related stimuli can develop into anxiety-related and substance abuse disorders respectively. These disorders are associated with abnormally persistent emotional memories and inadequate treatment, often leading to symptom relapse. Studies show that cannabidiol, the main non-psychotomimetic phytocannabinoid found in Cannabis sativa, reduces anxiety via 5-HT 1A and (indirect) cannabinoid receptor activation in paradigms assessing innate responses to threat. There is also accumulating evidence from animal studies investigating the effects of cannabidiol on fear memory processing indicating that it reduces learned fear in paradigms that are translationally relevant to phobias and post-traumatic stress disorder. Cannabidiol does so by reducing fear expression acutely and by disrupting fear memory reconsolidation and enhancing fear extinction, both of which can result in a lasting reduction of learned fear. Recent studies have also begun to elucidate the effects of cannabidiol on drug memory expression using paradigms with translational relevance to addiction. The findings suggest that cannabidiol reduces the expression of drug memories acutely and by disrupting their reconsolidation. Here, we review the literature demonstrating the anxiolytic effects of cannabidiol before focusing on studies investigating its effects on various fear and drug memory processes. Understanding how cannabidiol regulates emotion and emotional memory processing may eventually lead to its use as a treatment for anxiety-related and substance abuse disorders. LINKED ARTICLESThis article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit

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Section: Pharmacological Mechanisms and Brain Sites Involved In The Ementioning

confidence: 99%

Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety‐related and substance abuse disorders

Lee

Bertoglio

Guimarães

et al. 2017

British J Pharmacology

124

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“…CBD regulation of contextual fear expression in these regions depends on 5-HT 1A R activation as it is prevented by local 5-HT 1A R antagonist pretreatment (Gomes et al, 2012; Fogaça et al, 2014; Marinho et al, 2015). CBD disruption of fear memory reconsolidation depended on CB1R but not 5-HT 1A R activation in the PL (Stern et al, 2014). CBD infused into the IL cortex facilitated contextual fear extinction in a CB1R-dependent manner (Do Monte et al, 2013).…”

Section: Cbd Regulation Of Contextual Fear Memory Processingmentioning

confidence: 99%

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders

et al. 2016

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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.

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“…CBD-induced disruption of consolidation is blocked by CB1 and CB2 receptor antagonists infused centrally [ 28 ]. Disruption of reconsolidation by CBD is also blocked by systemic or central CB1 receptor antagonist treatment [ 38 , 51 ]. Extinction enhancement by CBD is blocked by central CB1 receptor antagonism [ 41 , 42 ].…”

Section: Phytocannabinoid Regulation Of Fear and Anxiety: The Case Fomentioning

confidence: 99%

Cannabinoid Regulation of Fear and Anxiety: an Update

Papagianni

Stevenson

2019

Curr Psychiatry Rep

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Purpose of Review Anxiety- and trauma-related disorders are prevalent and debilitating mental illnesses associated with a significant socioeconomic burden. Current treatment approaches often have inadequate therapeutic responses, leading to symptom relapse. Here we review recent preclinical and clinical findings on the potential of cannabinoids as novel therapeutics for regulating fear and anxiety. Recent Findings Evidence from preclinical studies has shown that the non-psychotropic phytocannabinoid cannabidiol and the endocannabinoid anandamide have acute anxiolytic effects and also regulate learned fear by dampening its expression, enhancing its extinction and disrupting its reconsolidation. The findings from the relevant clinical literature are still very preliminary but are nonetheless encouraging. Summary Based on this preclinical evidence, larger-scale placebo-controlled clinical studies are warranted to investigate the effects of cannabidiol in particular as an adjunct to psychological therapy or medication to determine its potential utility for treating anxiety-related disorders in the future.

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P.1.j.006 Involvement of the prelimbic cortex in the disruptive effect of cannabidiol on fear memory reconsolidation

Cited by 9 publications

References 0 publications

Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety‐related and substance abuse disorders

Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety‐related and substance abuse disorders

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders

Cannabinoid Regulation of Fear and Anxiety: an Update

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