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Effects of cannabidiol on fear conditioning in anxiety disorders: decreased threat expectation during retention, but no enhanced fear re-extinction.

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Title: Effects of cannabidiol on fear conditioning in anxiety disorders: decreased threat expectation during retention, but no enhanced fear re-extinction.
Authors: Kwee, C. M. B. (AUTHOR), van der Flier, F. E. (AUTHOR), Duits, P. (AUTHOR), van Balkom, A. J. L. M. (AUTHOR), Cath, D. C. (AUTHOR), Baas, J. M. P. (AUTHOR)
Source: Psychopharmacology. Apr2024, Vol. 241 Issue 4, p833-847. 15p.
Subjects: Anxiety disorders, Conditioned response, Cannabidiol, Startle reaction, Cannabinoid receptors, Exposure therapy, Social anxiety, Panic disorders
Abstract: Rationale: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. Objectives: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. Methods: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS−) were measured. Results: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. Conclusions: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Effects of cannabidiol on fear conditioning in anxiety disorders: decreased threat expectation during retention, but no enhanced fear re-extinction.
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Apr2024, Vol. 241 Issue 4, p833-847. 15p.
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  Data: <searchLink fieldCode="DE" term="%22Anxiety+disorders%22">Anxiety disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Conditioned+response%22">Conditioned response</searchLink><br /><searchLink fieldCode="DE" term="%22Cannabidiol%22">Cannabidiol</searchLink><br /><searchLink fieldCode="DE" term="%22Startle+reaction%22">Startle reaction</searchLink><br /><searchLink fieldCode="DE" term="%22Cannabinoid+receptors%22">Cannabinoid receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Exposure+therapy%22">Exposure therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Social+anxiety%22">Social anxiety</searchLink><br /><searchLink fieldCode="DE" term="%22Panic+disorders%22">Panic disorders</searchLink>
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  Data: Rationale: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. Objectives: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. Methods: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS−) were measured. Results: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. Conclusions: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Apr2024
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