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Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing
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CONTEXT: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. OBJECTIVE: To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. DESIGN: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. PARTICIPANTS: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. RESULTS: Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. CONCLUSIONS: Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions.
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“Moreover, CBD has shown to disrupt forward intrinsic connectivity between the amygdala and the anterior cingulate during the neural response to fearful faces (Fusar-Poli et al, 2009b).”
From Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011) · cites this paper as Fusar-Poli et al, 2009b
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“CBD (600 mg) modulated the patterns of brain activity while subjects processed stimuli depicting intensely fearful faces, attenuating responses in the anterior and posterior cingulate and amygdala.”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [60]
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“…under control or stressful situations (Belgrave et al., 1979; Zuardi et al., 1982, 1993; Gong et al., 1984; Borgwardt et al., 2008; Bhattacharyya et al., 2009, 2010; Fusar-Poli et al., 2009; Bergamaschi et al., 2011; Hallak et al., 2011; WintonBrown et al., 2011; Martin-Santos et al., 2012).”
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Metadata
- Authors
- Fusar-Poli, P., Crippa, J. A., Bhattacharyya, S., Borgwardt, S. J., Allen, P., Martin-Santos, R., Seal, M., Surguladze, S. A., O’Carrol, C., Atakan, Z., Zuardi, A. W., & McGuire, P. K.
- Affiliations
- The University of Melbourne (AU)
- King's College London (GB)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-01-01
- Volume
- 66
- Issue
- 1
- Pages
- 95
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W1967735252
- Cited by
- 465
- References
- 111
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 24 · 2023: 31 · 2022: 22 · 2021: 43 · 2020: 43 · 2019: 27 · 2018: 30 · 2017: 35 · 2016: 23 · 2015: 28 · 2014: 21 · 2013: 19 · 2012: 37
- FWCI
- 22.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- 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
- Psychiatry Research Trust
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Keywords
- delta-9-tetrahydrocannabinol, cannabidiol, cannabis, anxiety, emotional processing, fearful faces, amygdala, anterior cingulate cortex, posterior cingulate cortex, skin conductance response, autonomic arousal, brain activation, anxiogenic effects, anxiolytic effects
- MeSH terms
- Adult, Amygdala, Anxiety, Arousal, Brain, Cannabidiol, Double-Blind Method, Emotions, Facial Expression, Fear, Frontal Lobe, Galvanic Skin Response, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Oxygen, Parietal Lobe, Pattern Recognition, Visual, Psychiatric Status Rating Scales, Psychoses, Substance-Induced, Psychotropic Drugs, Dronabinol, Parahippocampal Gyrus, Young Adult
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