Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol
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Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg Delta 9-tetrahydrocannabinol (Delta 9-THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not Delta 9-THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocritical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.
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In healthy volunteers, CBD has anxiolytic properties associated with action on limbic and paralimbic brain areas.
“Using functional neuroimaging in healthy volunteers, we have observed that CBD has anxiolytic properties and that these effects are associated with an action on the limbic and paralimbic brain areas (Fusar-Poli et al, 2009a; Crippa et al, 2004).”
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, 2009a
CBD (600 mg) induced attenuated responses in the amygdala and in the cingulated cortex during the viewing of fearful facial stimuli.
“Functional magnetic resonance imaging (fMRI) detected attenuated responses in the amygdala and in the cingulated cortex induced by CBD (600 mg) during the viewing of fearful facial stimuli (Fusar-Poli et al, 2009a).”
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, 2009a
CBD attenuates regional brain reactivity to fear-inducing stimuli in functional magnetic resonance imaging studies.
“attenuates regional brain reactivity to fear-inducing stimuli in functional magnetic resonance imaging studies (Crippa et al., 2004; Fusar-Poli et al., 2010).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Fusar-Poli et al., 2010
CBD produces its anxiolytic effects by altering prefrontal-subcortical connectivity via amygdala and the anterior cingulate.
“In a subsequent study, it was also demonstrated that CBD produces its anxiolytic effects by altering prefrontal-subcortical connectivity via amygdala and the anterior cingulate (61).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [61]
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- Authors
- Fusar-Poli, P., Allen, P., Bhattacharyya, S., Crippa, J. A., Mechelli, A., Borgwardt, S., Martin-Santos, R., Seal, M. L., O'Carrol, C., Atakan, Z., Zuardi, A. W., & McGuire, P.
- Affiliations
- King's College London (GB)
- Universidade de São Paulo (BR)
- The University of Melbourne (AU)
- ORCID
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-09-24
- Volume
- 13
- Issue
- 04
- Pages
- 421
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2133512209
- Cited by
- 163
- References
- 72
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 13 · 2021: 12 · 2020: 15 · 2019: 9 · 2018: 5 · 2017: 14 · 2016: 10 · 2015: 7 · 2014: 15 · 2013: 7 · 2012: 13
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (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)
- edoc (University of Basel) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Psychiatry Research Trust
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- cannabidiol, delta-9-tetrahydrocannabinol, effective connectivity, emotional processing, anxiety, amygdala, anterior cingulate cortex, fearful faces, anxiolytic effects, cannabis, dynamic causal modeling, Bayesian model selection
- MeSH terms
- Adult, Amygdala, Cannabidiol, Double-Blind Method, Emotions, Facial Expression, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Models, Neurological, Neural Pathways, Placebos, Psychotropic Drugs, Dronabinol
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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