Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report
Abstract
Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.
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CBD does not produce psychotropic effects, probably because of its low affinity for CB1 receptors.
“Unlike THC, CBD does not produce psychotropic effects and this is probably because of its low affinity for CB1 receptors 55– 57.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [55]
In treatment-naïve patients with generalised SAD, a single dose of CBD significantly reduces anxiety and associated anticipatory alert, as well as discomfort provoked during a public-speaking test.
“In treatment-naïve patients with generalised SAD a single dose of CBD was found to significantly reduce anxiety and associated anticipatory alert, as well as discomfort provoked during a public-speaking test (Bergamaschi et al., 2011;Crippa et al., 2011).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Crippa et al., 2011
The anxiolytic effect of CBD in SAD patients was associated with reduced activity in the hippocampus, parahippocampal and left temporal gyrus, and increased activity in the posterior cingulated.
“The anxiolytic effect was associated with reduced activity in the hippocampus, parahippocampal and left temporal gyrus, and increased activity in the posterior cingulated (Figure 4).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [59]
In treatment-naive SAD patients, CBD reduced subjective measures of anxiety without inducing sedation compared to placebo.
“We found that, when compared to placebo, CBD was able to reduce subjective measures of anxiety without inducing sedation in treatment-naive SAD patients.”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [59]
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“Overall, there was no relationship between drug dose and the size of the effect on haemodynamics (BP p = 0.81, HR p = 0.97, BF p= 0.97; Figure 6).”
BackgroundInfluentialNeuroimaging studies of acute effects of THC and CBD in humans and animals: a systematic review
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Pharmacotherapy for Anxiety Disorders.
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- Authors
- Crippa, J. A. S., Derenusson, G. N., Ferrari, T. B., Wichert-Ana, L., Duran, F. L., Martin-Santos, R., Simões, M. V., Bhattacharyya, S., Fusar-Poli, P., Atakan, Z., Filho, A. S., Freitas-Ferrari, M. C., McGuire, P. K., Zuardi, A. W., Busatto, G. F., & Hallak, J. E. C.
- Affiliations
- Universidade de São Paulo (BR)
- NCT Translational Medicine.
- Department of Psychological Medicine, Section of Neuroimaging, Institute of Psychiatry, University of London, UK.
- Division of Neurology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
- University of London (GB)
- Departments of Neurosciences and Behavior, Division of Psychiatry, University of São Paulo, Brazil.
- Corresponding author
- Crippa, José Alexandre S
- ORCID
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2010-09-09
- Volume
- 25
- Issue
- 1
- Pages
- 121-130
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2044573242
- Cited by
- 535
- References
- 115
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 50 · 2023: 44 · 2022: 65 · 2021: 73 · 2020: 72 · 2019: 47 · 2018: 27 · 2017: 27 · 2016: 21 · 2015: 15 · 2014: 12 · 2013: 9 · 2012: 15
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (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)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Keywords
- cannabidiol, generalized social anxiety disorder, anxiolytic effects, regional cerebral blood flow, parahippocampal gyrus, hippocampus, inferior temporal gyrus, posterior cingulate cortex, limbic system, cannabis
- MeSH terms
- Adult, Anxiety, Anxiety Disorders, Brain, Cannabidiol, Cerebrovascular Circulation, Double-Blind Method, Humans, Male, Placebos, Psychiatric Status Rating Scales, Regional Blood Flow, Anti-Anxiety Agents, Tomography, Emission-Computed, Single-Photon, Cross-Over Studies, Young Adult
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