Effects of cannabidiol (CBD) on regional cerebral blood flow
Abstract
Animal and human studies have suggested that cannabidiol (CBD) may possess anxiolytic properties, but how these effects are mediated centrally is unknown. The aim of the present study was to investigate this using functional neuroimaging. Regional cerebral blood flow (rCBF) was measured at rest using (99m)Tc-ECD SPECT in 10 healthy male volunteers, randomly divided into two groups of five subjects. Each subject was studied on two occasions, 1 week apart. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. SPECT images were acquired 90 min after drug ingestion. The Visual Analogue Mood Scale was applied to assess subjective states. 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 (SPM). CBD significantly decreased subjective anxiety and increased mental sedation, while placebo did not induce significant changes. Assessment of brain regions where anxiolytic effects of CBD were predicted a priori revealed two voxel clusters of significantly decreased ECD uptake in the CBD relative to the placebo condition (p<0.001, uncorrected for multiple comparisons). These included a medial temporal cluster encompassing the left amygdala-hippocampal complex, extending into the hypothalamus, and a second cluster in the left posterior cingulate gyrus. There was also a cluster of greater activity with CBD than placebo in the left parahippocampal gyrus (p<0.001). These results suggest that CBD has anxiolytic properties, and that these effects are mediated by an action on limbic and paralimbic brain areas.
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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 Crippa et al, 2004
CBD's effects were associated with the activity of the parahippocampal gyrus and hippocampus.
“The SPECT analysis of this study and of a previous one with healthy volunteers (Crippa et al, 2004) showed that the CBD effects were associated with the activity of the parahippocampal gyrus and hippocampus.”
From Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011) · cites this paper as Crippa et al, 2004
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 Crippa et al., 2004
CBD reverses glossophobia (fear of public speaking).
“and glossophobia (fear of public speaking) (Bergamaschi et al., 2011; Crippa et al., 2004; Zuardi et al., 1993)”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Crippa et al., 2004
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Bergamaschi, M. M., Queiroz, R. H. C., Chagas, M. H. N., de Oliveira, D. C. G., De Martinis, B. S., Kapczinski, F., Quevedo, J., Roesler, R., Schröder, N., Nardi, A. E., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.6 · Cited by 771 · see citing works
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Self-citationSafety and side effects of cannabidiol, a Cannabis sativa constituent
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Endocannabinoid system and stress and anxiety responses
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Phytocannabinoids as novel therapeutic agents in {CNS} disorders.
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Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
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The endocannabinoid system as a target for novel anxiolytic drugs
Patel, S., Hill, M. N., Cheer, J. F., Wotjak, C. T., & Holmes, A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.033 · Cited by 233 · see citing works
Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test
Moreira, F. A., Aguiar, D. C., & Guimarães, F. S. (2006) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.06.004 · Cited by 207 · see citing works
Haney, M., Malcolm, R. J., Babalonis, S., Nuzzo, P. A., Cooper, Z. D., Bedi, G., Gray, K. M., McRae-Clark, A., Lofwall, M. R., Sparenborg, S., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.367 · Cited by 206 · see citing works
Bhattacharyya, S. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.161 · Cited by 203 · see citing works
Dronabinol and Marijuana in HIV-Positive Marijuana Smokers: Caloric Intake, Mood, and Sleep
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Winton-Brown, T. T., Allen, P., Bhattacharrya, S., Borgwardt, S. J., Fusar-Poli, P., Crippa, J. A., Seal, M. L., Martin-Santos, R., Ffytche, D., Zuardi, A. W., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.17 · Cited by 146 · see citing works
Cannabidiol inhibitory effect on marble-burying behaviour: involvement of CB1 receptors
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Crippa, J. A. S., Hallak, J. E. C., Machado-de-Sousa, J. P., Queiroz, R. H. C., Bergamaschi, M., Chagas, M. H. N., & Zuardi, A. W. (2013) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12018 · Cited by 101 · see citing works
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A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol
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“Two studies of healthy volunteers and patients with social anxiety disorders showed CBD (400mg) increased cerebral BF on the left parahippocampal and right posterior cingulate gyrus, respectively, but not in other brain regions when compared to control (Crippa et al., 2004, 2011).”
BackgroundNeuroimaging studies of acute effects of THC and CBD in humans and animals: a systematic review
Batalla, A., Crippa, J. A., Busatto, G. F., Guimaraes, F. S., Zuardi, A. W., Valverde, O., Atakan, Z., McGuire, P. K., Bhattacharyya, S., & Martín-Santos, R. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990432 · Cited by 91 · see citing works
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Réus, G. Z., Stringari, R. B., Ribeiro, K. F., Luft, T., Abelaira, H. M., Fries, G. R., Aguiar, B. W., Kapczinski, F., Hallak, J. E., Zuardi, A. W., et al. (2011) · Acta Neuropsychiatrica · doi:10.1111/j.1601-5215.2011.00579.x · Cited by 86 · see citing works
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Self-citationQuais são e pra que servem os medicamentos à base de Cannabis?
Pamplona, F. A. (2014) · Revista da Biologia · doi:10.7594/revbio.13.01.05 · Cited by 20 · see citing works
“Embora hoje se saiba que isso não é verdade (Crippa et al., 2004, Bhattacharyya et al., 2010, Bergamaschi et al., 2011a), é verdade que o CBD isolado não autorizadas ou proscritas, conforme classificação em schedules I, II e III.”
Background
- Authors
- Crippa, J. A. D. S., Zuardi, A. W., Garrido, G. E. J., Wichert-Ana, L., Guarnieri, R., Ferrari, L., Azevedo-Marques, P. M., Hallak, J. E. C., McGuire, P. K., & Busatto, G. F.
- Affiliations
- Universidade de São Paulo (BR)
- University of London (GB)
- Venue
- Neuropsychopharmacology
- Published
- 2003-10-29
- Volume
- 29
- Issue
- 2
- Pages
- 417-426
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2132947706
- Cited by
- 307
- References
- 115
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 23 · 2023: 21 · 2022: 25 · 2021: 22 · 2020: 33 · 2019: 20 · 2018: 11 · 2017: 16 · 2016: 7 · 2015: 12 · 2014: 7 · 2013: 9 · 2012: 19
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- cannabidiol, anxiolytic effects, regional cerebral blood flow, subjective anxiety, posterior cingulate cortex, parahippocampal gyrus, limbic system, placebo effect, healthy volunteers
- MeSH terms
- Adult, Anxiety, Brain Mapping, Cannabidiol, Cerebral Cortex, Cerebrovascular Circulation, Cysteine, Double-Blind Method, Humans, Image Processing, Computer-Assisted, Functional Laterality, Male, Neuropsychological Tests, Pain Measurement, Regional Blood Flow, Time Factors, Anti-Anxiety Agents, Organotechnetium Compounds, Tomography, Emission-Computed, Single-Photon, Radiopharmaceuticals
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.
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