Opposite Effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology
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Delta-9-tetrahydrocannabinol (Delta-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Delta-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Delta-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Delta-9-tetrahydrocannabinol. Delta-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Delta-9-THC.
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Δ9-THC-induced psychosis-like effects were associated with decreased activation of the ventral striatum and anterior cingulate gyrus during word recall.
“(ii) the ventral striatum and anterior cingulate gyrus during word recall (85);”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [85]
IV pre-treatment with CBD (5 mg) prevented psychotic symptoms induced by IV Δ9-THC (1.25 mg).
“In a subsequent experiment, IV pre-treatment with CBD (5 mg) prevented the psychotic symptoms induced by IV Δ9-THC (1.25 mg) (85).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [85]
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“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.”
BackgroundThe Changing Legal Landscape of Cannabis Use and Its Role in Youth-onset Psychosis
Wright, A., Cather, C., Gilman, J., & Evins, A. E. (2020) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2019.08.016 · Cited by 16 · see citing works
- Authors
- Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., Nosarti, C., O' Carroll, C. M., Seal, M., Allen, P., Mehta, M. A., Stone, J. M., Tunstall, N., Giampietro, V., Kapur, S., Murray, R. M., Zuardi, A. W., Crippa, J. A., Atakan, Z., & McGuire, P. K.
- Affiliations
- King's College London (GB)
- The University of Melbourne (AU)
- Universidade de São Paulo (BR)
- Corresponding author
- Bhattacharyya, Sagnik
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2009-11-18
- Volume
- 35
- Issue
- 3
- Pages
- 764-774
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055598
- OpenAlex
- W2096597937
- Cited by
- 680
- References
- 50
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 35 · 2023: 44 · 2022: 48 · 2021: 66 · 2020: 76 · 2019: 57 · 2018: 47 · 2017: 55 · 2016: 32 · 2015: 27 · 2014: 35 · 2013: 27 · 2012: 34
- FWCI
- 19.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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
- Beckley Foundation
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- delta-9-tetrahydrocannabinol, cannabidiol, cannabis, acute psychosis, psychotic symptoms, verbal memory, response inhibition, amygdala, hippocampus, striatum, superior temporal cortex, occipital cortex
- MeSH terms
- Acoustic Stimulation, Adult, Mental Disorders, Brain, Cannabidiol, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Photic Stimulation, Psychomotor Performance, Dronabinol, Young Adult
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