Induction of Psychosis byΔ9-Tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing
Abstract
CONTEXT: The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. OBJECTIVE: To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing. DESIGN: Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. SETTING: University center. PARTICIPANTS: Fifteen healthy men with minimal previous cannabis use. MAIN OUTCOME MEASURES: Symptom ratings, task performance, and regional brain activation. RESULTS: During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. CONCLUSIONS: Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.
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Δ9-THC-induced psychosis-like effects were associated with decreased activation of the dorsal striatum during oddball stimuli processing.
“In contrast to placebo, the psychosis-like effects provoked by Δ9-THC were associated with decreased activation of (i) the dorsal striatum during “oddball” stimuli processing (84);”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [84]
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- Authors
- Bhattacharyya, S.
- Affiliations
- King's College London (GB)
- Corresponding author
- Bhattacharyya, Sagnik
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2012-01-01
- Volume
- 69
- Issue
- 1
- Pages
- 27
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2158902140
- Cited by
- 203
- References
- 73
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 12 · 2023: 7 · 2022: 8 · 2021: 19 · 2020: 18 · 2019: 18 · 2018: 16 · 2017: 20 · 2016: 11 · 2015: 10 · 2014: 20 · 2013: 20 · 2012: 14
- FWCI
- 15.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NIHR-CS-011-001)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- delta-9-tetrahydrocannabinol, cannabidiol, cannabis-induced psychosis, caudate nucleus, prefrontal cortex, hippocampus, striatal function, psychotic symptoms, schizophrenia risk, response latency
- MeSH terms
- Adult, Attention, Cannabidiol, Corpus Striatum, Hallucinogens, Humans, Male, Psychotic Disorders, Reaction Time, Space Perception, Dronabinol, Prefrontal Cortex, Young Adult
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