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Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol : a neural basis for the effects of Cannabis sativa on learning and psychosis

Bhattacharyya, Sagnik and Fusar-Poli, Paolo and Borgwardt, Stefan and Martin-Santos, Rocio and Nosarti, Chiara and O'Carroll, Colin and Allen, Paul and Seal, Marc L. and Fletcher, Paul C. and Crippa, José A. and Giampietro, Vincent and Mechelli, Andrea and Atakan, Zerrin and McGuire, Philip. (2009) Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol : a neural basis for the effects of Cannabis sativa on learning and psychosis. Archives of general psychiatry, Vol. 66. pp. 442-451.

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Official URL: http://edoc.unibas.ch/dok/A6003876

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Abstract

CONTEXT: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. OBJECTIVES: To investigate the effects of 2 main psychoactive constituents of C. sativa, Delta9-tetrahydrocannabinol (Delta9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. DESIGN: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. SETTING: University research center. PARTICIPANTS: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. RESULTS: Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. CONCLUSION: The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms, respectively.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Neuropsychiatrie (Borgwardt)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Neuropsychiatrie (Borgwardt)
UniBasel Contributors:Borgwardt, Stefan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Medical Association
ISSN:0003-990X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:40

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