Induction of Psychosis by Delta 9-Tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing


Autoria(s): Bhattacharyya, Sagnik; Crippa, Jose Alexandre; Allen, Paul; Martin-Santos, Rocio; Borgwardt, Stefan; Fusar-Poli, Paolo; Rubia, Katya; Kambeitz, Joseph; O'Carroll, Colin; Seal, Marc L.; Giampietro, Vincent; Brammer, Michael; Zuardi, Antonio Waldo; Atakan, Zerrin; McGuire, Philip K.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

05/11/2013

05/11/2013

2012

Resumo

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 Delta 9-tetrahydrocannabinol (Delta 9-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 Delta 9-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, Delta 9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Delta 9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Delta 9-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 Delta 9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. Conclusions: Delta 9-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.

Joint Medical Research Council

Joint Medical Research Council

Medical Research Council, United Kingdom

Medical Research Council, United Kingdom

Psychiatry Research Trust, United Kingdom

Psychiatry Research Trust, United Kingdom

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil)

Identificador

ARCHIVES OF GENERAL PSYCHIATRY, CHICAGO, v. 69, n. 1, supl. 1, Part 2, pp. 27-36, JAN, 2012

0003-990X

http://www.producao.usp.br/handle/BDPI/41133

Idioma(s)

eng

Publicador

AMER MEDICAL ASSOC

CHICAGO

Relação

ARCHIVES OF GENERAL PSYCHIATRY

Direitos

closedAccess

Copyright AMER MEDICAL ASSOC

Palavras-Chave #ACUTE ORAL DELTA(9)-TETRAHYDROCANNABINOL #CEREBRAL-BLOOD-FLOW #CANNABIS USE #REINFORCING EFFICACY #REWARD PREDICTION #ABERRANT SALIENCE #HUMAN HIPPOCAMPAL #LINKING BIOLOGY #ACUTE MARIJUANA #SCHIZOPHRENIA #PSYCHIATRY
Tipo

article

original article

publishedVersion