Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing.
BACKGROUND
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.


METHODS
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.


METHODS
University center.


METHODS
Fifteen healthy men with minimal previous cannabis use.


METHODS
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.
Department of Psychosis Studies, Institute of Psychiatry, King's College London, De Crespigny Park, London, England. sagnik.2.bhattacharyya@kcl.ac.uk
Sagnik
S
Bhattacharyya
José Alexandre
JA
Crippa
Paul
P
Allen
Rocio
R
Martin-Santos
Stefan
S
Borgwardt
Paolo
P
Fusar-Poli
Katya
K
Rubia
Joseph
J
Kambeitz
Colin
C
O'Carroll
Marc L
ML
Seal
Vincent
V
Giampietro
Michael
M
Brammer
Antonio Waldo
AW
Zuardi
Zerrin
Z
Atakan
Philip K
PK
McGuire
D000328:Adult; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D002185:Cannabidiol / Q000009:adverse effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D013759:Dronabinol / Q000009:adverse effects*; D006213:Hallucinogens / Q000009:adverse effects*; D006801:Humans; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D011618:Psychotic Disorders / Q000503:physiopathology* / Q000523:psychology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D006213:Hallucinogens; D002185:Cannabidiol; D013759:Dronabinol