The psychotic effects of ?9-tetrahydrocannabinol and cannabidiol are mediated through distinct modulation of prefrontal, striatal, and hippocampal function during attentional salience processing, according to a study published in the January issue of the Archives of General Psychiatry.

Sagnik Bhattacharyya, M.B.B.S., M.D., Ph.D., from King’s College London, and colleagues investigated the psychotic effects of cannabis by examining the effects of ?9-THC and cannabidiol on regional brain function during salience processing.

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Fifteen healthy male volunteers with minimal previous cannabis use were administered either ?9-THC, cannabidiol, or placebo on three occasions while they performed a visual oddball detection paradigm, and were observed using event-related functional magnetic resonance imaging.

Symptom ratings, task performance, and regional brain activation were the main outcome measures.

The investigators found that, during the processing of the oddball stimuli, activation of the right caudate was attenuated, and that of the right prefrontal cortex was augmented by ?9-THC, relative to placebo.

The response latency to standard versus oddball stimuli was also reduced by ?9-THC. There was a negative correlation between the effect of ?9-THC on the right caudate, and the effect on response latency and the severity of psychotic symptoms it induced.

The effects of ?9-THC and cannabidiol on task-related activation were in the opposite directions.

Cannabidiol attenuated right prefrontal activation, and augmented the activation of the left caudate and hippocampus, relative to placebo.

“These data provide the first evidence, to our knowledge, that the effects of cannabis on psychosis may be mediated by influencing the neural substrate of attentional salience processing,” the authors write.

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