Abstract

Background There is currently a lack of effective pharmacological treatment for people at Clinical High Risk of Psychosis (CHR), who present with emotional dysregulation and high levels of anxiety. These individuals also show altered neural responses to emotional stimuli in key brain regions implicated in psychosis onset, including the striatum and medial temporal lobe. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, is thought to have antipsychotic and anxiolytic properties. The effects of CBD on brain function in CHR individuals during emotion processing has not been tested before.

Methods In a randomised, double-blind, placebo-controlled, parallel-group design, 33 CHR individuals received a single oral 600mg dose of CBD or matched placebo, while 19 healthy controls did not receive any drug. Participants were studied using an emotion processing functional magnetic resonance imaging (fMRI) paradigm. Using a region-of-interest approach, we examined the differences in brain activation related to the CHR state and the effects of CBD, indexed using the blood oxygen level-dependent haemodynamic response fMRI signal.

Results Compared to controls (n=19), CHR participants receiving placebo (n=15) showed significantly greater activation in the medial temporal lobe and less activation in the striatum during emotion processing. Within these same regions, activation in the CBD group (n=15) was (significantly) intermediate between that of the placebo and control groups. That is, CBD attenuated medial temporal and enhanced striatal activation in CHR participants.

Discussion These findings suggest that CBD modulates the function of brain regions strongly implicated in psychosis onset and altered emotion processing. Further research is required to examine whether these neurofunctional effects translate into clinical efficacy after a period of treatment.