A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis

Abstract

Emotional dysregulation and anxiety are common in people at clinical high risk for psychosis (CHR) and are associated with altered neural responses to emotional stimuli in the striatum and medial temporal lobe. Using a randomised, double-blind, parallel-group design, 33 CHR patients were randomised to a single oral dose of CBD (600 mg) or placebo. Healthy controls (n = 19) were studied under identical conditions but did not receive any drug. Participants were scanned with functional magnetic resonance imaging (fMRI) during a fearful face-processing paradigm. Activation related to the CHR state and to the effects of CBD was examined using a region-of-interest approach. During fear processing, CHR participants receiving placebo (n = 15) showed greater activation than controls (n = 19) in the parahippocampal gyrus but less activation in the striatum. Within these regions, activation in the CHR group that received CBD (n = 15) was intermediate between that of the CHR placebo and control groups. These findings suggest that in CHR patients, CBD modulates brain function in regions implicated in psychosis risk and emotion processing. These findings are similar to those previously evident using a memory paradigm, suggesting that the effects of CBD on medial temporal and striatal function may be task independent.

Altered relationship between cortisol response to social stress and mediotemporal function during fear processing in people at clinical high risk for psychosis: a preliminary report

“…Full details of image acquisition, fMRI task, preprocessing and fMRI analyses are detailed in the Supplementary Material and in our related publication [ 48 ]. In brief, participants were studied in one 6-min fMRI experiment at 3 T while performing a fearful face processing task.…”

“…A region-of-interest (ROI) approach was used after constructing a single ROI mask of limbic structures within bilateral medial temporal cortex (hippocampus, parahippocampal gyrus and amygdala) and striatum, with striatal findings omitted from the present study. These regions were selected a priori based on our previous findings [ 48 , 61 ]. The voxel-wise statistical threshold was set at p = 0.05, and the cluster-wise thresholds were adjusted to ensure that the number of false-positive clusters per brain would be less than 1; clusters that survived this critical statistical threshold and the corresponding p values are reported.…”

“…Moreover, these neuroendocrine and psychological alterations could be partially attenuated by a 7-day course of cannabidiol (CBD)—a non-intoxicating constituent of the cannabis plant with anxiolytic [ 41 , 42 ] and antipsychotic properties [ 43 – 47 ]. We also recently reported that CHR individuals show altered neural response to fear processing compared to healthy controls in mediotemporal limbic structures and the striatum [ 48 ]—regions strongly implicated in psychosis pathogenesis [ 31 , 32 ]. In addition, we found that a single dose of CBD (in a parallel group of CHR individuals) attenuated the deviation in neural responses in the same brain regions [ 48 ].…”

“…We also recently reported that CHR individuals show altered neural response to fear processing compared to healthy controls in mediotemporal limbic structures and the striatum [ 48 ]—regions strongly implicated in psychosis pathogenesis [ 31 , 32 ]. In addition, we found that a single dose of CBD (in a parallel group of CHR individuals) attenuated the deviation in neural responses in the same brain regions [ 48 ]. While this and previous work points to (a) alterations in neuroendocrine and psychological response to stress and (b) altered neural response during fear processing in CHR patients, whether (and how) these facets are associated with each other has not been tested before.…”

Is Cannabidiol During Neurodevelopment a Promising Therapy for Schizophrenia and Autism Spectrum Disorders?

“…Functional magnetic resonance imaging studies have shown that individuals at clinical high risk for psychosis (CHR, aging from 18 to 35 years) present altered activation of some brain regions—such as the striatum and the medial temporal cortex—during cognitive and emotional processing. Although the direction of changes in these regions may vary according to the task, the administration of a single dose of CBD (600 mg) promotes a normalization of the dysfunction observed ( Bhattacharyya et al, 2018 ; Davies et al, 2020 ). In addition, the insular dysfunction presented by CHR subjects during motivational salience processing is also attenuated by this same single dose of CBD ( Wilson et al, 2019 ).…”