Cannabidiol May Normalize Brain Function for Patients With Clinical High Risk for Psychosis

To a degree, cannabidiol may help normalize changes in the parahippocampal, striatal, and midbrain functions in individuals with clinical high risk for psychosis, according to research results published in JAMA Psychiatry.

For this study, researchers relied on 33 patients with clinical high risk of psychosis who had not taken antipsychotic medications. These participants were recruited from early intervention services in the United Kingdom. Nineteen age-matched control participants who did not have a clinical high risk for psychosis were recruited through an advertisement.

In a double-blind, placebo-controlled, parallel group study, participants with clinical high risk for psychosis received 600 mg of cannabidiol  (n=16) or a placebo capsule (n=17). Three hours after taking the cannabidiol or placebo capsule, participants underwent a functional MRI while performing a verbal-paired, associate-learning task. Researchers investigated control participants (n=19) who did not receive the drug using the same methods.

Participants with clinical high risk for psychosis receiving placebo demonstrated reduced commencement relative to controls in the right caudate during encoding (placebo: median, −0.027; interquartile range [IQR], −0.041 to −0.016; control: median, 0.020; IQR, −0.022 to 0.056; P <.001) and in the parahippocampal gyrus region and the midbrain during recall (placebo: median, 0.002; IQR, −0.016 to 0.010; control: median, 0.035; IQR, 0.015 to 0.039; P <.001). Participants with clinical high risk for psychosis who received cannabidiol had greater activation in these 3 areas compared with the placebo participants, but activation was lower when compared with the control group (parahippocampal gyrus/midbrain: cannabidiol: median, −0.013; IQR, −0.027 to 0.002; placebo: median, −0.007; IQR, −0.019 to 0.008; control: median, 0.034; IQR, 0.005 to 0.059). Level of activation in the cannabidiol group was intermediate compared with the other 2 groups. Researchers found no significant group differences, however, in task performance.

Researchers note that cannabidiol could play a role in normalizing the parahippocampal, striatal, and midbrain functions for patients with clinical high risk for psychosis state. Researchers conclude that “as these regions are critical to the pathophysiology of psychosis, the influence of cannabidiol at these sites could underlie its therapeutic effects on psychotic symptoms.”

Disclosure: One author disclosed an affiliation with pharmaceutical companies. Please see reference for a full list of disclosures.

Reference

Bhattacharyya S, Wilson R, Appiah-Kusi E, et al. Effect of cannabidiol on medial temporal, midbrain, and striatal dysfunction in people at clinical high risk of psychosis: a randomized clinical trial [published online August 29, 2018]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2018.2309