Journal Article

Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis

Wilson, Robin, Blest-Hopley, Grace, Giampietro, Vincent, Annibale, Luciano, O'Neill, Aisling, Brammer, Mick, Bhattacharyya, Sagnik, Colizzi, Marco

2021

Overview

Recent evidence suggests that cannabidiol (CBD), a non-intoxicating ingredient present in cannabis extract, has an antipsychotic effect in people with established psychosis. However, the effect of CBD on the neurocognitive mechanisms underlying psychosis is unknown. Patients with established psychosis on standard antipsychotic treatment were studied on separate days at least one week apart, to investigate the effects of a single dose of orally administered CBD (600 mg) compared to a matched placebo (PLB), using a double-blind, randomized, PLB-controlled, repeated-measures, within-subject cross-over design. Three hours after taking the study drug participants were scanned using a block design functional magnetic resonance imaging (fMRI) paradigm, while performing a verbal paired associate learning task. Fifteen psychosis patients completed both study days, 13 completed both scanning sessions. Nineteen healthy controls (HC) were also scanned using the same fMRI paradigm under identical conditions, but without any drug administration. Effects of CBD on brain activation measured using the blood oxygen level-dependent hemodynamic response fMRI signal were studied in the mediotemporal, prefrontal, and striatal regions of interest. Compared to HC, psychosis patients under PLB had altered prefrontal activation during verbal encoding, as well as altered mediotemporal and prefrontal activation and greater mediotemporal-striatal functional connectivity during verbal recall. CBD attenuated dysfunction in these regions such that activation under its influence was intermediate between the PLB condition and HC. CBD also attenuated hippocampal-striatal functional connectivity and caused trend-level symptom reduction in psychosis patients. This suggests that normalization of mediotemporal and prefrontal dysfunction and mediotemporal-striatal functional connectivity may underlie the antipsychotic effects of CBD.

• Publisher: Cambridge University Press
• Subject: Adult / Antipsychotic Agents - pharmacology / Antipsychotics / Associative learning / Attention - drug effects / Brain / Brain - drug effects / Brain mapping / Brain research / Cannabidiol / Cannabidiol - pharmacology / Cannabinoids / Cannabis / Cognition / Corpus Striatum - drug effects / Dopamine / Double-Blind Method / Drug development / Drug dosages / Drugs / Educational activities / Encoding / Encoding (Cognitive process) / Female / Functional connectivity / Functional magnetic resonance imaging / Hippocampus / Hippocampus - drug effects / Humans / Magnetic Resonance Imaging / Male / Marijuana / Medical imaging / Medical treatment / Mental disorders / Mental Recall - drug effects / Neostriatum / Neural networks / Neuroimaging / Normalization / Oral administration / Original Article / Oxygen / Paired associate learning / Paradigms / Patients / Placebos / Prefrontal Cortex - drug effects / Psychopathology / Psychosis / Psychotic Disorders - physiopathology / Psychotropic drugs / Regions / Tetrahydrocannabinol / THC / Urine / Young Adult