While the antipsychotic effects of cannabidiol (CBD) is well-known, the neurocognitive mechanisms that underlie psychosis is not well-established.

A team, led by Aisling O’Neil, PhD, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, examined patients with established psychosis on standard antipsychotic treatment on separate days a week apart to identify the effects of a single dose of 600 mg of orally administered CBD compared to a matched placebo.

In the double-blind, randomized, placebo-controlled study, the investigators scanned the patients 3 hours following CBD administration using a block design functional magnetic resonance imaging (fMRI) paradigm.

Each participant also performed a verbal paired associate learning task. A total of 15 patients completed both study days, while 13 participants completed both scanning sessions. The investigators also scanned 19 healthy controls using the same fMRI paradigm under identical conditions, but without any drug administration.

The investigators measured the effects of CBD on brain activation using the blood oxygen level-dependent hemodynamic response fMRI signal in the mediotemporal, prefrontal, and striatal regions of interest.

Compared to the healthy controls, psychosis patients taking the placebo had altered prefrontal activation during verbal encoding. This patient population also featured 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 [placebo] condition and [healthy controls],” the authors wrote. “CBD also attenuated hippocampal-striatal functional connectivity and caused trend-level symptom reduction in psychosis patients.”

The investigators suggest that normalization of mediotemporal and prefrontal dysfunction, as well as mediotemporal-striatal functional connectivity could underlie the antipsychotic effects of CBD.

Recently, a team, led by Sagnik Bhattacharya, MD, PhD, professor of Translational Neuroscience and Psychiatry at King's College London, announced they will be conducting a phase II clinical trial testing the safety and efficacy of CBD to alleviate psychosis symptoms characterized by hallucinations and delusions for patients suffering from Parkinson disease.

The new trial, which represents the first ever large-scale trial testing CBD for Parkinson patients, is expected to begin with a 6-week pilot to assess the safety, tolerability, and effectiveness of pharmaceutical-grade CBD in people with Parkinson-related psychosis.

In the trial, each patient will be delivered up to 1000 mg of CBD per day orally in capsules, in an effort to discover the optimal dosage needed to treat symptoms.

In the second stage of the trial, 120 people with psychosis will take part in a 12-week double-blind, placebo-controlled study and the team will assess psychotic, motor, and non-motor symptoms for both the group that receives the CBD compound and that receives the placebo. Brain imaging will also be used to investigate the effects of CBD.

"This trial will provide evidence of the value of CBD to treat the symptoms of hallucinations and delusions in people with Parkinson's,” Arthur Roach, PhD, Director of Research at Parkinson's UK, said in a statement. “This could result in a regulated cannabinoid-based medicine being prescribed and used in the clinic, as opposed to self-administration of expensive supplements that have not been monitored for their composition or effects.”

The study, “Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis,” was published online in Psychological Medicine.