Does CBD normalize brain activity patterns altered by psychosis? | Research

The takeaway

A double-blind crossover fMRI study found that a single 600 mg CBD dose partially normalized altered brain activation patterns in psychosis patients, shifting activity toward levels seen in healthy controls.

Readers interested in the neuroscience of psychosis and how CBD may work differently from conventional antipsychotics at the brain circuit level.

15 patients, brain activity shifted toward normal

What the researchers found

Psychosis patients on placebo showed altered prefrontal activation during verbal encoding and altered mediotemporal and prefrontal activation during recall, along with greater hippocampal-striatal connectivity. CBD attenuated these dysfunctions, producing activation patterns intermediate between the placebo condition and healthy controls. CBD also reduced hippocampal-striatal functional connectivity.

Why it matters

This study provides neuroimaging evidence for how CBD may exert antipsychotic effects, showing it partially corrects the specific brain activation patterns that differ between psychosis patients and healthy individuals.

The numbers in context

15 psychosis patients; 19 healthy controls; 600 mg CBD single dose; brain activation under CBD shifted toward healthy control patterns in mediotemporal, prefrontal, and striatal regions

How the study worked

Double-blind, randomized, placebo-controlled, within-subject crossover design. 15 psychosis patients scanned with fMRI on two days (CBD 600 mg vs placebo). 19 healthy controls scanned without drug for comparison. Task: verbal paired associate learning.

What this study cannot tell us

Small sample (15 patients, 13 completed scanning). Single-dose design. Healthy controls did not receive any drug, preventing direct comparison of CBD effects in healthy brains. Trend-level symptom reduction only.

How to read the evidence

Double-blind crossover RCT with fMRI, but very small sample and single-dose design.

When this study was published

Published in 2021; companion study to the glutamate findings (RTHC-03390).

The bigger picture

Together with the companion glutamate study, this work builds a picture of CBD acting through multiple brain mechanisms simultaneously. Normalizing both neurochemistry and functional connectivity could explain why CBD shows antipsychotic promise despite working differently from existing drugs.

Questions still open

Does chronic CBD treatment produce sustained normalization of brain activation? Would these effects be stronger or weaker in drug-naive patients? How do these fMRI changes relate to the glutamate changes observed in the companion study?

Common questions

What brain changes does psychosis cause?

Psychosis patients showed altered activation in prefrontal and mediotemporal regions during memory tasks, along with increased connectivity between the hippocampus and striatum compared to healthy controls.

How did CBD affect these brain changes?

CBD partially corrected the altered activation patterns, shifting brain activity to a level intermediate between the abnormal placebo condition and healthy control patterns. It also reduced the excessive hippocampal-striatal connectivity.

Read the original research

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

Psychological medicine, 51(4), 596-606

View on PubMed ↗Publisher’s paper ↗

Citation

O'Neill, Aisling; Wilson, Robin; Blest-Hopley, Grace; Annibale, Luciano; Colizzi, Marco; Brammer, Mick; Giampietro, Vincent; Bhattacharyya, Sagnik. (2021). Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis.. Psychological medicine, 51(4), 596-606. https://doi.org/10.1017/S0033291719003519