CBD Changed Brain Activation Without Improving Verbal Task Performance

An acute CBD study found differences in brain activation among people at clinical high risk of psychosis without significant differences in verbal task performance. The imaging result is a mechanistic observation, not proof that CBD prevented psychosis or improved everyday functioning.

A single-dose human imaging experiment

The randomized study enrolled 33 antipsychotic-naive participants at clinical high risk: 16 received 600 mg oral CBD and 17 received placebo. Nineteen healthy comparison participants received neither treatment. Imaging analyses included 15 CBD participants, 16 placebo participants and all 19 controls.

Participants performed a verbal paired-associate learning task during functional magnetic resonance imaging. The outcome was a blood-oxygen-level-dependent signal during encoding and recall, rather than a direct measurement of neurotransmitter concentration, cellular injury or future illness.

Intermediate activation requires careful wording

In selected striatal, medial temporal and midbrain regions, the CBD group’s activation was intermediate between the placebo and healthy comparison groups. The authors interpreted this as possible partial normalization of altered responses.

However, there were no significant group differences in task performance. A change in an imaging signal therefore cannot be described as demonstrated memory improvement. Nor does movement toward a healthy group average establish that a disease process has been reversed.

The design limits a before-and-after claim

Different high-risk participants received CBD and placebo. The investigators did not scan each person under both conditions, so the comparison cannot demonstrate that a particular participant’s previously abnormal activation became normal after CBD.

The small sample, acute exposure and selected task further restrict inference. The study could not establish whether imaging responses predicted subsequent transition to psychosis. Clinical prevention and sustained symptomatic benefit require longitudinal evidence with relevant outcomes.

The participants were also enrolled in a broader CBD research program. Reports of other outcomes from that program should not automatically be counted as independent replications of this imaging finding.

When assessing a cannabis-related treatment claim, identify whether the endpoint is a biomarker, a task score or a patient outcome. Our discussion of interpreting CBD clinical outcomes explains why those distinctions matter. This study offers a hypothesis about neural effects, while leaving the clinical-benefit question open.

Primary research

Sagnik Bhattacharyya and colleagues. JAMA Psychiatry (2018). Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis.