Meta-analysis finds elevated endocannabinoid levels in the brains and blood of people with psychosis

What the researchers found

CSF anandamide was significantly elevated in schizophrenia (SMD 0.97, p<.001). Blood anandamide was also higher (SMD 0.55, p=.03). CB1 receptor expression on peripheral immune cells was increased (SMD 0.57, p<.001). Higher endocannabinoid tone was found early in illness, in antipsychotic-naive patients, and was inversely associated with symptom severity.

Why it matters

This JAMA Psychiatry meta-analysis establishes the endocannabinoid system as a measurable biomarker in psychosis. The pattern (elevated early, normalized by treatment, inversely related to symptoms) suggests it may be a compensatory protective mechanism.

The numbers in context

CSF AEA: SMD 0.97 (95% CI 0.67-1.26, p<.001, I2=54.8%); blood AEA: SMD 0.55 (95% CI 0.05-1.04, p=.03, I2=89.6%); CB1R expression: SMD 0.57 (95% CI 0.31-0.84, p<.001, I2=0%).

How the study worked

Systematic review and meta-analysis per PRISMA, searching Web of Science and PubMed. 18 studies included with 3 separate meta-analyses for CSF anandamide (5 studies, 226 patients, 385 controls), blood anandamide (9 studies, 344 patients, 411 controls), and CB1R expression (3 studies, 88 patients, 179 controls).

What this study cannot tell us

Moderate to high heterogeneity, especially for blood anandamide (I2=89.6%). Not all studies controlled for cannabis use, a major confounder. Relatively small sample sizes for CB1R analysis.

How to read the evidence

Strong: JAMA Psychiatry meta-analysis of 18 studies with PROSPERO registration.

When this study was published

Published in 2019.

The bigger picture

If elevated anandamide is the brain's attempt to protect against psychosis (inversely correlated with symptoms), then enhancing the endocannabinoid system might be therapeutic. This aligns with CBD's antipsychotic properties, as CBD raises anandamide levels.

Questions still open

• Is elevated anandamide protective or a byproduct of psychosis? Could endocannabinoid levels serve as a clinical biomarker for psychosis treatment response?

Common questions

Read the original research

Measuring Disturbance of the Endocannabinoid System in Psychosis: A Systematic Review and Meta-analysis.

JAMA psychiatry, 76(9), 914-923

Citation

Minichino, Amedeo; Senior, Morwenna; Brondino, Natascia; Zhang, Sam H; Godwlewska, Beata R; Burnet, Philip W J; Cipriani, Andrea; Lennox, Belinda R. (2019). Measuring Disturbance of the Endocannabinoid System in Psychosis: A Systematic Review and Meta-analysis.. JAMA psychiatry, 76(9), 914-923. https://doi.org/10.1001/jamapsychiatry.2019.0970

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