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

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.

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).

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.

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.

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.