Gray Matter Volume Loss in Parkinson's Disease Psychosis and Cannabinoid Receptor Gene Expression in the Brain.

BACKGROUND

Serotonergic and dopaminergic pathways are implicated in Parkinson's disease psychosis (PDP), but preliminary evidence also implicates the endocannabinoid system (ECS).

OBJECTIVES

We examined the association of gray matter volume loss in PDP patients with brain expression of the genes coding for CB1 (cannabinoid type 1) and CB2 cannabinoid receptors obtained from an independent sample.

METHODS

Hedges' g effect sizes indexing gray matter volume loss were extracted from a previous meta-analytic comparison of PDP and PD without psychosis. The relationship of cortical and subcortical CB1 and CB2 gene expression in 6 healthy individuals extracted from the Allen Human Brain Atlas with meta-analytic estimates of PDP-related volume loss was examined correcting for spatial autocorrelation.

RESULTS

There was a significant association between gray matter volume loss in PDP and CB1 (r = 0.337, t(76) = 3.122, P < 0.001) but not CB2 (P = 0.132, corrected) receptor brain expression.

CONCLUSIONS

This finding underscores the importance of investigating the role of the ECS in PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.