The Brain Endocannabinoid System is Differentially Regulated in Male and Female Patients with First-Episode Psychosis
H. Laurikainen, R. Armio, L. Tuominen, Mikko Nyman, A. Kirjavainen, J. Rajander, M. Haaparanta-Solin, Olof Solin, J. Hietala
Schizophrenia Bulletin April 10, 2026 DOI: 10.1093/schbul/sbag038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional case-control study Peer reviewed |
|---|---|
| Sample size | 39 |
| Population | Male and female patients with first-episode psychosis and healthy control participants of similar age and sex |
| Measures | [18F]FMPEP-d2 PET, distribution volumes (VT) |
| Key findings | Male patients with first-episode psychosis had significantly lower overall brain CB1 receptor availability than male healthy controls, whereas female patients did not differ from female controls. A regionally specific difference between male and female patients did not survive correction for multiple comparisons. The authors argue that CB1 receptor availability is differentially altered by sex in early psychosis. |
Abstract
Abstract Background and Hypothesis A sex difference in the clinical presentation of schizophrenia is well known. Males have on average an earlier symptom onset, worse functional capacity, and more negative symptoms. Studies on the neurobiological correlates of psychosis show that brain endocannabinoid system (ECS) is dysregulated in male patients with first-episode psychosis (FEP). We now evaluated whether the brain ECS is also altered in female patients with FEP. Study Design In this cross-sectional case–control study, brain CB1R availability was measured in 39 participants, including groups of male and female patients with FEP, and healthy control participants (HC) of similar age and sex (n = 8-11/group). Brain CB1R availability was measured with the selective CB1R radiotracer [18F]FMPEP-d2 and positron emission tomography. Arterial input derived distribution volumes (VT) were extracted from regions of interest (ROI) representing the anterior cingulate cortex, hippocampus, thalamus, and putamen. Study Results Within-subjects analyses showed a regionally differential effect of ROI*sex*group (ε = 0.77; F(2.31,80.85) = 4.31, P = .013). Simple effect analyses indicates that male FEP had significantly lower overall CB1R VT when compared to male HC (F(1,17) = 15.64, pFWER = 0.018), while female FEP VT did not differ from female HC (F(1,18) = 0.12, pFWER = 1). A regionally specific difference of VT between males and females with FEP (F(3,48) = 3.43, P = .024) did not survive the correction for multiple comparisons (pFWER = 0.14). Conclusions The availability of brain CB1R is differentially altered in males and females with early psychosis. Sex-related neurobiological patterns including the ECS may offer new treatment strategies for alleviating the core symptoms of psychotic disorders in male and female patients.