Cannabis use linked to lower levels of a psychosis-associated brain enzyme | Research

The takeaway

First-episode psychosis patients who had previously used cannabis showed lower CDK5 levels and fewer social functioning deficits compared to those without cannabis history, suggesting CDK5 may be an early biomarker of psychosis.

Neuroscience researchers, psychiatrists, psychosis specialists

Blocking CDK5 in mice restored both sociability and PSD95 levels

What the researchers found

First-episode psychosis patients with prior cannabis use (FEP/c) had lower CDK5 and higher PSD95 levels compared to those without cannabis use (FEP/nc), and showed fewer social functioning deficits. Blocking CDK5 activity in a mouse model of psychosis restored both sociability and PSD95 levels.

Why it matters

This study provides translational evidence bridging human clinical observations with animal model data, suggesting that CDK5 could serve as an early biomarker for psychosis and that cannabinoids may modulate this pathway.

The numbers in context

Mice received WIN-55,212-2 (1 mg/kg) for 21 days and phencyclidine (10 mg/kg) for 10 days; CDK5 changes correlated with social skills but not cognitive deficits

How the study worked

Translational study combining human olfactory neuroepithelial cell analysis from first-episode psychosis patients (with and without cannabis history) with a dual-hit mouse model using a CB1R agonist and NMDAR blocker.

What this study cannot tell us

Human component was observational and cannot establish causation. Cannabis use history was self-reported. Mouse model uses synthetic cannabinoids, not cannabis itself. Small clinical sample.

How to read the evidence

Combines human observational data with animal experiments; provides mechanistic insight but clinical sample is small and cannabis use was self-reported.

When this study was published

Published 2023

The bigger picture

The complex relationship between cannabis and psychosis may involve specific molecular pathways. Rather than cannabis simply increasing psychosis risk, certain cannabinoid interactions with enzymes like CDK5 could have modulatory effects on social functioning.

Questions still open

Could CDK5 inhibitors be developed as targeted treatments for social deficits in psychosis? Does the type or timing of cannabis use influence its effects on CDK5?

Common questions

What is CDK5 and why does it matter for psychosis?

CDK5 is a brain enzyme that regulates neurotransmission. This study found elevated CDK5 may be an early indicator of psychosis, particularly associated with social functioning deficits.

How did cannabis use relate to CDK5 levels in psychosis patients?

Psychosis patients with prior cannabis use had lower CDK5 levels and fewer social deficits compared to those without cannabis history. Lab experiments confirmed that cannabinoid exposure reduced CDK5 levels.

Read the original research

Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids.

Neurobiology of disease, 176, 105942

View on PubMed ↗Publisher’s paper ↗

Citation

Barrera-Conde, Marta; Veza-Estévez, Emma; Gomis-Gonzalez, Maria; Garcia-Quintana, Jordi; Trabsa, Amira; Martínez-Sadurní, Laura; Pujades, Mitona; Perez, Víctor; de la Torre, Rafael; Bergé, Daniel; Robledo, Patricia. (2023). Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids.. Neurobiology of disease, 176, 105942. https://doi.org/10.1016/j.nbd.2022.105942