DNA methylation changes at cannabinoid and dopamine receptor genes were found in psychotic subjects but reversed by active THC use | Research

The takeaway

People with psychosis showed higher DNA methylation at cannabinoid receptor (CNR1) and dopamine receptor (DRD2) genes compared to controls, but psychotic subjects currently using THC had methylation levels closer to healthy controls.

Psychiatric genetics researchers; clinicians interested in epigenetic biomarkers for psychosis.

THC use reversed psychosis-linked DNA methylation changes

What the researchers found

DNA methylation at CNR1 and DRD2 genes was significantly higher in psychotic subjects than healthy controls, and the two genes' methylation levels were directly correlated. However, psychotic subjects reporting current THC consumption had lower methylation at both genes, resembling control levels at least for DRD2.

Why it matters

This study suggests epigenetic changes at two key receptor genes could serve as biomarkers for psychosis, but only in non-cannabis-using patients. The finding that THC use reverses these methylation changes complicates biomarker development and raises questions about how cannabis interacts with psychosis biology.

The numbers in context

CNR1 and DRD2 methylation were both significantly higher in psychotic subjects vs controls. The methylation levels of the two genes were directly correlated. THC-using psychotic subjects showed methylation levels resembling controls, particularly at DRD2.

How the study worked

Case-control study measuring DNA methylation via pyrosequencing in saliva samples from psychotic subjects and healthy controls, with subgroup analysis by current THC consumption status.

What this study cannot tell us

Saliva-based methylation may not reflect brain tissue patterns. Small study without reported sample sizes in abstract. Cross-sectional design cannot determine whether methylation changes cause psychosis or result from it. THC use was self-reported.

How to read the evidence

Case-control with objective methylation measurement, but small sample and saliva-based analysis limit generalizability.

When this study was published

2024 study

The bigger picture

If THC consumption masks the epigenetic signature of psychosis, this has implications for both biomarker research and understanding why cannabis use complicates psychosis diagnosis and treatment. The endocannabinoid and dopamine systems appear epigenetically linked in psychosis.

Questions still open

Does THC consumption truly reverse psychosis-related methylation, or does it reflect a different subtype of psychosis? Could these methylation markers predict treatment response?

Common questions

What is DNA methylation?

A chemical modification to DNA that can turn genes up or down without changing the genetic code. It is influenced by both genetics and environmental factors like drug use and is one of the main forms of epigenetic regulation.

Why would THC reverse the methylation changes?

THC directly activates the cannabinoid receptor (CB1/CNR1), which may trigger feedback mechanisms that alter how the gene is regulated. The downstream effects on dopamine receptor methylation suggest these systems are interconnected.

Read the original research

DNA methylation at cannabinoid type 1 and dopamine D2 receptor genes in saliva samples of psychotic subjects: Is there an effect of Cannabis use?

Pharmacological research, 208, 107343

View on PubMed ↗Publisher’s paper ↗

Citation

Di Bartolomeo, Martina; Čerňanová, Andrea; Petrušová, Veronika; Di Martino, Serena; Hodosy, Július; Drago, Filippo; Micale, Vincenzo; D'Addario, Claudio. (2024). DNA methylation at cannabinoid type 1 and dopamine D2 receptor genes in saliva samples of psychotic subjects: Is there an effect of Cannabis use?. Pharmacological research, 208, 107343. https://doi.org/10.1016/j.phrs.2024.107343