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

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.

Di Bartolomeo, Martina et al.·Pharmacological research·2024·Moderate EvidenceObservational
RTHC-05268ObservationalModerate Evidence2024RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Observational
Evidence
Moderate Evidence
Sample
Not reported

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

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

Trust & Context

Key Stat:
THC use reversed psychosis-linked DNA methylation changes
Evidence Grade:
Case-control with objective methylation measurement, but small sample and saliva-based analysis limit generalizability.
Study Age:
2024 study
Original Title:
DNA methylation at cannabinoid type 1 and dopamine D2 receptor genes in saliva samples of psychotic subjects: Is there an effect of Cannabis use?
Published In:
Pharmacological research, 208, 107343 (2024)
Database ID:
RTHC-05268

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

Watches what happens naturally without intervening.

What do these levels mean? →

Frequently Asked 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 More on RethinkTHC

Cite This Study

RTHC-05268·https://rethinkthc.com/research/RTHC-05268

APA

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

MLA

Di Bartolomeo, Martina, et al. "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, 2024. https://doi.org/10.1016/j.phrs.2024.107343

RethinkTHC

RethinkTHC Research Database. "DNA methylation at cannabinoid type 1 and dopamine D2 recept..." RTHC-05268. Retrieved from https://rethinkthc.com/research/di-2024-dna-methylation-at-cannabinoid

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.