DNA methylation at cannabinoid type 1 and dopamine D2 receptor genes in saliva samples of psychotic subjects: Is there an effect of Cannabis use?
Martina di Bartolomeo, Andrea Čerňanová, Veronika Petrušová, Serena di Martino, Július Hodosy, Filippo Drago, Vincenzo Micale, Claudio D'Addario
Pharmacological Research October 2024 DOI: 10.1016/j.phrs.2024.107343 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Peer reviewed |
|---|---|
| Population | Psychotic subjects and healthy controls, using saliva samples |
| Topics | Cannabis |
| Keywords | Cnr1 Dna methylation Drd2 Epigenetic Psychosis |
| Key findings | DNA methylation of CNR1 and DRD2 was significantly higher and directly correlated in psychotic subjects compared with healthy controls. Psychotic subjects reporting current THC consumption had lower methylation levels, similar to controls at least for DRD2. The authors suggest methylation at specific CpG sites may be a biomarker only in psychotic subjects not consuming THC. |
Abstract
Psychosis is a characterizing feature of many mental disorders that dramatically affects human thoughts and perceptions, influencing the ability to distinguish between what is real and what is not. Both genetic and environmental factors, such as stressful events or drug use, play a pivotal role in the development of symptomatology and therefore changes in the epigenome may be of relevance in modeling a psychotic phenotype. According to the well-documented dysregulation of endocannabinoid and dopaminergic system genes in schizophrenia, we investigated DNA methylation cannabinoid type 1 receptor (CNR1) and dopamine D2 receptor (DRD2) genes in saliva samples from psychotic subjects using pyrosequencing. The epigenetic mark was significantly higher and directly correlated for both genes in psychotic subjects compared to healthy controls. We also showed that these DNA methylation levels were lower in psychotic subjects reporting current delta-9-tetrahydrocannabinol (THC) consumption, a well-known risk factor for developing psychosis throughout the lifespan, resembling those of controls at least for the DRD2 gene. Overall, our data confirm the key role of CNR1 and DRD2 gene regulation in psychosis and suggest DNA methylation levels at specific CpG sites as potential biomarkers, but just in those psychotic subjects not consuming THC.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cites 10
- Causal association between cannabis and psychosis: examination of the evidence The British Journal of Psychiatry January 30, 2004
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
- The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology International Journal of Molecular Sciences February 15, 2023
- Cannabis induced psychosis: a systematic review on the role of genetic polymorphisms. Pharmacological Research May 1, 2022
- Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment. Pharmacological Research December 1, 2021
and 5 more in the library