Smoking high-THC cannabis changed DNA methylation enzyme levels in blood cells within hours
In 24 regular cannabis users, smoking high-concentration THC (13.4%) increased CB2 receptor and DNA methyltransferase mRNA levels in blood lymphocytes within hours, suggesting potential epigenetic effects.
Quick Facts
What This Study Found
The 13.4% THC group showed significantly increased CB2 and DNMT3A mRNA levels at 4 hours post-smoking compared to placebo. TET3 mRNA levels were higher at 55 minutes post-ingestion. These changes suggest THC may have acute epigenetic effects in human blood cells.
Key Numbers
24 participants. 13.4% THC group: CB2 mRNA increased (p=0.021), DNMT3A increased (p=0.027), DNMT1 trended up (p=0.056) at 4 hours. TET3 increased at 55 minutes. When high and low THC groups were combined, no differences from placebo remained significant.
How They Did This
Double-blind study with 24 regular cannabis users. Participants smoked cannabis cigarettes (5.9% or 13.4% THC) or placebo (0.02%) ad libitum. Blood drawn at baseline and multiple timepoints. Lymphocytes analyzed for mRNA content of cannabinoid receptors, methylation/demethylation enzymes, and immunological markers via qPCR.
Why This Research Matters
This is one of the first human studies to show that smoking cannabis can rapidly alter epigenetic enzyme expression in blood cells. Since increased DNMT activity has been linked to schizophrenia pathophysiology, this may represent one mechanism connecting cannabis use to psychosis risk.
The Bigger Picture
If acute cannabis exposure can change epigenetic enzyme levels within hours, it raises questions about what chronic use might do to gene regulation over time, potentially contributing to psychiatric vulnerability in some individuals.
What This Study Doesn't Tell Us
Very small sample (24 participants). The two THC groups did not differ in post-smoking blood THC levels despite different cigarette concentrations. Combined analysis showed no significant effects, suggesting the findings may be fragile. Only blood lymphocytes were examined.
Questions This Raises
- ?Do these acute epigenetic changes persist with chronic use?
- ?Are the same changes occurring in brain tissue?
- ?Could DNMT changes in lymphocytes serve as a biomarker for cannabis-related psychosis risk?
Trust & Context
- Key Stat:
- DNMT3A mRNA increased within 4 hours of smoking 13.4% THC
- Evidence Grade:
- Preliminary: very small sample (24), acute exposure only, and combined group analysis was non-significant.
- Study Age:
- Published in 2022.
- Original Title:
- Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.
- Published In:
- Frontiers in psychiatry, 13, 887700 (2022)
- Authors:
- Smith, Robert C, Sershen, Henry(2), Janowsky, David S, Lajtha, Abel, Grieco, Matthew, Gangoiti, Jon A, Gertsman, Ilya, Johnson, Wynnona S, Marcotte, Thomas D, Davis, John M
- Database ID:
- RTHC-04235
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
What are DNMT enzymes?
DNA methyltransferases (DNMTs) are enzymes that add methyl groups to DNA, which can turn genes on or off. Changes in DNMT activity can alter gene expression without changing the DNA sequence itself.
Why is the link to schizophrenia important?
Increased DNMT methylating enzyme activity has been associated with some of the biological processes underlying schizophrenia. If cannabis acutely increases these enzymes, it could be one mechanism explaining why cannabis use increases psychosis risk in vulnerable individuals.
Were there changes in immune markers?
No. Despite the increase in CB2 receptor mRNA (which is primarily expressed on immune cells), no changes in immunological markers like IL-1B or TNF-alpha were observed.
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Cite This Study
https://rethinkthc.com/research/RTHC-04235APA
Smith, Robert C; Sershen, Henry; Janowsky, David S; Lajtha, Abel; Grieco, Matthew; Gangoiti, Jon A; Gertsman, Ilya; Johnson, Wynnona S; Marcotte, Thomas D; Davis, John M. (2022). Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.. Frontiers in psychiatry, 13, 887700. https://doi.org/10.3389/fpsyt.2022.887700
MLA
Smith, Robert C, et al. "Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.." Frontiers in psychiatry, 2022. https://doi.org/10.3389/fpsyt.2022.887700
RethinkTHC
RethinkTHC Research Database. "Changes in Expression of DNA-Methyltransferase and Cannabino..." RTHC-04235. Retrieved from https://rethinkthc.com/research/smith-2022-changes-in-expression-of
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.