Smoking high-THC cannabis changed DNA methylation enzyme levels in blood cells within hours | Research

The takeaway

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.

Researchers studying epigenetic effects of cannabis, and those investigating biological links between cannabis use and schizophrenia risk.

DNMT3A mRNA increased within 4 hours of smoking 13.4% THC

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Preliminary: very small sample (24), acute exposure only, and combined group analysis was non-significant.

When this study was published

Published in 2022.

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.

Questions still open

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?

Common 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.

Read the original research

Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.

Frontiers in psychiatry, 13, 887700

View on PubMed ↗Publisher’s paper ↗

Citation

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