Maternal cannabis use during pregnancy did not significantly alter dopamine receptor gene methylation in newborns

In a study of 804 neonates, maternal cannabis use during pregnancy was not strongly associated with changes in DRD4 dopamine receptor gene methylation in infants, though very weak signals at individual sites did not survive correction for multiple testing.

Fransquet, Peter D et al.·The American journal of drug and alcohol abuse·2017·Moderate EvidenceObservational
RTHC-01384ObservationalModerate Evidence2017RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Observational
Evidence
Moderate Evidence
Sample
N=804

What This Study Found

Among 804 neonates whose mothers provided detailed trimester-by-trimester drug use information, 44 were exposed to maternal cannabis use during pregnancy. Testing 19 CpG sites in the DRD4 dopamine receptor gene promoter, cannabis exposure was associated with methylation at one site in multivariate models (p=0.047), but this would not survive correction for multiple testing.

At another CpG site, there was weak evidence that both cannabis and other drug use were independently associated with increased methylation, while tobacco showed a reverse association. However, none of the associations reached significance after multiple testing correction.

The overall conclusion was that there is no strong evidence of maternal cannabis affecting offspring DRD4 methylation.

Key Numbers

804 neonates. 44 with cannabis-exposed mothers. 19 CpG sites tested. 1 nominally significant (p=0.047, would not survive multiple testing correction). Overall: no strong association.

How They Did This

Mothers in the Triple B study provided detailed drug use information for each trimester. Buccal swabs were collected from neonates at 8 weeks (n=804). DRD4 promoter DNA methylation was measured using SEQUENOM MassARRAY. Multivariate models controlled for confounders.

Why This Research Matters

This is the first study to directly examine whether prenatal cannabis exposure affects offspring DNA methylation at a specific dopamine receptor gene. The largely null result is notable because maternal tobacco smoking (which was also assessed) has well-documented effects on infant DNA methylation. Cannabis may affect the developing brain through mechanisms other than epigenetic modification of dopamine receptor genes.

The Bigger Picture

Prenatal cannabis exposure has been linked to behavioral outcomes in children, and epigenetic changes (like DNA methylation) are a plausible mechanism. The null result for DRD4 does not rule out epigenetic effects at other genes or through other epigenetic mechanisms. It narrows the search by showing that the dopamine D4 receptor promoter is probably not a major target.

What This Study Doesn't Tell Us

Only 44 cannabis-exposed infants, limiting statistical power. Only one gene (DRD4) was examined; cannabis could affect methylation at thousands of other sites. Buccal cell methylation may not reflect brain methylation. Cannabis use was self-reported. The 8-week timepoint may not capture transient methylation changes at birth.

Questions This Raises

  • ?Would genome-wide methylation studies reveal cannabis-associated changes at other genes?
  • ?Does prenatal cannabis affect other epigenetic marks like histone modifications?
  • ?Would higher-potency modern cannabis products show different epigenetic effects?

Trust & Context

Key Stat:
No strong association between prenatal cannabis and DRD4 methylation in 804 neonates
Evidence Grade:
Observational study with detailed trimester-level exposure data. Well-designed but limited by small number of cannabis-exposed infants and single-gene focus.
Study Age:
Published in 2017. Epigenetic studies of prenatal cannabis exposure have expanded to genome-wide approaches.
Original Title:
Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4.
Published In:
The American journal of drug and alcohol abuse, 43(6), 671-677 (2017)
Database ID:
RTHC-01384

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

Does cannabis during pregnancy change the baby's genes?

This study found no strong evidence that cannabis use during pregnancy changed the methylation (epigenetic modification) of the DRD4 dopamine receptor gene in newborns. However, this is only one of thousands of genes, and cannabis could potentially affect others. The study does not address genetic mutations, only epigenetic marks.

Why test the dopamine receptor gene specifically?

DRD4 is involved in reward processing and attention, and prenatal cannabis exposure has been linked to behavioral changes in children. Methylation changes at DRD4 were a plausible mechanism. The negative result suggests the behavioral effects may occur through other biological pathways.

Read More on RethinkTHC

Cite This Study

RTHC-01384·https://rethinkthc.com/research/RTHC-01384

APA

Fransquet, Peter D; Hutchinson, Delyse; Olsson, Craig A; Allsop, Steve; Elliott, Elizabeth J; Burns, Lucinda; Mattick, Richard; Saffery, Richard; Ryan, Joanne. (2017). Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4.. The American journal of drug and alcohol abuse, 43(6), 671-677. https://doi.org/10.1080/00952990.2017.1314488

MLA

Fransquet, Peter D, et al. "Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4.." The American journal of drug and alcohol abuse, 2017. https://doi.org/10.1080/00952990.2017.1314488

RethinkTHC

RethinkTHC Research Database. "Cannabis use by women during pregnancy does not influence in..." RTHC-01384. Retrieved from https://rethinkthc.com/research/fransquet-2017-cannabis-use-by-women

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.