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.
Read this if you're interested in whether prenatal cannabis exposure affects infant gene regulation.
No strong association between prenatal cannabis and DRD4 methylation in 804 neonates
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Observational study with detailed trimester-level exposure data. Well-designed but limited by small number of cannabis-exposed infants and single-gene focus.
When this study was published
Published in 2017. Epigenetic studies of prenatal cannabis exposure have expanded to genome-wide approaches.
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.
Questions still open
- 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?
Common questions
Does cannabis during pregnancy change the baby's genes?
Why test the dopamine receptor gene specifically?
Read the original research
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
Citation
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
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