Prenatal cannabis exposure decreased dopamine D2 receptor expression in the human fetal brain's reward center, and in rats, THC exposure during pregnancy produced lasting epigenetic changes that reduced D2 receptors and increased opiate sensitivity in adult offspring.
Read this if you are pregnant or planning pregnancy and want to understand how cannabis may affect your child's developing brain.
Prenatal cannabis altered D2 receptor gene regulation through lasting epigenetic changes
What the researchers found
This study combined human fetal tissue analysis with a rat model to investigate how prenatal cannabis exposure affects the developing brain's reward system.
In human fetal subjects, prenatal cannabis exposure specifically decreased dopamine D2 receptor (DRD2) gene expression in the nucleus accumbens, the brain's key reward region. Other dopamine and opioid genes were not significantly affected by cannabis (though cigarettes affected prodynorphin and alcohol affected multiple genes).
In rats, prenatal THC exposure produced epigenetic changes at the D2 receptor gene that persisted into adulthood. Specifically, repressive epigenetic marks increased while activating marks decreased at the DRD2 gene locus. Adult offspring had fewer D2 receptor binding sites and were more sensitive to opiate reward.
This was direct evidence that prenatal cannabis exposure could alter gene regulation through epigenetic mechanisms, with lasting consequences for addiction vulnerability.
Why it matters
This was among the first studies to demonstrate a specific epigenetic mechanism by which prenatal cannabis exposure could permanently alter reward circuit development and increase addiction vulnerability in offspring.
The numbers in context
THC dose: 0.15 mg/kg during pregnancy. DRD2 mRNA decreased in human fetal nucleus accumbens. Increased 2meH3K9 (repressive) and decreased 3meH3K4 (activating) marks at Drd2 gene in adult rat offspring. Reduced D2R binding sites and increased opiate sensitivity.
How the study worked
Combined human fetal tissue study and rat model. Human: gene expression analysis in striatal tissue from cannabis-exposed (and cigarette/alcohol-exposed) fetuses. Rat: pregnant rats exposed to THC (0.15 mg/kg), offspring assessed at postnatal day 2 and adulthood by chromatin immunoprecipitation, receptor binding assays, and opiate reward sensitivity tests.
What this study cannot tell us
Human fetal tissue sample sizes were not reported in the abstract. Rat THC doses may not reflect typical human cannabis exposure during pregnancy. Epigenetic changes are complex and other genes may also be affected.
How to read the evidence
Translational study combining human fetal tissue data with a mechanistic rat model, published in Biological Psychiatry.
When this study was published
Published in 2011. Epigenetic effects of prenatal cannabis exposure have continued to be investigated.
The bigger picture
The epigenetic mechanism provided a molecular explanation for epidemiological observations linking prenatal cannabis exposure to increased substance use vulnerability in children and adolescents.
Questions still open
- Are these epigenetic changes reversible, or are they permanent? Would they also increase vulnerability to cannabis addiction specifically, or only to opiates?
Common questions
Can using cannabis during pregnancy affect the baby's brain?
What are epigenetic changes?
Read the original research
Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring.
Biological psychiatry, 70(8), 763-769
Citation
DiNieri, Jennifer A; Wang, Xinyu; Szutorisz, Henrietta; Spano, Sabrina M; Kaur, Jasbir; Casaccia, Patrizia; Dow-Edwards, Diana; Hurd, Yasmin L. (2011). Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring.. Biological psychiatry, 70(8), 763-769. https://doi.org/10.1016/j.biopsych.2011.06.027
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