THC consumption during pregnancy affects fetus development: Study

USA: Prenatal THC exposure could influence longer-term offspring outcomes by altering the placental and fetal DNA methylation at genes involved in neurobehavioral development, results from a preclinical study have revealed. The study by Oregon Health & Science University researchers was published in the journal Clinical Epigenetics.

Delta-9-tetrahydrocannabinol, or THC, is the main psychoactive ingredient in cannabis, a substance growing in popularity and availability in the United States. The prevalence of cannabis use in pregnancy is also rapidly increasing, especially during the first trimester — when the fetus is most vulnerable to environmental exposures- to mitigate common symptoms like morning sickness. However, the potential effects of prenatal cannabis use on fetal development remain inconclusive, partly due to a lack of safety data. This study aimed to identify THC use's potential long-term health impacts during pregnancy.

In a non-human primate model, OHSU researchers found that exposing a pregnant subject to THC altered the placental and fetal epigenome —including the chemical modifications to DNA responsible for gene regulation and expression, that is telling genes what, where and when to do something. Researchers also found that these gene regulation and expression changes are consistent with those seen with many common neurobehavioral conditions, including autism spectrum disorder.

“Cannabis is one of the most commonly used drugs and is widely available across the country, so there is a common perception that its completely safe to use,” said the study’s lead author Lyndsey Shorey-Kendrick, Ph.D., a computational biologist in the Division of Neurosciences at OHSU’s Oregon National Primate Research Center, or ONPRC. “The reality is that cannabis still carries many health risks for certain populations, including those pregnant. If we’re able to understand the impacts better, we can more effectively communicate the risks to patients and support safer habits during the vulnerable prenatal period.”

In a model using nonhuman primates, researchers administered THC in a daily edible and compared its effects to a group receiving a placebo. Specifically, researchers evaluated the epigenetic changes in several key areas that indicate healthy prenatal development: the placenta-the disc of tissue that connects the umbilical cord and uterus — and fetal lung, brain and heart.

When looking at these areas, analyses showed that THC exposure altered the epigenome, meaning a process in which the information encoded in a gene is turned into a function or observable trait. Genes-the segments which make up DNA-are all specifically coded to contribute to different functions of the body and brain, so any impact on epigenetic processes due to drug exposure is concerning, especially during a critical developmental window such as pregnancy.

Researchers found that significant changes involved genes associated with common neurobehavioral disorders, including autism spectrum disorder and attention deficit hyperactivity disorder. These conditions are linked to adverse health outcomes in childhood and adolescence, including poorer memory and verbal reasoning skills and increased hyperactivity, impulsivity and inattention.

The research team, which includes Eliot Spindel, M.D., Ph.D., Elinor Sullivan, Ph.D., Owen McCarty, Ph.D., and Jason Hedges, M.D., Ph.D., hopes findings from this study will add to the limited existing literature on THC use during pregnancy, and help guide patient counselling and public health policies focused on cannabis in the future.

“It’s not common practice for providers to discuss cannabis use with patients who are pregnant or trying to conceive,” said the study’s corresponding author, Jamie Lo, M.D., M.C.R., associate professor of obstetrics and gynaecology (maternal-fetal medicine), OHSU School of Medicine, and Division of Reproductive and Developmental Sciences at the ONPRC. “I hope our work can help open up a broader dialogue about the risks of cannabis use in the preconception and prenatal period so that we can improve children’s health in the long run.”

Reference:

Shorey-Kendrick, L.E., Roberts, V.H.J., D’Mello, R.J. et al. Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes. Clin Epigenet 15, 104 (2023). https://doi.org/10.1186/s13148-023-01519-4