The use of cannabidiol (CBD), the major non-psychoactive compound in cannabis, is on the rise across the United States. Pregnant women in particular may view CBD as more “natural” than other remedies for concerns such as nausea and pain, but the consequences of use for the developing fetus are unknown.
In a new study published in the journal Clinical Epigenetics, researchers at the University of Minnesota used a rodent model to investigate the impact of CBD during development and uncovered effects on the brain and behavior. They found that CBD use during pregnancy may affect mood and cognition in offspring long after the exposure has ceased. The study is the first to examine the effects of maternal CBD exposure during pregnancy on adult offspring in mammals.
The research team, made up of scientists at the University of Minnesota’s Department of Animal Science and College of Veterinary Medicine, began by using a human-relevant dose that is typical in adults purchasing CBD over the counter for a variety of ailments. Next, the team treated pregnant mice daily throughout pregnancy and lactation until the pups were weaned. The offspring were followed into adulthood without any additional CBD, at which time they were measured for persistent behavioral and molecular impacts of CBD.
Specifically, the team of scientists investigated rodent behavior and DNA methylation, an important mechanism known as an epigenetic mark in both rodents and humans that helps control the “when, where, and how much” of gene activity. CBD’s effects on gene activity markers were examined in two brain regions important for memory, mood, and cognition.
Among the study’s key findings:
- Chronic maternal CBD treatment increased anxiety and improved memory performance in adult female offspring, while males were unaffected.
- The effects of CBD during pregnancy persisted even though the offspring had no direct exposure as adults.
- Maternal CBD treatment shifted gene regulatory marks (DNA methylation) at hundreds of genes in the brains of adult female offspring.
- Genes affected by CBD were involved in the formation of new neurons and synapses, communication between neurons, and diseases like autism spectrum disorder, epilepsy and substance use disorder.
“CBD use has exploded in recent years, yet we still don’t have a clear picture of its impact on the brain, especially during development,” said study director Christopher Faulk, an assistant professor in the College of Food, Agricultural and Natural Resource Sciences. “We show here that use during pregnancy can permanently impact the resulting offspring in adulthood and potentially for the rest of their lives.”
“The effects we observed on memory and anxiety were in 12-week-old mouse offspring, a time that approximates human young adulthood, and is cause for concern,” said study co-author and project lead Nicole Wanner, a post-doctoral fellow in the College of Veterinary Medicine. “DNA methylation marks in the brain are largely set during fetal development, and the presence of CBD during that process appears to direct certain permanent changes. We were surprised at the extent that CBD linked gene pathways were associated with neurological disorders, and expect future work will be needed to understand how fetal exposure to CBD impacts long-term brain function and mental health.”
According to Faulk and Wanner, gaining more insight into how CBD affects the developing brain will be important for future safety recommendations.
The researchers are continuing to draw the epigenetic map of gestational CBD exposure and its impact on youth and adults. In the future, they hope to expand behavioral studies to include measures of sociability and drug reward, which are important for diseases like autism spectrum disorder and substance use disorder, respectively. They also plan to repeat these measurements in adolescent offspring in order to determine whether abnormalities are already present at an earlier age or whether they develop later.
Funding for the study was provided by the College of Food, Agricultural and Natural Resource Sciences at the University of Minnesota.