Prenatal cannabis exposure linked to changes in brain structure and connectivity

New research published in Nature Mental Health sheds light on the relationship between prenatal cannabis exposure and mental health issues in early adolescence. The study found that prenatal cannabis exposure is associated with specific changes in brain structure and connectivity, particularly affecting areas related to attention.

With increasing societal acceptance and legalization of cannabis, its use during pregnancy has risen significantly, doubling from 2002 to 2017. Despite warnings from health agencies and professional organizations about potential risks, many pregnant women continue to use cannabis.

Previous studies have indicated adverse outcomes such as low birth weight and preterm birth, but the neurobiological mechanisms behind these effects and their long-term impacts on child development remain unclear. This study aimed to explore whether prenatal cannabis exposure is associated with specific brain changes and mental health outcomes in adolescents.

“Cannabis use is becoming increasingly common in women who are pregnant (rates doubled between 2002 and 2017),” explained study author David Baranger, a postdoctoral research associate at Washington University at St. Louis. “Despite the wide use of cannabis use, and its legalization in many of the states in the United States, we actually know very little about how cannabis use during pregnancy might impact the child. In our prior work, we showed that prenatal cannabis exposure was associated with worse child mental health during childhood and early adolescence.”

“But, of course, these are just correlational findings, and in general it’s quite hard to establish whether cannabis could be having a causal effect on children, because there are so many plausible alternative explanations that are hard to rule out (for example, effects of family history or family environment). Our thought here was that if there is a causal effect of prenatal cannabis on mental health, then we might also expect to see effects on the brain.”

The researchers utilized data from the Adolescent Brain Cognitive Development (ABCD) Study, a large-scale, longitudinal study tracking the brain development and health of over 12,000 children across the United States. These children underwent various neuroimaging procedures, including structural MRI, diffusion MRI, and resting-state functional MRI. These scans provided detailed images of the brain’s structure, white matter integrity, and connectivity patterns.

The study measured prenatal cannabis exposure through retrospective reports from parents, distinguishing between exposure before and after the mother knew she was pregnant. Among the participants, 370 children were exposed to cannabis before the mother knew of the pregnancy, and 195 were exposed both before and after the mother became aware of the pregnancy. Mental health outcomes in the children were assessed using the Child Behavior Checklist, a widely used questionnaire where parents report various behavioral and emotional problems their children exhibited over the past six months.

The researchers discovered that prenatal cannabis exposure was associated with specific and localized alterations in brain structure and connectivity in adolescents. These changes were particularly evident in the gray and white matter of the frontal and parietal cortices, as well as in the striatum’s resting-state connectivity.

The gray matter consists of neuronal cell bodies and is crucial for processing information, while white matter contains nerve fibers that facilitate communication between different brain regions. The frontal cortex is involved in executive functions such as decision-making, problem-solving, and controlling behavior, whereas the parietal cortex plays a key role in processing sensory information and spatial awareness. The striatum is important for coordinating various aspects of cognition, including attention and reward processing.

The observed changes in these areas suggest that prenatal cannabis exposure may disrupt the neural circuits that underlie critical cognitive functions, potentially leading to attention problems and other related issues as the child grows.

One of the key findings was that prenatal cannabis exposure was specifically associated with attention problems in early adolescence. This association remained significant even after controlling for potential confounding factors, including family history of mental health issues, prenatal exposure to other substances, and various demographic variables.

“Perhaps one surprising thing was that even though prenatal cannabis use is associated with worse child mental health across the board, the associations we saw with the brain were fairly specific to attention problems and ADHD,” Baranger told PsyPost. This suggests that some of the associations we previously saw actually are attributable to those alternative explanations I mentioned earlier, and that prenatal cannabis exposure might have causal effects on a narrower range of mental health problems than we previously thought.”

The research also highlighted the importance of the timing of cannabis exposure during pregnancy. Children exposed to cannabis both before and after their mothers knew of the pregnancy exhibited stronger associations with the brain metrics analyzed. This suggests that the developmental timing of exposure plays an important role.

“This study adds some evidence indicating that it is plausible that cannabis use during pregnancy might have some small adverse mental health consequences for children,” Baranger said.

But the study, like all research, includes some caveats. The primary limitation is its observational nature, which prevents definitive conclusions about causality. Additionally, the data on prenatal cannabis exposure relied on retrospective self-reports from parents, which could be subject to recall bias. The study also lacked detailed information on the frequency, quantity, and form of cannabis used during pregnancy. Furthermore, the sample size of children exposed to cannabis prenatally was relatively small.

“We can’t rule out that these results might be due to confounding from a variable we were unable to measure,” Baranger said. However, he noted that “new studies are coming out that have much more detailed assessments of pregnancy and parent’s behavior during the pregnancy (see, for example, the HEALthy Brain and Child Development Study). This is going to allow us to probe these questions with much greater detail and will also allow us to ask when brain effects first arise, which will help point to the mechanisms that could be mediating the effects of prenatal cannabis exposure.”

“One main thing to keep in mind about this kind of work is that the effects we are talking about are terribly small,” Baranger added. “They help us to study what is happening, but we don’t have enough data to say anything about what the effects of prenatal cannabis exposure are on the individual level.”

The study, “Prenatal cannabis exposure, the brain, and psychopathology during early adolescence“, was authored by David A. A. Baranger, Alex P. Miller, Aaron J. Gorelik, Sarah E. Paul, Alexander S. Hatoum, Emma C. Johnson, Sarah M. C. Colbert, Christopher D. Smyser, Cynthia E. Rogers, Janine D. Bijsterbosch, Arpana Agrawal, and Ryan Bogdan.