Scientists are trying to understand how cannabis may affect long-term neurodevelopment when people were exposed to it in the womb. Previous work by Washington University in St. Louis researchers Sarah Paul and David Baranger in the Behavioral Research and Imaging Neurogenetics (BRAIN) lab led by Ryan Bogdan found associations between prenatal cannabis exposure and potential mental health conditions in childhood and adolescence, but potential biological mechanisms that could possibly explain this association were unclear.
In research published in Nature Mental Health this month, Bogdan, the Dean’s Distinguished Professor of Psychological & Brain Sciences in Arts & Sciences, and senior scientist Baranger outline some of those potential mechanisms, the intermediate biological steps that could play into how prenatal cannabis exposure leads to behavioral issues down the line.
“We see evidence that cannabis exposure may influence the developing brain, consistent with associations with mental health,” Baranger said.
Trying to draw out the long-term impacts of cannabis exposure during pregnancy is not a simple knot to untangle. There are many confounding factors that affect mental health and behavior.
For example, say someone was exposed in utero to cannabis and later develops attention deficit disorder as a teen — how do you differentiate that as an inherited trait or a trait influenced by environmental factors, versus a trait that cannabis exposure somehow contributed to early on in development? It is also possible that all three potentially could contribute to eventual psychopathology.
Another complication is the increasing prevalence of the drug, including among the pregnant population, where cannabis use has increased from 3% to 7% from 2002 to 2017.
Researchers have statistical methods to filter out some of those confounding factors that they used in the previous study, but now they can point to specific biological measurements that further signal a connection to cannabis exposure and adolescent behavioral problems.
Bogdan said that nothing can establish causation with certainty, “but we can look at the plausibility of causation and identifying biological correlates that are associated with exposure and these mental health outcomes suggests it’s plausible.”
Researchers have been using data on the children and their mothers from the Adolescent Brain and Cognitive Development (ABCD) Study, an ongoing research project that includes nearly 12,000 children across the country. As part of that study, they collected data about each mother’s substance use prior to the birth as well as the neuroimaging data of their offspring when they were between 9 and 10 and 11 and 12 years old. Some 370 children were exposed to cannabis prior to the mother’s knowledge of pregnancy, and 195 were exposed before and after learning of pregnancy.
The researchers looked at a variety of neuroimaging measurements that factor into brain development, including measures of brain thickness and surface area, as well as measures reflecting water diffusion in and outside of cells. The patterns found in the group exposed to cannabis are consistent with potential reductions in neuroinflammation.
“It’s possible what we’re seeing is an anti-inflammatory effect of cannabis, which is leading to differences in how the brain is being pruned during neurodevelopment,” Bogdan said.
Much has been touted about the anti-inflammatory effects of cannabis, but it’s not always good to reduce inflammation. It’s all about the timing — too much of a reduction of inflammation at the wrong time could affect how the brain is pruned and primed.
Another theory is that cannabis exposure leads to accelerated aging. But don’t expect to find the smoking gun of biological clues pinning mental health problems to early cannabis exposure.
It might not even be about cannabis effects on pruning but the post-combustion products from smoking cannabis that set off accelerated aging and the downstream cognitive effects, Bogdan said.
Or, it could all come down to sociological factors, he added.
Trying to find the one-to-one connection that proves that prenatal cannabis exposure has negative effects during the teenage years is a challenge and may not be possible with retrospective studies. Baranger notes that the major limitation of this data set is that it was retrospective; mothers reported what their cannabis use was 10 years ago, so he’s looking forward to new data from prospective, longitudinal studies that will offer more recent, accurate and detailed information about cannabis use in pregnancy.
“That will potentially give us more answers to these questions in the future,” Baranger said.
Baranger said these results reaffirm that if someone is thinking about using cannabis while pregnant, they should “talk to their doctor about their choices and what other options there might be.”
Baranger DA, Miller AP, Gorelik AJ, Paul SE, Hatoum AS, Johnson EC, Colbert SM, Smyser CD, Rogers CE, Bijsterbosch JD, Agrawal A, Bogdan R. Prenatal cannabis exposure is associated with localized brain differences that partially mediate associations with increased adolescent psychopathology. Nat. Mental Health (2024). https://doi.org/10.1038/s44220-024-00281-7
Research reported in this press release was supported by R01DA54750 (RB, AA). Additional funding included: DAAB (K99AA030808), APM (T32DA015035), AJG (DGE-213989), SEP (F31AA029934), ASH (K01AA030083), ECJ (K01DA051759; BBRF Young Investigator Grant 29571), CER (R01DA046224), AA (R01DA54750), RB (R01DA54750, R21AA027827, U01DA055367). Data for this study were provided by the Adolescent Brain Cognitive Development (ABCD) study which was funded by awards U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147 from the NIH and additional federal partners (https://abcdstudy.org/federal-partners.html). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
