Evidence is mounting that tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, might pose risks to developing fetuses, specifically affecting brain development. New preclinical research now indicates that exposure to THC during pregnancy could also heighten the likelihood of opioid addiction later in life.
As more states legalize recreational cannabis, it is estimated that around 1 in 5 pregnant women in the U.S. are using it to alleviate symptoms like morning sickness, lower back pain, or anxiety. However, research is increasingly indicating that THC, the key psychoactive element of cannabis, might negatively impact the developing brain of the fetus. Recent findings suggest that this exposure could elevate the risk of opioid addiction in the future.
Conducted by researchers at the University of Maryland School of Medicine, this preclinical study involved animal models and was published in the journal Science Advances. The research revealed that exposure to THC in utero leads to significant alterations in the fetal brain’s wiring. Specifically, THC made certain brain cells called dopamine neurons react excessively, resulting in increased dopamine release. This heightened response coincided with an enhanced sensitivity to reward-related signals, such as lights indicating the availability of food or opioids.
“Healthcare providers are facing an unprecedented rise in cannabis consumption, and the THC level in products has increased fourfold compared to previous generations,” highlighted Joseph Cheer, PhD, a Professor of Neurobiology and Psychiatry at the University of Maryland School of Medicine and the study’s lead author. “These findings reveal lasting effects of prenatal cannabis exposure on the brain’s reward system, leading to a biological predisposition for opioid addiction.”
The American College of Obstetricians and Gynecologists advises healthcare professionals to discuss the potential negative health effects of continued cannabis use during pregnancy with their patients. Dr. Cheer and fellow researchers are urgently exploring the health implications of THC exposure during pregnancy to help medical practitioners provide informed guidance to expecting mothers.
The study illustrated that male animals exposed to THC in the womb exhibited a stronger increase in the “reward-seeking” neurotransmitter dopamine when exposed to opioids during adolescence compared to those not exposed to THC.
The researchers discovered that fetuses exposed to a relatively low dose of THC, roughly equivalent to a mother smoking one or two joints daily, showed changes in their reward system that made them susceptible to seeking opioids. THC-exposed animals displayed a significantly greater motivation to activate a lever dispensing opioid doses than their THC-unexposed counterparts.
As these THC-exposed animals reached early adulthood, they demonstrated higher tendencies towards opioid-seeking behavior and a greater likelihood of relapsing when exposed to opioid-related environmental cues, in contrast to those not exposed to THC in utero. Additionally, they were more prone to engage in persistent addiction-like behaviors.
In subsequent experiments, tiny sensors were implanted in the brains of the animals, which revealed increased dopamine release tied to heightened activation of neurons responsive to opioid-related cues among those displaying strong addiction-like tendencies.
“These findings lend support to the theory of a hypersensitive ‘wanting’ system that develops during the brain’s prenatal THC exposure,” stated Dr. Cheer. “Notably, we observed that this opioid-seeking behavior was significantly more pronounced in males than females, prompting further research alongside our UMSOM colleagues to understand the underlying reasons.”
Dr. Cheer’s earlier research, published in Nature Neuroscience, found that prenatal THC exposure leads to hyperactivity in the brain’s dopamine neurons, which may heighten the risk for psychiatric disorders, including schizophrenia. His findings have been corroborated by three separate laboratories around the world.
Along with colleague Mary Kay Lobo, PhD, a Professor of Neurobiology at UMSOM, Dr. Cheer co-directs the Center for Substance Use in Pregnancy, part of UMSOM’s Kahlert Institute for Addiction Medicine. Together, they are examining the long-term effects of drug and alcohol exposure during pregnancy.
“It’s essential for us to comprehend the lasting implications of in-utero THC exposure and explore if some harmful effects can be reversed through CRISPR-based gene therapies or repurposed medications,” noted Mark T. Gladwin, MD, Dean of UMSOM and the John Z. and Akiko K. Bowers Distinguished Professor. “We also need to offer better guidance to pregnant patients, many of whom mistakenly believe cannabis is a safer alternative for managing anxiety compared to traditional medications.”
The study received funding from the National Institute on Drug Abuse (Grants: R01 DA022340, K99 DA060209). Miguel A. Lujan, PhD, a research associate in Neurobiology, was the principal author of the paper.
