Prenatal cannabis exposure is associated with increased risk of subsequent opioid addiction

With the legalization of cannabis as a recreational drug, one in five pregnant women in the United States uses it to relieve morning sickness, back pain, and anxiety. However, increasing evidence suggests that cannabis's main psychoactive ingredient, tetrahydrocannabinol (THC), can affect brain development and pose a risk to the developing fetus. Now a new study finds that this may increase the risk of opioid addiction later in life.

The preclinical animal study, led by researchers at the University of Maryland School of Medicine, was published in the journal Science. scientific progress. Prenatal exposure to THC was found to cause rewiring of the fetal brain. THC caused certain brain cells called dopamine neurons to overreact, causing an increase in dopamine release. This was accompanied by increased responsiveness of neurons to reward-related cues, such as a light turning on indicating the availability of food or opioid drugs.

Doctors are battling an explosion in cannabis use, with THC content quadrupling compared to a generation ago. This indicates that prenatal cannabis exposure has lasting effects on the brain's reward system, ultimately leading to neurobiological vulnerability to opioid drugs. ”

Dr. Joseph Chia, Research the corresponding author; professor of neurobiology and psychiatry At the University of Maryland School of Medicine

The American College of Obstetricians and Gynecologists recommends that physicians counsel patients about the potential negative health effects of continued cannabis use during pregnancy. Dr. Chia and other researchers studying THC exposure during pregnancy want to learn more about the health effects on the developing fetus so that doctors can better advise patients about the drug's effects. I'm working hard.

This figure shows that male animals exposed to THC in utero produce less of the “reward-seeking” brain chemical dopamine when exposed to opioid drugs during adolescence compared to animals not exposed to THC. This indicates that we will experience a significant spike.

To conduct this new study, he and his colleagues found that fetuses exposed to moderately low doses of THC (equivalent to the amount their mothers smoke one to two joints a day) were able to improve their reward systems. They discovered that it causes changes in function and causes abnormal conditions in the fetus. Opioid-seeking risk phenotype. Animals previously exposed to THC in utero had dramatically increased motivation to press the lever to administer the opioid drug compared to animals not previously exposed to THC.

Once THC-exposed animals reach early adulthood, they are more likely to exhibit increased opioid requirements and are more likely to relapse due to opioid-related environmental stimuli compared to animals not exposed to THC in utero. It was expensive. They were also more likely to develop persistent addiction-like behaviors.

In follow-up experiments, researchers implanted small sensors in the animals' brains and measured increased dopamine release, accompanied by activity in neurons that overexpress opioid-related cues, in rats that exhibited strong addiction-like behaviors. did.

“These observations support the hypothesis of a hypersensitive 'craving' system that develops in the brain after exposure to THC during prenatal development,” Dr. Chia said. “Interestingly, we found that this opioid-seeking phenotype occurs significantly more frequently in men than in women. Together with our colleagues at UMSOM, we are currently conducting research to understand why this happens. Masu.”

Dr. Cheer's previous research published in the journal natural neuroscience It turns out that prenatal exposure to THC causes the brain's dopamine neurons to become overactive, which may contribute to an increased risk of mental illnesses such as schizophrenia. His research has been independently verified by three independent laboratories around the world.

Dr. Chia is co-director of the Center for Substance Use in Pregnancy, part of UMSOM's Carlato Institute for Addiction Medicine, along with colleague Mary Kay Lobo, Ph.D., professor of neurobiology at UMSOM. They are working with a team of researchers to investigate the lasting effects of exposure to drugs and alcohol in the womb.

“We need to more fully understand the lasting effects of in utero THC exposure and whether CRISPR-based gene therapy or drug repurposing can reverse some of the deleterious effects.” said Mark T. Gladwin, M.D., Dean of UMSOM. John Z. Bowers and Akiko K. Bowers are distinguished professors and vice president for medical affairs at the University of Maryland, Baltimore. “We also need to provide better advice to pregnant patients. Many of our patients believe that this drug is safer for their baby than traditional anti-anxiety drugs and that it helps them manage their anxiety.” I use cannabis to

This research was funded by the National Institute on Drug Abuse (Grant: R01 DA022340) (Grant: K99 DA060209). Dr. Miguel A. Lujan, a UMSOM faculty member and research associate in neurobiology, was the paper's lead author.