UC Irvine Medical School Will Study THC’s Effects on Adolescents’ Brain Development

By, Valli Herman

Science may one day be able to answer a pressing question many parents have had about their adolescent children’s difficult behavior: Is it a passing teenage phase, or is it a result of using marijuana? And if cannabis is to blame, how, how much, and why?

Researchers in the School of Medicine at the University of California, Irvine, are embarking on a four-year study to understand the impact of cannabis use on adolescent brain development. The work is underway now that the university’s newly created Center for the Study of Cannabis in July 2018 formally won its first major grant, totaling $9 million from the National Institute on Drug Abuse, part of the National Institutes of Health.  

Daniele Piomelli, a professor of anatomy and neurobiology at the UCI School of Medicine, will lead the research at the university’s cannabis center, where he also serves as director. It’s significant that one of the first major, federally funded studies on cannabis will attempt to determine whether cannabis use has a lasting impact on the developing brains of adolescents, a demographic with high usage rates.

According to UCI:

“Teenage boys and girls experiment with cannabis more than any other recreational substance, and a substantial percentage of them (5.8 percent of 12th graders in 2013) also tried synthetic cannabis substitutes such as spice and K2. Though striking, these numbers are likely to grow in the near future as risk perception of cannabis’s potential consequences continues to decrease.”

Specifically, Piomelli and a group of UCI investigators will conduct animal studies to determine whether exposure to delta-9-tetrahydrocannabinol (THC) during adolescence causes persistent changes within the endocannabinoid system’s functions.

The millions of dollars from the NIH offer not just financial support, Piomelli said, “but the grant also gives validation to the whole effort.” Piomelli and his team spent two years gathering data and conducting preliminary research to compile the 750-page grant proposal. After scientists throughout the United States reviewed the proposal, Piomelli’s team received 50 pages of critiques.

The interdisciplinary team’s initial studies at UCI will build on those of other researchers that indicate THC has an effect on the adolescent brain.

“We can look at these effects in a very deep and mechanistic way and understand at the molecular level, at the cellular level, at the synaptic level how these changes occur,” he said. “Also, what is really important to us: At what dose level of THC do these changes start to appear?

“This is something other investigators don’t fully appreciate, but it’s important to understand, and not just that the substance produces an effect, but at what concentration, or rather what dose, that the substance produces the effect. This is fundamental to harm reduction and prevention.”

The study could help guide future regulations, public health policies, and additional research. It also may provide important context for parents who face a familiar scenario.

“Think about it this way: Your child, who is maybe 13 or 14, avows that she has smoked pot. How concerned should you be?  What advice can you give them?

“As a father of a daughter who went through adolescence at one point, I would have very much liked to know what exposure to cannabis — maybe once, or once a week or once a month — has no effect on the development of her brain. We don’t really know. I would have liked to have had that kind of information,” Piomelli said.

Other recent studies have indicated a need for additional research, according to Piomelli, especially one in particular: “They found if you are able somehow to boost the cannabinoid system in the rat brain when the rat is an adolescent, and if you keep the system activated, then when the rat becomes an adult, the rat behaves as an adult as if it was still adolescent.”

The rats didn’t ingest cannabis in that experiment, but instead were using their own cannabinoid system–their own cannabinoid-like molecules.

“Basically, this suggests having a cannabinoid system is an integral part for us, as mammals, being adolescent. An integral part of their behavior is adolescent. The fact that they are more prone to play than adults are. They have certain propensity to social behavior. They enjoy social behavior and interacting with their peers. These are all exquisite features of adolescence. They seem, at least in part, to be underpinned by the activity of the cannabinoid system,” Piomelli said.

“This is really important because if the [cannabinoid]  system is crucial to adolescent behavior then using too much THC during adolescence could be detrimental,” he said.

“The issue is actually quite puzzling and mysterious,” Piomelli said. “Despite some claims to the opposite, [THC] is actually a fairly safe molecule. It’s actually hard to kill people with THC. Actually, you can’t.

“So, the question is why is it that a compound that is not so toxic can, when the brain is exposed to it during adolescence, cause long-term changes? From a neurobiological perspective, it is a fascinating issue. It is not that easy to change the brain.”

Piomelli’s team aims to have an answer to that question and more in two to three years as the study progresses.

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