Pre-existing differences in brain structure are associated with earlier substance use in young people, according to a recent study. The research informs our limited understanding of the complexity of factors behind drug use.
Among its many implications, it lends support to the case that, when youth who try vaping nicotine are also more likely to try cigarettes, the reason is a so-called “common liability” to nicotine use in whatever form—and not some sort of “gateway” effect of vaping itself.
This, in turn, has policy implications when many restrictions on access to tobacco harm reduction products have been imposed in the name of preventing youth use and claimed cigarette uptake. Youth smoking has fallen to an all-time low during the period when vapes have been available.
The research, published in the Journal of the American Medical Association (JAMA), utilized data from nearly 10,000 participants in the Adolescent Brain Cognitive Development Study—a longitudinal study of behavioral and biological development, tracking people from childhood to early adulthood.
The researchers identified certain brain features that were associated with earlier initiation, “most of which are evident before any substance exposure.”
When they were aged 9-11, these children underwent MRI scans to produce images of their neuroanatomical features. Over the next three years, they were then regularly asked about whether they had used alcohol, nicotine, cannabis or state-banned drugs.
That information enabled a comparison of the earlier brain structures of 3,460 adolescents who reported using substances before the age of 15 with those of 6,344 adolescents who didn’t. (The former group included 431 participants who said they’d used nicotine.)
The researchers identified certain brain features that were associated with earlier initiation, “most of which are evident before any substance exposure.”
Among those adolescents who had used drugs, their previous MRI scans showed that on average, “the cortical mantle was thinner in prefrontal regions, but thicker in temporal, occipital, and parietal regions,” the researchers wrote. This suggests, they continued, that “regionally specific differences … may confer vulnerability to substance use initiation.”
Dr. Alex P. Miller, assistant professor of psychiatry at the Indiana University School of Medicine, was the lead author of the recent study.
“The findings of the study suggest that early adolescent substance use is associated with differences in brain structure measured in late childhood,” he told Filter. “Variability in brain structure may partially reflect predispositional risk for initiating substance use earlier in life, which is, in turn, associated with greater risk of developing a substance use disorder later in life.”
Opponents of greater access to safer nicotine products, including public health agencies, have long asserted that nicotine damages the developing brain. This has been shown in animal studies, but has never been conclusively demonstrated in humans, despite many generations of people having smoked cigarettes.
Dr. Brad Rodu, professor of medicine at the University of Louisville, is among experts to have stated, “There is absolutely no scientific evidence to support the claim that nicotine causes harm to human brain development.”
When structural differences are sometimes interpreted as being caused by nicotine, “What’s new in this study is showing that these differences, at least in part, were already there.”
Asked whether findings that significant brain differences pre-date the initiation of nicotine use might dampen the narrative that nicotine harms developing brains, Miller was cautious, saying further research is needed. “There is still a lot we don’t know about long-term effects of substance use, especially heavy or prolonged substance use, on brain structure and function more broadly and particularly in adolescence.”
Dr. Arielle Selya is a behavioral scientist with a background in adolescent substance use and addiction. Some of her published work has addressed the lack of evidence for the gateway hypothesis that vaping causes youth to smoke, and why common liability is a better interpretation of the association. She told Filter that the recent JAMA study, with which she was not involved, is “extremely important” and aligns with her own work in this area.
“It has previously been shown that there are structural differences in the brains of people who use substances compared to people who don’t, and this is sometimes interpreted as smoking causing those differences,” Selya said. “What’s new in this study is showing that these differences, at least in part, were already there before the person started using substances.”
In line with this, some research has suggested that pre-existing personality traits might be associated with a higher propensity to use drugs.
“People with risk-seeking personality are more likely to use substances,” Selya told Filter. “The personality trait was probably present well before substance use, since personality traits are relatively stable over the lifespan.”
There would be dangers, of course, in over-emphasizing brain structure or other traits as a predictor of later substance use—such as a feeling that for some people, it is inevitable, or that there’s a limit to how much they can be helped. The fatalistic idea that brain structure might determine whether someone will use drugs is taking it much too far.
The findings are just “one part of the puzzle,” Miller stressed, when other research has indicated sociodemographic factors playing a larger role.
Miller made clear that, “The results of our study, suggesting that differences in structure have a small, but meaningful, impact on likelihood of early substance use initiation, would not themselves be clinically or diagnostically informative for an individual.”
The research he led was just “one part of the puzzle,” he stressed, when differences in brain structure correlated to only a fraction of the overall likelihood of initiating substance use, and other research has indicated sociodemographic factors playing a larger role.
But what brings about the brain differences that might indicate a higher predisposition to use drugs? Is it purely genetic? Or could changes to the brain be a result of a person’s life circumstances, which might help partially explain why certain groups use some substances at higher rates?
“As with many differences observed between individuals, it’s almost certainly both,” Miller said.
This chimed with Selya’s view. “I don’t think anyone knows how much of the structural brain differences are hereditary versus environmental,” she said.
Miller said a follow-up study is now looking at the degrees to which genetics and environment are associated with the brain-structure differences observed in the recent research: “We hope that this will shed some light on some of the reasons why these differences arise.”
Photograph (cropped) by Anna Shvets via Pexels
Dr. Selya’s employer, Pinney Associates, consults for the vape company Juul. The Influence Foundation, the nonprofit which operates Filter, previously received unrestricted grants from Juul Labs, Inc. Joe Gitchell, the CEO of Pinney Associates, has made personal donations to The Influence Foundation. Filter’s Editorial Independence Policy applies.
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