How teen marijuana use may alter the shape of the brain

Since the sizzling fried egg in the iconic 1987 Partnership for a Drug-Free America ad, we’ve been asked to think about what a “brain on drugs” looks like. Now, we have a slightly better idea, thanks to a study that used MRI scans of adolescent brains at 14 and again at 18 to paint a picture of one plausible effect of marijuana.

In the JAMA Psychiatry report published Wednesday, that effect boiled down to this: accelerated thinning of parts of the brain called the right and left prefrontal cortices.

The authors write that their study is the “largest longitudinal neuroimaging study of cannabis use to date” and is particularly pertinent because of what we know about adolescent cannabis use: Most people trying marijuana for the first time (78 percent) are between the ages of 12 and 20.

“What we found was that the more cannabis use, that people were reporting, from 14 to 19, the faster certain cortical areas were thinning,” lead author Matthew Albaugh tells Inverse. Albaugh is a clinical psychologist and assistant professor of psychiatry at the Larner College of Medicine at the University of Vermont.

The findings, he says, “might suggest that cannabis is indeed having some sort of an effect on this neuro-maturation process.”

What you need to know first — Historically, it’s been difficult to study how cannabis affects the brain over time.

Some studies do suggest a link between early cannabis use and altered volume in some parts of the brain, changes in decision-making, and even claim it can moderate a genetic risk for schizophrenia.

“... cannabis is indeed having some sort of effect on this neuro-maturation process.”

But past research on cannabis and the brain also has its flaws. For one thing, many of these studies used small sample sizes, and this makes it difficult to generalize findings to the population at large. Other studies have examined a cross-section of youths and their brains at just one point in time, making it hard to determine whether or not their brains were any different from before. And some have looked at people of all different ages. This means, in a world where scientists are still learning the mysteries of our brains, that changes that could be attributed to cannabis could also have happened through normal brain development.

From what scientists gather, adolescence is a crucial time for brain development — one you don’t want to mess with. Once teens reach early adolescence, outer layers of the brain begin to decrease in thickness slightly, in a process Albaugh likens to pruning a bonsai tree. As synapses are trimmed away, he says, the brain appears to make room for further connections, essentially becoming more efficient.

This “cortical thinning” process is a normal part of brain development, but if it happens too fast it’s unclear what will happen, Albaugh says.

Prolonged cannabis exposure, however, has been shown to reduce social behavior in rats, drive memory problems in monkeys, and reduce motivation in rats. “With this bonsai tree analogy, you could imagine someone maybe kind of trying to prune really rapidly, hastily, and maybe the end product is not as nice,” Albaugh says.

What was discovered — Albaugh and his team had access to data from a larger study called IMAGEN. This included information on 799 students from European countries who were all around the age of 14 and had never tried cannabis.

The team took MRI scans of the teen’s brains to determine cortical thickness. Then, five years later, the students were asked how many times they estimated they had used cannabis so far, among other questions. Their brain scans were taken again to determine cortical thickness.

Five years down the line at age 19, around half of the students never tried cannabis and half had. This allowed the researchers to compare how fast the cortices of the cannabis users — as opposed to the “never tried” group — had thinned.

The more times the cannabis-using teens reported they had used cannabis, the faster it turned out their cortices had “pruned” themselves.

The areas that had thinned, the researchers found, were also the areas most prone to change in adolescence — what Albaugh describes as the more “plastic” parts. Students at five years also took an assessment of impulsiveness: These responses suggest cannabis-related thinning was also associated with increased impulsiveness.

There was further overlap, Albaugh says, with parts of the brain that have a high density of cannabinoid receptors. Though Albaugh says they don’t know for sure what the thinning does, “Taken all together, it starts to look like quite a bit of circumstantial evidence for there being some sort of cannabis effect.”

Why this matters — Albaugh and colleagues cite evidence suggesting that, as more states legalize cannabis, more adolescents are using it more heavily. This has corresponded to a slight uptick in reported cannabis use disorder.

States that legalize cannabis have made efforts to prevent adolescent use. Meanwhile, some argue cannabis may be less of a concern than alcohol and other substances that pose a threat to adolescent health.

“I wonder if we're in a situation where the policy is kind of outpacing the science here.”

An understanding of what exactly is going on in the brains of marijuana users, and how that compares to other risk factors, is still a bit murky. But at the very least, Albaugh says, it’s worth knowing more about cannabis’s effect on the developing brain.

“There hasn't been a lot of high-quality research in this area, and I wonder if we're in a situation where the policy is kind of outpacing the science here,” he says.

What’s next — Now, Albaugh and his team are working on a study that examines the same adolescent users when they are 23 years old. The goal is to determine what, if any, changes might present themselves in the brain later on.

“Some of these brain changes that we're finding [in the first study], they may proceed cognitive and behavioral outcomes,” Albaugh says. “It may take time for some of these behavioral and or cognitive outcomes to manifest.”

Although some reviews of the evidence on cannabis and age have suggested that adults may not respond in the same ways as adolescents, the research is far from conclusive.

“As we continue with this work, it is looking like there might be kind of this developmental vulnerability, which again, kind of dovetails with the animal research,” Albaugh says.

Abstract:

IMPORTANCE: Animal studies have shown that the adolescent brain is sensitive to disruptions in endocannabinoid signaling, resulting in altered neurodevelopment and lasting behavioral effects. However, few studies have investigated ties between cannabis use and adolescent brain development in humans.

OBJECTIVE: To examine the degree to which magnetic resonance (MR) imaging–assessed cerebral cortical thickness development is associated with cannabis use in a longitudinal sample of adolescents.

DESIGN, SETTING, AND PARTICIPANTS: Data were obtained from the community-based IMAGEN cohort study, conducted across 8 European sites. Baseline data used in the present study were acquired from March 1, 2008, to December 31, 2011, and follow-up data were acquired from January 1, 2013, to December 31, 2016. A total of 799 IMAGEN participants were identified who reported being cannabis naive at study baseline and had behavioral and neuroimaging data available at baseline and 5-year follow-up. Statistical analysis was performed from October 1, 2019, to August 31, 2020.

MAIN OUTCOMES AND MEASURES: Cannabis use was assessed at baseline and 5-year follow-up with the European School Survey Project on Alcohol and Other Drugs. Anatomical MR images were acquired with a 3-dimensional T1-weighted magnetization prepared gradient echo sequence. Quality-controlled native MR images were processed through the CIVET pipeline, version 2.1.0.

RESULTS: The study evaluated 1598 MR images from 799 participants (450 female participants [56.3%]; mean [SD] age, 14.4 [0.4] years at baseline and 19.0 [0.7] years at follow-up). At 5-year follow-up, cannabis use (from 0 to >40 uses) was negatively associated with thickness in left prefrontal (peak: t785 = –4.87, cluster size = 1558 vertices; P = 1.10 × 10−6, random field theory cluster corrected) and right prefrontal (peak: t785 = –4.27, cluster size = 1551 vertices; P = 2.81 × 10−5, random field theory cluster corrected) cortices. There were no significant associations between lifetime cannabis use at 5-year follow-up and baseline cortical thickness, suggesting that the observed neuroanatomical differences did not precede initiation of cannabis use. Longitudinal analysis revealed that age-related cortical thinning was qualified by cannabis use in a dose-dependent fashion such that greater use, from baseline to follow-up, was associated with increased thinning in left prefrontal (peak: t815.27 = –4.24, cluster size = 3643 vertices; P = 2.28 × 10−8, random field theory cluster corrected) and right prefrontal (peak: t813.30 = –4.71, cluster size = 2675 vertices; P = 3.72 × 10−8, random field theory cluster corrected) cortices. The spatial pattern of cannabis-related thinning was associated with age-related thinning in this sample (r = 0.540; P < .001), and a positron emission tomography–assessed cannabinoid 1 receptor–binding map derived from a separate sample of participants (r = −0.189; P < .001). Analysis revealed that thinning in right prefrontal cortices, from baseline to follow-up, was associated with attentional impulsiveness at follow-up.

CONCLUSIONS AND RELEVANCE: Results suggest that cannabis use during adolescence is associated with altered neurodevelopment, particularly in cortices rich in cannabinoid 1 receptors and undergoing the greatest age-related thickness change in middle to late adolescence.