The experiment’s setup, or “rig” as professor Kuei Tseng calls it, looks like a cartoon version of something cobbled together by a mad scientist.
Clear plastic hoses snake from jars and containers, down to two large liquid-filled beakers on the floor and back up and around, ending in a tiny pipette poised at an angle under a high-powered microscope. It’s called a patch clamp, and it sounds like a backyard water fountain gurgling on the sixth floor of the University of Illinois Chicago medical building on Wood Street in Chicago.
A lab assistant spins a dial, bringing into focus on a screen a single rodent brain cell about one-seventh the diameter of a human hair. This tiny cell is from a teenage lab rat who had been high on tetrahydrocannabinol, or THC, the psychoactive ingredient in the marijuana plant, Cannabis sativa.
The cell will live only about five hours in this solution, but its reaction to stimuli during the experiment offers Tseng and his research team evidence to a question that has eluded scientists, parents, even educators: How bad is smoking pot for a teenager?
Tseng, 50, is one of the country’s foremost neuroscientists, and his lab rats, high on weed, are aiding our understanding of the long-term effects of cannabis on the teen brain. Over the past 20 years working in advanced research, mostly in Chicago institutions, Tseng has carved out a niche studying adolescent brain changes in Rattus.
It’s no secret that getting high makes it harder for teens — and adults — to learn, remember, focus, use motor skills and do complicated things. And THC stays in the body for days, even weeks. But as for long-term effects — e.g., Will smoking pot regularly at 16 make my kid a bust at age 30? — Tseng’s research suggests there is much more the public needs to know.
Modeling the adolescent brain
The rapid wave of marijuana legalization has moved faster than the research on its health impact, particularly when it comes to teens.
In 2020, Illinois became the 11th state to legalize marijuana for recreational use. The law, which requires buyers of recreational marijuana to be 21, presumed adult use. But no one doubts that weed, in all its forms, is more freely available, and perhaps more appealing in all its variety, to teens than ever before. More teens think of it as a “natural” substance, not a harmful drug, surveys show.
So far, the federal government hasn’t witnessed a dramatic increase in young users, according to Dr. Wilson Compton, deputy director at the National Institute on Drug Abuse. One-fifth of the 17 million high school seniors have used cannabis in the last 30 days, according to Monitoring the Future, a recurring University of Michigan survey.
What has changed is the scientific evidence about what marijuana can do to the developing teen brain. Teens who use marijuana regularly are more likely to quit high school or not get a college degree, warns the Centers for Disease Control and Prevention. But what’s the biological evidence for the concern?
Tseng’s rodent studies indicate that regular marijuana use prevents the teen brain from fully maturing. Older studies showed IQ deficits in adults who were teens users. But those results were hotly contested by the scientific community itself, making the new research on both rodents and humans–aided by recent advances in technology and more robust funding from American health agencies–so important.
Tseng, who trained as a medical doctor in Argentina, has become a key figure in the emerging field of biological psychiatry in the United States, and his research has uncovered big differences in the brains of adolescent and adult rodents.
Key to these differences are the brain’s internal cannabinoid system, a relatively recent discovery. Our brains are a virtual cannabis factory, producing their own supply that helps carry chemical messages to and from neurons. Cannabinoid receptors are in parts of the brain that influence pleasure, memory, thinking, concentration, movement and others — and act like traffic signals to regulate almost every aspect of our functioning.
They turn up the heat, or signal hunger. They are also, Tseng’s research shows, a vital mechanism in engineering an adaptive, mature brain through adolescence into adulthood.
When a person uses a vape pen or eats a gummy infused with THC, they ingest a substance that looks about the same to the brain as its natural cannabinoids. The ingested THC molecules flood the receptors with a wave of excess chemical messages that hijack the brain’s normal processing.
But in a teenager, the prefrontal cortex is still under construction, so to speak, and not fully developed until about age 20-25. Toying with that circuitry while it is still malleable appears to have long-lasting effects on intelligence, social behavior and other capabilities, according to the research of Tseng and other neuroscientists. In one of his studies, teenage lab rats, about 30 to 50 days old, were injected with THC. Rodents who were “high” during adolescence showed impaired learning lasting long into adulthood.
In such experiments, typically a rat will hear a buzzer, and receive a mild electrical pulse. When the rat hears the buzzer again, it freezes up, anticipating the pulse. After a few instances of a buzzer but no shock, the rat will “learn” and stop freezing up.
But when adult rats who were given THC as adolescents heard the buzzer, they kept freezing up again and again in the absence of any shock.
Tseng concluded that the rats’ adolescent brains were impaired by cannabis, and did not develop to their full potential in adulthood. They couldn’t process the new information. “That brain maturation process stopped somewhere. The normal gain of that maturation didn’t happen.”
Confronting the human questions
It is a nightmare scenario for human parents: Having a child who is stuck in adolescence like one of Tseng’s rats.
One night a few years ago, Tseng was invited to speak about his research at a bar in Lincoln Park in front of an audience of parents and teenagers. Parents wanted to know if it was healthy for their kids to smoke pot. The kids wanted to know how much was too much.
Tseng, who does not have kids of his own, told them he would rather the teens not use cannabis. But he added, “I would never say, ‘Don’t do it.’ It’s your call, not my call.”
Tseng is hesitant to answer such questions authoritatively because there’s so much more to learn, especially when it comes to human brains. How long is the period of susceptibility in adolescence? Why is cannabis delaying or stopping brain development? Can the effect be reversed?
This slow, painstaking research to investigate these questions is being carried on all over the world, including by a young cohort of scientists who worked in Tseng’s lab.
Hanna Molla, 34, co-authored with Tseng a 2020 overview of rodent and human adolescent brain performance on cannabis. Molla’s scholarly path began after she worked in a drug detox facility and became curious about why various drugs had such profound effects on people’s lives.
“There’s so much that’s not known about cannabis,” said Molla, who is now conducting studies on microdosing LSD in the lab of veteran drug researcher Harriet de Wit, founder of the Human Behavioral Pharmacology Lab at the University of Chicago.
Another graduate student who rotated through Tseng’s lab, Conor Murray, 33, is finishing up an experiment to see whether Tseng’s rat results can be reproduced in humans. In a study at the UCLA Center for Cannabis and Cannabinoids, Murray is using mobile headbands to measure brain waves and see if heavy, lifetime cannabis use shows up as a biomarker of brain development.
Tseng, meanwhile, is building new rigs for one of his most innovative studies yet. In the past, Tseng’s lab injected rodents with straight THC. Under a five-year, $2 million grant proposal, a group of lab rats would inhale cannabis that is piped into a specially made box called a “smoke jammer.” They would get five puffs over 30 minutes; the next day, same thing, for about five days running.
He hopes it will help researchers learn more about how and why cannabis alters the normal maturing process of the teenage prefrontal cortex.
A more potent marijuana
While Tseng is studying rodent brains, U.S. researchers are five years into the most comprehensive and thorough study ever done of brain development in young people. More than 11,000 children from age 9 are being tracked by more than 100 scientists at 21 study sites around the country, as they grow up, develop and mature to age 20. The Adolescent Brain Cognitive Development (ABCD) study will track drug and alcohol use, screen time and many other formative influences.
Such a study has only become possible in the last 10 years, because of technological improvements in data storage and brain imaging as well as leaps in understanding of the brain, said professor Krista Lisdahl, director of the University of Wisconsin-Milwaukee’s Brain Imaging and Neuropsychology Laboratory.
For Lisdahl, the ABCD study that she coordinates for UWM, is close to home. Her 14-year old son is the same age as the study volunteers.
“I’ve been living it,” Lisdahl said. “Having a kid and being a parent, it just increases my motivation to provide some evidence-based parenting advice.”
Like Tseng, she is not anti-cannabis, but age and potency are two big risk factors in her eyes. The weed that previous generations got their hands on was pretty mild, about 2-6% THC. Today, it’s 15-25% for plant products, or “flower.” Some cannabis extract products – such as edibles, oil, shatter and dab — contain stratospheric THC levels, from 50% up to 90%. Vaping cannabis is especially risky, Lisdahl said, because the THC concentrations are higher, and the device is portable and easy to hide.
“The way I explain it to my own son: I don’t think it’s worth it in your teenage years. You’re laying the groundwork for your career, for your social groups, your physical and mental health.
“The effects are subtle,” Lisdahl said, “but to me, if you’re trying to build your brain, you want to avoid risk factors like cannabis and alcohol. It does not optimize your cognitive development.”
These scientists view cannabis legalization in the United States as a gigantic national experiment involving almost 50 million Americans, and they eagerly anticipate the valuable data being generated. A nation once frightened by the 1936 propaganda film Reefer Madness now sees almost half its states collecting millions of dollars in new taxes, and a business sector earning billions in new revenue. Each day the powerful new industry continues its search for profitability and new markets.
The concerns of parents, and the health of their children, have gotten less attention. Scientists like Tseng and Lisdahl are doing their best to fill that void.
Want to dive deeper into the research?
Zachary Nauth is a freelance writer who lives in Oak Park.