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The University of Minnesota's vaunted twins study had as good a shot as any to sort out the murky health effects of recreational marijuana.

By factoring out differences in genetics, upbringing and age, the study offered a purer comparison of twins who smoked marijuana vs. siblings who didn't. After comparing 364 sets of identical twins, the U researchers found in 2021 that the marijuana users had lower grades and were less likely to attend college and earn higher incomes.

But the study didn't find the cognitive declines and mental health problems others have ascribed to marijuana. Even twins lead different lives, so it's also possible other influences were at work, said Jonathan Schaefer, a lead author and researcher at the U's Institute of Child Development.

"By virtue of comparing twins, we can get a much more accurate estimate of the true effect of the drug," he said. "But it is still an estimate, and it's not necessarily wholly attributable to the drug."

Those uncertainties reflect Minnesota's paradox as its leaders debate whether to join 18 states in legalizing recreational marijuana. Few studies let marijuana off the hook, and yet its harms seem unclear or modest compared to tobacco or alcohol — making it hard to stand in the way of the people who want to smoke it, the industry that wants to sell it, and the politicians who want to spend its tax revenues.

Dr. Charles Reznikoff, an addiction medicine expert with Hennepin Healthcare, said persistent marijuana use has hurt some patients' health, jobs and families.

However, marijuana doesn't present the same lethal risk as opioids or alcohol, he said: "Cannabis use disorder, marijuana addiction, it's less destructive than other forms of addiction, and I think that's why it gets downplayed."

Research has focused on marijuana use from adolescence through young adulthood, because it could hamper brain development that continues through age 25.

Cortical thinning is a form of brain degeneration associated with older age, but Vermont researchers in 2021 found through medical imaging that it accelerated in adolescents who regularly used marijuana. The degeneration can inhibit arousal, attention and memory.

Substance abuse also rewires the brain's reward system to prefer drugs, including marijuana, over other sources of happiness, said Anna Zilverstand, a U neuroimaging expert.

"The brain changes such that the other things, they don't generate as much pleasure anymore," she said. "That's the danger of it."

Imaging studies show it takes months of sobriety to restore typical brain function.

Push to raise legal age

Mental health advocates and the Minnesota Medical Association have asked lawmakers to increase the proposed age limit for recreational marijuana to 25. House and Senate bills rapidly advancing through the Legislature set the limit at 21 to make it consistent with alcohol policy.

Sue Abderholden of NAMI Minnesota proposed a packaging warning as an alternative, so "at least we'll be telling young people, 'You know, it's not such a good idea.'"

A potency cap also could limit the percentage of THC, the psychoactive ingredient in marijuana, in legal products, said Dr. George Realmuto, a U psychiatry professor emeritus.

"The length of time you use it, the potency of it, and the age at which you start using it are all predictive of psychosis, depression, anxiety, cognitive difficulties, addiction and polyaddiction," he said.

Vermont imposed a cap in 2021; earlier states legalized marijuana before high-content THC products existed. Research hasn't identified a safe consumption level, though, or a cap threshold that works. Banning high-THC products could reduce the risk of health problems, or just sustain the illicit market for the stronger stuff, Realmuto said.

Realmuto is motivated by his daughter, whose marijuana use in her teens preceded meth use and an overdose death at age 36 in 2019. He said he also saw the psychotic effects of marijuana when he directed a state behavioral health hospital in Willmar.

Marijuana's effects on older adults are less established — though researchers are studying them. The U's Tobacco Research Programs just finished recruiting people age 25 to 40 to assess marijuana's impact on their thinking, impulsivity and stress response.

Reznikoff didn't think Minnesota was ready for medical cannabis in 2014 when the state approved a tightly-regulated program that now provides access to 40,000 people with 19 different qualifying conditions. And he said he doesn't think doctors are ready now to counsel patients on recreational marijuana, but said they will have to learn on the fly.

"If one can use cannabis in a sort of moderate way without it developing into an addiction or causing other harms, there's nothing wrong with having joy in your life," Reznikoff said. "And boy do we need a little bit of joy right now, because things have been tough for the last couple years."

Limited societal change?

Minnesota shouldn't expect legalization to prompt dramatic societal change, other than a windfall of tax revenues, according to a 2021 analysis by the Cato Institute, a libertarian think tank in Washington, D.C.

Traffic fatalities, violent crime and suicide rates held steady in other states that legalized marijuana, the analysis showed. Proponents thought legalized marijuana would result in self-medication and less suicide while opponents thought it would fuel psychoses and more self-harm.

Little changed because government prohibitions weren't slowing marijuana usage in the first place, said Jeffrey Miron, a lead author and Harvard University economist.

"People just get around the laws," Miron said. "When the Soviet Union prohibited its people from getting Levi's jeans from the West, that didn't work either."

Emergency room visits for cannabis disorders increased nearly 7% from 2017 to 2021, when the total reached 11,093, according to the Minnesota Hospital Association. However, ER visits appeared to sharply decline in 2022 — when Minnesota opened the door toward legalization with limited THC-infused products.

Identifying risks for marijuana-related health problems will be important, so doctors can screen and counsel patients like they do for smoking and drinking. Dr. Mustafa al'Absi at the U medical school's Duluth campus has been studying how trauma alters brain function and makes people more susceptible to marijuana use and addiction.

"They may even have a harder time quitting," he said.

The psychologist said he doesn't think the state knows enough about the harms of marijuana to legalize it. Ironically, legalization would make it easier to study the drug.

Realmuto said legalization could increase access for teens — who are quite capable of sneaking beer out of parents' refrigerators.

In the 2022 Minnesota Student Survey, 12% of high school juniors had used marijuana once or more in the past month. Only 19% thought marijuana use once or twice a week was risky, compared to 63% who felt that way about cigarettes and 35% about alcohol.

"Teenagers are very clever," he said. "There is no way to change that."