And with a recent Gallup poll finding that 58 percent of the American public favors legalization - and with marijuana already legal in Washington state and Colorado - understanding any negative effects of marijuana has gained fresh urgency.
"This is really hard research to do," admits Sharon Levy, medical director of the Adolescent Substance Abuse Program at Boston Children's Hospital. "We can look at big groups of kids that decided to smoke and look at their outcomes, but that data can only show us associations. But this was how we did tobacco research and discovered problems with nicotine.
"It's always hard to study something that is an illegal behavior - we're never going to do a study where we take 100 14-year-olds and ask half of them to smoke marijuana," Levy said. "Our advantage today is that we can look at the brain, and we have a more sophisticated sense of neurobiology."
"As the rates of smokers go up," she added, "more and more studies will show findings pointing in the same direction. More and more, we will come to say that this is not just an association."
Thomas McLellan, CEO of the Treatment Research Institute in Philadelphia and a former high-ranking drug adviser to the Obama administration, agrees with Levy.
"There are known problems with marijuana. It's a fact that as use of marijuana becomes more regular and done by a person who has a developing brain, you have concentration, motivation, and cognitive problems associated with the drug," McLellan said. "The effects vary with dose, duration, and population. If you have a smart, capable, older adolescent smoking every once in a while, there may be a very minimal effect. But for 14-year-olds who have underlying problems of depression and concentration, you have a much more serious problem. How significant and how pervasive isn't clear, but they exist.
"You can be a proponent of marijuana or you can be against marijuana," he said, "but you can't say marijuana is good for a developing brain."
A number of new studies support that. In research in the journal Schizophrenia Bulletin, healthy and schizophrenic teens who smoked cannabis daily for three years, then abstained for two years, showed abnormal brain structures on MRIs and had declines in memory when compared with nonsmokers.
Memory-related structures in the brains of adolescent smokers appeared to shrink and collapse inward, perhaps reflecting a decrease in neurons. The younger the smokers were when they started using marijuana, the greater the abnormalities.
"We observed a lower level of performance in the marijuana groups that was associated with the pattern of how the brain looked," said lead author Matthew Smith, assistant research professor of psychiatry at Northwestern University.
While documenting these abnormal MRIs in heavy marijuana smokers, Smith warned that the study provided a picture "at one point of time" rather than over a long period. So he could not say definitively that marijuana alone caused the changes.
"One thing we can be sure of is that marijuana has a stronger effect on younger brains," Smith said. "At that age, the brain is changing on a daily basis, and it's risky to introduce substances into the brain that have detrimental effects. And if someone has a family history of schizophrenia, data shows that there could be an increased risk for developing that disorder if someone uses marijuana."
Smoking marijuana regularly before age 18 "has been linked with the greatest neurocognitive deficits," according to a recent study in Frontiers in Psychiatry. The study notes that cannabis has been tied to structural abnormalities in brain areas that underlie "inhibitory control, working memory and attention, emotional regulation, and processing speed in teenagers 15-19, all of which translate into poorer cognitive functioning," said lead author Krista Lisdahl, assistant professor of psychology at the University of Wisconsin-Milwaukee.
"There is substantial resistance to the idea that regular marijuana use is detrimental to health," Lisdahl said. "I can see why this gets confusing. For example, demonstrating that part of the marijuana plant (e.g. THC) significantly improves nausea in a clinical trial over a limited time period in individuals with life-threatening conditions does not mean that marijuana is good for your health."
"Most teens and young adults care about their brain and physical health," Lisdahl continued. "Marijuana has several psychoactive ingredients, especially THC, that attach to cannabinoid receptors throughout the brain. Over time, if you keep using regularly, you will begin to change your brain structure and how the brain connects. You will likely experience symptoms of craving and other cognitive and emotional symptoms."
Another study, from Duke University in PNAS, linked persistent cannabis use to neuropsychological decline from adolescence to midlife, as measured by lower IQs among 1,000 New Zealanders. Subjects who smoked marijuana in adolescence and continued to use it for years afterward showed a drop in IQ of eight points between ages 13 and 38. Quitting pot did not appear to reverse the loss, said lead researcher Madeline Meier, now an assistant professor of psychology at Arizona State University.
Meier's findings were challenged by economist Ole Rogeberg, senior research fellow at the Frisch Centre in Norway, who blamed socioeconomic factors for the reported drops in IQ. In a response in PNAS, Meier discounted Rogeberg's objections, but also noted, "Observational studies like ours cannot prove causation."
There is much less debate about the wisdom of adolescents using marijuana. Colorado, which began allowing limited retail sales of marijuana on Jan. 1, forbids use by anyone under 21.
"Young people should not be using marijuana, alcohol, or any other illegal drugs," said Mason Tvert, director of communications for the Marijuana Policy Project, a pro-legalization group.
He also maintained that "marijuana causes far less harm than alcohol."
So what's a parent to do?
"These are things I know," said Gary Emmett, clinical professor of pediatrics at Thomas Jefferson University Hospital. "That when smoked by a mother, marijuana is transferred to the fetus. That when a mother is breastfeeding, the marijuana gets to the baby in large amounts. My gut feeling is that marijuana is bad for infants and children."
When it comes to adolescents, those who self-medicate with alcohol or drugs may already have problems, Emmett said. "People who use substances get in a lot more trouble, they have poorer academic achievements, and often have preexisting reasons which prompt them to use drugs."
Yet, this doesn't detract from the drug's effects, which can include poor school performance and reckless driving, he added.
Levy, who views marijuana as an addictive drug, worries about the effects of secondhand smoke on children and toddlers who might ingest marijuana. She also warned that public-health authorities and parents are behind in talking about marijuana to children and teens.
"More and more people believe that marijuana is entirely benign and don't know what to think about or do about their kids using marijuana," she said. "Ten years ago, a kid who smoked would be brought in to a substance-abuse center right away, but now there is so much information out there saying that marijuana is really benign."
"I was recently in a New York City subway car and noticed all the messaging against sugar-sweetened beverages," Levy said. "I know parents who won't let their kids have a Coca-Cola but don't know what to do about marijuana."
In the end, Lisdahl offers this advice: "Do not try marijuana under age 18. If you have used marijuana, make sure that you use it less than once a month.
"Life is challenging and you want every advantage you can get."