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LEGALIZATION TREND FORCES REVIEW OF MARIJUANA'S DANGERS

Pot May Be Far Less Risky Than Highly Addictive Drugs, but It's Not Harmless

Some people think marijuana is nature's gift to humankind: a nonaddictive drug, safe at any dose, that opens the mind, lifts the spirit and transports the user to a more profound reality. 

"The illegality of cannabis is outrageous, an impediment to full utilization of a drug which helps produce the serenity and insight, sensitivity and fellowship so desperately needed in this increasingly mad and dangerous world," a user named Mr.  X wrote in the 1971 book Marihuana Reconsidered. 

Close to 30 years later, Mr.  X was revealed to be the legendary science communicator and astronomer Carl Sagan.  His message still reverberates with many Americans, whose support for legalizing marijuana has tripled since 1989 - from 16 percent to 54 percent today.  In Colorado and Washington state, voters legalized recreational marijuana use in November 2012.  That formal embrace of marijuana may signal a growing shift in acceptance.  Today, 21 states and the District of Columbia sanction medical use ( up from 16 in 2010 ) and 17 have curbed punishments for possession of small amounts of recreational cannabis. 

Marijuana as medicine is gaining support in studies, both to tamp down nausea and pain and to directly counter insidious diseases such as epilepsy, cancer and multiple sclerosis ( SN: 6/19/10, p.  16 ).  But what about for healthy people? Is marijuana really a safe way to rise above the tumult and distress of daily life?

Michele Leonhart, the head of the U.S.  Drug Enforcement Administration, says no.  In congressional testimony in 2012, she portrayed marijuana as a dangerous addictive drug on par with methamphetamines or heroin.  Like other drugs cordoned off by her agency to a list called Schedule I, she said, marijuana has no medical use and a high potential for abuse. 

Convinced of marijuana's dangers, the DEA and vocal groups of police officers, educators and public health officials remain steadfastly opposed to the growing legalization movement.  Legalization poses significant health and safety risks to Americans, they argue.  This addictive drug wipes out memories, steals IQ points and triggers psychosis, leaving behind a zombie nation of slackers vegetating in their parents' basements, opponents say.  The consequences may be especially damaging for teens. 

Who is right? The people who contend that marijuana is a misunderstood salve for the soul or those who claim it's a dangerous narcotic that turns people into dimwitted potheads?

Turns out it's neither.  Though the research is far from definitive, the scientific evidence that does exist suggests that marijuana is far less dangerous than highly addictive drugs like heroin, methamphetamines and alcohol.  But it is not harmless.  Pot can probably cause permanent changes in the developing brains of adolescents.  And though marijuana is not highly addictive, about 10 percent of users become dependent. 

It's unlikely that existing research will be able to provide a clear-cut answer about whether legalization is a good idea.  But in a way, that debate is already over.  As popular sentiment shifts and laws become more lenient, marijuana becomes a bigger piece of the social fabric. 

"We're at this point, whether we like it or not, where things are changing, and they're changing fast," says Susan Weiss, associate director for scientific affairs at the National Institute on Drug Abuse ( NIDA ) at the National Institutes of Health.  Her agency is funding studies to better understand the effects of marijuana, she says, so that the science can better inform public policy. 

Your brain on pot

When a person tokes, eats or vapes cannabis, a wave of THC, or tetrahydrocannabinol, washes into the brain.  Thought to be the major psychoactive ingredient in marijuana, THC latches on to a protein in the brain called cannabinoid receptor type 1, or CB1.  These receptors are sprinkled liberally throughout the brain, especially in the cortex, where thinking takes place; the basal ganglia, which helps control movement; the appetite-regulating hypothalamus; and the hippocampus, a structure involved in forming memories. 

CB1 receptors are an important part of how the brain works, says neuroscientist Valerie Curran of University College London.  "They're not put there by God so we can all enjoy cannabis," she says.  "They're put there because we have our own cannabis in our brains."

The brain's self-made cannabis consists of molecules called endocannabinoids, which hit the targets that cannabis hijacks.  One of the primary endocannabinoids is named anandamide, after the Sanskrit word for bliss.  The brain's endocannabinoid system influences pain, memory, mood and appetite, and plays a role in helping the brain grow. 

So when foreign THC taps into this system, the effects can feel profound, says psychologist Mitch Earleywine of the University at Albany in New York.  "It's got a novelty," he says.  "It's got its own receptor system and its own set of effects.  The fact is that not a lot of other substances hit that CB1 receptor." That's how cannabis elicits its particular brand of euphoria and cognitive flexibility, says Earleywine, who also serves on the board of NORML, the National Organization for the Reform of Marijuana Laws, which pushes to legalize the drug. 

Unlike some other reality-altering drugs, cannabis doesn't seem to be lethal, even in high doses.  "Can you die from alcohol just by drinking yourself to death? Yes, you can," says pharmacologist Kari Franson of the University of Colorado Denver.  "Can you die from marijuana just from ingesting too much or smoking too much? Well, not really.  You pretty much have to fall down and hit your head to die from it." ( A paper published in the April Forensic Science International does describe the deaths of two presumably healthy young men from heart trouble under the acute effects of cannabis.  But overall, deaths seem to be rare.  )

Marijuana may not be deadly, but there are some clear downsides.  A mental juggling act called working memory, the ability to hold pieces of information in mind, is diminished in someone who's high, 40 years' worth of studies show.  Marijuana use has been linked to cardiovascular problems, most recently in a paper in the April Journal of the American Heart Association that describes heart problems in young cannabis users.  Cannabis intoxication may double a driver's risk of a car crash, scientists reported in 2012 in BMJ.  And heavy smokers can show more signs of lung damage compared with nonsmokers, though whether that actually leads to more disease is unclear, according to a 2013 review published in the Annals of the American Thoracic Society. 

"We're worried about having another drug that's highly prevalent and very accepted by society," says Weiss of NIDA.  The burden of problems will only get worse, she says, including altered brain development, poorer school and work performance and higher numbers of people who are addicted.  Between 2009 and 2011, as use rates went up, the rate of emergency room visits for cannabis intoxication rose by 19 percent, according to the Drug Abuse Warning Network. 

Addiction

The concept of addiction plays front and center in the debate.  Marijuana proponents are fond of pointing out that the drug is less addicting than tobacco and alcohol, substances that are legal for adults.  And that is correct.  On a relative scale, marijuana just isn't as addictive as other substances, says Franson. 

"Think about those poor little rats pushing levers to get cocaine.  They forgo eating, forgo sex, forgo everything because they just want to hit that lever," she says.  Marijuana's addictive allure doesn't compete with opiates, or even alcohol or tobacco.  But that doesn't let marijuana off the hook, she says.  "It's not the worst offender, but it still does have some of those addictive components," Franson says. 

It's not clear what goes on in the brain to cause pot addiction, or why so many people escape it.  Marijuana somehow reduces the number of CB1 receptors in the brains of people who smoke regularly, an effect that might contribute to addiction, scientists reported in Molecular Psychiatry in 2012.  But after a month of abstinence, the receptors bounced back to normal levels everywhere except the memory-forming hippocampus.  Regular marijuana use might also influence an addiction-linked pathway that involves the neurochemical dopamine, though the details of that interaction aren't clear.  Studies, mainly on animals, suggest that over time, cannabis might change the feel-good parts of the brain, including the neurons that produce dopamine, in ways that prompt people to keep using it. 

Those changes might explain why some people struggle to stop using marijuana.  About one user in 10 becomes dependent, defined by criteria described in the Diagnostic and Statistical Manual of Mental Disorders.  Those criteria include two key features: tolerance and withdrawal.  Experienced marijuana users need to up their dose as they become tolerant.  "You need more of the drug to have the same effect," says Franson.  Animal studies bear that out: Mice exposed habitually to THC need more and more of the drug to show the same motor deficits. 

Marijuana withdrawal is even more contentious than tolerance.  After stopping heavy marijuana use, some people - but not everyone - experience irritability, anxiety and loss of appetite.  Still, those symptoms are mild compared with an opiate or alcohol withdrawal, Earleywine says.  "If you tell an opiate addict you're 'addicted' to marijuana, you're probably going to get kicked in the crotch," he says. 

But if cannabis isn't lethal and doesn't cause debilitating withdrawal, then is habitual use really such a bad thing? The answer, it turns out, probably depends on the age of the smoker. 

Trouble for teens

Scientists can't say with confidence what marijuana does to the body and brain long-term, for several reasons.  It would be unethical to randomly assign study participants to use an illicit drug for months, so the best scientists can do is look for associations - particular traits, abilities or limitations that appear more frequently in people who use cannabis.  This approach leaves open all sorts of variables: People are from different backgrounds and smoke marijuana from different sources, for starters.  The most these studies can offer is possible links. 

One of the strongest links found so far comes from studies of young people.  The teenage brain is still growing and refining its neural connections - a process that's regulated in part by the brain's natural endocannabinoid system.  Marijuana use when the brain is vulnerable may interfere with its normal development.  "The developing brain is at risk," Franson says. 

Young adults, ages 18-25, who used marijuana at least once a week were more likely than nonsmokers to have structural differences in two brain areas thought to be involved in addiction, the nucleus accumbens and the amygdala.  The differences were more pronounced with increased use, researchers reported April 16 in the Journal of Neuro-science.  Scientists don't know whether these brain differences track with any behavioral deficits. 

Adolescents who heavily use marijuana are more likely to perform poorly in school and drop out, though the effects of cannabis can't be easily separated from other social factors.  New Zealanders in one study who used marijuana heavily during their teens showed an IQ drop of about eight points by the time they'd reached age 38.  Because the study began before the participants started using marijuana and ran for decades, the results offer some of the strongest evidence yet that marijuana contributes to an IQ decline.  But even these results come with caveats and methodological limitations. 

Marijuana's long-term effects on people who start using the drug as adults are even less understood, but the hints provided from some studies suggest that it's not as harmful as adolescent use.  That same IQ study, for instance, found no decline in people who began using cannabis as adults. 

A different study, published in the May Addictive Behaviors, looked at whether the cognitive effects of marijuana in adults go away when people stop using.  "It's generally known that the acute effects are there," says study author April Thames of UCLA.  "The question is, do these reverse over time?"

Most of the negative effects of marijuana - poorer attention, working memory and mental nimbleness - were absent in adults who had not used the drug for a month, Thames and her colleagues found.  However, a person's ability to plan and make complicated decisions was still impaired a month out. 

The results offer just a "snapshot at the time we did the testing," Thames says.  They describe an association, not causation.  "The question down the road is, what kind of implications does that have for everyday functioning?"

Scientists have largely failed to turn up compelling evidence that adult pot smokers risk permanent brain problems, Earleywine says.  "Being stoned all the time is a strange way to live your life," he says, but data just aren't there to argue that a cannabis-fueled lifestyle is permanently harmful to the adult body and brain. 

The new reality

As researchers try to make sense of study results, the nascent marijuana industry is charging ahead in a Wild West capitalistic society.  That's worrisome, many scientists say.  Policies should regulate the quality and strength of marijuana, and keep it away from children, Franson says. 

In Colorado, where drug laws have been loosened, first for medical marijuana and then for recreational use, a growing number of children under 12 have been admitted to emergency rooms for acute marijuana intoxication, according to a study in the July 2013 JAMA Pediatrics.  There ought to be tighter controls over shops, particularly those that sell marijuana-infused products like chocolates and cookies that entice children.  Many marijuana retailers "look like sweets shops," Curran says. 

NIDA is keeping tabs on ER visits as well as the increasing levels of THC in cannabis seized by law enforcement agencies, and how marijuana legalization has affected the health of people in Colorado and Washington State. 

Some researchers see the growing availability of marijuana as inevitable and are advocating ways to keep the drug out of the hands of young people. 

"Kids are growing up on a much more toxic form of marijuana than they would have done years ago," Curran says.  Today's plants are very high in THC and low in a compound thought to counter its effects called cannabidiol, or CBD.  THC levels in marijuana have increased from 3.4 percent in 1993 to 8.8 percent in 2008, according to a marijuana potency-monitoring project at the University of Mississippi.  A more regulated market might keep the most potent marijuana out of the hands of young people, Curran says. 

More accurate testing and labeling of marijuana products would help, many researchers believe.  THC concentrations can vary from seller to seller and even batch to batch.  "People need to know what they're getting," Franson says.  "It's just named these weird names." Purple Urkel, Girl Scout Cookies and Super Silver Sour Diesel Haze are some of the options available in stores.  Colorado is trying to improve labeling to describe important differences, which is particularly urgent for people who rely on certain doses of THC or CBD to treat medical conditions. 

When marijuana is eaten, THC takes longer to reach the bloodstream, and its absorption rates can vary greatly.  This imprecise delivery system can cause people to take much more than they intended.  Proper labeling might help people better titrate their dose, Franson says. 

Even Earleywine, who supports legalization, says he's concerned about commercialization of marijuana.  "America is so free market and wild that it's going to take some reining in to make sure that no one is penalized for it and medical users have access, but it's not sponsoring every sport event or on TV every five seconds," he says.  Current restrictions on cigarettes might be a good model for the burgeoning marijuana industry, he says. 

Imperfect science leaves people on both sides of the marijuana debate wanting more.  But in a way, the good-or-bad, yes-or-no argument is over: Marijuana is creeping across the country.  That's probably not catastrophic for adults, but for young people, the implications are more worrisome.  Just how worrisome is something scientists are still figuring out.  That knowledge may help ease the transition to an ever-greener world.