Research Deep Dive: Little-Known Health Effects Of Medical Marijuana

As marijuana use becomes ever more socially and legally acceptable in the developed world, researchers are scrambling to understand how the plant — more potent today than ever before — impacts our health. Marijuana is now legal in 28 U.S. states for medical use and in eight for recreation. But policy has far outpaced science, with almost every clinical study calling for further inquiry and many researchers complaining their work is stymied by federal regulations, which still treat cannabis as an illegal substance.

Judging by the available research, ample evidence exists to say that marijuana can treat pain, nausea and multiple sclerosis. It can harm lungs and the developing adolescent brain. Under certain circumstances, it can be addictive and increase the likelihood of auto accidents, low birth weight and, in cases of heavy use, schizophrenia.

The open questions about marijuana and its derivatives are far more numerous. How do benefits balance against side effects? How well can these substances treat seizures? How exactly do they affect the brain? How dangerous are the barely regulated chemicals used in processing weed for commercial use, like butane, pesticides and food additives? What other regulatory loopholes could lead to dangerous effects on consumers?

• Related Story: Medical Cannabis Research: Where It Is and Where It’s Going

Without more rigorous study, these questions will remain unanswered and new ones will crop up, leaving policymakers and citizens to argue based on piecemeal research and personal convictions instead of adequate empirical data.

What’s In It And How It’s Used 

Cannabis has dozens of chemical compounds unique to the plant, known as cannabinoids. The one most famous for the high it gives is tetrahydrocannabinol (THC). But another one, cannabidiol (CBD), is largely non-psychoactive and is often the focus of research on marijuana’s medicinal properties: It may lessen the frequency and intensity of seizures and may even improve cognitive function in adults. Medical marijuana is generally higher in CBD. Both THC and CBD are present in the cannabis plant as inactive acids. Heating — whether by smoking, vaporizing, baking, infusion or other methods — transforms them into active compounds.

What We Know

A January 2017 report by the National Academies of Sciences, Engineering, and Medicine reviews most of the known research published since 1999 about marijuana and its impacts on health, making for one of the most comprehensive reads available. “The Health Effects of Cannabis and Cannabinoids” draws almost 100 conclusions, arguing that enough evidence exists to declare that marijuana can be used to treat pain, chemotherapy-induced nausea, and multiple sclerosis.

The report finds substantial evidence that marijuana use may: worsen respiratory function and cause bronchitis (when smoked); increase the likelihood of car accidents; and cause heavy users to develop schizophrenia. It also shows that males who both smoke cigarettes and use marijuana are more likely to develop an addiction to weed than either females or those who don’t smoke cigarettes. Starting to use marijuana before age 16 also raises the risk of addiction. For expectant mothers, considerable evidence suggests that marijuana can negatively impact birthweight.

• Related Story: Landmark Study: Marijuana Is Indeed Effective Medicine

The report finds moderate evidence: that marijuana use impairs learning, memory and attention, especially in adolescents; that it may improve cognitive performance among some people with certain psychotic disorders; and that it does not worsen schizophrenia. (There is no evidence it can treat the disorder.)

No known association has been found with lung cancer and there is limited evidence that marijuana use increases the risk of heart attacks.

Why We Don’t Know More 

One problem in compiling the report, and in exploring the health effects of marijuana more generally, is a dearth of studies and funding for research because of federal regulations, said the lead author, Marie McCormick, during a March 2017 event at Harvard’s T.H. Chan School of Public Health.

For one thing, researchers complain about their limited legal access to real weed, the kind people outside of labs use: “It is often difficult for researchers to gain access to the quantity, quality, and type of cannabis product necessary to address specific research questions on the health effects of cannabis use,” the National Academies report declares.

The Drug Enforcement Agency (DEA) classifies marijuana as a Schedule I narcotic. By definition, that means, like heroin, it is highly prone to abuse and has no medical purpose — a rating that Scientific American has called “highly controversial and dubious.” So researchers cannot simply use what they might buy on a street corner or even at a pot shop in states where it is legal under local laws.

The plant clinical researchers do use comes from a farm at the University of Mississippi that the National Institute on Drug Abuse (NIDA) licenses to grow marijuana for research purposes. But scientists complain that what they receive is far less potent than marijuana consumed by the public and even looks like an entirely different plant. The result, The Washington Post declared in 2017, is “akin to investigating the effects of bourbon by giving people Bud Light.”

In August 2016, the DEA announced it would loosen control over the cultivation of government marijuana, though it remains unclear when the changes will go into effect.

Other difficulties studying the effects of marijuana relate to metrics. There is no standard definition of what constitutes frequent use, moderate use or low use, noted Staci Gruber of McLean Hospital at the Harvard event. Researchers have yet to look closely at the effects of marijuana use on those who smoke or eat it once or twice a month. Federal health surveys, moreover, do not ask detailed questions of users.

Kids And Pot

One question that has loomed large as more places have legalized marijuana use is, “How bad is it for children?”

Two recent studies observe that regular marijuana use is likely much worse for children before age 16 than it is for adults. A 2015 study in Developmental Cognitive Neuroscience found that kids who start using marijuana before age 16 may have lower cognitive function than people who start using later: “Given that the brain undergoes significant development during adolescence and emerging adulthood and that the frontal cortex is among the last of the brain regions to mature, it is perhaps not surprising that individuals with earlier exposure to [marijuana] have difficulty with tasks requiring frontal/executive function.” A 2014 study in Psychopharmacology also found a correlation between smoking marijuana and impulsive behavior, especially among those who begin regular use before they turn 16.

• Related Story: A Guide For Talking To Your Teens About Marijuana

Other research includes studies on addiction, IQ and the links between legalization and usage:

• One 2017 review in The Lancet notes that while about 1 in 11 people who use marijuana will develop a dependence, that number almost doubles among people who started as adolescents.
• A 2011 study of twins — where one uses pot and one does not — finds no evidence to associate the drug with a lower IQ, though it calls for more research.
• A 2016 study in Drug and Alcohol Dependence analyzes the design of medical marijuana laws and use by adolescents. Looking at 45 states, it finds slightly higher use of marijuana among teenagers in states where medical marijuana is legal (22.7 percent in the previous 30 days) compared to states where it is not (19.8 percent). But after adjusting for demographics and other factors, the authors discover a small decline in adolescent use in those states where medical marijuana is legal.
• Research in Washington and Colorado before and after recreational marijuana was legalized in both states in 2012 found perceptions of its harmfulness fell among youth in Washington but not in Colorado, where medical marijuana had already been well-established. Eighth- and 10^th-grade students in Washington increased their usage over the same period; youth marijuana consumption in Colorado did not appear to change, the authors report in JAMA Pediatrics.

The Canadian Pediatric Society in 2016 released a position statement recommending that Ottawa — where full recreational legalization is being considered — take a number of steps to keep marijuana out of the hands of anyone younger than 18 and regulate the amount of THC in legal marijuana products.

“Dang, That’s Strong!”

It’s not your parents’ grass anymore: The marijuana available today is many times more potent than it was in the days of “Reefer Madness” or Woodstock. In 2015, the American Chemical Society reported that THC content in some marijuana strains had roughly tripled in three decades.

One of the most potent products on the market is butane hash oil, sometimes known as marijuana wax. Used in increasingly popular “vape pens” and in the production of edibles, it is made by passing butane (a liver-damaging, explosive and all-around dangerous hydrocarbon gas) through marijuana buds to make a viscous liquid and then evaporating off some of the butane. It is illegal in many states. Not only is the production process dangerous, but smoking “wax made with butane leaves small molecules that adhere to the lungs and creates a black spot much like miners’ lung,” says a handout from the Department of Health and Human Services.

Medical Marijuana

With medical marijuana now available in more than half of U.S. states and a growing number of countries, the plant is being used to treat all sorts of ailments including pain and chemotherapy side-effects such as nausea, loss of appetite, and insomnia. Each of these uses is addressed (and generally endorsed) in the 2017 National Academies report.

A major area of study is the use of medical marijuana in treating epileptic seizures, discussed separately below. Other research has explored its effects on cognitive function, on the use of opiates and on the use of recreational marijuana:

• One 2016 study in Frontiers in Pharmacology finds signs that medical marijuana may help improve cognitive function in adults. The researchers suspect this is because some medical marijuana products contain higher amounts of CBD and other cannabinoids than does recreational marijuana, “which may mitigate the adverse effects of THC on cognitive performance.”
• Some scholars see a decline in the use and abuse of opiates by cannabis users, though the National Academies report uncovers no evidence to support or refute this finding.
• Writing in JAMA Internal Medicine in 2014, Marcus Bachhuber of the Philadelphia Veterans Affairs Medical Center and his colleagues find “medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates.” Patients seem to be using marijuana as an opioid substitute; marijuana is far less addictive and dangerous than drugs derived from the opium poppy. A 2016 study by Columbia University researchers confirms those findings and observes that states with medical-marijuana laws have fewer opioid-related car accidents.
• A 2015 study sees an association between medical marijuana and the lower use of addictive opioids as pain medication; it also reports fewer opioid-related deaths. At the same time, the paper finds a correlation between the availability of medical marijuana and higher rates of recreational marijuana use.

A 2017 study in Drug and Alcohol Dependence finds no indication that CBD, the “medical” cannabinoid, might be addictive.

Treating Epilepsy

A fast-growing body of research suggests that CBD — now sometimes called Charlotte’s Web after a CBD-based medicine that reportedly helped a severely ill child — might alleviate treatment-resistant seizures among epilepsy patients. In 2013 the Food and Drug Administration (FDA) allowed tests of Epidiolex, a CBD oil concentrate developed by GW Pharmaceuticals, which is not yet commercially available.

In 2016, the American Epilepsy Society (AES) called on the federal government to support further research into the use of marijuana to treat the neurological disorder. “Robust scientific evidence for the use of marijuana is limited. The lack of information does not mean that marijuana is ineffective for epilepsy. It merely means that we do not know if marijuana is a safe and effective treatment for epilepsy, which is why it should be studied using the well-founded research methods that all other effective treatments for epilepsy have undergone,” the AES statement says.

It also calls on the DEA to review its classification of marijuana as a Schedule I drug: “AES’s call for rescheduling is not an endorsement of the legalization of marijuana, but is a recognition that the current restrictions on the use of medical marijuana for research continue to stand in the way of scientifically rigorous research into the development of cannabinoid-based treatments.”

A 2016 study of CBD in Lancet Neurology finds a 36.5 percent decline in monthly seizures among 162 patients suffering severe, childhood-onset, treatment-resistant epilepsy. The trial was open, meaning patients knew what they were receiving, which is not a preferred way to do medical research; the authors call for randomized controlled trials. Besides the decline in seizures, they find side effects including fatigue, diarrhea, decreased appetite and convulsions.

A number of recent studies — such as this 2017 paper in Epilepsy Behavior and this 2014 paper in Epilepsia – summarize the research and anecdotal evidence that CBD can help control epileptic seizures. They both call for randomized, controlled research trials that are double-blind – i.e., where neither the patients nor the doctors know who is receiving the drug and who is receiving a placebo.

The National Academies report takes a dimmer view of the available clinical data, noting that it consists “solely of uncontrolled case series, which do not provide high-quality evidence of efficacy.” It acknowledges the need for more research into CBD’s potential effect on neurological disorders such as epilepsy and seizures, but concludes that “there is insufficient evidence to support or refute the conclusion that cannabinoids are an effective treatment for epilepsy.”

Regulations, Pesticides, Food Production

Some of the biggest holes in research concern the production of marijuana and its derivatives, including the use of pesticides and the preparation of edibles. Like other deficits in research they stem in part from the disconnect between federal and state laws on marijuana.

In agriculture, pesticides are usually regulated by federal bodies such as the Environmental Protection Agency and approved for specific crops after the pesticide manufacturer pays for testing that the EPA deems reliable. But because the EPA is a federal agency, it will not label a chemical safe for marijuana. So regulation is handled by individual states, which often lack the capacity to investigate problematic pesticides. State governments “have never been made to play the detective role in this,” Andrew Freedman, the former director of the Office of Marijuana Coordination for the state of Colorado, tells Journalist’s Resource.

States where marijuana is legal have been known to recall batches believed to have been exposed to unapproved pesticides such as the insecticides imidacloprid or pyrethrin. (Some states have websites with regulatory information, including California, Colorado and Washington.) Some researchers, meanwhile, express concern about lobbying by the chemical industry to weaken pesticide regulations. Very little has been published about the effects of marijuana pesticides on human health.

Another area in need of study is the production of edibles. The FDA has not approved any product containing CBD as a dietary supplement, but, at the time of writing, has not aggressively enforced federal laws that the FDA interprets to ban marijuana compounds in food.

Marijuana marketing is another topic worthy of greater scrutiny. A 2015 commentary in The New England Journal of Medicine sounds the alarm about the popularity of edible snacks containing THC that are “packaged to closely mimic popular candies and other sweets.” Citing the risk of consumption by children, the authors, two researchers at Stanford, call on the federal government and the courts to regulate the sale of edibles.

Other Resources

The number of American cannabis users is rising. According to an August 2016 Gallup Poll, 13 percent of Americans say they use the drug, up from 7 percent in 2007. Slightly older data from the National Survey on Drug Use and Health, published by the U.S. Department of Health and Human Services, say over 22 million Americans aged 12 or older have used marijuana in the past month. That is 8.4 percent of the population.

Journalist’s Resource has reviewed literature on how crime and drunk driving tend to fall after marijuana legalization. We also have looked at potential tax revenue from legal weed.

The National Institute on Drug Abuse regularly updates its fact sheet on marijuana.

This story originally appeared on the webpage for Journalist’s Resources, based at Harvard’s Shorenstein Center on Media, Politics and Public Policy.