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The Evidence—and Lack Thereof—About Cannabis

Research is still needed on cannabis’s risks and benefits. 

Lindsay Smith Rogers

Although the use and possession of cannabis is illegal under federal law, medicinal and recreational cannabis use has become increasingly widespread.

Thirty-eight states and Washington, D.C., have legalized medical cannabis, while 23 states and D.C. have legalized recreational use. Cannabis legalization has benefits, such as removing the product from the illegal market so it can be taxed and regulated, but science is still trying to catch up as social norms evolve and different products become available. 

In this Q&A, adapted from the August 25 episode of Public Health On Call , Lindsay Smith Rogers talks with Johannes Thrul, PhD, MS , associate professor of Mental Health , about cannabis as medicine, potential risks involved with its use, and what research is showing about its safety and efficacy. 

Do you think medicinal cannabis paved the way for legalization of recreational use?

The momentum has been clear for a few years now. California was the first to legalize it for medical reasons [in 1996]. Washington and Colorado were the first states to legalize recreational use back in 2012. You see one state after another changing their laws, and over time, you see a change in social norms. It's clear from the national surveys that people are becoming more and more in favor of cannabis legalization. That started with medical use, and has now continued into recreational use.

But there is a murky differentiation between medical and recreational cannabis. I think a lot of people are using cannabis to self-medicate. It's not like a medication you get prescribed for a very narrow symptom or a specific disease. Anyone with a medical cannabis prescription, or who meets the age limit for recreational cannabis, can purchase it. Then what they use it for is really all over the place—maybe because it makes them feel good, or because it helps them deal with certain symptoms, diseases, and disorders.

Does cannabis have viable medicinal uses?

The evidence is mixed at this point. There hasn’t been a lot of funding going into testing cannabis in a rigorous way. There is more evidence for certain indications than for others, like CBD for seizures—one of the first indications that cannabis was approved for. And THC has been used effectively for things like nausea and appetite for people with cancer.

There are other indications where the evidence is a lot more mixed. For example, pain—one of the main reasons that people report for using cannabis. When we talk to patients, they say cannabis improved their quality of life. In the big studies that have been done so far, there are some indications from animal models that cannabis might help [with pain]. When we look at human studies, it's very much a mixed bag. 

And, when we say cannabis, in a way it's a misnomer because cannabis is so many things. We have different cannabinoids and different concentrations of different cannabinoids. The main cannabinoids that are being studied are THC and CBD, but there are dozens of other minor cannabinoids and terpenes in cannabis products, all of varying concentrations. And then you also have a lot of different routes of administration available. You can smoke, vape, take edibles, use tinctures and topicals. When you think about the explosion of all of the different combinations of different products and different routes of administration, it tells you how complicated it gets to study this in a rigorous way. You almost need a randomized trial for every single one of those and then for every single indication.

What do we know about the risks of marijuana use?  

Cannabis use disorder is a legitimate disorder in the DSM. There are, unfortunately, a lot of people who develop a problematic use of cannabis. We know there are risks for mental health consequences. The evidence is probably the strongest that if you have a family history of psychosis or schizophrenia, using cannabis early in adolescence is not the best idea. We know cannabis can trigger psychotic symptoms and potentially longer lasting problems with psychosis and schizophrenia. 

It is hard to study, because you also don't know if people are medicating early negative symptoms of schizophrenia. They wouldn't necessarily have a diagnosis yet, but maybe cannabis helps them to deal with negative symptoms, and then they develop psychosis. There is also some evidence that there could be something going on with the impact of cannabis on the developing brain that could prime you to be at greater risk of using other substances later down the road, or finding the use of other substances more reinforcing. 

What benefits do you see to legalization?

When we look at the public health landscape and the effect of legislation, in this case legalization, one of the big benefits is taking cannabis out of the underground illegal market. Taking cannabis out of that particular space is a great idea. You're taking it out of the illegal market and giving it to legitimate businesses where there is going to be oversight and testing of products, so you know what you're getting. And these products undergo quality control and are labeled. Those labels so far are a bit variable, but at least we're getting there. If you're picking up cannabis at the street corner, you have no idea what's in it. 

And we know that drug laws in general have been used to criminalize communities of color and minorities. Legalizing cannabis [can help] reduce the overpolicing of these populations.

What big questions about cannabis would you most like to see answered?

We know there are certain, most-often-mentioned conditions that people are already using medical cannabis for: pain, insomnia, anxiety, and PTSD. We really need to improve the evidence base for those. I think clinical trials for different cannabis products for those conditions are warranted.

Another question is, now that the states are getting more tax revenue from cannabis sales, what are they doing with that money? If you look at tobacco legislation, for example, certain states have required that those funds get used for research on those particular issues. To me, that would be a very good use of the tax revenue that is now coming in. We know, for example, that there’s a lot more tax revenue now that Maryland has legalized recreational use. Maryland could really step up here and help provide some of that evidence.

Are there studies looking into the risks you mentioned?

Large national studies are done every year or every other year to collect data, so we already have a pretty good sense of the prevalence of cannabis use disorder. Obviously, we'll keep tracking that to see if those numbers increase, for example, in states that are legalizing. But, you wouldn't necessarily expect to see an uptick in cannabis use disorder a month after legalization. The evidence from states that have legalized it has not demonstrated that we might all of a sudden see an increase in psychosis or in cannabis use disorder. This happens slowly over time with a change in social norms and availability, and potentially also with a change in marketing. And, with increasing use of an addictive substance, you will see over time a potential increase in problematic use and then also an increase in use disorder.

If you're interested in seeing if cannabis is right for you, is this something you can talk to your doctor about?

I think your mileage may vary there with how much your doctor is comfortable and knows about it. It's still relatively fringe. That will very much depend on who you talk to. But I think as providers and professionals, everybody needs to learn more about this, because patients are going to ask no matter what.

Lindsay Smith Rogers, MA, is the producer of the Public Health On Call podcast , an editor for Expert Insights , and the director of content strategy for the Johns Hopkins Bloomberg School of Public Health.

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How does marijuana affect the brain? Psychological researchers examine impact on different age groups over time

New legislation is helping scientists and manufacturers study the effects of cannabis and develop guidelines for use

Vol. 54 No. 4 Print version: page 20

• Cognition and the Brain
• Substance Use, Abuse, and Addiction
• Neuropsychology

In 2021, more than 36 million people 12 and older reported using cannabis in the past month—double the number compared with a decade earlier, according to data from the Substance Abuse and Mental Health Services Administration’s National Survey of Drug Use and Health . Cannabis users have access to an unprecedented variety of purported antidotes for everything from anxiety to insomnia to posttraumatic stress disorder (PTSD)—claims that have yet to be validated by research. Among the popular offerings are cannabis concentrates with extremely high levels of tetrahydrocannabinol (THC), the main psychoactive compound in cannabis that produces the euphoric “high” sensation.

“Science is having a hard time keeping up with the enormous increase in products available, especially because researchers have been hamstrung by regulatory hurdles,” said Columbia University’s Margaret Haney, PhD, a professor of neurobiology and director of the school’s Cannabis Research Laboratory. Those hurdles include marijuana’s classification as a Schedule I substance, which requires researchers to earn approval from multiple federal agencies for studies.

APA has been advocating for reforms in cannabis research regulations to ensure that science is available to inform product policies, clinical decisions for therapeutic use, and public understanding about the health effects across the life span. In December 2022, President Joe Biden signed into law the Medical Marijuana and Cannabidiol Research Expansion Act—legislation that will make it easier for scientists and manufacturers to study the effects of marijuana and develop guidelines for use. For decades, the University of Mississippi was the only federally approved cultivator of cannabis for scientists, but the new law will allow other entities to manufacture and distribute the drug for research.

Although the legislation does not allow scientists to buy and study products available in dispensaries, psychologists hope that the new policy is a harbinger of increasing federal support for gathering more science-based data to educate the public and health care providers. The latest findings are shedding light on how biological brain differences may influence cognitive effects in adolescent users, how cannabis can interfere with pharmaceutical medications for depression and other mental health issues, and the potential mental benefits for older adults. “For many years, cannabis was demonized, but now we’ve swung to the other extreme because it’s advertised as the cure for everything,” said Haney. “We need data to inform honest discussions about the risk of drug abuse, the therapeutic potential, and the impact on different age groups over time.”

The adolescent user

One of the top priorities among cannabis researchers is clarifying how the drug—which has been legalized for recreational use in 21 states and for medical use in 37 states—affects the developing brain. “I’m concerned by the increase in the number of people who are using cannabis at higher doses on a daily basis,” said Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA). “Adolescents are more vulnerable to addiction, and once they are using compulsively, cannabis can interfere with memory and learning.” In one study, 15% of people of all ages who used cannabis in the past 30 days met the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for cannabis use disorder, and rates specifically among youth ages 12 to 20 were significantly higher at 23% ( Richter, L., et al., The American Journal of Drug and Alcohol Abuse , Vol. 43, No. 3, 2017 ).

To investigate the effects of cannabis use on adolescents, Joanna Jacobus, PhD, an associate professor of psychiatry at the University of California San Diego (UCSD), launched longitudinal studies that followed teenagers who had started using and compared them with nonusing controls. Adolescents who continued using for 3 years at least 2 times per week had thicker cerebral cortices, particularly in the frontal and parietal regions than controls ( Developmental Cognitive Neuroscience , Vol. 16, 2015 ). The cannabis users performed more poorly on cognitive tests, especially in attention and memory tasks, and teenagers who started using earlier in life performed more poorly than those who started using later or nonusers ( Neuropsychology , Vol. 29, No. 6, 2015 ).

More recently, Jacobus began collecting data on youth before they started using cannabis to understand if the drug caused the poorer neural health outcomes, or if there were preexisting biological brain differences that were also influencing cognitive outcomes. A 6-year study showed preexisting differences in gray matter and functional brain activation that could be contributing to poorer cognitive performance in adolescent cannabis users. “We found that there are biological brain differences that can increase the chances that an adolescent will start using cannabis, and these differences may also increase their vulnerability to negative developmental outcomes,” said Jacobus.

Jacobus is optimistic that there will be more data soon about which youth are at higher risk of initiating cannabis use as researchers follow more than 11,000 youth enrolled in the NIH’s ABCD Study, the largest long-term study of brain development and child health in the United States. The study began in 2015 when children were 9 or 10, and Jacobus and her colleagues are collecting data on 700 participants from San Diego County with tools such as MRI imaging, cognitive and genetic marker testing, and questionnaires about family environment, school activities, and more.

Like Jacobus, Jonathan Schaefer, PhD, a researcher in the psychology department at the University of Minnesota, was eager to explore the cause of emotional and cognitive problems among adolescents who used cannabis. He tapped into data collected from more than 3,000 twins who had been followed from adolescence into their early 30s. By comparing identical twins who shared genetics and a home environment, he could better separate the effects of cannabis use on negative outcomes from the effects of these background factors.

He did not find evidence that cannabis caused more mental health problems or decreased cognitive ability, but the drug was linked to lower educational attainment, occupational status, and income ( PNAS , Vol. 118, No. 14, 2021 ). In a subsequent exploratory analysis, the data revealed that in identical twins, the twins who used more cannabis than their cotwins also had lower GPAs and academic motivation. “Our findings provide evidence against the idea that cannabis has dramatic, long-lasting effects on the brain,” Schaefer said. “Instead, they raise the possibility that we should be more concerned about acute, shorter-term drug effects that have lingering consequences.” For example, students who are using cannabis regularly may have trouble focusing and feeling motivated during school, which might ultimately affect their educational and career trajectory. Schaefer cautions that even if cannabis does not cause permanent, deleterious changes in the brain, it is still risky for adolescents to use because it may negatively impact other important longer-term life outcomes, such as educational attainment, risk of developing a cannabis use disorder, and lung health. These findings were also based on twins who were using in the 1990s and early 2000s, so the results do not account for the effects of newer, high-potency products, Schaefer said.

Data collected from more than 1,000 New Zealanders over 4 decades has also given researchers a glimpse into how frequent, long-term cannabis use—often starting in the teen years—affects the aging process. The study participants were followed from birth to age 45, and the long-term users were less financially prepared for aging, with lower credit scores and less money in savings and investments. They also reported more social problems, such as loneliness, lower life satisfaction, and less social support ( The Lancet: Healthy Longevity , Vol. 3, No. 10, 2022 ).

“Social support and financial preparedness in midlife are related to better aging and longer lives,” said Madeline Meier, PhD, an associate professor of psychology at Arizona State University and author of the study. “People may not realize that if they become dependent on cannabis, there could be consequences for healthy aging and well-being.” The researchers investigated whether factors in childhood—like IQ, low self-control, or socioeconomic status—could explain the outcomes, but they did not find evidence for this in the study. Long-term cannabis users frequently developed dependence on other substances, such as alcohol and tobacco, and the polysubstance use could also be contributing to at least some of the financial and social problems in midlife, Meier said.

Mixing marijuana with mental health issues

Psychologists also share a sense of urgency to clarify how cannabis affects people who suffer from preexisting mental health conditions. Many veterans who suffer from PTSD view cannabis as a safe alternative to other drugs to alleviate their symptoms ( Wilkinson, S. T., et al., Psychiatric Quarterly , Vol. 87. No. 1, 2016 ). To investigate whether marijuana does in fact provide relief for PTSD symptoms, Jane Metrik, PhD, a professor of behavioral and social sciences at the Brown University School of Public Health and a core faculty member at the university’s Center for Alcohol and Addiction Studies, and colleagues followed more than 350 veterans for a year. They found that more frequent cannabis use worsened trauma-related intrusion symptoms—such as upsetting memories and nightmares—over time ( Psychological Medicine , Vol. 52, No. 3, 2022 ). A PTSD diagnosis was also strongly linked with cannabis use disorder a year later. “Cannabis may give temporary relief from PTSD because there is a numbing feeling, but this fades and then people want to use again,” Metrik said. “Cannabis seems to worsen PTSD and lead to greater dependence on the drug.”

Metrik, who also works as a psychologist at the Providence VA Medical Center, has also been studying the effects of using cannabis and alcohol at the same time. “We need to understand whether cannabis can act as a substitute for alcohol or if it leads to heavier drinking,” she said. “What should we tell patients who are in treatment for problem drinking but are unwilling to stop using cannabis? Is some mild cannabis use OK? What types of cannabis formulations are helpful or harmful for people who have alcohol use disorder?”

Though there are still many unanswered questions, Metrik has seen cases that suggest adding cannabis to heavy drinking behavior is risky. Sometimes people can successfully quit drinking but are unable to stop using cannabis, which can also intensify depression and lead to cannabis hyperemesis syndrome—repeated and severe bouts of vomiting that can occur in heavy cannabis users, she said. Cannabis withdrawal symptoms such as irritability, anxiety, increased cravings, aggression, and restlessness usually subside after 1 to 2 weeks of abstinence, but insomnia tends to persist longer than the other symptoms, she said.

Cannabis may also interfere with pharmaceutical medications patients are taking to treat mental health issues. Cannabidiol (CBD) can inhibit the liver enzymes that metabolize medications such as antidepressants and antipsychotics, said Ryan Vandrey, PhD, a professor of psychiatry and behavioral sciences at Johns Hopkins University and president of APA’s Division 28 (Society for Psychopharmacology and Substance Use). “This could lead to side effects because the medication is in the body longer and at higher concentrations,” he said. In a recent study, he found that a high dose of oral CBD also inhibited the metabolism of THC, so the impairment and the subjective “high” was significantly stronger and lasted for a longer time ( JAMA Network Open , Vol. 6, No. 2, 2023 ). This contradicts the common conception that high levels of CBD reduce the effects of THC, he said. “This interaction could lead to more adverse events, such as people feeling sedated, dizzy, [or] nervous, or experiencing low blood pressure for longer periods of time,” Vandrey said.

The interactions between CBD, THC, and pharmaceutical medications also depend on the dosing and the route of administration (oral, topical, or inhalation). Vandrey is advocating for more accurate labeling to inform the public about the health risks and benefits of different products. “Cannabis is the only drug approved for therapeutic use through legislative measures rather than clinical trials,” he said. “It’s really challenging for patients and medical providers to know what dose and frequency will be effective for a specific condition.”

Keeping an open mind

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March 1, 2024

Is Marijuana Bad for Health? Here’s What We Know So Far

Marijuana’s health impacts—good and bad—are coming into focus

By Jesse Greenspan

Cappi Thompson/Getty Images

With decades of legal and social opprobrium fading fast, marijuana has become an extremely popular commercial product with more than 48 million users across the U.S. Health concerns, once exaggerated, now often seem to be downplayed or overlooked. For example, pregnant patients “often tell me they had no idea there's any risk,” says University of Utah obstetrician Torri Metz, lead author of a recent paper in the Journal of the American Medical Association on cannabis and adverse pregnancy outcomes.

Fortunately, legal reforms are also gradually making it easier to study marijuana's health effects by giving U.S. scientists more access to the drug and a wider population of users to study. Although much research remains in “early stages,” the number of studies has finally been increasing, says Tiffany Sanchez, an environmental health scientist at Columbia University. As new results accumulate, they offer a long-overdue update on what science really knows about the drug.

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In addition to minor side effects that many users joke about—such as short-term memory loss—recent studies have linked marijuana to adverse health outcomes involving the lungs, heart, brain and gonads. For example, heavy marijuana consumption seems to increase the risk of clogged arteries and heart failure , and it may impact male fertility . Smoking weed likewise can lead to chronic bronchitis and other respiratory ailments (although, unlike tobacco, it hasn't been definitively tied to lung cancer). And cannabis plants hyperaccumulate metal pollutants, such as lead, which Sanchez found can enter users' bloodstreams .

Developing adolescent brains, particularly those predisposed to mental illness, may be most at risk from overconsumption. Although psychiatric effects are hotly debated , studies suggest that heavy weed use exacerbates—or may trigger— schizophrenia , psychosis and depression in youths and that it affects behavior and academic performance. “From a safety viewpoint, young people should definitely stay away from it,” says University of Ottawa psychiatrist Marco Solmi, lead author of a recent review of cannabis and health in the British Medical Journal .

24 states have legalized recreational marijuana, with 38 allowing medical use

Moreover, the drug can cross over to fetuses during pregnancy. Several studies have linked it to low birth weights , and researchers suspect it raises the likelihood of neonatal intensive care unit admissions and stillbirths . Some cannabis dispensaries have advertised their products as a cure for morning sickness, but Metz emphasizes that safer alternatives exist.

Of course, many adults use marijuana responsibly for pleasure and relaxation. Unlike with, say, opioids, there's effectively zero risk of life-threatening overdose. Plus, “people get addicted with tobacco way faster,” says Columbia University epidemiologist Silvia Martins, who studies substance use and related laws.

Cannabis, and its derivatives, also may help alleviate pain—although some researchers contend that it performs little better than a placebo . It may also decrease chemotherapy-induced nausea, calm epileptic seizures , ease the symptoms of multiple sclerosis and serve as a sleep aid .

Recent studies have hinted that the drug might slightly reduce opioid dependency rates, although this, too, is disputed . There's some evidence that weed users tend to be more empathetic , and researchers found that elderly mice get a mental boost from the drug. Still, experts caution against self-medicating: “You should ask your doctor,” Solmi says.

Some of the recent research into marijuana is more lighthearted. One study, for instance, found that, just like people, nematode worms dosed with cannabis get the munchies .

THREE ESSAYS ON THE EFFECT OF LEGALIZING MARIJUANA ON HEALTH, EDUCATION, AND SOCIAL SECURITY

The legalization of marijuana has emerged as a critical public policy issue, with far-reaching implications for health, education, and government programs at both the state and federal levels. The three essays of this dissertation show that medical marijuana legalization (MML) has a negative effect in each of these areas. The first essay shows, that the enactment of MMLs can exacerbate the crisis of overdose deaths in the United States. The study analyzes three key areas: the rate of overdose deaths caused by both legal and illegal drugs, the impact of MML on social norms regarding the perceived harm of marijuana, and an investigation into the gateway theory by examining the use of other addictive drugs. I find that MMLs increase deaths attributed to overdose by 21.5% population. MMLs s also indicate increase the number of deaths due to prescribed opioids by 44.6%, and deaths from all opioids (heroin and cocaine in addition to prescribed opioids) by 37.2 % Results suggest an overall increase in the use of marijuana, primarily due to lower perceived risk among adolescents. Additionally, results show an increase in hospital admissions due to substance abuse. The analysis suggests that legalizing medical marijuana may exaggerate the current problem of drug overdose in the United States. The second essay examines the impact of improved access to medical marijuana, measured by the proximity of schools to the nearest dispensary, on the academic performance of high school students in California. Students in schools farther from a marijuana dispensary have higher academic performance as measured through AP, ACT, SAT scores, and average GPA, and lower number of suspensions due to violence and illicit drug use. To show this, I construct the first geocoded dataset on marijuana dispensary and high school locations, use newly developed difference-in-differences estimators that rule out any bias due to heterogeneous treatment effects over time, and explore dynamic responses. This essay reveals the importance of ensuring a largest possible distance between schools and dispensaries to protect adolescents from the potential harm caused by medical marijuana. Finally, the third essay shows that in the long term, MMLs increase the number of disabled workers who receive Social Security Disability Income (SSDI) because of mental health issues. SSDI is a major social insurance program that provides benefits to workers who become disabled, and understanding how policy changes in other areas may impact this program is important. In this study, there were important differences between the results of a two-way fixed effects model and a new model by Callaway and Santa’Anna. MMLs, in theory, could either increase or decrease the number of SSDI recipients, and traditional fixed effects models suggest both could be at play; however, only the negative effect is robust to correction for heterogeneous effects. This highlights the need for future research to understand the true impact of medical marijuana legalization

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The benefits and harms of marijuana, explained by the most thorough research review yet

A new report looks at more than 10,000 studies on marijuana. It has good and bad news for pot users.

by German Lopez

Marijuana has been with humans in some way or another for thousands of years. But after all this time, there is still a lot of public debate about what, exactly, pot’s risks and benefits are.

A recent review of the research from the National Academies of Sciences, Engineering, and Medicine attempts to fill the gap in our knowledge. By combing through more than 10,000 studies published since 1999, the review, conducted by more than a dozen experts, provides the clearest look at the scientific evidence on marijuana yet.

The research finds both some strong benefits and major downsides to cannabis. It seems to be promising for chronic pain, multiple sclerosis, and cancer patients. But it also seems to pose a significant risk for respiratory problems if smoked, schizophrenia and psychosis, car crashes, lagging social achievement in life, and perhaps pregnancy-related problems.

• How Obama quietly reshaped America’s war on drugs

The findings aren’t just for marijuana; they’re for marijuana or cannabinoids, chemical compounds commonly found in pot. It’s possible that, down the line, some of the benefits in particular will be split from the marijuana leaf itself — although many drug experts believe that there’s an “entourage effect” with marijuana in which all of its cannabinoids and chemicals, which number in the hundreds , work together to make its effects as potent as possible.

One major caveat to this: The report is, by its own admission, only a best guess for a lot of its findings, because much of the research out there just isn’t very good. The report pins the lack of good research largely on government policies — particularly regulatory barriers linked to marijuana’s federal classification as a highly restricted Schedule 1 substance — that make it hard to conduct good studies on the drug. The National Academies ultimately calls for these barriers to be cut down and more research to be funded so we can get a better idea of what pot is capable of, especially as more states legalize it for both medical and recreational uses.

Still, the report is the best look at marijuana yet. It is nearly 400 pages; if you want a really deep dive into the benefits and harms of marijuana, you should read it in full . But here I’ve provided a summary of what the researchers found.

What are marijuana’s benefits?

Since the mid-1990s, 28 states have legalized marijuana for medical uses. But in all that time, the benefits of pot have remained hazy. Despite some research showing that it can be good for pain and muscle stiffness, many of the claims about what pot can do for other ailments — such as epilepsy and irritable bowel syndrome — are based on anecdotal evidence and have yet to be scientifically proven.

The report can’t fully validate or invalidate all of the claims about marijuana’s medical benefits, given that there are still no studies on some of these questions, and many of the studies that are out there are bad or lacking. But it does have some solid findings.

For one, the review confirms what previous studies have found: There is “substantial evidence” that marijuana is good for treating chronic pain. This is one of the most common reasons cited for marijuana’s medical use — particularly in light of the opioid painkiller epidemic , which has spawned in part as patients turn to opioids to try to treat debilitating pain. The report concludes that marijuana can treat chronic pain. And that may allow it to substitute more dangerous, deadlier opioid painkillers.

The report also found “conclusive evidence” that marijuana is effective for treating chemotherapy-induced nausea and vomiting. Coupled with the findings on pain, this suggests that marijuana really is a potent treatment for cancer patients in particular, who can suffer from debilitating pain and severe nausea as a result of their illness.

• One way to fight the opioid epidemic? Medical marijuana.

And the report found “substantial evidence” that marijuana can improve patient-reported multiple sclerosis spasticity symptoms. But it only found “limited evidence” for marijuana improving doctor-reported symptoms of this kind.

Beyond the strongest findings, the report found “moderate evidence” that marijuana is effective for “improving short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis.” It also found “limited evidence” for marijuana’s ability to treat appetite and weight loss associated with HIV/AIDS, improving Tourette syndrome symptoms, improving anxiety symptoms in individuals with social anxiety disorders, and improving PTSD. And there’s “limited evidence” of a correlation between marijuana and better outcomes after a traumatic brain injury.

The report also disproved — or at least cast a lot of doubt — on some of the claimed benefits of pot. It found “limited evidence” that marijuana is ineffective for treating symptoms associated with dementia and glaucoma, as well as depressive symptoms in individuals with chronic pain or multiple sclerosis.

And it found “no or insufficient evidence” for marijuana as a treatment for cancers, cancer-associated anorexia, irritable bowel syndrome, epilepsy, spasticity in patients with paralysis due to spinal cord injury, amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, dystonia, drug addiction, and schizophrenia. This doesn’t mean that marijuana can’t treat any of these — some patients, who are prescribed pot for these ailments today, will swear that marijuana helped treat their epilepsy, for example — but that there’s just not enough evidence so far to evaluate the claims.

Overall, the report suggests that, as far as therapeutic benefits go, marijuana is a solid treatment for multiple symptoms associated to chronic pain, chemotherapy-induced nausea and vomiting, and multiple sclerosis. Everything else, from epilepsy to HIV/AIDS, needs more research before pot is more definitively shown to be effective or ineffective.

What are marijuana’s harms?

Marijuana is often described as one of the safest drugs out there, in part because it’s never been definitively linked to an overdose death and it’s broadly safer than other drugs like alcohol, tobacco, cocaine, and heroin. And while the National Academies’ report doesn’t find evidence of a marijuana overdose death, it does add a few wrinkles to the narrative of marijuana as a safe drug.

For one, the report finds “substantial evidence” of marijuana’s negative effects for a few conditions. For long-term marijuana smokers, there’s a risk of worse respiratory symptoms and more frequent chronic bronchitis episodes. For pregnant women who smoke pot, there’s a risk of lower birth weight for the baby. For marijuana users in general, there’s a greater risk of developing schizophrenia and other psychoses. And there’s a link between marijuana use and increased risk of car crashes.

The report also found “limited evidence” of links between marijuana use and several other negative outcomes, including an increased risk of testicular cancer, triggering a heart attack, chronic obstructive pulmonary disease, and pregnancy complications. And it found “moderate” to “limited” evidence that marijuana use might worsen symptoms or risk for some mental health issues, including depressive disorders, bipolar disorder, suicidal ideation and suicide attempts among heavier users, and anxiety disorders, particularly social anxiety disorder among regular users.

Besides medical conditions, the report found evidence for some psychosocial problems. There’s “moderate evidence” that acute marijuana use impairs learning, memory, and attention. There’s “limited evidence” of marijuana use and worse outcomes in education, employment, income, and social functioning.

• America can end its war on drugs. Here's how.

There was some good news: The report found “moderate evidence” of no link between marijuana smoking and lung cancer or marijuana use and head and neck cancers, which are commonly linked to tobacco. There was also “moderate evidence” of better cognitive performance among individuals with psychotic disorders and a history of marijuana use.

The report, however, couldn’t find sufficient evidence for pot’s links to a lot of problems: other types of cancer, an increased chronic risk of heart attack, asthma, later outcomes for infants born of mothers that used marijuana during pregnancy, deadly pot overdoses, and PTSD.

With the problems specifically linked to smoking marijuana, it’s worth noting that other forms of consumption — vaping and edibles in particular — may not carry the same risk. More research will be needed to evaluate that, particularly for vaping.

The report also found some “substantial evidence” that more pot use can lead to problematic marijuana use — what one typically thinks of as excessive use or even dependence. It also outlined, with “limited” to “substantial” evidence, some of the risk factors for problematic marijuana use, including being male, smoking cigarettes, a major depressive order, exposure to combined use of other drugs, and use at an earlier age. But it also cited “limited” to “moderate” evidence to rule out a few risk factors, including anxiety, personality, and bipolar disorders, adolescent ADHD, and alcohol or nicotine dependence.

It also found a “limited” to “moderate” evidence of a correlation between marijuana use and use of other illicit drugs. This is the typical evidence cited for the so-called “gateway” effect: that marijuana use may lead to the use of harder drugs.

One caveat to much of the research: correlation is not always causation. For example, in the case of the “gateway” effect, other researchers argue that the correlation between pot and harder drug use may just indicate that people prone to all sorts of drug use only start with marijuana because it’s the cheapest and most accessible of the illicit drugs. If cocaine or heroin were cheaper and more accessible, there’s a good chance people would start with those drugs first.

Still, the bottom line is that marijuana does pose some harms — particularly for people at risk of developing mental health disorders, pregnant women, those vulnerable to respiratory problems, and anyone getting into a car. And while some of these harms may be overcome by marijuana’s benefits or curtailed by consuming pot without smoking it, the evidence shows that weed’s reputation as a safe drug is undeserved.

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The Public Health Effects of Legalizing Marijuana

Thirty-six states have legalized medical marijuana and 14 states have legalized the use of marijuana for recreational purposes. In this paper, we review the literature on the public health consequences of legalizing marijuana, focusing on studies that have appeared in economics journals as well as leading public policy, public health, and medical journals. Among the outcomes considered are: youth marijuana use, alcohol consumption, the abuse of prescription opioids, traffic fatalities, and crime. For some of these outcomes, there is a near consensus in the literature regarding the effects of medical marijuana laws (MMLs). As an example, leveraging geographic and temporal variation in MMLs, researchers have produced little credible evidence to suggest that legalization promotes marijuana use among teenagers. Likewise, there is convincing evidence that young adults consume less alcohol when medical marijuana is legalized. For other public health outcomes such as mortality involving prescription opioids, the effect of legalizing medical marijuana has proven more difficult to gauge and, as a consequence, we are less comfortable drawing firm conclusions. Finally, it is not yet clear how legalizing marijuana for recreational purposes will affect these and other important public health outcomes. We will be able to draw stronger conclusions when more post-treatment data are collected in states that have recently legalized recreational marijuana.

The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research.

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Published Versions

D. Mark Anderson & Daniel I. Rees, 2023. " The Public Health Effects of Legalizing Marijuana, " Journal of Economic Literature, vol 61(1), pages 86-143.

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Cannabis (Marijuana) DrugFacts

What is marijuana.

Marijuana refers to the dried leaves, flowers, stems, and seeds from the Cannabis sativa or Cannabis indica plant. The plant contains the mind-altering chemical THC and other similar compounds. Extracts can also be made from the cannabis plant (see " Marijuana Extracts ").

According to the National Survey on Drug Use and Health , cannabis (marijuana) is one of the most used drugs in the United States, and its use is widespread among young people. In 2021, 35.4% of young adults aged 18 to 25 (11.8 million people) reported using marijuana in the past year. 1 According to the Monitoring the Future survey , rates of past year marijuana use among middle and high school students have remained relatively steady since the late 1990s. In 2022, 30.7% of 12th graders reported using marijuana in the past year and 6.3% reported using marijuana daily. In addition, many young people also use vaping devices to consume cannabis products. In 2022, nearly 20.6% of 12th graders reported that they vaped marijuana in the past year and 2.1% reported that they did so daily. 2

Legalization of marijuana for medical use or adult recreational use in a growing number of states may affect these views. Read more about marijuana as medicine in our DrugFacts: Marijuana as Medicine .

How do people use marijuana?

People smoke marijuana in hand-rolled cigarettes (joints) or in pipes or water pipes (bongs). They also smoke it in blunts—emptied cigars that have been partly or completely refilled with marijuana. To avoid inhaling smoke, some people are using vaporizers. These devices pull the active ingredients (including THC) from the marijuana and collect their vapor in a storage unit. A person then inhales the vapor, not the smoke. Some vaporizers use a liquid marijuana extract.

People can mix marijuana in food ( edibles ), such as brownies, cookies, or candy, or brew it as a tea. A newly popular method of use is smoking or eating different forms of THC-rich resins (see " Marijuana Extracts ").

Marijuana Extracts

Smoking THC-rich resins extracted from the marijuana plant is on the rise. People call this practice dabbing . These extracts come in various forms, such as:

• hash oil or honey oil —a gooey liquid
• wax or budder —a soft solid with a texture like lip balm
• shatter —a hard, amber-colored solid

These extracts can deliver extremely large amounts of THC to the body, and their use has sent some people to the emergency room. Another danger is in preparing these extracts, which usually involves butane (lighter fluid). A number of people have caused fires and explosions and have been seriously burned from using butane to make extracts at home. 3,4

How does marijuana affect the brain?

Marijuana has both short-and long-term effects on the brain.

Short-Term Effects

When a person smokes marijuana, THC quickly passes from the lungs into the bloodstream. The blood carries the chemical to the brain and other organs throughout the body. The body absorbs THC more slowly when the person eats or drinks it. In that case, they generally feel the effects after 30 minutes to 1 hour.

THC acts on specific brain cell receptors that ordinarily react to natural THC-like chemicals. These natural chemicals play a role in normal brain development and function.

Marijuana over activates parts of the brain that contain the highest number of these receptors. This causes the "high" that people feel. Other effects include:

• altered senses (for example, seeing brighter colors)
• altered sense of time
• changes in mood
• impaired body movement
• difficulty with thinking and problem-solving
• impaired memory
• hallucinations (when taken in high doses)
• delusions (when taken in high doses)
• psychosis (risk is highest with regular use of high potency marijuana)

Long-Term Effects

Marijuana also affects brain development. When people begin using marijuana as teenagers, the drug may impair thinking, memory, and learning functions and affect how the brain builds connections between the areas necessary for these functions. Researchers are still studying how long marijuana's effects last and whether some changes may be permanent.

For example, a study from New Zealand conducted in part by researchers at Duke University showed that people who started smoking marijuana heavily in their teens and had an ongoing marijuana use disorder lost an average of 8 IQ points between ages 13 and 38. The lost mental abilities didn't fully return in those who quit marijuana as adults. Those who started smoking marijuana as adults didn't show notable IQ declines. 5

In another recent study on twins, those who used marijuana showed a significant decline in general knowledge and in verbal ability (equivalent to 4 IQ points) between the preteen years and early adulthood, but no predictable difference was found between twins when one used marijuana and the other didn't. This suggests that the IQ decline in marijuana users may be caused by something other than marijuana, such as shared familial factors (e.g., genetics, family environment). 6 NIDA’s Adolescent Brain Cognitive Development (ABCD) study, a major longitudinal study, is tracking a large sample of young Americans from late childhood to early adulthood to help clarify how and to what extent marijuana and other substances, alone and in combination, affect adolescent brain development. Read more about the ABCD study on our Longitudinal Study of Adolescent Brain and Cognitive Development (ABCD Study) webpage.

A Rise in Marijuana’s THC Levels

The amount of THC in marijuana has been increasing steadily over the past few decades. 7 For a person who's new to marijuana use, this may mean exposure to higher THC levels with a greater chance of a harmful reaction. Higher THC levels may explain the rise in emergency room visits involving marijuana use.

The popularity of edibles also increases the chance of harmful reactions. Edibles take longer to digest and produce a high. Therefore, people may consume more to feel the effects faster, leading to dangerous results.

Higher THC levels may also mean a greater risk for addiction if people are regularly exposing themselves to high doses.

What are the other health effects of marijuana?

Marijuana use may have a wide range of effects, both physical and mental.

Physical Effects

• Breathing problems. Marijuana smoke irritates the lungs, and people who smoke marijuana frequently can have the same breathing problems as those who smoke tobacco. These problems include daily cough and phlegm, more frequent lung illness, and a higher risk of lung infections. Researchers so far haven't found a higher risk for lung cancer in people who smoke marijuana. 8
• Increased heart rate. Marijuana raises heart rate for up to 3 hours after smoking. This effect may increase the chance of heart attack. Older people and those with heart problems may be at higher risk.
• Problems with child development during and after pregnancy. One study found that about 20% of pregnant women 24-years-old and younger screened positive for marijuana. However, this study also found that women were about twice as likely to screen positive for marijuana use via a drug test than they state in self-reported measures. 9 This suggests that self-reported rates of marijuana use in pregnant females is not an accurate measure of marijuana use and may be underreporting their use. Additionally, in one study of dispensaries, nonmedical personnel at marijuana dispensaries were recommending marijuana to pregnant women for nausea, but medical experts warn against it. This concerns medical experts because marijuana use during pregnancy is linked to lower birth weight 10 and increased risk of both brain and behavioral problems in babies. If a pregnant woman uses marijuana, the drug may affect certain developing parts of the fetus's brain. Children exposed to marijuana in the womb have an increased risk of problems with attention, 11 memory, and problem-solving compared to unexposed children. 12 Some research also suggests that moderate amounts of THC are excreted into the breast milk of nursing mothers. 13 With regular use, THC can reach amounts in breast milk that could affect the baby's developing brain. Other recent research suggests an increased risk of preterm births. 27 More research is needed. Read our Marijuana Research Report for more information about marijuana and pregnancy.
• Intense nausea and vomiting. Regular, long-term marijuana use can lead to some people to develop Cannabinoid Hyperemesis Syndrome. This causes users to experience regular cycles of severe nausea, vomiting, and dehydration, sometimes requiring emergency medical attention. 14

Reports of Deaths Related to Vaping

The Food and Drug Administration has alerted the public to hundreds of reports of serious lung illnesses associated with vaping, including several deaths. They are working with the Centers for Disease Control and Prevention (CDC) to investigate the cause of these illnesses. Many of the suspect products tested by the states or federal health officials have been identified as vaping products containing THC, the main psychotropic ingredient in marijuana. Some of the patients reported a mixture of THC and nicotine; and some reported vaping nicotine alone. No one substance has been identified in all of the samples tested, and it is unclear if the illnesses are related to one single compound. Until more details are known, FDA officials have warned people not to use any vaping products bought on the street, and they warn against modifying any products purchased in stores. They are also asking people and health professionals to report any adverse effects. The CDC has posted an information page for consumers.

Mental Effects

Long-term marijuana use has been linked to mental illness in some people, such as:

• temporary hallucinations
• temporary paranoia
• worsening symptoms in patients with schizophrenia —a severe mental disorder with symptoms such as hallucinations, paranoia, and disorganized thinking

Marijuana use has also been linked to other mental health problems, such as depression, anxiety, and suicidal thoughts among teens. However, study findings have been mixed.

Are there effects of inhaling secondhand marijuana smoke?

Failing a drug test.

While it's possible to fail a drug test after inhaling secondhand marijuana smoke, it's unlikely. Studies show that very little THC is released in the air when a person exhales. Research findings suggest that, unless people are in an enclosed room, breathing in lots of smoke for hours at close range, they aren't likely to fail a drug test. 15,16 Even if some THC was found in the blood, it wouldn't be enough to fail a test.

Getting High from Passive Exposure?

Similarly, it's unlikely that secondhand marijuana smoke would give nonsmoking people in a confined space a high from passive exposure. Studies have shown that people who don't use marijuana report only mild effects of the drug from a nearby smoker, under extreme conditions (breathing in lots of marijuana smoke for hours in an enclosed room). 17

Other Health Effects?

More research is needed to know if secondhand marijuana smoke has similar health risks as secondhand tobacco smoke. A recent study on rats suggests that secondhand marijuana smoke can do as much damage to the heart and blood vessels as secondhand tobacco smoke. 20 But researchers haven't fully explored the effect of secondhand marijuana smoke on humans. What they do know is that the toxins and tar found in marijuana smoke could affect vulnerable people, such as children or people with asthma.

How Does Marijuana Affect a Person's Life?

Compared to those who don't use marijuana, those who frequently use large amounts report the following:

• lower life satisfaction
• poorer mental health
• poorer physical health
• more relationship problems

People also report less academic and career success. For example, marijuana use is linked to a higher likelihood of dropping out of school. 18 It's also linked to more job absences, accidents, and injuries. 19

Is marijuana a gateway drug?

Use of alcohol, tobacco, and marijuana are likely to come before use of other drugs. 21,22 Animal studies have shown that early exposure to addictive substances, including THC, may change how the brain responds to other drugs. For example, when rodents are repeatedly exposed to THC when they're young, they later show an enhanced response to other addictive substances—such as morphine or nicotine—in the areas of the brain that control reward, and they're more likely to show addiction-like behaviors. 23,24

Although these findings support the idea of marijuana as a "gateway drug," the majority of people who use marijuana don't go on to use other "harder" drugs. It's also important to note that other factors besides biological mechanisms, such as a person’s social environment, are also critical in a person’s risk for drug use and addiction. Read more about marijuana as a gateway drug in our Marijuana Research Report .

Can a person overdose on marijuana?

An overdose occurs when a person uses enough of the drug to produce life-threatening symptoms or death. There are no reports of teens or adults dying from marijuana alone. However, some people who use marijuana can feel some very uncomfortable side effects, especially when using marijuana products with high THC levels. People have reported symptoms such as anxiety and paranoia, and in rare cases, an extreme psychotic reaction (which can include delusions and hallucinations) that can lead them to seek treatment in an emergency room.

While a psychotic reaction can occur following any method of use, emergency room responders have seen an increasing number of cases involving marijuana edibles. Some people (especially preteens and teens) who know very little about edibles don't realize that it takes longer for the body to feel marijuana’s effects when eaten rather than smoked. So they consume more of the edible, trying to get high faster or thinking they haven't taken enough. In addition, some babies and toddlers have been seriously ill after ingesting marijuana or marijuana edibles left around the house.

Is marijuana addictive?

Marijuana use can lead to the development of a substance use disorder, a medical illness in which the person is unable to stop using even though it's causing health and social problems in their life. Severe substance use disorders are also known as addiction. Research suggests that between 9 and 30 percent of those who use marijuana may develop some degree of marijuana use disorder. 25 People who begin using marijuana before age 18 are four to seven times more likely than adults to develop a marijuana use disorder. 26

Many people who use marijuana long term and are trying to quit report mild withdrawal symptoms that make quitting difficult. These include:

• grouchiness
• sleeplessness
• decreased appetite

What treatments are available for marijuana use disorder?

No medications are currently available to treat marijuana use disorder, but behavioral support has been shown to be effective. Examples include therapy and motivational incentives (providing rewards to patients who remain drug-free). Continuing research may lead to new medications that help ease withdrawal symptoms, block the effects of marijuana, and prevent relapse.

Points to Remember

• Marijuana refers to the dried leaves, flowers, stems, and seeds from the Cannabis sativa or Cannabis indica plant .
• The plant contains the mind-altering chemical THC and other related compounds.
• People use marijuana by smoking, eating, drinking, or inhaling it.
• Smoking and vaping THC-rich extracts from the marijuana plant (a practice called dabbing ) is on the rise.
• altered senses
• impaired memory and learning
• hallucinations and paranoia
• breathing problems
• possible harm to a fetus's brain in pregnant women
• The amount of THC in marijuana has been increasing steadily in recent decades, creating more harmful effects in some people.
• It's unlikely that a person will fail a drug test or get high from passive exposure by inhaling secondhand marijuana smoke.
• There aren’t any reports of teens and adults dying from using marijuana alone, but marijuana use can cause some very uncomfortable side effects, such as anxiety and paranoia and, in rare cases, extreme psychotic reactions.
• Marijuana use can lead to a substance use disorder, which can develop into an addiction in severe cases.
• No medications are currently available to treat marijuana use disorder, but behavioral support can be effective.

For more information about marijuana and marijuana use, visit our:

• Marijuana webpage
• Drugged Driving DrugFacts
• Substance Abuse Center for Behavioral Health Statistics and Quality. Results from the 2018 National Survey on Drug Use and Health: Detailed Tables. SAMHSA. https://www.samhsa.gov/data/report/2018-nsduh-detailed-tables . Accessed December 2019.
• Miech, R. A., Johnston, L. D., Patrick, M. E., O’Malley, P. M., Bachman, J. G., & Schulenberg J. E. (2023). Monitoring the Future National Survey Results on Drug Use, 1975-2022 . Monitoring the Future Monograph Series. Ann Arbor: Institute for Social Research, The University of Michigan.
• Bell C, Slim J, Flaten HK, Lindberg G, Arek W, Monte AA. Butane Hash Oil Burns Associated with Marijuana Liberalization in Colorado. J Med Toxicol Off J Am Coll Med Toxicol. 2015;11(4):422-425. doi:10.1007/s13181-015-0501-0.
• Romanowski KS, Barsun A, Kwan P, et al. Butane Hash Oil Burns: A 7-Year Perspective on a Growing Problem. J Burn Care Res Off Publ Am Burn Assoc. 2017;38(1):e165-e171. doi:10.1097/BCR.0000000000000334.
• Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A. 2012;109(40):E2657-E2664. doi:10.1073/pnas.1206820109.
• Jackson NJ, Isen JD, Khoddam R, et al. Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies. Proc Natl Acad Sci U S A. 2016;113(5):E500-E508. doi:10.1073/pnas.1516648113.
• Mehmedic Z, Chandra S, Slade D, et al. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci. 2010;55(5):1209-1217. doi:10.1111/j.1556-4029.2010.01441.x.
• National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017.
• Young-Wolff KC, Tucker L-Y, Alexeeff S, et al. Trends in Self-reported and Biochemically Tested Marijuana Use Among Pregnant Females in California From 2009-2016. JAMA. 2017;318(24):2490. doi:10.1001/jama.2017.17225
• The National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. http://nationalacademies.org/hmd/Reports/2017/health-effects-of-cannabis-and-cannabinoids.aspx . Accessed January 19, 2017.
• Goldschmidt L, Day NL, Richardson GA. Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol. 2000;22(3):325-336.
• Richardson GA, Ryan C, Willford J, Day NL, Goldschmidt L. Prenatal alcohol and marijuana exposure: effects on neuropsychological outcomes at 10 years. Neurotoxicol Teratol. 2002;24(3):309-320.
• Perez-Reyes M, Wall ME. Presence of delta9-tetrahydrocannabinol in human milk. N Engl J Med. 1982;307(13):819-820. doi:10.1056/NEJM198209233071311.
• Galli JA, Sawaya RA, Friedenberg FK. Cannabinoid Hyperemesis Syndrome. Curr Drug Abuse Rev . 2011;4(4):241-249.
• Röhrich J, Schimmel I, Zörntlein S, et al. Concentrations of delta9-tetrahydrocannabinol and 11-nor-9-carboxytetrahydrocannabinol in blood and urine after passive exposure to Cannabis smoke in a coffee shop. J Anal Toxicol. 2010;34(4):196-203.
• Cone EJ, Bigelow GE, Herrmann ES, et al. Non-smoker exposure to secondhand cannabis smoke. I. Urine screening and confirmation results. J Anal Toxicol. 2015;39(1):1-12. doi:10.1093/jat/bku116.
• Herrmann ES, Cone EJ, Mitchell JM, et al. Non-smoker exposure to secondhand cannabis smoke II: Effect of room ventilation on the physiological, subjective, and behavioral/cognitive effects. Drug Alcohol Depend. 2015;151:194-202. doi:10.1016/j.drugalcdep.2015.03.019.
• McCaffrey DF, Pacula RL, Han B, Ellickson P. Marijuana Use and High School Dropout: The Influence of Unobservables. Health Econ. 2010;19(11):1281-1299. doi:10.1002/hec.1561.
• Zwerling C, Ryan J, Orav EJ. The efficacy of preemployment drug screening for marijuana and cocaine in predicting employment outcome. JAMA. 1990;264(20):2639-2643.
• Wang X, Derakhshandeh R, Liu J, et al. One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function. J Am Heart Assoc. 2016;5(8). doi:10.1161/JAHA.116.003858.
• Secades-Villa R, Garcia-Rodríguez O, Jin CJ, Wang S, Blanco C. Probability and predictors of the cannabis gateway effect: a national study. Int J Drug Policy. 2015;26(2):135-142. doi:10.1016/j.drugpo.2014.07.011.
• Levine A, Huang Y, Drisaldi B, et al. Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine. Sci Transl Med. 2011;3(107):107ra109. doi:10.1126/scitranslmed.3003062.
• Panlilio LV, Zanettini C, Barnes C, Solinas M, Goldberg SR. Prior exposure to THC increases the addictive effects of nicotine in rats. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2013;38(7):1198-1208. doi:10.1038/npp.2013.16.
• Cadoni C, Pisanu A, Solinas M, Acquas E, Di Chiara G. Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. Psychopharmacology (Berl). 2001;158(3):259-266. doi:10.1007/s002130100875.
• Hasin DS, Saha TD, Kerridge BT, et al. Prevalence of Marijuana Use Disorders in the United States Between 2001-2002 and 2012-2013. JAMA Psychiatry. 2015;72(12):1235-1242. doi:10.1001/jamapsychiatry.2015.1858.
• Winters KC, Lee C-YS. Likelihood of developing an alcohol and cannabis use disorder during youth: association with recent use and age. Drug Alcohol Depend. 2008;92(1-3):239-247. doi:10.1016/j.drugalcdep.2007.08.005.
• Corsi DJ, Walsh L, Weiss D, et al. Association Between Self-reported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes. JAMA . Published online June 18, 2019322(2):145–152. doi:10.1001/jama.2019.8734

This publication is available for your use and may be reproduced in its entirety without permission from NIDA. Citation of the source is appreciated, using the following language: Source: National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services.

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Legalization of Marijuana

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Marijuana and Its Effects on Mental Health Essay

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Marijuana is a drug used commonly in the world among teenagers. The countries most affected are New Zealand, United States of America, Australia and several countries in Western Europe. It is estimated that around162 million people all over the world use marijuana and this represents 3.9 percent of the population worldwide (Sundram, 2006).

It is believed that the consumption of this drug is associated with several negative impacts on human health. Therefore, this paper seeks to analyze the epidemiological research study findings that will show the relationship between marijuana and its effects on mental health.

Marijuana is a drug that is smoked like a cigarette. Studies show that the drug has adverse effects on the brain of the users. It has an active herbal component that is referred to as tetrahydrocannabinal that is known for its negative effects on cannabinoid receptors (Murray & Bevins 2010). Delta-9-tetrahydrocannabinal greatly affects the CB receptors.

To understand the altering role of cannabis, it is necessary to understand that CB receptors are divided into CB1 and CB2. CB1 plays a variety of regulatory roles in the body and is found in many parts of the brain. On the other hand, CB2 receptors play the role of regulating the immune system. CB! Activates G-proteins then reduce the production of Calcium ions while increasing Potassium ion distribution.

These processes lead to “…depolarization-induced suppression of inhibition” (Murray and Bevins, 2010, p. 266). This process generally leads to impeding of transmission from the presynaptic terminal.” Endogenous cannabinoid becomes more at the post synaptic stage causing further postsynaptic excitation.

The effect of marijuana on the CB1 receptors have has great impacts on the daily activities of an individual. The synaptic processes are great factors in learning and the process of memorization. In precision, use of marijuana affects an individual’s memory and learning process through the impact of Delta-9-tetrahydrocannabinal component that affects the CB1 receptors.

This happens through the inhibition of endocannabinoid signaling which is a prerequisite for the learning process that takes place in the cerebrum. Furthermore, the same endocannabinoid signaling is a prerequisite for the processes of memorization that take place in the amygdale (Murray, Morrison, Henquet & Forti, 2007).

Other studies have also pointed out that early stages of marijuana use leads to reduced blood flow to the brain. This is referred to as cerebral blood flow. However, the effect is not similar with experienced marijuana users of whom the study pointed out increase in cerebral blood flow.

As compared to placebo, the use of marijuana generally increased cerebral blood flow in the globe especially in the frontal lobe and the right hemisphere. Another study pointed out increased metabolism in the cerebral after induction of marijuana (OLeary, Block, Koeppel, Flaum, Schultz, Andreasen,Ponto, Watkins,Hurtig &Hichwa,2002).

Short-term memory is another victim of increased use of cannabis. According to Iversen (2003), several studies have been carried out and proved that short term memory is greatly impaired by increased use of cannabis. It has been proved that most users of marijuana faired poorly in tests that included attention.

On other studies carried out on animals, it was clearly founded that THC which is the most active component of marijuana, synthetic cannabinoids and anandamide affect an individual’s short term memory. This was very evident also in tasks that involved spatial learning. He further shows that cannabinoids affect to a great extend the hippocampus.

The effects of the use of marijuana can be comparable to those exhibited by the removal of this important part of the brain (Richardson, 2010). Cannabinoids impair with the ability of this part to process the sensory information through disrupting of the hippocampal circuits.

There are other effects of marijuana on the brain that have not been scientifically proved. For instance, medical research on deceases associated with brains show that there is an increase in chances of having several of these deceases in individuals who smoke marijuana.

For instance, Sundram (2006) argues that the use of marijuana can be associated with most of the common mental health problems. Among them are strong links between use of cannabis and depression. In addition, cannabis was also linked to anxiety, bipolar disorder, manic and hypomanic symptoms, psychosis et cetera.

In his conclusion, it is clear that there is a complex relationship between the use cannabis and these mental diseases. However, it calls for further research because so far no clear causes have been identified. Even so, use of cannabis has been scientifically tested and proved to have exacerbate the symptoms of most of the mental diseases.

Murray et al (2007) bring out another negative effect of marijuana on the brain. In their argument, they purport that use of marijuana negatively implicates on higher brain functions. This can be attributed to the effects of THC on the neocortex. Neocortex is affected by marijuana given the high concentration of CB1 in it. The effect of THC on pre and post synaptic processes is explained earlier in the paper.

As a result of these, marijuana users tend to experience time moving faster than the normal speed at which the rest of the people experience. If asked t estimate the time spent during a period, they tend to over-estimate time. On the other side, if asked to give cue after an estimated period of time, they tend to give the cue after a shorter duration that outlined.

Laaris, Good &Lupica (2010) argue that marijuana has great effects on the hypothalamus. The endocannabinoid anandamide had been proved to be a great stimulant of food intake in animals. The study concluded that the hypothalamus contained the endocannabinoids which play an integral role in regulation of food intake.

This points out that impairment of the CB1 receptors in the hypothalamus might have effects on the control of food intake. Use of marijuana (which is actually the injection of THC) inhibits the production of leptin and hence increases the appetite of the individual. This means that use of marijuana impairs with an individual’s ability to control food intake.

In conclusion, research has clearly pointed out that use of marijuana has drastic effects on the functioning of the brain. The CB1 receptors which are very common in the brain when impaired can have negative effects on high level functioning of the brain, short term memory, food intake regulation, increase in cerebral blood flow and exacerbation of symptoms of mental health complications.

All these effects of marijuana are caused by the Delta-9-tetrahydrocannabinal, and other active chemical elements found in marijuana that alter the functioning of the CB1 elements in the brain. Although the use of marijuana has been associated with some few positive effects, the negative ones simply outweigh them.

It is therefore important that an individual understands the effects that the drug has on their brain and how this impacts their day to day lives before making the decision of using marijuana.

Reference List

Iversen, L. (2003). Cannabis and the brain. Brain , 126, 1252-1270.

Laaris, N., Good, C., & Lupica, C. (201O).Tetrahydrocannabinol is a full at CB1 Receptors on GABA neuron axon terminals in the hippocampus. Neuropharmacolo gy, 59, 121-127.

Murray, J., & Bevins, R., (2010). Cannabinoid conditioned reward and aversion: Behavioral and neural process. ACS Chemical neuroscience , 1, 265 -278.

Murray, R., Morrison, P., Henquet, C., & Forti, M. (2007). Cannabis, and mind the Society: the hash realities. Science and society , 8, 885.

OLeary, D., Block, R., Koeppel, J., Faum, M., Schultz, S., Andreasen, A., Ponto, L.,Watkins, G., Hurtig, G., & Hichwa, R. (2002). Effects of smoking

marijuana on perfusion and cognition. Neuropsychopharmacology, 26(6), 802-816.

Richardson, T. (2010). Cannabis use and mental health: A review of recent epidemiological research. International journal of pharmacology , 6(6), 796-807

Sundram, S., (2006).Cannabis and neurodevelopment: implications for psychiatric disorders. Human psychopharmacology , 21, 245.

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Know the Risks of Marijuana

Marijuana is the most commonly used illegal substance in the U.S. and its use is growing. Marijuana use among all adult age groups, both sexes, and pregnant women is going up. At the same time, the perception of how harmful marijuana use can be is declining. Increasingly, young people today do not consider marijuana use a risky behavior.

But there are real risks for people who use marijuana, especially youth and young adults, and women who are pregnant or nursing. Today’s marijuana is stronger than ever before. People can and do become addicted to marijuana.

Approximately 1 in 10 people who use marijuana will become addicted. When they start before age 18, the rate of addiction rises to 1 in 6.

Marijuana Risks

Marijuana use can have negative and long-term effects:

Marijuana and Pregnancy

Marijuana use during pregnancy can be harmful to a baby’s health and cause many serious problems.

What is Your Marijuana IQ?

How much do you really want to know about the risks of marijuana? You might be surprised.

Marijuana Addiction

Contrary to popular belief, marijuana is addictive. Research shows that:

• 1-in-6 people who start using the drug before the age of 18 can become addicted.
• 1-in-10 adults who use the drug can become addicted.

Over the past few decades, the amount of THC in marijuana has steadily climbed; today's marijuana has three times the concentration of THC compared to 25 years ago. The higher the THC amount, the stronger the effects on the brain—likely contributing to increased rates of marijuana-related emergency room visits. While there is no research yet on how higher potency affects the long-term risks of marijuana use, more THC is likely to lead to higher rates of dependency and addiction.

About Marijuana

Marijuana refers to the dried leaves, flowers, stems, and seeds from the Cannabis sativa or Cannabis indica plant. Marijuana is a psychoactive drug that contains close to 500 chemicals, including THC, a mind-altering compound that causes harmful health effects.

People smoke marijuana in hand-rolled cigarettes, in pipes or water pipes, in blunts, and by using vaporizers that pull THC from the marijuana. Marijuana can also be mixed in food (edibles), such as brownies, cookies, and candy, or brewed as a tea. People also smoke or eat different forms of marijuana extracts, which deliver a large amount of THC and can be potentially more dangerous.

Rise of Marijuana Use

Today, marijuana use is on the rise among all adult age groups, both sexes, and pregnant women. People ages 18-25 have the highest rate of use.

Marijuana and THC remain illegal at the federal level, even though many states have legalized its use. In states where legal, marijuana is a fast-growing industry with sales to individuals over 21 in retail stores, wineries, breweries, coffee shops, dispensaries, online, as well as grown at home.

Get the Files

» View and share the following marijuana videos and resources

Video: Marijuana Use while Pregnant or Breastfeeding

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7 Ways Marijuana Can Affect Your Brain Health (PDF | 901 KB)

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If you, or someone you know, need help to stop using substances – whether the problem is methamphetamine, alcohol or another drug – call SAMHSA’s National Helpline at 1-800-662-HELP (4357) or TTY: 1-800-487-4889 , or text your zip code to  435748 (HELP4U), or use the SAMHSA’s Behavioral Health Treatment Services Locator to get help.

References and Relevant Resources

• Find Treatment
• Technology Transfer Centers (TTC) Program marijuana resources
• Tips for Teens: Marijuana
• Changes in Cannabis Potency over the Last Two Decades (1995-2014) - Analysis of Current Data in the United States: National Center for Biotechnology Information
• Drugged Driving DrugFacts | NIDA
• Drug Facts: Marijuana | NIDA
• Drug Facts: Marijuana | United States Drug Enforcement Administration
• Early-Onset, Regular Cannabis Use Is Linked to IQ Decline | NIDA
• Is Marijuana Addictive? | NIDA
• National Survey on Drug Use and Health | SAMHSA
• Marijuana and Public Health | Centers for Disease Control and Prevention
• Marijuana: Facts for Teens | NIDA
• The Contribution of Cannabis Use to Variation in the Incidence of Psychotic Disorder Across Europe | The Lancet

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The Effect of Preprocessing Steps on the Classification Accuracy of Brain-Computer Interface Systems

25 Pages Posted: 6 Sep 2024

András Adolf

affiliation not provided to SSRN

Csaba Márton Köllőd

Gergely márton, istván ulbert.

Research Centre for Natural Sciences - Institute of Cognitive Neuroscience and Psychology

Accurate classification of Electroencephalography (EEG) signals is a crucial step for Brain-Computer Interfaces (BCI); however, artifacts are often present in those recordings. To mitigate this problem, Artifact Rejection (AR) methods, such as the FASTER algorithm are frequently utilized. In this study, we investigate the effects of preprocessing steps on classification accuracy, namely the FASTER algorithm, frequency filtering, transfer learning, and cropped training. We have found that applying the AR method can enhance but even deteriorate classification performance, in a subject- and network-specific manner. Transfer learning was found to be effective in improving the performance of all networks, whether dealing with raw or artifact-rejected data. However, it was observed that the classification accuracy of artifact-rejected data did not improve as markedly as it did for unfiltered data, resulting in less precision.Our findings also uncovered an unexpected outcome regarding frequency filtering: the tested networks exhibited strong classification performance based primarily on low-frequency components during learning. We noted that higher frequency ranges proved to be more discriminative for EEGNet and Shallow ConvNet when cropped training was applied. This highlights the complex interplay between preprocessing techniques and neural network performance, underscoring the need for tailored approaches based on specific subject and network characteristics.

Keywords: Artifact Rejection, Brain-Computer Interface, Electroencephalography, Motor Imagery, FASTER, CNN

Suggested Citation: Suggested Citation

András Adolf (Contact Author)

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Adverse Health Effects of Marijuana Use

In light of the rapidly shifting landscape regarding the legalization of marijuana for medical and recreational purposes, patients may be more likely to ask physicians about its potential adverse and beneficial effects on health. The popular notion seems to be that marijuana is a harmless pleasure, access to which should not be regulated or considered illegal. Currently, marijuana is the most commonly used “illicit” drug in the United States, with about 12% of people 12 years of age or older reporting use in the past year and particularly high rates of use among young people. 1 The most common route of administration is inhalation. The greenish-gray shredded leaves and flowers of the Cannabis sativa plant are smoked (along with stems and seeds) in cigarettes, cigars, pipes, water pipes, or “blunts” (marijuana rolled in the tobacco-leaf wrapper from a cigar). Hashish is a related product created from the resin of marijuana flowers and is usually smoked (by itself or in a mixture with tobacco) but can be ingested orally. Marijuana can also be used to brew tea, and its oil-based extract can be mixed into food products.

The regular use of marijuana during adolescence is of particular concern, since use by this age group is associated with an increased likelihood of deleterious consequences 2 ( Table 1 ). Although multiple studies have reported detrimental effects, others have not, and the question of whether marijuana is harmful remains the subject of heated debate. Here we review the current state of the science related to the adverse health effects of the recreational use of marijuana, focusing on those areas for which the evidence is strongest.

Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana.

ADVERSE EFFECTS

Risk of addiction.

Despite some contentious discussions regarding the addictiveness of marijuana, the evidence clearly indicates that long-term marijuana use can lead to addiction. Indeed, approximately 9% of those who experiment with marijuana will become addicted 3 (according to the criteria for dependence in the Diagnostic and Statistical Manual of Mental Disorders , 4th edition [DSM-IV]). The number goes up to about 1 in 6 among those who start using marijuana as teenagers and to 25 to 50% among those who smoke marijuana daily. 4 According to the 2012 National Survey on Drug Use and Health, an estimated 2.7 million people 12 years of age and older met the DSM-IV criteria for dependence on marijuana, and 5.1 million people met the criteria for dependence on any illicit drug 1 (8.6 million met the criteria for dependence on alcohol 1 ). There is also recognition of a bona fide cannabis withdrawal syndrome 5 (with symptoms that include irritability, sleeping difficulties, dysphoria, craving, and anxiety), which makes cessation difficult and contributes to relapse. Marijuana use by adolescents is particularly troublesome. Adolescents’ increased vulnerability to adverse long-term outcomes from marijuana use is probably related to the fact that the brain, including the endocannabinoid system, undergoes active development during adolescence. 6 Indeed, early and regular marijuana use predicts an increased risk of marijuana addiction, which in turn predicts an increased risk of the use of other illicit drugs. 7 As compared with persons who begin to use marijuana in adulthood, those who begin in adolescence are approximately 2 to 4 times as likely to have symptoms of cannabis dependence within 2 years after first use. 8

EFFECT ON BRAIN DEVELOPMENT

The brain remains in a state of active, experience-guided development from the prenatal period through childhood and adolescence until the age of approximately 21 years. 9 During these developmental periods, it is intrinsically more vulnerable than a mature brain to the adverse long-term effects of environmental insults, such as exposure to tetrahydrocannabinol, or THC, the primary active ingredient in marijuana. This view has received considerable support from studies in animals, which have shown, for example, that prenatal or adolescent exposure to THC can recalibrate the sensitivity of the reward system to other drugs 10 and that prenatal exposure interferes with cytoskeletal dynamics, which are critical for the establishment of axonal connections between neurons. 11

As compared with unexposed controls, adults who smoked marijuana regularly during adolescence have impaired neural connectivity (fewer fibers) in specific brain regions. These include the precuneus, a key node that is involved in functions that require a high degree of integration (e.g., alertness and self-conscious awareness), and the fimbria, an area of the hippocampus that is important in learning and memory. 12 Reduced functional connectivity has also been reported in the prefrontal networks responsible for executive function (including inhibitory control) and the subcortical networks, which process habits and routines. 13 In addition, imaging studies in persons who use cannabis have revealed decreased activity in prefrontal regions and reduced volumes in the hippocampus. 14 Thus, certain brain regions may be more vulnerable than others to the long-term effects of marijuana. One study showed that selective down-regulation of cannabinoid-1 (CB1) receptors in several cortical brain regions in long-term marijuana smokers was correlated with years of cannabis smoking and was reversible after 4 weeks of abstinence. 15 Changes in CB1 receptors were not seen in subcortical regions.

The negative effect of marijuana use on the functional connectivity of the brain is particularly prominent if use starts in adolescence or young adulthood, 12 which may help to explain the finding of an association between frequent use of marijuana from adolescence into adulthood and significant declines in IQ. 16 The impairments in brain connectivity associated with exposure to marijuana in adolescence are consistent with preclinical findings indicating that the cannabinoid system plays a prominent role in synapse formation during brain development. 17

POSSIBLE ROLE AS GATEWAY DRUG

Epidemiologic and preclinical data suggest that the use of marijuana in adolescence could influence multiple addictive behaviors in adulthood. In rodents exposed to cannabinoids during adolescence, there is decreased reactivity of the dopamine neurons that modulate the brain’s reward regions. 18 The exposure of rodents to cannabis in utero alters the developmental regulation of the mesolimbic dopamine system of affected offspring. 19 If reduced dopamine reactivity in the brain’s reward regions does follow early exposure to marijuana, this effect could help to explain the increased susceptibility to drug abuse and addiction to several drugs later in life, which has been reported in most epidemiologic studies. 20 This theory is also consistent with animal models showing that THC can prime the brain for enhanced responses to other drugs. 21 Although these findings support the idea that marijuana is a gateway drug, other drugs, such as alcohol and nicotine, can also be categorized as gateway drugs, since they also prime the brain for a heightened response to other drugs. 22 However, an alternative explanation is that people who are more susceptible to drug-taking behavior are simply more likely to start with marijuana because of its accessibility and that their subsequent social interactions with other drug users would increase the probability that they would try other drugs.

RELATION TO MENTAL ILLNESS

Regular marijuana use is associated with an increased risk of anxiety and depression, 23 but causality has not been established. Marijuana is also linked with psychoses (including those associated with schizophrenia), especially among people with a preexisting genetic vulnerability, 24 and exacerbates the course of illness in patients with schizophrenia. Heavier marijuana use, greater drug potency, and exposure at a younger age can all negatively affect the disease trajectory (e.g., by advancing the time of a first psychotic episode by 2 to 6 years). 25

However, it is inherently difficult to establish causality in these types of studies because factors other than marijuana use may be directly associated with the risk of mental illness. In addition, other factors could predispose a person to both marijuana use and mental illness. This makes it difficult to confidently attribute the increased risk of mental illness to marijuana use.

EFFECT ON SCHOOL PERFORMANCE AND LIFETIME ACHIEVEMENT

In the 2013 Monitoring the Future survey of high-school students, 26 6.5% of students in grade 12 reported daily or near-daily marijuana use, and this figure probably represents an underestimate of use, since young people who have dropped out of school may have particularly high rates of frequent marijuana use. 27 Since marijuana use impairs critical cognitive functions, both during acute intoxication and for days after use, 28 many students could be functioning at a cognitive level that is below their natural capability for considerable periods of time. Although acute effects may subside after THC is cleared from the brain, it nonetheless poses serious risks to health that can be expected to accumulate with long-term or heavy use. The evidence suggests that such use results in measurable and long-lasting cognitive impairments, 16 particularly among those who started to use marijuana in early adolescence. Moreover, failure to learn at school, even for short or sporadic periods (a secondary effect of acute intoxication), will interfere with the subsequent capacity to achieve increasingly challenging educational goals, a finding that may also explain the association between regular marijuana use and poor grades. 29

The relationship between cannabis use by young people and psychosocial harm is likely to be multifaceted, which may explain the inconsistencies among studies. For example, some studies suggest that long-term deficits may be reversible and remain subtle rather than disabling once a person abstains from use. 30 Other studies show that long-term, heavy use of marijuana results in impairments in memory and attention that persist and worsen with increasing years of regular use 31 and with the initiation of use during adolescence. 32 As noted above, early marijuana use is associated with impaired school performance and an increased risk of dropping out of school, 27 , 29 although reports of shared environmental factors that influence the risks of using cannabis at a young age and dropping out of school 33 suggest that the relationship may be more complex. Heavy marijuana use has been linked to lower income, greater need for socioeconomic assistance, unemployment, criminal behavior, and lower satisfaction with life. 2 , 34

RISK OF MOTOR-VEHICLE ACCIDENTS

Both immediate exposure and long-term exposure to marijuana impair driving ability; marijuana is the illicit drug most frequently reported in connection with impaired driving and accidents, including fatal accidents. 35 There is a relationship between the blood THC concentration and performance in controlled driving-simulation studies, 36 which are a good predictor of real-world driving ability. Recent marijuana smoking and blood THC levels of 2 to 5 ng per milliliter are associated with substantial driving impairment. 37 According to a meta-analysis, the overall risk of involvement in an accident increases by a factor of about 2 when a person drives soon after using marijuana. 37 In an accident culpability analysis, persons testing positive for THC (typical minimum level of detection, 1 ng per milliliter), and particularly those with higher blood levels, were 3 to 7 times as likely to be responsible for a motor-vehicle accident as persons who had not used drugs or alcohol before driving. 38 In comparison, the overall risk of a vehicular accident increases by a factor of almost 5 for drivers with a blood alcohol level above 0.08%, the legal limit in most countries, and increases by a factor of 27 for persons younger than 21 years of age. 39 Not surprisingly, the risk associated with the use of alcohol in combination with marijuana appears to be greater than that associated with the use of either drug alone. 37

RISK OF CANCER AND OTHER EFFECTS ON HEALTH

The effects of long-term marijuana smoking on the risk of lung cancer are unclear. For example, the use of marijuana for the equivalent of 30 or more joint-years (with 1 joint-year of marijuana use equal to 1 cigarette [joint] of marijuana smoked per day for 1 year) was associated with an increased incidence of lung cancer and several cancers of the upper aerodigestive tract; however, the association disappeared after adjustment for potential confounders such as cigarette smoking. 40 Although the possibility of a positive association between marijuana smoking and cancer cannot be ruled out, 41 the evidence suggests that the risk is lower with marijuana than with tobacco. 40 However, the smoking of cigarettes that contain both marijuana and tobacco products is a potential confounding factor with a prevalence that varies dramatically among countries.

Marijuana smoking is also associated with inflammation of the large airways, increased airway resistance, and lung hyperinflation, associations that are consistent with the fact that regular marijuana smokers are more likely to report symptoms of chronic bronchitis than are nonsmokers 42 ; however, the long-term effect of low levels of marijuana exposure does not appear to be significant. 43 The immunologic competence of the respiratory system in marijuana smokers may also be compromised, as indicated by increased rates of respiratory infections and pneumonia. 44 Marijuana use has also been associated with vascular conditions that increase the risks of myocardial infarction, stroke, and transient ischemic attacks during marijuana intoxication. 45 The actual mechanisms underlying the effects of marijuana on the cardiovascular and cerebrovascular systems are complex and not fully understood. However, the direct effects of cannabinoids on various target receptors (i.e., CB1 receptors in arterial blood vessels) and the indirect effects on vasoactive compounds 46 may help explain the detrimental effects of marijuana on vascular resistance and coronary microcirculation. 47

LIMITATIONS OF THE EVIDENCE AND GAPS IN KNOWLEDGE

Most of the long-term effects of marijuana use that are summarized here have been observed among heavy or long-term users, but multiple (often hidden) confounding factors detract from our ability to establish causality (including the frequent use of marijuana in combination with other drugs). These factors also complicate our ability to assess the true effect of intrauterine exposure to marijuana. Indeed, despite the use of marijuana by pregnant women, 48 and animal models suggesting that cannabis exposure during pregnancy may alter the normal processes and trajectories of brain development, 49 our understanding of the long-term effects of prenatal exposure to marijuana in humans is very poor.

The THC content, or potency, of marijuana, as detected in confiscated samples, has been steadily increasing from about 3% in the 1980s to 12% in 2012 50 ( Fig. 1A ). This increase in THC content raises concerns that the consequences of marijuana use may be worse now than in the past and may account for the significant increases in emergency department visits by persons reporting marijuana use 51 ( Fig. 1B ) and the increases in fatal motor-vehicle accidents. 35 This increase in THC potency over time also raises questions about the current relevance of the findings in older studies on the effects of marijuana use, especially studies that assessed long-term outcomes.

Panel A shows the increasing potency of marijuana (i.e., the percentage of THC) in samples seized by the Drug Enforcement Administration (DEA) between 1995 and 2012. 50 Panel B provides estimates of the number of emergency department visits involving the use of selected illicit drugs (marijuana, cocaine, and heroin) either singly or in combination with other drugs between 2004 and 2011. 51 Among these three drugs, only marijuana, used either in combination with other drugs or alone, was associated with significant increases in the number of visits during this period (a 62% increase when used in combination with other drugs and a 100% increase when used alone, P<0.05 for the two comparisons).

There is also a need to improve our understanding of how to harness the potential medical benefits of the marijuana plant without exposing people who are sick to its intrinsic risks. The authoritative report by the Institute of Medicine, Marijuana and Medicine , 52 acknowledges the potential benefits of smoking marijuana in stimulating appetite, particularly in patients with the acquired immunodeficiency syndrome (AIDS) and the related wasting syndrome, and in combating chemotherapy-induced nausea and vomiting, severe pain, and some forms of spasticity. The report also indicates that there is some evidence for the benefit of using marijuana to decrease intraocular pressure in the treatment of glaucoma. Nonetheless, the report stresses the importance of focusing research efforts on the therapeutic potential of synthetic or pharmaceutically pure cannabinoids. 52 Some physicians continue to prescribe marijuana for medicinal purposes despite limited evidence of a benefit (see box ). This practice raises particular concerns with regard to long-term use by vulnerable populations. For example, there is some evidence to suggest that in patients with symptoms of human immunodeficiency virus (HIV) infection or AIDS, marijuana use may actually exacerbate HIV-associated cognitive deficits. 75 Similarly, more research is needed to understand the potential effects of marijuana use on age-related cognitive decline in general and on memory impairment in particular.

Clinical Conditions with Symptoms That May Be Relieved by Treatment with Marijuana or Other Cannabinoids.*

Early evidence of the benefits of marijuana in patients with glaucoma (a disease associated with increased pressure in the eye) may be consistent with its ability to effect a transient decrease in intraocular pressure, 53 , 54 but other, standard treatments are currently more effective. THC, cannabinol, and nabilone (a synthetic cannabinoid similar to THC), but not cannabidiol, were shown to lower intraocular pressure in rabbits. 55 , 56 More research is needed to establish whether molecules that modulate the endocannabinoid system may not only reduce intraocular pressure but also provide a neuroprotective benefit in patients with glaucoma. 57

Treatment of the nausea and vomiting associated with chemotherapy was one of the first medical uses of THC and other cannabinoids. 58 THC is an effective antiemetic agent in patients undergoing chemotherapy, 59 but patients often state that marijuana is more effective in suppressing nausea. Other, unidentified compounds in marijuana may enhance the effect of THC (as appears to be the case with THC and cannabidiol, which operate through different antiemetic mechanisms). 60 Paradoxically, increased vomiting (hyperemesis) has been reported with repeated marijuana use.

AIDS-associated anorexia and wasting syndrome

Reports have indicated that smoked or ingested cannabis improves appetite and leads to weight gain and improved mood and quality of life among patients with AIDS. 61 However, there is no long-term or rigorous evidence of a sustained effect of cannabis on AIDS-related morbidity and mortality, with an acceptable safety profile, that would justify its incorporation into current clinical practice for patients who are receiving effective antiretroviral therapy. 62 Data from the few studies that have explored the potential therapeutic value of cannabinoids for this patient population are inconclusive. 62

Chronic pain

Marijuana has been used to relieve pain for centuries. Studies have shown that cannabinoids acting through central CB1 receptors, and possibly peripheral CB1 and CB2 receptors, 63 play important roles in modeling nociceptive responses in various models of pain. These findings are consistent with reports that marijuana may be effective in ameliorating neuropathic pain, 64 , 65 even at very low levels of THC (1.29%). 66 Both marijuana and dronabinol, a pharmaceutical formulation of THC, decrease pain, but dronabinol may lead to longer-lasting reductions in pain sensitivity and lower ratings of rewarding effects. 67

Inflammation

Cannabinoids (e.g., THC and cannabidiol) have substantial antiinflammatory effects because of their ability to induce apoptosis, inhibit cell proliferation, and suppress cytokine production. 68 Cannabidiol has attracted particular interest as an antiinflammatory agent because of its lack of psychoactive effects. 58 Animal models have shown that cannabidiol is a promising candidate for the treatment of rheumatoid arthritis 58 and for inflammatory diseases of the gastrointestinal tract (e.g., ulcerative colitis and Crohn’s disease). 69

Multiple sclerosis

Nabiximols (Sativex, GW Pharmaceuticals), an oromucosal spray that delivers a mix of THC and cannabidiol, appears to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis. Sativex is available in the United Kingdom, Canada, and several other countries 70 , 71 and is currently being reviewed in phase 3 trials in the United States in order to gain approval from the Food and Drug Administration.

In a recent small survey of parents who use marijuana with a high cannabidiol content to treat epileptic seizures in their children, 72 11% (2 families out of the 19 that met the inclusion criteria) reported complete freedom from seizures, 42% (8 families) reported a reduction of more than 80% in seizure frequency, and 32% (6 families) reported a reduction of 25 to 60% in seizure frequency. Although such reports are promising, insufficient safety and efficacy data are available on the use of cannabis botanicals for the treatment of epilepsy. 73 However, there is increasing evidence of the role of cannabidiol as an antiepileptic agent in animal models. 74

*AIDS denotes acquired immunodeficiency syndrome, CB1 cannabinoid-1 receptor, and CB2 cannabinoid-2 receptor, HIV human immunodeficiency virus, and THC tetrahydrocannabinol.

Research is needed on the ways in which government policies on marijuana affect public health outcomes. Our understanding of the effects of policy on market forces is quite limited (e.g., the allure of new tax-revenue streams from the legal sale of marijuana, pricing wars, youth-targeted advertising, and the emergence of cannabis-based medicines approved by the Food and Drug Administration), as is our understanding of the interrelated variables of perceptions about use, types of use, and outcomes. Historically, there has been an inverse correlation between marijuana use and the perception of its risks among adolescents ( Fig. 2A ). Assuming that this inverse relationship is causal, would greater permissiveness in culture and social policy lead to an increase in the number of young people who are exposed to cannabis on a regular basis? Among students in grade 12, the reported prevalence of regular marijuana smoking has been steadily increasing in recent years and may soon intersect the trend line for regular tobacco smoking ( Fig. 2B ). We also need information about the effects of second-hand exposure to cannabis smoke and cannabinoids. Second-hand exposure is an important public health issue in the context of tobacco smoking, but we do not have a clear understanding of the effects of second-hand exposure to marijuana smoking. 76 Studies in states (e.g., Colorado, California, and Washington) and countries (e.g., Uruguay, Portugal, and the Netherlands) where social and legal policies are shifting may provide important data for shaping future policies.

Panel A shows the inverse correlation between the perception of the risk associated with marijuana use and actual use. Perceived risk corresponds to the percentage of teenagers who reported that the use of marijuana is dangerous. Panel B shows the percentage of students who reported daily use of tobacco cigarettes or marijuana in the previous 30 days. Data for both graphs are from Johnston et al. 26

CONCLUSIONS

Marijuana use has been associated with substantial adverse effects, some of which have been determined with a high level of confidence ( Table 2 ). Marijuana, like other drugs of abuse, can result in addiction. During intoxication, marijuana can interfere with cognitive function (e.g., memory and perception of time) and motor function (e.g., coordination), and these effects can have detrimental consequences (e.g., motor-vehicle accidents). Repeated marijuana use during adolescence may result in long-lasting changes in brain function that can jeopardize educational, professional, and social achievements. However, the effects of a drug (legal or illegal) on individual health are determined not only by its pharmacologic properties but also by its availability and social acceptability. In this respect, legal drugs (alcohol and tobacco) offer a sobering perspective, accounting for the greatest burden of disease associated with drugs 77 not because they are more dangerous than illegal drugs but because their legal status allows for more widespread exposure. As policy shifts toward legalization of marijuana, it is reasonable and probably prudent to hypothesize that its use will increase and that, by extension, so will the number of persons for whom there will be negative health consequences.

Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being.

No potential conflict of interest relevant to this article was reported.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org .