Three days before he died in 2019, Johnny Stack told his mother, Laura, that marijuana had ruined his mind and his life.

Johnny first tried the drug when he was 14 at a high school party. It had recently been legalized in Colorado, and an older brother of one of his friends had a medical marijuana card. But when Johnny got home, he felt guilty and confessed to Laura that he had felt pressured to use it. “I thought the marijuana was the same marijuana I had used when I was 17,” she recalls. “I told him to never do it again—but I didn’t understand how different it was or feel a sense of urgency about it.”

Gradually, Laura noticed Johnny becoming more isolated and verbally abusive. And when he went off to college a few years later, he grew extremely paranoid. He told her that the FBI had bugged his dorm room. He was convinced “the mob” was after him, but “he couldn’t describe who the mob was or what they wanted from him,” she remembers. He also began expressing thoughts of self-harm. “He sent me a text saying he had been dabbing nonstop with his roommate for two weeks and felt like killing himself every day,” she says. (Dabbing is a relatively new form of marijuana consumption that involves inhaling a concentrated form with extremely high levels of THC.) “I didn’t even know what ‘dabbing’ was. I thought it was a bad dance move.”

Shortly after, Johnny went to the hospital. The doctor wrote in his chart, “THC abuse, severe.” He never tested positive for any other drug.

For five years, Johnny and his family battled marijuana addiction and marijuana-induced psychosis. In times of sobriety, “he was Johnny again,” Laura says. But eventually, he would start using again and the suspicion, delusions, and agitation would shortly follow. As Laura desperately searched for help, she was often met with dismissal or disbelief. One psychiatrist suggested Johnny try smoking a different strain. One rehabilitation center told them to lie about what he was addicted to—by saying he was addicted to LSD instead, the center told them, they would be more likely to obtain insurance coverage. Their insurance company refused to cover treatment for marijuana addiction, which would cost $60,000 out of pocket. “Nobody believed us … nobody!” says Laura, who would go on to start the non-profit, Johnny’s Ambassadors.

In the last photo ever taken of Johnny, he was standing on top of a six-story parking garage in the midst of a psychotic episode with his arms outstretched. He took his life on November 20, 2019.

As THC potency increases, science fails to keep up

Cannabis sativa has more than 500 distinct chemical entities, the most significant and well-known components being cannabidiol [CBD] and delta-9-tetrahydrocannabinol [THC]. While the term “cannabis” includes any product derived from the plant, marijuana encompasses the parts that contain significant levels of THC, which produces the drug’s psychoactive effects.

Over the last several decades, the THC content of cannabis has changed substantially. In 1995, the average THC content in cannabis seized by the Drug Enforcement Administration was about 4%. By 2017, it had risen to 17% and continues to increase. Beyond the plant, a staggering array of other cannabis products with an even higher THC content like dabs, oils, and edibles are readily available—some as high as 90%. “The marijuana and cannabis products that your grandparents may have used are very different from what’s out there now,” says Deepak Cyril D’Souza, MD, Albert E Kent Professor of Psychiatry at Yale School of Medicine.

The marijuana and cannabis products that your grandparents may have used are very different from what’s out there now.

Deepak Cyril D’Souza, MD

It’s true that cannabis has evidence-backed medical benefits. The U.S. Food and Drug Administration (FDA) has approved several commercially available products, including Dronabinol for chemotherapy-induced nausea and vomiting and Epidiolex for a rare form of epilepsy in young people. Both of these drugs are available by prescription only.

Many people use cannabis recreationally without experiencing evident adverse effects. However, for some, the health risks associated with cannabis, such as addiction and cannabis withdrawal syndrome are genuine and potentially debilitating. “Nearly one-third of regular cannabis users may develop problematic use patterns. While certain cannabis-derived products show therapeutic potential, they are not without risks,” says Joao De Aquino, MD, assistant professor of psychiatry. “The challenge lies in maximizing therapeutic benefits, like pain relief, while minimizing negative consequences. Achieving this balance necessitates comprehensive, controlled studies that evaluate both the therapeutic and adverse effects.”

And as cannabis grows more potent, there is limited high-quality scientific evidence about the safety of increasingly available products. “A lot of our views about cannabis, unfortunately, are not driven by good science, but driven more by opinion,” says D’Souza, who is launching one of the first centers of its kind on the east coast dedicated to high-quality research on the drug. “As we are legalizing cannabis and making it commercially available, we need to understand the implications of that on human health.”

Growing evidence points to potentially severe side effects of cannabis

As the drug becomes more and more potent, there has been a parallel increase in both medical and recreational marijuana’s accessibility and acceptance in the United States. Most users are aware of the common side effects, including impairments in memory and attention, greater inclination for risk-taking, and diminished capacity to drive. And while for most people, cannabis produces a feeling of relaxation, in others, for poorly understood reasons, it can trigger anxiety and panic.

Now, growing research is pointing to other concerning, potentially severe consequences of cannabis use. This not only affects adults over the age of 21, who can legally buy marijuana in many jurisdictions, but also adolescents. “Data suggests that as cannabis becomes more available in the environment for adults, its access also increases to children and young adults who may be particularly vulnerable to its long-term effects,” says Mohini Ranganathan, MBBS, associate professor of psychiatry.

There is compelling data showing that cannabis may be associated with changes in brain structure in young people, particularly in the prefrontal cortex, which is associated with decision-making and executive function. Other epidemiological evidence suggests that heavy and early use of cannabis is associated with increased risk of developing schizophrenia, bipolar disorder, depression, and anxiety.

For over two decades, D’Souza has been studying the relationship between cannabis and psychosis, in which an individual experiences a loss of reality after using a high-potency product. Emerging studies suggest that cannabis use leads to an increased risk of reporting psychotic symptoms. A 2022 study, for instance, found a significant correlation between the number of cannabis dispensaries and rates of psychosis presenting in emergency departments.

Ethan Andrew, a 24-year-old studying informational technology at Colorado State University Global, suffered a psychotic episode in the summer of 2017 after getting into dabbing with his friend. He had been regularly “smoking flower” and at first didn’t think much of the higher potency of dabs. “We thought of it as beer versus tequila—it’s still alcohol, but one will just get you there faster,” he remembers. Over time, dabs became his preferred method of cannabis ingestion, until he began experiencing worsening paranoia.

“I started obsessing over random objects and tried to find the meaning in useless things—I thought everything was a message to me, and I had to get to the bottom of it,” he says. “Weed was not giggly and fun anymore.” He recalls vividly hearing his mother yell his name “at the top of her lungs,” but when he ran upstairs, he found her fast asleep. Soon after, he decided to quit smoking—cold turkey.

The withdrawal worsened his psychosis, and he recalls the following two months as the worst months of his entire life. His paranoia skyrocketed and the voices in his head became so distracting that he quit his summer job. He sought out several psychiatrists, but they were of little help. Eventually, the symptoms faded away on their own. “There are few things I could experience that would be more terrifying than those two months,” he says.

Recent research is also revealing the cardiovascular effects of cannabis, and that cannabis may be associated with a higher risk of heart attacks. In his lab, D’Souza has seen that cannabis impacts physio-cardiovascular function and usually leads to increased heart rate in healthy individuals. But the drug’s impact on the cardiovascular system may have more sobering consequences especially in those with unrecognized cardiovascular problems. “There are now higher rates of young people with no obvious cardiac histories who are going to the emergency room with heart attacks,” says D’Souza. Many of these ER visits have occurred within about an hour of the individual consuming cannabis.

Furthermore, regular, heavy consumption of cannabis may lead to chronic impairments in memory, attention, and motivation. Alex, who asked for her name to be changed for privacy, first tried the drug when she was 17 and a high school student. At the peak of her cannabis use, she was smoking three to four times a week. This was when she noticed that she was struggling with her memory, and losing a concerning amount of weight.

Now in her 30s, Alex continues to smoke, but only socially. She says her weight is restored, but her issues with short-term memory persist. “I’ll forget what I did yesterday, or I’ll start one project and then leave it and forget it,” she says. “This is a big issue that teenagers should at least be warned about before smoking marijuana.”

There is a widespread misconception that cannabis is not addictive. “This couldn’t be further from the truth,” says D’Souza. “There is compelling evidence from both animal studies and humans that some people get addicted to cannabis (~30%) for reasons we don’t fully understand.” Addiction to cannabis is directly related to its THC content. D’Souza believes that the false perception may stem from several decades ago, when the THC content was lower, and the drug was likely less addictive. But as cannabis becomes more potent, he fears that there may be greater rates of addiction in the future.

A critical opportunity for new research on cannabis

Until recently, the federal government “made it challenging” to conduct research on the potential effects of cannabis, says D’Souza. But now, it finally has begun relaxing on some of the obstacles it previously imposed, presenting a critical opportunity to generate high-quality evidence and understand how to support those who have suffered negative consequences after marijuana use. In pursuit of this goal, D’Souza and his colleagues have founded Yale School of Medicine’s new Center for the Science of Cannabis and Cannabinoids. “We hope to be leaders here at Yale as we embark on a very important and grand social experiment (referring to the commercialization of cannabis),” he says. The center will strive to better understand the therapeutic applications of cannabis through double-blind, randomized, placebo-controlled studies. But it will also investigate the potential harmful consequences.

One area in need of research is brain development across the lifespan using animal and organoid models. This includes during adolescence, when young people are likely to try cannabis for the first time while also undergoing significant neurodevelopment.

But it will also be important to study this exposure in utero, as there is an “alarming increase” in women who are using cannabis during pregnancy to manage morning sickness, says D’Souza. “They’re using it because they believe that, since cannabis is plant-based, it’s natural and therefore not harmful.” Now, new studies suggest that children born to mothers who used cannabis during pregnancy have cognitive deficits that can persist into adolescence.

Young people aren’t the only ones using cannabis. A growing number of older individuals, including people 65 and older, are turning to cannabis, but the vast majority of existing research excludes this population. “If you go to a cannabis dispensary and ask them what their average customer is like—it’s young people with permitted disorders who want medicinal cannabis and young people who want to get intoxicated,” says Godfrey Pearlson, MBBS, professor of psychiatry and of neuroscience. “But then it’s also older people who either have problems sleeping, problems with pain like arthritis, or individuals who used cannabis in the ‘60s and want to try it again.” Future research will be needed to fill the glaring gap and elucidate how cannabis may impact older individuals differently from young people.

Beyond brain development, the link between cannabis and mental disorders also warrants further investigation. D’Souza is especially interested in understanding how exposure may impact the risk for schizophrenia. “Schizophrenia is perhaps one of the most devastating mental disorders, because it usually strikes between the ages of 15 and 25, preventing young people from reaching their potential,” he says. “We don’t have any way of treating it. So, if we find that cannabis is a risk factor, then there’s something we can do about it.”

Finally, cannabis and car safety is another urgently needed area of study. There is minimal data on how cannabis affects driving, and while there is a legal blood alcohol concentration limit for operating a motor vehicle, researchers know very little about how to detect drivers under the influence of cannabis. “When we get people intoxicated in the lab and ask them how safe they think their driving is in a driving simulator, they often think their driving is safe even when they’re fairly impaired,” says Pearlson. “People are not good judges of their driving impairment in terms of their safety to drive. They think they’re safer than they actually are.”

The commercialization of cannabis

In May, Minnesota became the 23rd state to legalize recreational marijuana. Furthermore, 31 states have decriminalized the drug, meaning that an individual cannot be prosecuted for low-level possession. D’Souza feels that the growing movement toward decriminalization and legalization in the United States is a positive one. Despite these efforts, in 2020, over 300,000 people were arrested for possessing cannabis. And these convictions disproportionately target people of color. Over 40% of the arrests were of Black Americans, even though they only account for 14% of the U.S. population and use marijuana at the same rate as white Americans. “The real issue is not legalization, but commercialization,” D’Souza explains.

The increased commercialization of cannabis mirrors what happened with the tobacco industry, he says. Both industries share a goal of making a money and selling at high volume through designing highly attractive products. Adolescents and young adults, who are especially vulnerable to developing an addiction, make attractive consumers. “It shouldn’t surprise us that THC is being sold as gummy bears or ‘Krondike’ bars, or that the vaping fluids with flavors like pineapple or mango come in thinly disguised packages that attract young people,” says D’Souza. “The idea is that if you have a young customer, you have a lifelong customer.”

Gladys Longoria discovered her son’s marijuana stash when he was a high school student, after a neighbor warned her that he might be hanging out with an at-risk crowd. He would go on to develop an addiction to cannabis and cannabinoid hyperemesis syndrome, in which using the drug induced severe abdominal pain, nausea, and vomiting that drove Longoria to take him to the hospital multiple times. She is frustrated by how the products she found targeted young users like her son. “I would find packaging for ‘birthday cake,’ or the bag would look like Skittles,” she recalls. “They entice young people with flavors like birthday cake or brownie. You name it, and it’s out there.”

It took decades for people to recognize the true harmfulness of tobacco because “these commercial establishments had armies of lawyers and lobbyists actively suppressing the science that showed a clear link between tobacco and negative health consequences,” says D’Souza. Many of these same tobacco companies have now invested in the cannabis industry, where they are again finding ways to draw in young customers. Combatting this will require scientists working together to produce strong evidence that cannabis is not the harmless product the industry is making it out to be. “I will leave you with this question,” says D’Souza. “Is it going to take us another 50 years to recognize the consequences, as it took us with tobacco?”