The Highs and Lows of Marijuana Research

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By Rachel Krieger

When the subject of your research is weed, it’s likely that your experimental methodologies will differ a tad. “Our research pharmacy actually baked marijuana brownies and fed them to people,” said Dr. Kelly Dunn, a professor at the Johns Hopkins School of Medicine. She’s a behavioral pharmacologist.

“It’s a crazy place to work,” she added. While baking pot brownies may not be what comes to mind when one thinks about cutting-edge research, investigators at Johns Hopkins defy that notion to gain crucial insight into a poorly understood but widely available substance. Ghe brownie experiment referenced by Dr. Dunn is part of currently unpublished research measuring how long the psychoactive effects of marijuana last, depending on its route of administration.

Part of it is AIDS activism and thinking that people shouldn’t have to suffer long-term. Other things [include] a libertarian belief that we should be able to choose the harms we engage in.

Dr. Dunn described this research at a talk in March alongside Dr. Renee Johnson, a professor of mental health at the Bloomberg School of Public Health and a researcher on the epidemiology of marijuana use. The talk was part of a “Brain Week” series of neuroscience events hosted by Nu Rho Psi, the neuroscience honors organization.

It was far more popular than the organizers had expected. Hodson 211 overflowed with fifty-plus eager students. The outpouring of interested undergrads may come as less of a surprise when you consider that the topic was marijuana use. Dr. Johnson says as much as a fifth of full-time college students report using marijuana in the past 30 days. It’s unlikely Hopkins is any different.

Widespread enthusiasm for marijuana use among younger generations is a major component of the growing public acceptance of the drug. A 2015 Gallup poll found that a record high 58% of Americans supported legalizing marijuana use, including 71% of 18-34-year-olds but only 30% of senior citizens. The last period of high approval for marijuana was in the seventies under President Jimmy Carter, who issued this statement on drugs: “Penalties against possession of a drug should not be more damaging to an individual than the use of the drug itself.”

That stance, however, was reversed by Ronald Reaganin 1980 with his ‘War on Drugs’, which included marijuana. Reagan’s stringent prohibitions, upheld by a 2005 Supreme Court ruling, still remain in place today at the federal level. However, state-level legalization of marijuana for medical purposes began in California in 1996 and has since spread to twenty-two states, while legalization for recreational purposes was first passed in 2012 and is now the policy for four states as well as Washington, D.C. The federal government’s demonstrated its own policy shift during the Obama administration, calling the “War on Drugs counterproductive.”

What’s causing this growing public acceptance of marijuana?

At the “Brain Week” talk, Dr. Johnson linked it to a variety of factors. She said, “Part of it is AIDS activism and thinking that people shouldn’t have to suffer long-term. Other things [include] a libertarian belief that we should be able to choose the harms we engage in, perceived hypocrisy on the part of the government for having alcohol and tobacco be legal but not marijuana, and racial disparities and injustices in a criminal justice context.” Regardless of the cause, the increased acceptance of marijuana use has led to the proposal of legalization laws in more and more state legislatures, despite the fact that relatively little research has been conducted on the properties of the drug.

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Where science lacks the funding, the legal permissions, or the interest to study marijuana, college students have always been perfectly happy to conduct their own personal research on pot, and Hopkins students are no exception. Two Hopkins seniors, who requested anonymity due to concerns about parental or legal repercussions, shared their stories of how the drug first found its way into their hands.
“The first time I smoked I was 16, in high school,” said a student who we’ll call Johnny, sitting in the kitchen of his house. “For me it was literally peer pressure… I didn’t know anyone there except my one friend, and we literally got into someone’s fucking white van and my friend who I came with, he just turns around like ‘we’re gonna smoke weed today.’ I was like, what the fuck?” Johnny said. He and his friend Jay (whose name was also changed) were hanging out in the kitchen as they shared their stories. Coincidentally, it was also April 20th, or 4/20. Jay described his own first experience: “Dude, mine was totally voluntary. I was seeking it out at this point, like I have nothing to lose from trying this new experience.” For both Jay and Johnny, it’s been years since those first experiences, and they both know a lot more about marijuana now than they did then.

It’s the only drug where it’s been made legally available for medical use before clinical trials and proper drug development.

That first time Jay got high, he’d been cautious about how pot might affect him, but the second time was more intense. “Life was like a slideshow. I would be at the corner of Jerry Road and Independence Drive, and click, halfway up Jerry Road. Click, all the way up Jerry Road. Click, it’s in front of my friend’s house and now we’re inside playing video games.” He thought to himself, “wow, this stuff is so fun. Why didn’t I try it before?”

From then, his frequency of use gradually increased. In sophomore year, Jay fell into a routine of working as efficiently early in the day as possible, in order to be able to smoke every evening. After a while he found himself becoming more dependent on marijuana to get to sleep at night, and noticed himself becoming more anxious and having little appetite when he wasn’t high. He built his friendships around marijuana. Two years later, he regrets that. By some standards, Jay’s dependence would have qualified as a substance use disorder, because although many college students may not know it, marijuana can be addictive.

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A recent study of two thousand college students found that students thought marijuana was half as addictive as cigarettes. However, Hopkins experts believe that dependence is quite real. According to Dr. Ryan Vandrey, a professor of psychiatry at the School of Medicine who studies marijuana at the Behavioral Pharmacology Research Unit, around one in ten people who try marijuana will have problems with its use. “I’ve seen people in my clinic that have horrible problems related to their cannabis use. They can’t get through a day without it, they suffer psychosocial problems, they suffer physical health problems, and they try to quit but can’t. And they’re spending half or more of their monthly income on the drug.”

‘If you get a GPA below a 2.0, they put you on ac pro, right? And if you get ac pro again, you’re out.” Johnny drew a hand across his throat: the end.’

Misuse of marijuana falls into the category of substance use disorder, the new clinical term for what was previously called either substance abuse or dependence. To be diagnosed, a patient must meet at least two of the eleven diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, which include developing cravings for the substance, tolerance to its effects, and withdrawal when use is stopped. According to Dr. Vandrey, people who suffer from this disorder with cannabis will have the same struggles as those who become addicted to nicotine or alcohol, and similar success rates in their attempts to quit: about 30% who go to treatment are able to quit, and of those, about half relapse within a year.

In Jay’s case, the addictive potential of marijuana is all too real. As he continued preparing the pasta for dinner, Jay explained part of the drug’s appeal. “It makes being alone okay, it makes being bored okay, it makes not going out with your friends okay. It just makes things okay.”
Johnny watched Jay cook from a seat in the kitchen. He’d used marijuana regularly with Jay during their sophomore year, which led to some difficulties with classes and then academic probation, or ‘ac pro’ as he calls it. “If you get a GPA below a 2.0, they put you on ac pro, right? And if you get ac pro again, you’re out.” Johnny drew a hand across his throat: the end. “So I went in to the next semester still smoking [marijuana], but with a fire under my ass… I barely got a GPA above a 2-whatever.” Then he paused, laughed, and asked, “What was the question again?” Again, it was an interview about pot on April 20th.

Luckily, Johnny avoided expulsion and even quit smoking marijuana for six months, partly because of growing anxiety issues. These issues had been gradually worsening, and the decision to quit was precipitated by a particularly bad experience that made him so paranoid he had to hold Jay’s hand for hours. But even after successfully quitting, people like Johnny still have to endure the symptoms of withdrawal.

One effect of withdrawal from marijuana use is REM rebound, which Dr. Dunn explains as a result of the fact that using marijuana before bed can leave you unable to enter REM sleep or dream. Upon cessation, “people either have trouble going to sleep, or they have such disturbing dreams that they wake up. And so a lot of the treatment for marijuana withdrawal is to help people sleep, because that’s such a frustrating symptom, that people are more likely to go back and smoke marijuana just so they can sleep.” Johnny has experienced this, too: “There’s three sets of dreams. One is where I’m running to my parents’ room from my bedroom, which originated when I was a kid. I would go out to the hallway, and everything just starts falling apart. Everything’s dark, and there’s this tune – it’s from fucking Mario 64 when you die.” He imitates the song for me – do dooooo daaa – but somehow, the ominous quality is lost outside of the dream.

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These anecdotes serve to show what can happen with marijuana use, not necessarily what does happen for the average user. As America faces more and more policy decisions related to marijuana, it’s important to know where the research on this substance stands, outside of the anecdotes we hear and the stories of personal experience we tell. This type of information, Dr. Vandrey says, can be prone to bias – especially for claims related to medical marijuana. “When you rely on anecdotes, you’re only relying on extremes, typically. A person who has an amazing response wants to tell everyone in the world… what you don’t hear people shouting to the streets about is, I tried it and it did nothing for me.” While anecdotes have provided researchers with starting points for new studies, such as investigating claims that certain strains of marijuana are better for different types of ailment, controlled studies are still very necessary. Just because you hear a story from someone who had a certain experience with marijuana doesn’t mean that’s representative of how it affects the average user.

Though small, there is an existing body of research supporting the use of marijuana for various medical indications, especially pain. According to Dr. Dunn, marijuana’s psychoactive ingredient THC is actually FDA-approved for the treatment of pain and nausea in cancer patients, though that’s something of a special case. “They’re considered to be treatment-refractory – they need access to treatment but their treatments may not work for them, so they’ve got nothing to lose and everything to gain.” In 23 states (including Maryland), marijuana is approved for other medical uses such as relief of seizures, glaucoma, or loss of appetite.

Despite this approved use, Dr. Vandrey points to what we still don’t know about marijuana as medicine: “You don’t know what’s a recommended starting dose. At an effective dose, what are the side effects, and how does that compare to other pain relievers? And at the effective doses, if you find comparable efficacy, what’s the risk profile?” These questions would typically be answered in clinical trials long before a drug is put on the market, but for marijuana, he says, “That science hasn’t been done. It’s the only drug where it’s been made legally available for medical use before clinical trials and proper drug development.” With proposals underway in many states to legalize medical marijuana and potentially impact the lives of many Americans, the need for more information on the drug is clear. “We need the answer to those questions to be able to do this the right way,” Vandrey said.

While the researchers were unanimous in their call for more research to answer the questions surrounding marijuana use, they readily acknowledged the difficulty posed in conducting this research. “It is painful to get through the regulatory processes to do the research that we do,” said Dr. Vandrey. “If you’re starting from scratch, it can take about 18 months to get all the approvals to do a research project with cannabis.”

One factor contributing to this hassle is that, because of its classification since 1970 by the DEA as a Schedule I drug – a category which also includes heroin and LSD – legal marijuana products, including those used for research, can’t be transported across state lines, restricting the area in which researchers are able to work and collaborate. If marijuana were a Schedule II drug, a less restricted category that actually includes cocaine and methamphetamine, it might be easier to research. Dr. Johnson acknowledged the controversy over the current scheduling of marijuana, which classifies it as one of “the most dangerous drugs” with “no currently accepted medical use.” But this inconsistency doesn’t stop the Schedule I label from making it hard to obtain the research we need on the drug. Dr. Johnson put it bluntly: “We don’t have as much information about the medical efficacy of marijuana because of the way it’s classified.”

As with any drug, research on marijuana is crucial in order for those using it to understand the risks they’re taking and what effects they can expect it to have on them. This includes a very large number of college students – an ongoing study by the University of Michigan found that in 2014, 21% of college students surveyed reported using marijuana in the past 30 days. Jay, as much as he enjoys it right now, worries about the long-term consequences of his marijuana use. “Personally, that’s my biggest concern with weed,” Jay said, his tone growing serious. “I have this fear that it’s fundamentally changing me in some way that once I notice it, it’ll be too late.”

Despite the lack of research to go on, we as a society will have to decide what approach to take to marijuana policy, and that’s one decision that researchers can’t make for us. Dr. Johnson offered her expert recommendation, saying: “If we legalize it, make it legal seven years from now, because there is SO much we don’t know about marijuana.” But when asked about whether he would like to see more or less restrictive regulations on marijuana use, Dr. Vandrey declined to answer. “I don’t have a position on that, and I don’t have a stake in it honestly. My interest is in providing research that can help other people make those decisions.”