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Today we’re embracing the cliche of writing about marijuana on 4/20, because there is a lot we still don’t know about the drug. While most drugs go through years of clinical trials before they’re approved and widely consumed by the public, the process for legalizing cannabis has essentially happened in reverse. Millions of Americans have used the drug, and now, after decades of debate, a wave of states are choosing to authorize its use. So we’re zeroing in on some of the questions we still haven’t answered about pot. We’ll hear from a research physician about why marijuana is so hard to test and regulate, and from Olga Khazan, who covers the pot beat for The Atlantic, on whether marijuana could be a substitute for opioids. Then Abdallah Fayyad explores why Mexico banned marijuana in the early 20th century.  

—Caroline Kitchener

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How Does Actual Marijuana Use Differ from Clinical Trials?

I spoke with Barth Wilsey, a research physician at the University of California San Diego, about his experience conducting clinical trials with marijuana.

Caroline Kitchener: You’ve been conducting research with marijuana for over 15 years. What’s it like to get government approval for your studies?

Barth Wilsey: The process is incredibly long and difficult. My first approval process took about two years. You go to the Federal Drug Administration to apply for an Investigational New Drug (IND) Application. That is a very lengthy document that you have to produce. Once you accomplish that, you have to get a Schedule I license for marijuana from the Drug Enforcement Agency. After those two federal agencies have granted approval, you go to the National Institute for Drug Abuse (NIDA) to actually get the marijuana, because they are the only people in the country who are allowed to supply it. They contract with the University of Mississippi, which produces marijuana on a farm, and has done so for many, many years.  

Caroline: Is it difficult for researchers to have only one source for marijuana?

Wilsey: The concentrations of cannabidiol that they give you are not always what you would desire to test. NIDA’s contract with the University of Mississippi calls for them to have four to seven hundred kilograms of marijuana on hand, but it doesn’t specify what types. But researchers need to have sources of study material that is actually being used and sold by dispensaries. We don’t have that now.

Caroline: Is that a problem?

Wilsey: Yes. One example: Law enforcement reports apprehending people with very high concentrations of THC, sometimes as high as 30 percent. But the highest concentration of TNC that we’ve been able to get is 13 percent. Also, people are using edibles—wax oils, concentrates—but we can’t get those from NIDA.

Caroline: So, essentially, it’s hard for you to simulate the way people actually use marijuana when you conduct trials?  

Wilsey: Exactly. We have a grant from the state of California to look at driving under the influence [of marijuana]. We do these driving simulations: We test what happens when a person has to decide whether or not to drive through a light, to swerve around a pedestrian, or to make a left-hand turn with oncoming traffic. We’d like to assess all these scenarios with the driving simulator under different concentrations, and different modes of administration, of cannabis. We need to have these things to see what driving under the influence is really like.

Caroline: Is there likely to be more than one source of marijuana for researchers in the future?  

Wilsey: In 2016, the DEA said they would allow other people to produce marijuana. They said they recognized that it’s always better to have more than one source for research. A bunch of applications were received—but Jeff Sessions or someone else in the Justice Department is holding them up, so we still only have the single source.  

Caroline: Edibles are becoming an extremely common way for people to consume marijuana. Do they pose a particular challenge for researchers?

Wilsey: The effects of edibles are very, very different from the effects of inhalation. That’s because the liver metabolizes the THC to an active metabolite. And that active metabolite has effects that are delayed: You generally experience the most active effects two to six hours after you take it. Another problem: If I prepare brownies, if I cut those brownies into 16 equal parts, I can’t be sure that there will be an equal amount of cannabidiol in each brownie. It would be much better if I had a manufacturer say, “This is the product that we give to the populace at large; it’s a candy. You can use this.” We want to see exactly what the populace is receiving, and test that.

Caroline: Are there particular negative effects of marijuana that you think need to be studied more?  

Wilsey: If I’m giving marijuana to people with neuropathic pain who are in their 60s and 70s, I’m still wondering, “How does that affect them?” Will they be looped, hammered, all day? Are they not going to be able to pay bills? There needs to be more studies. But those studies are hard to do.

Could Pot Be a Substitute for Opioids?

By Olga Khazan, Atlantic staff writer

A growing body of research is considering marijuana legalization from a public-health perspective. These studies are suggesting what might be a surprising finding: Marijuana might be helping to curb the opioid epidemic.

There is currently fairly good evidence supporting the use of marijuana to treat chronic pain. So perhaps it’s no surprise that in studies, people who have chronic pain and visit marijuana dispensaries are able to cut their opioid use.

This trend appears to be cutting opioid deaths in states that liberalize their marijuana laws. As early as 2010, the 13 states that had legalized medical marijuana saw a 25 percent lower rate of opioid deaths than other states—or 1,729 fewer painkiller deaths in one year. Last year, my colleague, Sarah Zhang, wrote how “a handful of observational studies have also found correlations between states legalizing medical marijuana and a drop in painkiller prescriptions, opioid use, and deaths from opioid overdose.”

Most recently, a study published this month in JAMA Internal Medicine found that there are “substantial reductions”—about 14 percent—in opiate use in states that have medical-marijuana dispensaries. Another recent study reached a similar conclusion.

But there are still reasons not to get too excited. For one thing, people who use marijuana are six times more likely than those who don’t to abuse opioids in the first place. Another study found marijuana use actually made chronic-pain patients feel more depressed and anxious about their pain, not less.

"Like any drug in our FDA-approved pharmacopeia, it can be misused,” is how W. David Bradford, a professor of public policy at the University of Georgia and the author of one of these studies, put it to NPR recently. “So I hope nobody reading our study will say, ‘Oh, great, the answer to the opiate problem is just put cannabis in everybody's medicine chest and we are good to go.’”

Instead, everyone agrees we need more studies to show just how much marijuana helps people avoid opioid use. And with marijuana still illegal at the federal level, that research is still a long way away.

What Caused Reefer Madness in Mexico?

By Abdallah Fayyad

In his blockbuster 1994 piece for The Atlantic, “Reefer Madness,” Eric Schlosser wrote about the strange path of marijuana policy in America. He traced the trajectory from 1619—when the first American law concerning marijuana was passed, requiring Virginia farmers to grow hemp—to the ’90s, when data suggested that one out of every six people in federal prison had been incarcerated primarily for a marijuana-related offense. The criminalization of cannabis, Schlosser wrote, was fueled in part by racism against Mexican immigrants and African Americans. The demonization of the drug and stereotypes of its users helped spur a series of regulations that ultimately led to its prohibition in 1937.

But well before 1937, even before a wave of Mexican immigration to the U.S. touched off a corresponding wave of anti-immigrant fervor, Mexico had its own version of reefer madness. Several Mexican states had already begun banning sales of marijuana by the late 19th century.

According to Isaac Campos, author of Home Grown: Marijuana and the Origins of Mexico's War on Drugs, marijuana prohibition in Mexico came about because of a genuine, widespread fear among Mexicans of the negative consequences of the drug. Despite marijuana’s reputation today as a mild intoxicant, Campos pointed out, the effects of a particular drug are very much influenced by the conditions that surround its use. In Mexico, before it was prohibited, cannabis was overwhelmingly used by marginalized populations, including soldiers and prisoners, who lived in tough conditions. Many of them likely suffered from mental illness. And they may have consumed much larger doses than what would be considered normal today, resulting in irregular and potentially dangerous effects.

“All of this combined to produce occasionally violent incidents when marijuana was used—not because marijuana necessarily causes such outcomes, but because when you combine all those factors in that setting, you wound up with these occasional undesirable results,” Campos said. “This led to an extraordinarily widespread belief in Mexico that marijuana caused madness and violence.”

But just as racism steered drug policy in the United States, classism played a role in marijuana prohibition in Mexico. And racism probably was a factor as well—a disproportionate number of marijuana users in the nation around prohibition were likely Mestizos, a mixed-race group with Spanish and indigenous ancestry. “This was a group that was often associated with degeneration and was feared as lower-class people who could resort to violence at any moment,” Campos said. Even within Mexico, in other words, the effects of prejudice and discrimination shaped policy, just as they have in the U.S. “When we try to explain historical events, there’s always supposition and there’s always interpretation,” Schlosser told me. “But I think racism is a good place to start.”

Today’s Wrap Up

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  • Question of the day: What don’t you know about pot, but would like to learn?

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