Weak Weed and Red Tape: Marijuana Research Is Slow Going

February 28, 2017

U. of Mississippi
The "grow room" at the U. of Mississippi’s School of Pharmacy produces marijuana for scholarly research, but critics say its usefulness is limited.

Some researchers studying marijuana want better stuff from their dealers.

"We can’t get very far with the Mississippi weed. That’s just the reality," says Nicholas Lovrich, a professor emeritus of political science at Washington State University who is chair of its Cannabis Committee on Research and Outreach.

Mr. Lovrich is referring to the marijuana that comes from the University of Mississippi School of Pharmacy’s cannabis-research lab, the only federally approved marijuana-growing facility in the United States. It’s the easiest weed for a researcher to score, but many scholars say there’s a downside: It’s lacking in potency and diversity.

More than half of the states have legalized medical marijuana, but researchers say they are still limited in their efforts to test its health benefits.
More than half of states have legalized medical marijuana; eight states have approved recreational use of the drug. Researchers, however, say they are hamstrung by federal regulations that can inundate them with paperwork and put their funding at risk.

On top of that, there’s the matter of the marijuana grown by the federal government. A preprint paper by researchers at the University of Colorado at Boulder and elsewhere says scholars are being held back by the fact that federal marijuana doesn’t measure up to what is sold by retail dispensaries.

"It’s not equivalent to what’s being grown and produced in states that have growing industries," says Ken Gershman, a physician with the Colorado Department of Public Health.

A ruling issued by the U.S. Drug Enforcement Administration in August could make it possible for other research institutions to grow marijuana. But it will take some time before universities can gain federal approval and build facilities. In the meantime, research is limited to the Mississippi facility, in Oxford.

The DEA classifies marijuana as a Schedule 1 narcotic, the same category as heroin. Cocaine, by contrast, is listed as a Schedule 2 controlled substance, which acknowledges a medical application. Growing or creating Schedule 1 substances for research is severely restricted.

"The cannabis strain that Mississippi has been providing is so low in THC" — the chemical compound in marijuana that produces a high — that "it’s not really possible to do actual use-patterns analysis with," Mr. Lovrich says. Among the public, "no one uses that. Everyone’s been using really powerful stuff."

Not everyone agrees that the really powerful stuff is always necessary. The National Institute on Drug Abuse, which manages the federal production of marijuana, declined to comment but said in a statement that weaker weed probably hampers only public-health research, such as studies of impaired driving, and not medical research.

“We can't try to match everything that everybody has out there. This is not a candy store.”

But last year, when the National Institute on Drug Abuse issued a request for information regarding the Mississippi marijuana it supplied, the most common recommendation "was to provide marijuana strains and products that reflect the diversity of products available in state dispensaries."

It’s true that the Mississippi facility can’t mirror every strain produced in the private sector, says Mahmoud A. ElSohly, a professor of pharmaceutics who has overseen the Oxford lab for more than three decades. But he dismisses the notion that a lack of variety holds back research.

"We can’t try to match everything that everybody has out there," he says. "This is not a candy store."

Raising Production

The Coy W. Waller Laboratory Complex — named for a former director of the Research Institute of Pharmaceutical Sciences at the university — houses the nation’s only federally authorized marijuana farm — a status it’s held since 1968, when it was awarded a contract by the drug-abuse institute, part of the National Institutes of Health, to grow cannabis for research purposes. The facility is in the university’s research park, about a mile from where the Ole Miss football team plays. Cameras, motion detectors, security guards, and barbed wire protect 12 acres of Uncle Sam’s marijuana.

The lab has an indoor facility and an outdoor garden for when demand rises. Most of the production there, Mr. ElSohly says, is dictated by the drug-abuse institute, which requests what and how much to grow.

He hasn’t noticed an uptick in demand, even with states’ legalizing retail marijuana.

Mississippi was awarded an extension in 2015 on a federal contract that could have been worth as much as nearly $70-million, if demand for research marijuana were to skyrocket. In 2014 the farm increased production, and it has widened the variety of strains it offers to researchers, who can mix and match based on potency. The current diversity should be sufficient for research purposes, says Mr. ElSohly.

"There’s a lot of noise out there. There’s a lot of talk," he says. "But it really has absolutely no basis. The whole idea of people saying these things is prompted and motivated by the pro-legalization people, and they are much quieter now that some of the states have decided to make it legal."

Placing an Order

Heike Newman, senior regulatory manager in the clinical-research-support center at the University of Colorado at Denver, jumps through hoops so her university’s researchers don’t have to. She can stomach an alphabet-soup of agency acronyms as well as anyone, but even she gets tangled in marijuana restrictions when placing an order with the Oxford lab.

"Initially we thought that once we had the IND from the FDA, we have IRB approval, we have the DEA registration, then we can submit to NIDA, and NIDA will authorize the shipment," she says. "But apparently there is now yet another entity involved. I think the name is RTI? Something like that."

Ms. Newman has encountered every hurdle associated with new marijuana research. The state of Colorado put up $9 million for medical-marijuana research in addition to grants related to public-health research. She has been grappling with many of the details, including $55,000 in improvements in research facilities to comply with rules for studying Schedule 1 narcotics.

"Nothing was insurmountable, don’t get me wrong, but I had this image in my head that it was going to be easy," Ms. Newman says. "I thought six months, maybe nine, and then we’re going to be done — and here we are two and half years later, and we’re still not quite ready with one of the studies."

The studies that are taking the longest to organize are the clinical trials, in which researchers actually administer marijuana to patients. For observational trials, researchers can base their study on a subject’s self-medication. But in order to administer marijuana, researchers need to get the federal stuff.

Given the constraints, researchers basically have two options. One is to spend months applying for approval to administer marijuana in a clinical trial, and then use the federally grown version, which researchers say doesn’t actually reflect the drug everyone is using. The other is to conduct an observational trial, in which researchers monitor patients who are using marijuana on their own.

In observational trials, researchers can’t control for how much people are using or what variety, specifically, they’re taking. That level of uncertainty doesn’t sit well with researchers.

High Hurdles

Even so, for Ashley Brooks-Russell, who has a Colorado-funded grant at Denver to look into the public-health effects of marijuana, observational trials are the preferred route. "If you use that lower-potency product, then the generalizability of those findings is pretty limited, because we know that’s not what’s being sold in the state of Colorado," she says.

Besides, it’s much harder to get research approval for a clinical test, she notes. "For people like me, who just feel like that’s too much of a hurdle and maybe doesn’t get to the solution that’s needed anyway, what we’re left with is having people smoke at will or to the desired effect."

“Initially we thought that once we had the IND from the FDA, we have IRB approval, we have the DEA registration, then we can submit to NIDA, and NIDA will authorize the shipment. But apparently there is now yet another entity involved. I think the name is RTI? Something like that.”
Ms. Newman, who has helped both observational and clinical researchers navigate the field of study, says researchers pursuing clinical trials did indeed run into more problems than did those looking at observational trials. Federal permitting and concerns within the university over where to house Schedule 1 facilities and federal compliance created more headaches.

"I don’t think they knew what they were getting into," she says. "Like everyone else, I think they had no idea how complicated and time-consuming and resource-intensive it would be to get these studies going."

That describes the challenges that Emily Lindley faced in starting a study of marijuana as a treatment for spinal pain. A 2012 survey of Colorado patients found that nearly 20 percent were treating their back pain with medical cannabis, leading Ms. Lindley to propose her own study.

The research will compare cannabis with oxycodone, a commonly prescribed opioid. Patients will test both treatments to evaluate if cannabis has a future as a pain-relief alternative to opioids.

The project hasn’t started yet. Ms. Lindley needed seven months for DEA approval, and she’s still waiting to receive marijuana from the Mississippi facility, which she was hoping to have last November. (As a Ph.D., and not an M.D., she cannot hold the necessary Schedule 1 permit, so she has worked with a doctor on setting up the study.)

Even with the extra hurdles and concerns about the federally supplied cannabis, Ms. Lindley says her study is important for laying groundwork for further research. "Doing an actual clinical trial is stronger evidence than doing an observational trial," she says. "It’s a lot cleaner data and more controlled for what you’re looking at."

She acknowledges that the federal marijuana will have to better reflect what’s available commercially if research is going to get very far.

"As this research goes forward, they are going to have to produce strains that are more equivalent to what patients are getting at dispensaries," Ms. Lindley says. "Otherwise the research that we’re doing isn’t real-world examples of what is happening."

More Questions Than Answers

Mr. ElSohly says the regulations on research "shouldn’t be a hindrance," but a growing number of cannabis scholars want research to happen faster.

"There are very rigorous research standards and rules that restrict the researchers," says Sam Méndez, director of the Cannabis Law and Policy Project at the University of Washington. "And there’s a lot of researchers that just don’t have the resources via time or funding to obtain that license."

Many research advocates have asked that marijuana be taken off the Schedule 1 list of narcotics, but the Drug Enforcement Administration has declined to do so, citing a lack of evidence that marijuana demonstrates health benefits.

Mr. ElSohly doesn’t think marijuana is going to be reclassified anytime soon. For it to become a Schedule 2 narcotic, like opioids or cocaine, researchers would need to prove not just that marijuana can be beneficial, but in what doses and for what diseases.

Much existing research on cannabis is anecdotal and not "legitimate work," he adds "People are just doing whatever the heck they want to do, claiming this and that with absolutely no data to support that, other than anecdotal stuff. That’s not the way we approve drugs in this country."

The Cannabis Law and Policy Project is helping the state answer a number of questions about marijuana, including matters of research, policy, and its use on campus.

"It’s been part of human civilization for thousands of years, and yet we still don’t know, at least from a Western-medicine, rigorous, double-blind-tested standard, exactly what the substance can do," Mr. Méndez says.

If universities are going to catch up to the level of research needed, they’ll have to sort out issues both federally and within their own walls. Institutional review boards have to be cautious of approving any marijuana research, because it could jeopardize other research funding.

"If you go in this area, you have to be prepared to work with lawyers, you have to be prepared to work with hostile colleagues," says Washington State University’s Mr. Lovrich. "On the other hand, the questions you get about public health and public safety, you can’t ignore those and say we’re not really doing research in that area. Then you’re violating your trust in the state of Washington or Oregon or Colorado."

Mr. Lovrich thinks public support for marijuana research would make it difficult to shut down. But he does worry that the federal government could obstruct much-needed work.

"There’s uncertainty," he says. "What’s not uncertain is that people will be using marijuana, whether it’s legal or not."

Clarification (3/14/2017, 11:59 a.m.): This article has been updated to clarify that the U. of Mississippi's federal contract to grow marijuana, while valued at nearly $70-million, will probably pay out less. It has also been updated to clarify that Emily Lindley has been cleared to receive marijuana from the facility.