What the rescheduling of marijuana might — and might not — mean for scientific research

WASHINGTON — After years of inertia, the field of research into the health effects of marijuana may be about to get a boost. Maybe.

The Biden administration’s announcement this month that it intends to begin regulating marijuana more in line with how it regulates drugs like anabolic steroids and ketamine would seem to open up new avenues for researchers who have long been stymied by the federal government’s decades-old declaration that the drug is just as dangerous as heroin and LSD.

That classification has made getting permission to study marijuana in an academic lab a laborious process filled with paperwork, and often visits from local DEA agents. The morass has meant that researchers still don’t know basic information about pot’s impact on people, despite the fact that the drug is legal in some form in 41 states, and half of Americans have reported trying marijuana.

“The public health use of cannabis has gone far ahead of what we know from the research. We’re really at this point trying to play catch-up,” said David Shurtleff, deputy director of the National Center for Complementary and Integrative Health. “The real issue here is getting access to diverse products that are being used by the public.”

Now, there is at least hope that the situation might change. But researchers who spoke with STAT said there are myriad unanswered questions about what happens next. Any change is better than the status quo, they argued.

“I would welcome just having one of the 50 wet mattresses that lay on top of me every time I try and do something to slide off the stack,” said Suzaynn Schick, an associate professor of medicine at the University of California, San Francisco, who studies the impact of secondhand cannabis smoke.

Below, STAT walks through four questions that will determine how significantly the Biden administration’s decision will shape medical cannabis research and our understanding of the wildly popular plant.

Will running cannabis clinical trials get any easier?

Some of the nation’s top cannabis researchers are already skeptical that reclassifying cannabis will have much of an impact on clinical trials that could test the drug’s potential as a medicine to treat conditions ranging from PTSD to chronic pain.

That’s because the Food and Drug Administration requires nearly every researcher who tests a new drug in humans to submit a litany of data to the agency outlining everything from statistics on a drug’s absorption and metabolism rates to the results of toxicology studies conducted on lab animals. Cannabis is no different, and that’s almost certainly not going to change if the drug is rescheduled.

While the FDA’s so-called investigational new drug application process helps protect clinical trial participants from being unnecessarily harmed by dangerous drugs, researchers and advocates have complained that the FDA’s review of cannabis INDs has been exceptionally stringent and slow.

Some have criticized the FDA for creating a backlog. In March two congressional lawmakers wrote to the FDA claiming more than 150 research applications for studies into cannabis were pending before the agency. The FDA said it “cannot confirm or deny the existence of or comment on” pending research applications. The agency also said that the oft-cited 150 figure actually relates to the ongoing studies that have also been authorized by FDA.

Suzanne Sisley, whose Scottsdale Research Institute lab is one of a handful in the nation allowed to grow cannabis for medical research, told STAT that her lab’s application to study the potential benefits of cannabis for veterans with PTSD has been before agency reviewers for two years.

“I’m not optimistic that this change is going to mean anything for our research,” said Sisley. “As long as the FDA is in pole position, they’re the starting point.”

Sen. Mark Kelly (D-Ariz.) wrote to the FDA last year asking why the Scottsdale Research Institute’s application had not advanced. The agency simply directed the senator to the research project’s website, Scottsdale researchers said.

A big part of the problem for FDA regulators is the complexity of the cannabis plant compared to some other medications. Drugs that are in pill and capsule form, for example, can be made identically, in consistent batches; researchers attempting to use the cannabis plant itself — and study it in ways that ordinary consumers use it, like inhaling a smoked product — struggle to provide identical products.

While the FDA’s oversight of cannabis trials is unlikely to change much, researchers are hopeful that rescheduling will nonetheless make it easier to do large-scale clinical trials once they are approved, particularly so-called decentralized clinical trials in which participants are allowed to bring home their drugs rather than having to repeatedly come into a clinic to get them.

Three researchers currently conducting clinical trials on cannabis lamented that, under existing rules, running anything resembling a traditional clinical trial is nearly impossible.

“It’s remarkably hard to do outpatient dosing with a Schedule I drug,” said Shanna Babalonis, an associate professor at the University of Kentucky. With rescheduling, Babalonis said, “it goes from being extremely difficult to absolutely possible.”

When asked for comment, the FDA referred STAT to the U.S. health department. A spokesperson for the department said in a statement that it expects that a move to reschedule cannabis “may allow for greater access to marijuana for research purposes.”

“If marijuana is moved to Schedule III, researchers would still need to obtain a DEA registration, though the process is easier and less time consuming for Schedule III substances,” the spokesperson wrote.

Will rescheduling help researchers finally get to the bottom of basic questions about cannabis?

There’s a lot we don’t know about cannabis from a basic science perspective. How a plant’s dozens of components influence the brain, how that changes when people consume cannabis in different forms, and what that all means for the potential of misuse are among the open questions. The innumerable aspects of the still-mysterious human endocannabinoid system are mostly unknown, too.

Researchers are hopeful that rescheduling cannabis will make it infinitely easier to do basic science research, because they will no longer need to have a Schedule I drug license from the DEA.

“There is going to be a tremendous impact,” said Jon Reuter, associate vice chancellor of research integrity and compliance at the University of Colorado, Boulder. “Much more streamlined, less regulation, less hurdles to [overcome] … I know I have a long list of faculty here on campus who have been waiting for this to happen.”

Others are more cautiously optimistic.

“We’re hopeful that it would help facilitate research, [to] do things maybe quicker, faster than we were able to do now. That’s our hope,” said Shurtleff, whose office, the NCCIH, has the second-smallest budget in the National Institutes of Health’s network, but is nonetheless one of the most active in this arena behind the National Institute on Drug Abuse.

Other corners of NIH, like the National Cancer Institute, have also become increasingly interested in studying cannabis, Shurtleff said, but clearing research with other federal agencies remains a challenge. “We don’t know all the nuances of what this rescheduling will look like. … Will there be a provision for research? We don’t know.”

The process of obtaining a Schedule I license is lengthy, and it requires researchers to submit their research protocols to DEA headquarters for approval before they can begin conducting any sort of experiment. Those protocols must detail everything from the amount of drug used and the source of that drug to a step-by-step accounting of how the research itself will be conducted. Any changes to the research must be cleared by the DEA in advance.

But the biggest barrier might be the lack of information on how to actually apply for a permit. Schick, the UCSF professor, told STAT it took her over a year to obtain her permit, and that she had to ask a friend for tips on applying because there was so little publicly available information about the process.

“So much of what you really need to know does not reside on any website,” she said.

It’s unclear how many researchers are denied Schedule I research permits, and how many researchers simply do not apply for such a permit due to the potential hassle, or because they do not know how.

The DEA declined to tell STAT how many researchers currently hold a Schedule I license, though the agency disclosed in 2019 that 750 researchers had such a permit.

While the permitting process required to do basic cannabis research is likely to get easier with rescheduling, there’s still a number of unanswered questions about what sorts of studies scientists will be allowed to conduct.

Researchers studying cannabis cannot go to a local dispensary and purchase products off of the shelves because cannabis is still federally illegal. That classification means researchers cannot use federal research dollars to purchase consumer products. Universities are also reluctant to allow these products on campus for fear of losing federal funding — including financial aid funds — because of a law from the 1980s that requires universities to combat the use of illegal drugs on campus.

Instead, researchers must purchase cannabis from government-approved suppliers. The problem is that it typically isn’t sold in ways that mimic the look and feel of products that are available in dispensaries. Cannabis suppliers, for example, typically only produce smokable flower and high-concentration extracts, while dispensaries typically also offer vapes, edibles, topicals, and even drinks.

The prohibition on studying dispensary products means researchers have to get creative or forgo studying these types of products altogether. Ryan Vandrey, a professor of psychiatry and behavioral sciences at Johns Hopkins University, told STAT his lab has to use those raw materials to manufacture their own dispensary look-alike products, like THC drinks, which can then be used in experiments. Others said they’ve simply stayed away from similar research.

The researchers who spoke with STAT were divided on the question of whether rescheduling would fix this problem. While some said they were hopeful this change would allow them to study products sold in dispensaries, others believed that issue won’t be solved until cannabis is legalized federally.

“As long as there’s this conflict between federal and state law, we are not going to be able to really study things people are actually using,” said Igor Grant, a professor of psychiatry at the University of California, San Diego.

Will cannabis research finally get cheaper?

The legalization of cannabis in states around the country may have dramatically lowered the cost of pot for the average consumer, but studying cannabis in a lab is still astronomically expensive.

Researchers studying cannabis only have seven options of DEA-licensed manufacturers from which to buy, and they often charge far more than your local dispensary.

Schick, the UCSF professor, for example, told STAT she spent $28,000 on 750 grams of cannabis for her research. Your average weed smoker could buy that in San Francisco for between $4,000 and $5,000, according to local dispensary websites.

Researchers also must spend thousands to assure the government that their cannabis isn’t at risk of being stolen or diverted into the recreational drug supply.

Schick told STAT that in addition to tracking and storing every butt of every marijuana joint she uses in her lab, which studies secondhand smoke, she will likely have to pay thousands of dollars to dispose of the butts.

“I should be able to throw cannabis butts into something slightly more regulated than I throw tobacco butts but I should not have to pay thousands of dollars to dispose of them as hazardous waste,” said Schick.

It remains an open question how much the relaxing of regulations will lower these costs.

While researchers are hopeful that rescheduling will lead more suppliers to enter the manufacturing industry, thus lowering the cost of the cannabis they sell, DEA-approved suppliers of cannabis told STAT they don’t expect rescheduling to have a major impact on the supply of research cannabis. They note the DEA will still have ultimate say over how many companies can produce research-grade cannabis, and there will still be substantial compliance costs for companies growing the product, regardless of whether it is considered Schedule I or III.

“We are an oligopoly,” said Richard Shain, the founder of Maridose LLC, a DEA-approved manufacturer. “There’s no incentive for any one supplier to drop their price. It just doesn’t happen in an oligopoly. You’re going against the laws of economics.”

Shain believes the DEA is unlikely to approve a significant increase in suppliers.

What role will politics play in mucking up this whole process?

It’s going to be supremely difficult for the Biden White House to reschedule cannabis before the November election. And even if it achieves that lofty goal, politics could get in the way.

The formal regulatory process takes time, especially when a change as weighty as this one is being proposed by the federal government. Under a law known as the Administrative Procedure Act, the government is required to solicit public comment and consider those comments on a proposed policy before it’s finalized. The more comments received, the more work typically facing the administration. The Biden administration’s proposal has been public for less than a month and it has already received nearly 7,000 comments, according to regulations.gov.

While there’s no minimum amount of time the administration needs to take to review the comments it receives before finalizing a regulation, that process usually takes months, if not years, according to Susan Dudley, the director of the George Washington University Regulatory Studies Center.

Dudley called the idea of the Biden administration finalizing the proposal before January “ambitious, but not out of the question.”

There’s also no telling what Republicans in Congress, or a Trump White House, might do if the Biden administration makes a last-minute dash to get this regulation over the finish line before January. If that occurs, and Republicans wrest control of the White House and the Senate, it could mean a swift undoing of the Biden administration’s plans. That’s because a federal law known as the Congressional Review Act gives Congress the chance to swiftly send a regulation finalized in the waning days of an administration to the waste bin. Under the law, only a simple majority of senators and House members are needed to vote down a regulation.

Already, Republicans are mounting that fight. The health department’s recommendation to downgrade cannabis relied on “cherry-picked data” that “completely ignores the realities of a drug that is causing enormous consequences in children and adults,” Rep. Pete Sessions (R-Texas) told FDA Commissioner Robert Califf during an April budget hearing.

“Let me remind you that a Schedule III [classification] does not put marijuana on the market in the United States,” Califf responded.

Rep. Andy Harris (R-Md.), in another hearing that month, hit on the issue already stymieing studies under FDA review — that cannabis is tricky to reproduce identically for clinical use. “It is absolutely wrong” to make it more accessible because “obviously marijuana’s chemistry is not known and reproducible,” he said.

“If you go into a marijuana dispensary there are about — I haven’t been in one — but there are probably 50 different products, all with a different variety,” Harris argued. “Marijuana is not a drug. It is a group of things.”

But it remains to be seen whether lawmakers are so opposed to rescheduling cannabis that they would sink the proposal in its entirety. After all, past legislation meant to prompt research into cannabis has been strikingly bipartisan.

An unusual coalition of Republican and Democratic senators banded together in 2020 on a bill meant to lower research barriers and press federal agencies for these answers. The legislation stalled after the Senate’s approval that year, but advanced to the president in 2022 and was signed into law that December.

That legislation “was interesting because the pro-marijuana and the anti-marijuana people both thought that further medical research would prove their point,” said Sen. Brian Schatz (D-Hawaii), a bill sponsor. “My view is, let’s find out.”