Still waiting: ureaucratic hurdles frustrate researchers seeking to study medical marijuana
MINNEAPOLIS — A year ago, University of Minnesota researchers received a $9.5 million grant from the National Institutes of Health to study pain in patients with sickle cell disease.
Normally, such an award would quickly launch a study, but lead researcher Kalpna Gupta is still waiting on a critical part of the research — and moved the work to California to speed the process.
Gupta wants to see whether medical marijuana can treat pain.
Completing such a study involves so much red tape that Gupta has decided to collaborate with researchers in San Francisco who have experience threading the bureaucratic needle.
“Our grant has been funded for the last year,” Gupta said, “and we are still waiting.”
The problem, researchers say, is a tangle of federal regulations that can delay research or prompt scientists to give up on marijuana studies altogether. The issue came up repeatedly this spring at the state Capitol, as both supporters and opponents of legislation to legalize medical marijuana in Minnesota agreed that there’s just not enough top-notch scientific evidence about how it works for patients.
There are some small signs of improvement, however, including a bumper crop of marijuana that’s been planted in Mississippi this spring specifically for researchers. But access is controlled by the National Institute on Drug Abuse, also known as NIDA.
“NIDA has a mandate from Congress” that its marijuana studies focus on preventing drug abuse, said Dr. Donald Abrams, a University of California-San Francisco researcher who is collaborating on the sickle cell disease research. “You cannot really be funded by NIDA to study cannabis as a potential treatment … hence the lack of research.”
Researchers who want marijuana for medical studies must confront multiple federal agencies.
They must submit an application to the U.S. Drug Enforcement Administration, which seeks advice from the U.S. Department of Health and Human Services on the quality of the research proposal. Drug development studies typically are approved by the Food and Drug Administration, too.
Marijuana is a Schedule I controlled substance, which means it has no accepted medical use and a high potential for abuse, according to the federal government. So, researchers must obtain a registration to work with Schedule I drugs, a classification that includes heroin and LSD.
To obtain marijuana, researchers must turn to the only federally approved source: a farm at the University of Mississippi that has had contracts with the federal government since 1968. The university’s Marijuana Project maintains a supply of research-grade cannabis and even provides marijuana to a few patients who decades ago successfully sued for access.
Research applications for marijuana are handled by NIDA, where agency officials say they have supported a limited number of studies over the years touching on medical aspects of marijuana.
Even so, the agency acknowledged in a statement that its focus is “solving the devastating problem of drug addiction and related health conditions.”
“We are experts on addiction and drug abuse,” the agency said. “We do not do research into treatment for epilepsy, PTSD (post-traumatic stress disorder), glaucoma, cancer or many other problems and conditions that have been possible targets for medicinal marijuana.”
At the state Capitol this spring, patients pushing for access to medical marijuana said they were well aware of the lack of research.
The most powerful force for legalization came from parents of children with seizure disorders who provided anecdotal evidence about the effectiveness of marijuana provided in a liquid form. In this version, the psychoactive components of marijuana are minimized, and children receive a greater concentration of a compound called cannabidiol, or CBD.
Jessica Hauser of Woodbury said that as she started to hear stories about medical marijuana, she wondered: “Where’s the research if it’s so great?” But after talking with parents of children treated in other states, Hauser became convinced that she wanted her son Wyatt to have access.
“There are a lot of bureaucratic problems at the federal level that make it incredibly difficult for doctors to do the research they need,” Hauser said.
Minnesota lawmakers this month passed a bill that would provide terminally ill patients and those with any of eight serious medical conditions access to medical marijuana from two state-regulated manufacturers. Physicians would have to certify that a patient has a qualifying condition and agree to submit information so the Minnesota Department of Health could maintain a research registry on patient outcomes.
Gov. Mark Dayton has not yet signed the legislation but pledged to do so.
The research registry might help some patients, but it won’t provide the sort of scientific data on medical marijuana that many physicians are looking for, argued Dr. Sue Sisley, a psychiatrist at the University of Arizona.
In 2009, Sisley started working with reviewers at the FDA on a proposal to study medical marijuana for veterans with PTSD. Approval came in 2011. Then it took another three years for a different federal health agency to approve the study, said Sisley, who twice testified this spring at the state Capitol.
Sisley still must work with the DEA to obtain a Schedule I registration. There’s now a hang-up, she said, in obtaining the sort of marijuana she needs from the federal government’s marijuana farm.
“Why would any scientist do this?” asked Sisley, who also works in private practice and has research support from a California-based nonprofit. “Why would they go through this hassle, if you’re in a publish-or-perish system in a university? How could you ever survive with this kind of nonsense?”
DEA officials say that 236 investigators were registered to study marijuana as of May 1, and the number has held steady for the past several years. The agency says it has not denied registration to an HHS-approved marijuana study in more than 20 years.
“DEA supports and provides the access necessary to study all Schedule I substances once the study is approved by HHS,” the agency said in a statement. “Complete applications (for registration) take about five months to approve.”
But Gupta of the University of Minnesota said she spent six months just trying to fill out her application for a Schedule I registration and ultimately gave up.
“I would call, and they would not call back,” Gupta said. “I was so surprised — I couldn’t believe it.”
The DEA requires that marijuana be kept in a specific type of safe, which is subject to certain state regulations and federal inspection. The university could have met this and other security requirements, Gupta said, but she decided it was a safer bet to do the patient work at the University of California-San Francisco, which already has such facilities. Statistical analysis will be conducted in Minnesota.
In the end, the sickle cell study required approvals from eight regulatory agencies, said Abrams, the researcher in California.
“You have eight different people reviewing it, and everybody wants to make a change,” he said in an interview.
There are signs the research environment could be improving.
Earlier this month, GW Pharmaceuticals of Britain announced FDA approval to study whether a medication with cannabidiol, or CBD, might help children with Dravet Syndrome, a rare and catastrophic form of childhood epilepsy. The company also is studying in the U.S. whether medication containing marijuana compounds can help patients suffering from cancer pain and spasticity with multiple sclerosis.
“We have conducted, or will conduct, trials at more than 50 sites in the U.S.,” company spokesman Mark Rogerson wrote in an email. “So, it is perfectly possible for a pharmaceutical company to go through the process — it just takes more time.”
And at the University of Mississippi, federal officials approved a significant expansion of this year’s marijuana crop. In April, the federal government upped its 2014 quota of marijuana for researchers from 21 kilos to 650 kilos.
That means about 4,000 to 6,000 new marijuana plants, said Mahmoud ElSohly, a pharmacy professor and director of the Marijuana Project. Some already have been growing in a greenhouse and are in the process of being planted in the ground.
“This year, because of the tremendous interest in the CBD-rich variety of cannabis — because of the epilepsy patients — investigators are beginning to look at requesting some material with that kind of chemical composition to do some research with it,” ElSohly said. “I honestly anticipate that there is going to be tremendous demand for this material.”
ElSohly said he believes there is “some truth” to the concerns researchers have raised about red tape in getting access to marijuana through the federal government. Still, he said, “if you really want to do some research, the mechanism is there.”
Regulatory hurdles, however, aren’t the only reason that medical marijuana research hasn’t moved forward. In the case of epilepsy, researchers have published about the potential application of marijuana since the early 1970s, ElSohly said, adding that those publications have eliminated the financial incentives for development by drug companies.
“They can’t patent it anymore,” he said. “If they don’t have the (patent) protection, they can’t take something and spend millions and millions of dollars to produce a drug and then the next guy comes along and makes a generic version.”