View attachment 53030 Whatever happens November 8, marijuana won. It’s hit an all time high in popularity—60 percent of Americans now support legalization. That handily beats both major-party candidates in favorability. Twenty-five states and Washington, DC have already legalized it for medical use. And come election day, nine states will decide whether to loosen laws further (five voting on legalization, four more on medical use).
The psychoactive plant is no longer the gateway drug of deadbeats and loafers; it’s becoming acceptable socially and politically. And with the public opinion that it’s largely harmless, users have stoked hopes that it can safely and effectively treat a range of medical ailments, from chronic pain and migraines to epilepsy and autism
Marijuana advocates are delighted by these shifts, of course. But as voters, lawmakers, patients, and doctors look to make informed decisions on legislation and usage, they’re coming up with questions—and some are pretty simple. Are there long term effects? What diseases or symptoms can it really treat? In which patients? And how? What strains and products are best? Is it OK to mix it with prescription meds? What all does marijuana’s 60 or so active cannabinoids do in our brains exactly?
Despite decades of federally-funded research, researchers still don’t have a lot of clear or detailed answers. Stigma has been one of the most obvious barriers to getting them. Much of the early research burnt in the idea that marijuana is simply an addictive drug that saps intelligence and boosts laziness—a characterization that’s been hard to shake in the medical community. But inconspicuous bureaucratic barriers may have played a larger role.
“We knew that there were going to be hurdles, but we didn’t think that there’d be quite this many,” said Jacci Bainbridge, a clinical pharmacist specializing in neurology at the University of Colorado. This month she and her team are starting a clinical trial using marijuana to treat chronic back pain—something many of her patients are already doing on their own. In Colorado, a state that legalized marijuana, her patients can simply stroll into dispensaries and sample a variety of cannabis products. But Bainbridge, a federally funded researcher, is bound by federal laws.
There’s extra paperwork, committees, planning, and inspections, she said—some hurdles researchers studying heroin don’t even face. By the time she and her team got the final go ahead for their trial, they had renovated the campus’ clinical trial center to contain a room with a specialized ventilation system. They shuffled their study design to comply with federal laws on dispensing marijuana. They installed digital passcodes on the entry doors to their trial area. And they now have a designated freezer for pot storage, set to -70°C and fitted with a giant coil lock that snuggly wraps around the frozen box to clench it closed—a contraption Bainbridge describes as “craziness.”
In some ways, the loosened pot laws and public favor has exacerbated the research hurdles and data shortage, Bainbridge said. More patients are now experimenting with the vast variety of marijuana-based products offered on unbridled markets. Patients mix those products with different treatment strategies and prescription medications with unknown interactions and effects. In many cases, researchers aren’t even sure what’s in the dried plant material, resins, liquids, and oils that their patients are smoking, vaporizing, or eating. These real life experiments raise swathes of new research and medical questions.
“You kinda need that data so that you can really tell patients ‘do this’ or ‘don’t do this’,” Bainbridge said.
On the other hand, the soaring support for weed has fired up some researchers like Bainbridge to finally get those answers. And the federal government recently made a rather dramatic shift in its stance. In August, the US Drug Enforcement Agency reaffirmed that marijuana should be a Schedule I controlled substance. That designation is the same one used for LSD, heroin, and ecstasy, meaning that marijuana has no accepted medical use and a high potential for abuse. But also in its announcement, the agency made the stunning move to open the door to more marijuana research. Proponents are optimistic that it will usher in the clinical data needed to reverse the government’s Schedule I listing and get answers to patients.
“It’s a really great moment to be talking about this,” said Brad Burge, Director of Communications and Marketing at the Multidisciplinary Association for Psychedelic Studies (MAPS), a California-based nonprofit that has fought for for decades to get more clinical research on marijuana.
Right now, MAPs is finally kicking off its own marijuana clinical trial, run by researchers at Johns Hopkins University and independent researchers in Arizona. Their triple-blind, randomized controlled trial will examine whether smoking marijuana can help 76 U.S. veterans suffering with treatment-resistant posttraumatic stress disorder (PTSD). The trial has been in the works for about 17 years, Burge said, dragged down by paperwork and government approval among other things. But on August 25, the MAPS-backed researchers got their first batch of government-grown pot—sent with the blessing of the National Institute of Drug Abuse or NIDA.
Of the 27 institutes and centers in the National Institutes of Health, NIDA may not be the first to springs to mind. But NIDA looms large in the medical marijuana field; it is the gatekeeper of all of the federal government’s marijuana for research.
Since 1968, six years before NIDA was even established, the DEA struck up a deal to let the University of Mississippi have the only license to grow marijuana for research purposes. The deal started informally, said Steven Gust, Special Assistant to the Director at NIDA. Some researchers were looking to study marijuana, he explained, and a scientist at Ole Miss just happened to offer to grow it for them. That scientific favor turned into a decades-long monopoly.
A few years later, as research interest grew, the NIH decided to make things more formal. NIDA contracted with the University of Mississippi to fund the DEA-approved pot production and use the University as a supplier for any government-funded marijuana research. The contract only lasts for five year increments, after which other institutions can compete to take over marijuana production. But in the decades since, no institution has ever beat out Ole Miss for the gig.
Currently, the NIDA-funded researchers there have a 12.5-acre plot of land for growing government pot—although they usually only use about one and a half acres of it—plus an indoor growing room that is in use all year round. Production is based on requests and can fluctuate. In 2014, the facility cranked out about 600 kilograms in total, Gust said. That includes marijuana of various strengths, containing tetrahydrocannabinol (THC), the main psychoactive component of marijuana, at concentrations of one percent to more than 10 percent. Researchers at Ole Miss are now working on offering high-concentration extracts of THC as well as ones of cannabidiol (CBD), the marijuana component thought to be most promising for medical treatments.
Getting access to that government weed
isn’t as easy as it was in 1968, however. Instead of asking nicely, researchers interested in conducting clinical research with marijuana must first register with the DEA and prove they have a secure location for storage and use. Then they have to get approval from the Food and Drug Administration to test out a marijuana treatment on patients as an “investigational new drug” or IND. And last, they must be able to demonstrate that the project is legit and worth doing, such as by winning an NIH grant, often through NIDA. Until last year, a special committee high up in the Department of Health and Human Services would also need to sign off on the worthiness of the research project—a hurdle researchers using other Schedule I drugs didn’t have to do. However, the Obama administration scrapped the requirement, saying it was redundant with the FDA’s sign-off.
In 2015, NIDA funded 281 marijuana-based research projects, shelling out more than $111 million. Forty-nine of those projects were looking at therapeutic uses of marijuana or cannabinoids.
“There’s a lot of complaining out there that we’ve gotten wind of,” Gust said of the approval process. “But to be honest with you, I don’t think it’s any more difficult to do research on marijuana than it is on any other Schedule I drug.” Noting the decades of NIDA-funded marijuana research, he added: “While it may be a hassle, it’s obviously doable.”
High time for change
While doable, the hassles can have had a chilling effect on research, scientists told Ars. As Bainbridge and her colleagues slogged through the federal approval process, they also had to navigate institutional and state approval processes and oversight. With the trial getting underway this month, the researchers know they have to stay on their toes—the DEA can do surprise inspections at any point, making sure everything is under the proper lock and key and every bit of marijuana is accounted for.
“There were so many days were we just thought: What are we doing? Why are we doing this? Do we really need this?” Bainbridge said. But she said they kept going. “It’s really important to gather this information, because people are doing it,” she said, referring to her marijuana-using patients.
Marcus Bachhuber, a primary care doctor at Albert Einstein College of Medicine, agrees. With more patients turning to marijuana, “there’s a lot of interest now more than ever” in medical marijuana research. He said that some of his patients struggling with chronic pain have told him that marijuana is the only thing that works for them and that it helped them completely kick prescription pain killers. In 2014, Bachhuber and colleagues published a study that found that states with medical marijuana laws have lower rates of death by opioid overdoses. But it’s difficult to prove causation without more clinical work. “The thing that frustrates me and frustrates a lot of people is that doing the research is so difficult… I think there’s a lot of people who would be interested in doing more research and are stymied by the hurdles.” Right now, Bachhuber and his colleagues are in the planning stages of a study to look at patterns of opioid usage and marijuana usage among pain patients in New York state. They’re working to get internal approval and will be applying for funding through NIDA.
While the logistics and hassle are hard to avoid, Burge of MAPS also thinks that NIDA’s monopoly has held back research. The institute, which is focused on drug abuse by mandate, gives preference to studies that look for marijuana’s negative effects, Burge says. And as the sole source of the government’s stash, researchers are limited to doing research on only the marijuana strains and products that Ole Miss can produce. Burge notes that some of the varieties of marijuana that were approved for their PTSD trial won’t be included after all because NIDA didn’t have them available. Meanwhile, patients are sampling the wide variety of products on the market that NIDA isn’t keeping up with. Those products may have wildly different benefits and risks that warrant research.
The DEA agrees with Burge on this last point. “The DEA wants answers to the same questions everyone else wants answers to,” Russ Baer, a spokesperson for the DEA, said. That’s why in August, the agency announced that it would open up marijuana production, eliminating NIDA’s monopoly. Now, any institution can apply to grow marijuana for research purposes and those growers will have no interactions with NIDA. The DEA will still require Fort-Knox-level securities measures for any new growers, but is hopeful that institutions and other organizations will step up. In the end, they want to see an increase in the strains, varieties, and products available for researchers so that they can finally get clear answers on pot’s effects.
At the time that Ars spoke with Baer, the DEA hadn’t received any applications. But Burge said that MAPS, in collaboration with a researcher Lyle Craker at the University of Massachusetts Amherst, is preparing to submit their application by the end of the year. The group had tried for a permit earlier, long before the DEA announced it would open up licensing. MAPS effort failed only after lengthy legal proceeding. “We have a great shot,” he said of their upcoming try.
And from there, Burge is hopeful that the DEA and the rest of the federal government are just waiting to see positive clinical data to roll in and—at a politically opportunistic moment—change their stance. “The DEA is never going to say ‘we restricted research all these years and now we just changed our minds,’ he said. The DEA needs to seem cutting edge and say they’re looking at new data that shows for the first time that marijuana should no longer be Schedule I, he added. “And we’re happy to let them do that.”
By Beth Mole - Ars Technica/Nov. 5, 2016
Art: 1-Frederick J. Brown; 2-University Mississippi