Summary: Healthline reports on medical marijuana’s increasingly prominent role in science, medicine, and politics, highlighting MAPS’ work to conduct the clinical research necessary to develop medical marijuana into a government-approved prescription treatment for PTSD. The article explores the history of marijuana research, emphasizing how a reduction in government obstacles could facilitate a significant expansion of marijuana research in the United States. “When we decided to legalize alcohol after Prohibition, we still wanted to know what amount of ethanol was in it,” explains Rosalie Pacula of the RAND Corporation’s Drug Policy Research Center.
Originally appearing here.
The popular explanation for medical marijuana dispensaries that have popped up in states from Washington to New York is that marijuana is a wonder drug — treating not just nausea and lack of appetite, but also pain, anxiety, epileptic seizures, and the symptoms of multiple sclerosis and schizophrenia.
The federal government refuses to allow people to use it, proponents say.
The story, however, isn’t quite so simple.
Few doubt that the plant has at least a handful of valid medical uses. But research into those uses isn’t yet up to scientific snuff. Many U.S. studies are based on observations of patients who use marijuana on their own, meaning the dose and balance of active ingredients often aren’t standardized.
If the claims for marijuana are true, then by rights it should be made available for medical use. But there isn’t a single FDA-approved drug in use that is as loosely regulated or as poorly understood as the buds, brownies, and candies for sale at those dispensaries. Legal and logistical barriers to clinical research on marijuana are among the biggest reasons why.
It wasn’t until the mid-1990s that researchers explained how marijuana’s best known ingredient, THC, works. There are at least 79 other potentially active chemicals in marijuana, many with no research on their effects.
“You have to know what you’re describing in terms of what is the specific plant and what are the dosages. On a medicine bottle, that’s very clear. In medical marijuana studies, those details aren’t there,” said Rosalie Pacula, who co-directs the Drug Policy Research Center at the RAND Corporation think tank.
To better understand marijuana’s medical uses, research would have to look a lot more like the drug development research pharmaceutical companies do for their drug candidates.
“If it turns out that a certain strain is really, really valuable, we’ll understand that better if it’s done through standard medical process rather than just being done where people can come in [to a dispensary] and pick one,” Pacula said.
Few academics and no American pharmaceutical companies are investigating cannabis-based drugs the same way they once did synthetic opioids.
Why hasn’t interest in medical marijuana led to controlled dosages, written prescriptions, and insurance coverage? After all, aspirin is made from a compound found in willow tree bark, but people don’t buy willow bark and consume it in the way they see fit to treat headaches and fever.
The Research Gauntlet
Rick Doblin’s answer to the question of marijuana medicalization is long — more than two decades long, actually.
Doblin, who holds a Ph.D. in public policy from Harvard’s Kennedy School of Government, founded and directs the Multidisciplinary Association of Psychedelic Studies (MAPS). MAPS is a California-based nonprofit whose mission is to develop low-cost prescription medications from psychedelic drugs, including marijuana.
Since 1992, MAPS has been trying to obtain marijuana to use in medical research. MAPS first tried to get a government license to grow its own marijuana to explore whether vaporizers were a safer drug delivery system than marijuana cigarettes.
Marijuana is the only Schedule I drug that the Drug Enforcement Agency (DEA) doesn’t permit to be commercially produced for research. MAPS sued the DEA with a University of Massachusetts, Amherst, professor who sought a license to become a second approved marijuana grower. In 2008, a judge sided with MAPS, recommending that the DEA issue a license. It never did.
The agency says that international treaties bind the government to using only a single source of marijuana.
That left MAPS just one option: to buy marijuana from the National Institute on Drug Abuse (NIDA). The University of Mississippi manages an acre-and-a-half plot under its exclusive contract with NIDA to supply marijuana for research.
In 2010, MAPS proposed a study on using marijuana to treat post-traumatic stress disorder in veterans with NIDA marijuana. The proposal got the green light from the DEA and the FDA. But it was rejected by another federal agency, the U.S. Public Health Service.
The Public Health Service review was set up to help NIDA evaluate medical research proposals as it broadened its focus after the Institute of Medicine argued in 1999 that cannabis deserved more study. Research on other, arguably harder drugs, does not require the Public Health Service review, which critics say only adds to the challenges of getting medical marijuana research approved.
MAPS made some tweaks to its study design and got the OK from the Public Health Service. Last month, the group got pricing and availability information from NIDA. After it secures a Schedule I license for one of its researchers, it will launch a study testing the drug’s effects on 76 veterans with post-traumatic stress disorder.
“It’s taken us 23 years,” Doblin said wearily.
MAPS has reason to be frustrated with the single-source system, and some academic researchers share Doblin’s complaints. Much of the most promising recent research on medical marijuana focuses on cannabidiol, or CBD, a non-psychoactive ingredient.
The British drug company GW Pharmaceuticals began testing a mixed CBD/THC product in 1998. But NIDA only began measuring and controlling the concentration of CBD in its supply earlier this year. Researchers interested in the possible uses of any of the other 70-plus ingredients in marijuana have nowhere to turn.
After its phase 2 study is complete, MAPS will have to look for another legal source of cannabis. NIDA doesn’t supply the drug for commercial purposes, and MAPS wants to get FDA approved to sell cannabis as a prescription medication. For any drug to get FDA approval, the product tested in the phase 3 trial must be exactly what will be brought to market. Government pot won’t do.
The number of bureaucratic hurdles has led some groups to allege the federal government purposely blocks research into medical uses of marijuana, a charge government agencies have denied. Earlier this month, the government said it would more than double its planned 2015 production of marijuana for medical research.
Federal agencies may be turning away from the “reefer madness” biases of their past, but now the floodgates are open and a patchwork of state programs that supply marijuana directly to patients has stepped in to fill the void.
State Legalization Is No Cure-All
The rise of more liberal marijuana laws — 20 states have passed them since 2010 — is a victory for marijuana advocates and anti-drug war reformers. But it’s not clear that the gray market for marijuana these laws create is the best option for researchers and patients whose interest in the drug is strictly medical.
Sure, more patients can get marijuana. But they turn to it based on anecdote rather than research, according to John Hudak, a governance expert at the Brookings Institution. And their use of marijuana forces the
tside of the medical system.
Brian Keller, a 52-year-old former optician in Scottsdale, Arizona, suffers from osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. Chronic pain forced him into medical retirement. Keller told Healthline that his pursuit of medical marijuana began with a trip to a strip of seedy doctor’s offices of the kind advertised in many alternative weeklies.
A 2013 survey of Colorado physicians found that most felt they should have more training and education before recommending marijuana to patients. Their concerns have pushed medical marijuana to the fringes of the medical establishment.
Smoking marijuana “makes me feel better because I like to be on the computer, I like to be able to focus, and you can’t do that when you’re stoned,” Keller said.
Keller’s doctors have supported his choice — particularly because the alternative is opioid painkillers, which are more addictive than marijuana and just as mind-altering. But they didn’t suggest marijuana. Nor did they ask about Keller’s use of it on the standard medical paperwork he filled out.
It was dispensary staff — who aren’t required to have any special training — who guided Keller through early trial-and-error efforts to find a strain that relieved his pain without getting him too stoned or keeping him up at night. As he found the right type and strength of marijuana, he found himself unpleasantly drugged once or twice. (He joked an indica strain has earned the nickname “in da couch.”)
Colorado has reported an uptick in young people showing up in hospital emergency rooms after using marijuana since the state made recreational use of marijuana legal in 2010. Mold on the buds is a risk for people with compromised immune systems, Pacula noted. But even with the loose system of oversight that has formed around medical marijuana, the drug has caused few bad medical outcomes.
Though it is easy for Keller to get marijuana, it’s not cheap. He pays about $400 a month out of pocket. Keller would ideally like to be allowed to grow the plant himself, he said. He’d rather go through standard medical and insurance channels.
Keller isn’t alone. The American Academy of Pediatrics and the Epilepsy Foundation say they support the development of cannabis-based drugs under the FDA process.
Last year, The New York Times reported that one family’s public success using a high-CBD strain of marijuana oil to bring their young daughter’s seizures under control was driving a migration of families with children with severe seizure disorders to Colorado. Drs. Orrin Devinsky and Daniel Friedman of New York University’s Comprehensive Epilepsy Center responded with an op-ed in the same paper urging caution.
“The truth is we lack evidence not only for the efficacy of marijuana, but also for its safety,” especially in children, the doctors wrote. “It is troubling that while few barriers exist for parents to give their children marijuana in Colorado, there are significant federal roadblocks preventing doctors from studying it in a rigorous scientific manner.”
Patients have the most to gain from access, which comes with more information about marijuana’s medicinal properties — and its potential side effects.
“I think there’s tremendous value in the clinical trial process,” said Kenneth Kaitin, Ph.D., director of the Center for Drug Development at Tufts University. “You’d understand the clinical pharmacology of the drug, a lot about the correct mode of administration, and more about effects and side effects. That all comes about with rigorous clinical trials, and in many respects if you’re a patient I think you’re better served by having something that’s gone through that process.”
Experiences like Keller’s demonstrate that marijuana can have concrete medical benefits for some patients, and they shouldn’t be kept in the dark about what they’re putting into their bodies.
“There are some states that are trying very hard to regulate the production and quality of the product, but there’s certainly a huge gap in terms of what states are doing versus what the FDA does in pharmaceuticals,” said Hudak, of the Brookings Institution. “I think there is a lot of space to improve the quality of testing, titrating and dosing when it comes to medical cannabis.”
A Scheduling Conflict
The biggest roadblock to higher quality research is the drug’s labeling as a Schedule I controlled substance. That listing means the federal government considers marijuana to have a high risk of abuse and no legitimate medical use. Congress or the FDA could demote marijuana to a less stringent schedule. Opioid painkillers such as OxyContin are Schedule II drugs, for example.
The AAP, the Epilepsy Foundation, and the American Medical Association (AMA) have all called on the federal government to move marijuana to a lesser schedule.
“Pharmaceutical companies’ ability to conduct research on marijuana is oftentimes stymied by federal scheduling. That creates a burden that just adds to their costs. Even if they started to do research that could be used to create cannabis-based medicines, the Schedule I status makes it extraordinarily difficult for them to bring those drugs to market,” Hudak said.
Researchers don’t just have to jump through hoops to get marijuana. They have to demonstrate to the DEA that they can account for every ounce of it once they’ve gotten it. Devinsky and Friedman said in their op-ed that they were keeping their high-CBD strain — which doesn’t make users high — “in a 1,200-pound safe in a locked room, in a building with an alarm system.”
Federal laws have created roadblocks imposing enough that even with global interest in the medical uses of marijuana, foreign drug companies like GW Pharmaceuticals and a handful of Israeli companies have the field more or less to themselves. Even GW, with the support of the British government has “struggled to get through clinical trials” in the United States, Pacula said.
MAPS’s move to pursue drug development through a benefits corporation nestled within a non-profit makes clear that few expect cannabis drugs to deliver lavish financial returns. Bringing a new drug to market costs $2.5 billion, according to Tufts research. A drug based on marijuana could shortcut part of the process, and chip away at the price, because some of the work has already been done.
Whatever the cost, drug companies would look to recoup their investment by guarding against competition with patents. Marijuana, a plant with a 2,000-year history, isn’t a great fit for the patent system.
“You can’t take a plant and patent it,” said Kaitin. “You’d have to have some sort of a process for isolating the active compound. But once you get away from product patents, the patent strength starts to diminish. Patents are progressively less and less of a protection because it’s a lot easier to reproduce a compound using a slightly different process.”
In the mid-1980s, with the AIDS crisis raging, AbbVie Pharmaceuticals, then called Abbott Laboratories, won a patent and FDA approval for a synthetic version of THC. The drug, taken in capsule form to treat nausea and weight loss, never took off. Many patients reportedly prefer smoking.
Pharmaceutical companies may also bring some of their own biases to the table.
“These pharmaceutical companies answer to boards of directors, and often times there are corporate interests that are still leery and skeptical of cannabis,” Hudak said.
Even as the social stigma erodes, the pharmaceutical industry won’t necessarily see its incentives increase.
“If more and more states allow legalized marijuana in the states and you can buy it legally, what happens to your market?” Kaitin said.
State-by-state laws aren’t ideal from any perspective. Patient advocates claim that access to a drug shouldn’t be d
etermined by ZIP code.
“You have not just different rules at the state and federal level, but you have different rules from state to state. That’s not really an effective system of governance,” he said. “It creates a pretty messy system of federalism that … isn’t ideal and at the end of the day may not be sustainable.”
The Calm After the Storm?
Things can’t remain in the state of chaotic exuberance we’re seeing now. But it would be hard to unring the bell now that people in states like Arizona and Colorado expect to be able to buy marijuana at their local dispensary.
A few things could happen to bring medical knowledge about cannabis and patient access to the drug into better sync, even if efforts at federal rescheduling continue to fail in Congress.
As more evidence comes through suggesting marijuana can help patients, pressure could build on federal agencies to facilitate more research. The AMA has asked the government to do just that, and to guarantee that NIDA will supply “cannabis of various and consistent strengths.”
If researchers found that a delivery system other than smoking — a patch or spray, for example — or an unknown compound or process delivered better results or fewer unwanted side effects, we could start to see cannabis-based medicines appear within the medical system.
“What would be required now would be some smart academic clinicians who develop a new understanding or a better idea of how to use it that would suggest that, if I really want a medical product that’s been tested, I should get that. I think that would change the environment,” Kaitin said.
Short of that, states could require that marijuana be identified by strength and strain, a direction some are already headed as regulations shift.
Many of these steps could be taken independent of the policy conversation about whether people should be able to use marijuana recreationally.
“When we decided to legalize alcohol after Prohibition, we still wanted to know what amount of ethanol was in it,” Pacula said.