Medical cannabis: US researchers battle for access to the plant
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g6997 (Published 21 November 2014) Cite this as: BMJ 2014;349:g6997
- Suzy Frisch, freelance journalist, Minneapolis, USA
- suzyfrisch{at}yahoo.com
Last summer, Kalpna Gupta, professor of medicine at the University of Minnesota, secured $9.5m (£6m; €7.6m) in funding from the National Institutes of Health (NIH) to study whether cannabis can ease the crippling pain experienced by people with sickle cell anemia.
Gupta wanted to focus on sickle cell anemia because more people are developing the disease. “The pain can be intense and increase throughout their life, and then they have crises, which is the worst pain. They need to be hospitalized and they require narcotics again and again,” which can lead to addiction, Gupta says. “We found that cannabinoids are one of the most promising treatments available.”
Yet a year later, in August 2014, Gupta still was unable to launch her study. She encountered strict controls on the study because cannabis is classed as a schedule 1 drug (equivalent to class A in the UK) by the federal Drug Enforcement Administration (DEA). Gupta was told she would need to register with the DEA as a cannabis researcher and make changes to her laboratory, including building a safe to store the marijuana and modifying the clinic where she would carry out the study to ensure that vapors could not seep out. To save time and money, Gupta instead moved her study across the country to the University of California–San Francisco to work with Donald Abrams, a cancer and integrative medicine specialist and professor of clinical medicine, who already had the necessary approvals and had completed five medical cannabis studies since the mid-1990s.
Twenty three states, the District of Columbia, and, most recently, the overseas US territory of Guam have legalized the use of medical marijuana since 1996.1 However, because at the federal level it is still classed as a schedule 1 drug (along with heroin, LSD, and MDMA) scientists who want to investigate its therapeutic potential face layers of regulation, scrutiny, and very limited access to the plant.
“Every study I do requires eight different approvals,” Abrams told The BMJ. “It’s why we don’t see that many people do this kind of research. It’s time consuming, and there are a lot of hoops. It’s not for the faint of heart.”
The result is that although one million Americans were already legally using marijuana for medical purposes in 20122—and the trend towards legalization at the state level means that number is likely to increase—there is limited research exploring how cannabis affects various diseases in humans, its safety, and the most effective form of delivery.
“At every level my research has been impeded,” says Jahan Marcu, a cell biologist turned campaigner who says he had to give up his attempt to study whether marijuana halts the progression of neurodegenerative diseases like amyotrophic lateral sclerosis, Parkinson’s, and multiple sclerosis because of the bureaucracy. “When you want to work with cannabis, the government holds the hoops and lights them on fire, and you have to jump through them.” Marcu now works as chief scientist at a pro-medical cannabis group Americans for Safe Access and is director of research and development at Green Standard Diagnostics, a company developing scientific standards for medical cannabis laboratories.
Since the Controlled Substances Act of 1970 designated marijuana as a schedule 1 drug, the DEA has considered cannabis to be one of the most dangerous substances available, with “no currently accepted medical use and a high potential for abuse.”3
To research the drug’s therapeutic potential, a scientist must secure approval from an institutional review board, the Food and Drug Administration, the DEA, and the Department of Health and Human Services’s Public Health Service (PHS). Proposed trials can bounce around from agency to agency, especially if one of them asks for modifications to the protocols. Then the study needs to go back to the other agencies to make sure they approve the changes. Scientists can spend years going through the process, after which successful applicants must obtain marijuana from the National Institute on Drug Abuse (NIDA)—the only legal source of research grade cannabis in the United States.
In the 38 years from 1971 to 2009, only 33 controlled clinical studies conducted in the US were published, according to the Journal of Opioid Management, but nearly all of those showed “significant and measurable benefits in subjects receiving the treatment” to manage chronic pain, muscle spasticity, cachexia, and other debilitating problems.4
Shifting opinions
Plenty of patients believe that cannabis and its derivatives can relieve symptoms and pain associated with conditions such as cancer, HIV/AIDS, seizures, glaucoma, migraines, and spasticity. There is debate among the medical community, however, on which forms of cannabis and which delivery system are most effective.
Synthetic cannabis has been licensed for medical use. Dronabinol and nabilone are classified as schedule III and II medications, respectively, but some studies have found these drugs to be less effective in treating pain and other symptoms than non-synthetic forms of cannabis.
On the flip side, a chief complaint about natural cannabis is that it is difficult to standardize a plant based medication and regulate doses. The delivery method—smoking, vaporizing, or pills—adds another level of variability that makes it difficult for physicians to prescribe specific quantities.5
In recent years, polls suggest that more and more physicians have become convinced of the medicinal benefits of cannabis. A survey by Web MD of 1544 doctors in 10 US states reported that 67% of respondents would support making cannabis a medical option for patients, while 69% said that it can help with certain treatments and conditions.6 In 2005 the Journal of Addictive Diseases reported that 36% of the 960 respondents to a survey thought that prescribed cannabis should be legal.7 The National Institutes of Health, the Institute of Medicine, the American Medical Association, and the American College of Physicians have also issued statements supporting further clinical research and development of cannabis based therapies over the past five years.
In addition, state and federal leaders have become more vocal about their support for easing restrictions on cannabis research. Governors from Rhode Island, Washington state, and Colorado filed a petition in 2011 asking the DEA to reclassify cannabis in a lower schedule. The DEA has not yet ruled on the petition. There is no time limit on how long the agency can take to respond, unlike the FDA, which must respond to petitions or requests within a certain amount of time (usually 30 days).
This summer, 30 bipartisan members of Congress urged the federal government to lift research regulations, such as securing approval from the PHS.
“We believe the widespread use of medical marijuana should necessitate research into what specific relief it offers and how it can best be delivered for different people and different conditions. Yet the scientific research clearly documenting these benefits has often been hampered by federal barriers,” the members of Congress wrote in a letter addressed to Department of Health and Human Services (HHS) secretary, Sylvia Burwell.8 “In light of the fact that opioids and barbiturates have been researched and developed for human use, it would seem that we should investigate the legitimate medical uses of marijuana.” They also asked that NIDA give the plant, at cost, to all studies that have received approval from the regulating agencies instead of giving NIDA power to decide which studies get the plant. Burwell, unlike the DEA, recognizes the potential for cannabis compounds to provide new treatments, but she defended the current research approval system in a written response to the members of Congress. “HHS is committed to making this process efficient and welcomes your input as we consider improvements,” she wrote.
In the meantime, “patients are being sacrificed on the altar of marijuana prohibition,” says Rick Doblin, founder and executive director of the Multidisciplinary Association for Psychedelic Research, a non-profit educational and research organization that works to develop cannabis and other psychedelics into prescription medication.
Doblin and the Drug Policy Alliance, a non-profit organization campaigning for drug policy reform, issued a report in June 2014, The DEA: Four Decades of Impeding and Rejecting Science.9 Its case studies show a “pattern of behavior that demonstrates the agency’s inability . . . to be fair and impartial [when classifying cannabis and making it available for research], or to act in accordance with the scientific evidence,” the report says.
The DEA has held fast to its opposition on medical cannabis, arguing in a 2013 position paper that the drug is not medicine and that it is properly categorized as a schedule 1 drug because of its high potential for misuse.10 The agency has consistently fought efforts to reschedule cannabis to a lower category or to allow entities other than NIDA to grow it for research purposes, and it has not responded to recent criticism.
There are signs, however, that the tide is turning. NIDA’s spending on cannabis research has increased to $30m in 2012 from $6m in 2003,11 and the organization said in January that 15 of the 28 studies it is currently funding are related to therapeutic uses of cannabis and cannabinoids for conditions like seizures, inflammation, pain, and psychiatric disorder; only 13 are into substance misuse, withdrawal, or dependence.
The NIH is also supporting research into marijuana and its constituents, including 54 active grants studying the potential therapeutic benefits of cannabinoids in nine disease categories.
This May the DEA approved a far larger crop than in previous years of marijuana to be produced for NIDA at the University of Mississippi, which has run the government’s only marijuana farm since 1968. The annual production quota increased to 650 kg from 21kg.
“The additional supply to be manufactured in 2014 is designed to meet the current and anticipated research efforts involving marijuana,” NIDA confirmed in an email to The BMJ. “This projection of increased demand is due in part to the recent increased interest in the possible therapeutic uses of marijuana.”
It remains to be seen how much of this increased supply of the plant will be authorized for research into its medicinal potential rather than into the dangers of patients becoming addicted.
State research
Even state governments face tough obstacles. Minnesota’s new law approving the medical use of cannabis, passed in May 2014, requires the Department of Health to conduct research on people taking cannabis for medical purposes to try to learn more about how it works. Manny Munson-Regala, an assistant commissioner for the Department of Health, says Minnesota intended to conduct a double blind, placebo controlled clinical trial to see how effectively cannabis treats eight conditions, what is the required dose, and which is the best formulation (pills, liquid, or vapor).
“We wanted to design a program that doesn’t start with the assumption that this stuff is good for you. Let’s try to answer the question of whether it works, and if so, what specifically works, how much do you need to take, and are there any contraindications with other medications people might take for their conditions?” says Munson-Regala. “From talking with colleagues in other states, it’s apparent that there is a thirst for this kind of information, but it’s not easy to get.”
Yet when officials found out about all the regulatory hurdles involved with cannabis research—and the amount of time it would take to overcome them—Minnesota decided to change course. Instead, it will conduct observational studies of every patient who receives therapeutic cannabis, using objective measures to build a database of information on what worked and what didn’t.
Only researchers with substantial funding seem to have managed to complete clinical studies in the US over the past 15 years. In 2001, the state of California provided funding that has allowed the University of California Center for Medicinal Cannabis Research to complete seven clinical studies on inhaled cannabis.12 All results indicated efficacy in short term trials. “While such studies are clearly possible,” said Igor Grant, director of the center, “the resources needed to obtain approval and conduct such trials makes them not feasible for most researchers.”
Notes
Cite this as: BMJ 2014;349:g6997
Footnotes
Competing interests: I have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer reviewed.