How procedural and legal restrictions make studying the effects of medical marijuana difficult.
Despite several efforts to make marijuana more mainstream, the idea of legal pot is still too much for many voters to bear. California’s Proposition 19, which would legalize, tax, and regulate marijuana, was defeated yesterday, while Arizona, South Dakota, and Oregon all voted no on issues relating to medical marijuana. (News was better in Massachusetts, where voters said yes to a nonbinding ballot question asking whether elected officials should support legislation efforts.)
For all the arguments about the drug’s effects and the ramifications of legalization made by pot proponents, there are still many questions about how pot and its various components affect humans on a physiological level. There are scores of chemicals that have already been isolated from the cannabis plant, which taken together may represent a treasure of potential medicines and provide clues about how the brain is wired. Some of these chemicals have already been turned into prescription medicines, like Marinol and Sativex. And via a little-known program that stopped taking new patients in 1992, called the Compassionate Investigational New Drug program, a few people are still receiving marijuana from the federal government for their medical ailments, even though no research is being done on their experience. In fact, due to regulatory hurdles, it’s incredibly difficult to study the effect of smoked or vaporized marijuana in humans. So as states move closer to legalizing medical marijuana, there’s still a dearth of data to quantify the many claims about pot’s safety or medical efficacy.
To study marijuana in human subjects in the United States, researchers need to go through a number of steps. Marijuana is classified by the Drug Enforcement Agency as a Schedule 1 drug, a category that has the highest level of restriction, so researchers must apply for a license from the DEA before they begin their studies. Because of the fear of drugs being diverted for nonresearch purposes, the DEA has strict eligibility requirements for Schedule 1 licenses. Researchers also need approval from their institution (usually a university or research center), which can be a challenge—employers may be skittish about the fallout of studies on illicit drugs, whether from disgruntled university or foundation donors, bad press, or unforeseen consequences of the research.
If the first two steps are satisfied, getting funded is the next hurdle, followed by actually acquiring the marijuana for study. There’s only so much money for research—in any field—and competition is intense. For Schedule 1 drugs like marijuana, the vast majority of money for research comes from the National Institute on Drug Abuse (NIDA). “NIDA…has a congressional mandate to only study substances of abuse as substances of abuse,” says Don Abrams, chief of hematology/oncology at San Francisco General Hospital and professor of clinical medicine at the University of California, San Francisco, who has done studies on marijuana in the past. In his experience, studies that aren’t targeted at the dangers of marijuana or ways to treat marijuana abuse and addiction rarely pique the interest of NIDA, which is also the only legal marijuana source for research in America.
NIDA may refuse to supply researchers with marijuana or fund research if the study is deemed to be lacking in “scientific value,” says Steven Gust, special assistant to the director of NIDA. But, he adds, “the proof is in the pudding”: NIDA has approved some research and provided marijuana for some studies, like Abrams’s.
(Other highly restricted drugs are not subject to what Rick Doblin, founder and director of the Multidisciplinary Association for Psychedelic Studies (MAPS), and Abrams have independently referred to as a “NIDA monopoly” on supply. For instance, MDMA, the drug commonly known as ecstasy, is currently in FDA trials for its use as an adjunct to therapy for PTSD and end-of-life anxiety, but there are multiple, legal sources of the drug for medical MDMA research, such as chemists with a license to produce the substance, like David Nichols at Purdue University. NIDA plays no role in approving the MDMA trials. Though MDMA and marijuana are both Schedule 1 drugs, Gust says there are unique rules governing marijuana production and distribution that are dictated by an international treaty called The Single Convention on Narcotic Drugs and that restrict control of marijuana to a single organization in the U.S.
U.S.-based researchers sometimes try to circumvent the restrictions by playing the semantics game. In the 1990s, Abrams was interested in testing the hypothesis that smoked marijuana might help HIV patients with nausea and reduced appetites. His first protocol for the study was approved by the Food and Drug Administration, but rejected by NIDA. Abrams then “reformatted” his protocol, instead proposing to study the potentially deleterious effects smoked marijuana might have on viral counts in HIV patients taking prescription protease inhibitors. This time, the study was approved, and NIDA provided him with marijuana.
As he suspected, Abrams found that marijuana did not negatively affect viral counts in HIV patients, but it did appear to increase average body weight by 7.7 pounds, a positive indicator of health, compared with only 2.9 pounds in those who received a placebo. However, since the study was designed to look at risks, Abrams did not have enough data to confirm the weight-gain findings with a high degree of confidence.
In the U.K., researchers got around similar restrictions by skirting traditional scientific methods. A team of scientists at University College London (UCL) concluded that short-term memory disruption under the influence of smoked marijuana varied depending on the ratio of two chemicals in cannabis: tetrahydrocannabinol (THC) and cannabidiol (CBD). But the researchers didn’t come to this conclusion by studying marijuana use in the controlled environment of a lab. “We didn’t think we’d get permission for that,” says Valerie Curran, a psychopharmacologist at UCL. “And we thought that would be a step too far to go to get government approval.” Instead, Curran and the rest of the team tested subjects smoking the subjects’ own pot in the subjects’ own homes, and took samples back to the lab for analysis.
Other researchers are hoping to change, rather than subvert, the current system. Lyle Craker, a professor of plant, soil, and insect sciences at the University of Massachusetts, Amherst, with the help of Doblin and MAPS, has been petitioning the DEA for nearly a decade for a license to grow cannabis for FDA-approved research, which would eliminate the need for NIDA approval. In 2007, an administrative law judge recommended that the DEA grant Craker the license. But just six days before Barack Obama was sworn in as president, the DEA issued its final ruling and rejected Craker’s petition.
Recent anecdotal evidence suggests that marijuana might yield additional medical treatments for difficult conditions, like fibromyalgia and autism. And cannabinoids, the active ingredients in marijuana, have strong antioxidant and neuroprotectant properties, according to a Department of Health and Human Services patent for these uses.
These possibilities, combined with the unknown implications of widespread marijuana use by adolescents, says University College’s Curran, makes studying marijuana all the more important. “I think, in a way, it’s unethical not to do research on it,” she says.
But until pot becomes more politically accepted, the science may have to wait.
NOTE: there is a small picture gallery linked on the above story of "the most marijuana friendly nations"