Even though Maryland is following the lead of 23 other states in setting up a medical marijuana industry, the collective experience of those states has translated to relatively little understanding of how the dozens of active substances within the plant affect health.
As a result, Maryland will launch what likely will become a multimillion-dollar industry to make a psychoactive drug more available statewide without the benefit of proven information about the health implications.
Research is limited because the federal government classifies the drug in the same category as heroin and ecstasy, and restricts the cultivation of marijuana plants. Scientists need federal approval before launching studies that bring pot into labs and face oversight to ensure the drug doesn't end up in the hands of felons.
With marijuana plants on track to sprout in Maryland in the new year, companies vying for licenses and at least two state universities plan to expand on that knowledge here. Researchers at Frostburg State University and the University of Maryland Eastern Shore want to know how and why marijuana eases nausea or prevents seizures, whether it is any more effective than standard medical treatments and what side effects it can cause.
Two companies have formed partnerships with researchers in Frostburg and Princess Anne. If they are chosen out of the more than 1,000 businesses vying for licenses to grow, process or dispense marijuana, they could fund science that experts say is lacking in the controversial field.
"Most research has been anecdotal," said Michael Horberg, a member of the Maryland Medical Cannabis Commission and executive director of the Mid-Atlantic Permanente Research Institute. "While they're formative and suggestive, they're anything but our standard scientific research."
While the partnerships are tentative — state officials said this week they don't expect to award the first licenses to grow and process marijuana until the summer — they illustrate untapped demand from both investors in the state's budding pot industry and from scientists looking for data to inform discussions over drug policy.
"The intent with the research is just to start collecting a lot of the data," said Ethan Ruby, CEO of Peak Harvest Health, a Cumberland-based venture tied to a Connecticut medical cannabis company. "Marijuana is illegal because there are no studies, and there are no studies because it's illegal."
Maryland legalized medical marijuana in 2013, but only allowed teaching hospitals to distribute it. None did, so new laws were passed in 2014 and 2015 allowing for private manufacturing and retail sales.
By the time the Nov. 6 deadline for applications arrived last month, the state had received 146 applications for a maximum of 15 marijuana growing licenses; 124 applications for an unlimited number of licenses to process marijuana into oils, tinctures and other products; and 811 applications to open up to 94 dispensaries spread equally across the state's 47 legislative districts.
Peak Harvest signed a memorandum of understanding earlier this month with Frostburg State, where faculty of the university's ethnobotany program hope to study marijuana in the same way they analyze substances like ginseng or black cohosh, two plants with medicinal applications.
That followed a similar partnership formed by Wellness Farms, a company with eight medical marijuana licenses across the country, with UMES. That university has programs in agriculture, pharmacy and pharmacology that could host studies of medical marijuana.
The research would differ from ongoing federally funded studies, which largely explore issues of addiction or brain development and do not bring any marijuana into lab settings, according to a National Institutes of Health database.
For example, a study at the University of Puget Sound is analyzing sewer waste to gauge marijuana consumption in Washington state, where pot is legal. The University of California, Los Angeles is studying how marijuana use during adolescence has affected the memory and cognitive function of baby boomers. And Michigan State University is testing the effects of chemicals found in marijuana on the generation of neurons in mice brains.
The researchers at Frostburg and UMES instead plan to conduct more basic research, analyzing marijuana plants themselves, the chemicals they contain and the way those chemicals behave in the body. They also could conduct research that more directly benefits growers and dispensers of marijuana, exploring how to most efficiently and effectively grow the plant and engineer it for desired qualities or levels of strength.
Any research that puts marijuana in the hands of scientists is regulated by the Drug Enforcement Agency, the National Institute on Drug Abuse, a branch of the NIH, and the Food and Drug Administration. The FDA and DEA review projects to ensure they are scientifically valid and safe.
The government also controls the supply of marijuana that can be used in federally funded research — it all comes from a marijuana farm at the University of Mississippi that is licensed by the DEA and under contract with the federal drug abuse institute.
That is all because marijuana is classified as a Schedule I drug, a category under the federal Controlled Substance Act that contains what are considered to be the most dangerous drugs that have the potential to cause severe psychological or physical dependence. They include heroin and LSD.
The oversight is required to ensure the drugs are kept in a secure place and that they are out of the hands of anyone with drug or felony convictions, as required by federal law, said Barbara Carreno, a DEA spokeswoman.
Asaf Keller, a professor of anatomy and neurobiology at the University of Maryland School of Medicine, said conducting research involving marijuana requires a cumbersome process that can take longer than a year even before a study begins. He is studying the role of marijuana use during adolescence in causing permanent harm to cognition.
Even after getting federal and state approval for the research, Keller said, his lab is subject to "serious monitoring," including random inspections by DEA agents, a level of scrutiny he thinks is too high.
"It's appropriate for anything except marijuana," he said of the restrictions on use of Schedule I drugs in research.
Groups like the National Cannabis Industry Association have argued to have marijuana placed in a different category of drugs under federal law, if not to make more aggressive changes in the law, said Taylor West, the group's deputy director.
A Brookings Institution report released in October suggests the intense oversight of marijuana research has "paralyzed" efforts to study it and "threatened the integrity of research freedom." The report advocated for broader production of marijuana for use in research, and reforms to licensing and registration requirements.
Carreno said the concerns are unfounded because there are 300 researchers approved to do research on marijuana.
"The DEA has facilitated marijuana research for decades," she said. "It's not correct to say that our limitations keep research from being done."
Researchers at Frostburg are unsure of what sort of research they might be able to do. Joseph Hoffman, dean the university's College of Liberal Arts and Sciences and administrator of its Appalachian Center for Ethnobotanical Studies, said faculty and students may be limited to analysis of data that Peak Harvest would share.
"We know what we can't do, and that's almost anything," Hoffman said.
Despite the lack of clarity about what may be permitted, the research possibilities are still exciting, said Dominick Murray, executive director of business and economic development for UMES.
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"It's too early for us to be worried about that part of it," he said. "Certainly we will have all appropriate attorneys general looking at whatever processes are happening."
Horberg, the state cannabis commission member who chairs its research subcommittee, said the rollout of Maryland's medical marijuana program at least means the chance to gather larger sets of data on pot users and their health. Researchers may be able to conduct natural experiments or use sophisticated statistical models to make conclusions about the effects of medical marijuana use, he said.
Studies that have been conducted show mixed results. A review of 79 studies published by the Journal of the American Medical Association in June found some success treating chronic pain and the effects of multiple sclerosis but less evidence supporting other common medicinal applications of pot, including in people with cancer and those infected with HIV.
Without more of that sort of data, it will be hard to evaluate any benefits or risks of medical marijuana.
"I think that's only going to be through well-sponsored research," Horberg said.