Researchers at two Oregon universities made waves across the internet this week after offering evidence that compounds from cannabis could be a valuable defense against COVID-19 infection.
In a paper published in the the peer-reviewed Journal of Natural Products, Oregon State University’s Dr. Richard van Breemen and six other researchers outlined a groundbreaking discovery that, when attached to select non-psychoactive acids from cannabis—precursors to psychoactive compounds Cannabidiol (CBD) and Tetrahydrocannabinol (THC)—SARS-CoV-2 spike proteins had difficulty entering and infecting human cells in a lab setting.
Their findings could offer an additional pathway to slowing the spread of COVID-19 and subsequent variants, and could play a significant role in global response to the pandemic. But van Breemen told Motherboard his findings didn’t come without significant legal hurdles; conducting research on a substance that’s strictly monitored in his state, and illegal federally, proved difficult, despite the urgency of the pandemic.
Van Breemen and his colleagues aren’t the only scientists looking into the possible benefits of cannabis-derived products when it comes to COVID-19. Scientists at the University of Waterloo and the University of Chicago are also conducting work looking into, for example, the effects of CBD on COVID-19 infection. Despite this, many researchers like van Breemen encounter roadblocks on the way to scientific understanding of the plant’s benefits and pitfalls because of federal cannabis prohibition.
As a Schedule 1 Controlled Substance under the Drug Enforcement Agency’s (DEA) Controlled Substances Act, use and possession of cannabis is illegal under federal law, defined as having “no currently accepted medical use and a high potential for abuse.” That’s made life hard for researchers hoping to get their hands on the stuff, and is doubly frustrating during a global pandemic where exploring every avenue of inquiry to find treatments is an urgent priority.
“We weren't allowed to purify [precursor THC-A] and even test it alone, because it can be converted to THC,” van Breemen previously told Motherboard. “If one heats it, the acid group can be removed and chemically it transforms into a psychoactive substance, but THC-A alone is not psychoactive.”
In a 2017 literature review on the medical potential of cannabis from the National Academies of Sciences, Engineering and Medicine, a team of researchers describe the difficulties inherent to studying weed: “While a myriad of studies have examined cannabis use in all its various forms, often these research conclusions are not appropriately synthesized, translated for, or communicated to policy makers, health care providers, state health officials,” the researchers write.
“Studying the potential health impacts of cannabis presents its own set of unique challenges,” the authors continue, citing regulations like Schedule 1 status, which restrict access to cannabis for research, limited funding opportunities and the challenge in obtaining sufficient quantities of specific cannabis products “to address cutting-edge public health research questions.”
Van Breemen had to preclude the study of THC-A, which is converted into psychoactive THC with the application of heat, from his study, noting in the paper that “insufficient quantities were available for determination of binding affinity or antiviral activity,” because of its status as a controlled substance. This is despite THC-A showing empirical promise as a compound that can bind with the SARS-COV-2 spike protein and potentially block infection in human cells.
Conducting research on Schedule 1 substances like psychoactive cannabis (versus hemp, which is just cannabis with less than .03 percent THC) typically requires navigating review processes with a few different federal agencies: Researchers must register with the DEA, request research-grade cannabis through the National Institute on Drug Abuse (NIDA) Drug Supply Program—which is currently grown at one farm at the University of Mississippi—and, should they opt to move into clinical trials on human subjects, apply for Investigational New Drug (IND) permission from the Food and Drug Administration. Many researchers must also work with institutional review boards at their home institutions, state regulators, and potential funders, a web of bureaucratic threads that the authors of the 2017 National Academies review say is a “daunting experience for researchers.”
These extensive regulations are “reported to have discouraged a number of cannabis researchers from applying for grant funding or pursuing additional research efforts,” the authors write. But beyond being laborious and time-consuming, the authors say, they’re also dangerous.
“Research on the health effects of cannabis and cannabinoids has been limited in the United States, leaving patients, health care professionals, and policy makers without the evidence they need to make sound decisions,” the authors write. “This lack of evidence-based information on the health effects of cannabis and cannabinoids poses a public health risk.”
Though van Breemen was conducting his research in Oregon, where recreational use and possession of cannabis has been legal since the passage of Measure 91 in 2014, campus policy at Oregon State University (OSU) precluded him from experimenting with the substance in any manner that violates federal law. Measure 91 does not include provisions around research. Where there are inconsistencies between state and federal laws, a fact sheet on the school’s website notes, federal law applies to its teaching and research activities.
Landing federal grant dollars in support of his research also proved tiresome, van Breemen told Motherboard. He was left with no choice but to bootstrap, relying on hemp extracts from OSU’s Global Hemp Innovation Center and supplies from private sources.
In fact, the NIH did not fund studies on cannabidiol or cannabinoids as grant categories until 2015, according to a spending breakdown on the agency’s website. Though annual research spend has skyrocketed since then—from $9 and $111-million on cannabidiol and cannabinoid research in 2015 to $29 and $184-million in 2021, respectively—funding for this area still pales in comparison to other research areas. It does not appear that any studies on COVID-19 and cannabis compounds have ever been funded by the NIH — van Breemen’s work is no exception.
“It's almost comical because it takes months and months to get it done”
The journey Dr. Robin Duncan—a Canadian researcher at the University of Waterloo in Ontario—took to uncovering the ability of CBD to potentially “prime” cells against COVID-19 was smoother, but not without its own “comical” hangups, she said. Though cannabis and research around it are both highly-regulated by Health Canada, the country’s federal health agency, use and possession of cannabis has been legal federally since 2018, sold to consumers through provincial retailers and doled out to researchers for study and growth through the federal Cannabis Act.
Unlike van Breemen, Duncan received federal funding from a Canadian research council for her work, but she, like many in the US, underwent layers of bureaucracy to do it. Per federal policy, she was required to implement security protocols around her lab and had to apply for a research license from the federal health agency for her latest paper, which was published as a pre-print this week while under review in the peer-reviewed Journal Life Sciences.
Unlike in the states, Duncan had the option to purchase synthetic preparations of cannabis compounds from a private supplier—in this case, a research company, at around $5,000 per gram.
“I can't just go to the Ontario Cannabis Store and then use that in my research,” she said. “That wouldn't be considered acceptable. I need a research license for this, even though it's available.”
“It's almost comical because it takes months and months to get it done,” Duncan said. “It takes probably a week to fill out the paperwork. And in the end, I'm buying, like, a milligram at a time of CBD.”
Duncan’s research offers a promising expansion of the global COVID-19 prevention and treatment arsenal, but roadblocks in the research process, like those that van Breemen has faced, have kept her findings from publication until nearly two years into the pandemic.
In the US, there’s some movement at the federal level to change the conditions that led to this reality. For the last few years, Rep. Earl Blumenaur (D - OR) has introduced a bipartisan Medical Marijuana Research Act to expand the supply of research-grade cannabis beyond the NIDA stream and introduce state-authorized supply programs. If passed into law, the act would allow researchers to obtain marijuana for study from dispensaries, significantly shortening the research approval odyssey. The bill passed the house but died in senate upon first introduction in 2019-2020; a newer version of the legislation has yet to be voted on.
“The cannabis laws in this country are broken, especially those that deal with research,” Blumenaur said on the House floor in 2020 after introducing the bill for the first time. “It’s illegal everywhere in America to drive under the influence of alcohol, cannabis, or any other substance. But we do not have a good test for impairment because we can’t study it … This is insane and we need to change it.”
A seemingly small step, passing the bill could reap huge rewards for the scientific community. But broader policy steps, like an end to prohibition entirely (most recently outlined by the republican-led States Reform Act and a draft of the yet-to-be-introduced Democrat-sponsored Cannabis Administration and Opportunity Act), would accomplish the same thing.
When asked whether an end to federal prohibition would usher in a new frontier of cannabis research, van Breemen didn’t mince words.
“Absolutely,” he said.
This would have been especially useful during the time crunch that the pandemic introduced to researchers—many of whom put other studies aside to work on COVID-19 studies. Van Breemen hopes momentum from his study could change the reality of studying cannabis compounds, not just for COVID-19, but for all diseases.