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Researchers at two Oregon universities making waves on the internet this week after providing evidence that cannabis compounds could provide valuable defense against COVID-19 infection.
In an article published in the peer-reviewed Natural Products Journal, Dr. Richard van Breemen of Oregon State University and six other researchers have described a breakthrough discovery that, when attached to certain non-psychoactive acids in cannabis – precursors to the psychoactive compounds Cannabidiol (CBD) and tetrahydrocannabinol (THC) – SARS-CoV-2 spike proteins struggled to enter and infect human cells in the lab.
Their findings could offer an additional pathway to slow the spread of COVID-19 and later variants, and could play an important role in the global response to the pandemic. But van Breemen tell the motherboard his findings did not come without significant legal hurdles; conducting research on a substance strictly controlled in his state and federally illegal has proven difficult, despite the urgency of the pandemic.
Van Breemen and his colleagues aren’t the only scientists studying the possible benefits of cannabis-derived products in relation to COVID-19. Scientists from the University of Waterloo and the University of Chicago are also carries out work examining, for example, the effects of CBD on COVID-19 infection. Despite this, many researchers like van Breemen encounter obstacles on the way to scientific understanding of the benefits and harms of the plant due to the federal ban on cannabis.
As a Schedule 1 controlled substance under the Drug Enforcement Agency (DEA) Controlled Substances Act, the use and possession of cannabis is illegal under federal law, defined as having “no currently accepted medical use and high potential for abuse”. This has made life difficult for researchers hoping to get their hands on the material, and is doubly frustrating during a global pandemic where exploring all avenues of investigation to find treatments is an urgent priority.
“We had no right to purify [precursor THC-A] and even test it on its own, because it can be converted into THC”, van Breemen previously told the motherboard. “If heated, the acid group can be removed and chemically it turns into a psychoactive substance, but THC-A alone is not psychoactive.”
In a 2017 literature review on the medical potential of cannabis of the National Academies of Sciences, Engineering and Medicine, a team of researchers describes the inherent difficulties of studying weed: “While a myriad of studies have examined cannabis use in all its forms , often these research findings are not properly synthesized, translated for, or communicated to policy makers, health care providers, state health officials,” the researchers write.
“Exploring the potential health impacts of cannabis presents its own unique set of challenges,” the authors continue, citing regulations such as Schedule 1 status, which limits access to cannabis for research, limited funding opportunities and the challenge of obtaining sufficient quantities of specific cannabis products. “to answer cutting-edge public health research questions.”
Van Breemen had to exclude the study of THC-A, which is converted into psychoactive THC with the application of heat, from his study, noting in the article that “insufficient quantities were available for determination of the affinity of binding or antiviral activity”, due to its controlled substance status. This is despite the fact that THC-A shows promise as a compound that can bind to the SARS-COV-2 spike protein and potentially block infection in human cells.
Conducting research on Schedule 1 substances like psychoactive cannabis (vs. hemp, which is just cannabis with less than 0.03% 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 in a farm at the University of Mississippi and, if they choose to proceed to clinical trials with human subjects, seek Investigational New Drug (IND) clearance from the Food and Drug Administration. Many scholars must also work with institutional review boards at their home institutions, state regulators and potential funders, a network of bureaucratic threads which, according to the authors of the review of National Academies of 2017, is an “intimidating experience for researchers”.
These expansive regulations “would have discouraged a number of cannabis researchers from applying for a grant or pursuing additional research efforts,” the authors write. But in addition to being laborious and time-consuming, say the authors, they are also dangerous.
“Research on the health effects of cannabis and cannabinoids has been limited in the United States, leaving patients, healthcare professionals and policy makers without the evidence they need to make informed decisions,” write writers. “This lack of evidence-based information on the health effects of cannabis and cannabinoids poses a risk to public health.”
Although van Breemen was conducting his research in Oregon, where recreational use and possession of cannabis has been legal since the enactment of Measure 91 in 2014, campus politics at Oregon State University (OSU) prevented him from experimenting with the substance in a way that violates federal law. Measure 91 does not include provisions regarding research. In the event of inconsistencies between state and federal laws, a fact sheet in the notes on the school’s website, federal law applies to its teaching and research activities.
Securing federal grants to support his research also proved tedious, van Breemen told Motherboard. He had no choice but to start, relying on hemp extracts from OSU’s Global Hemp Innovation Center and supplies from private sources.
In fact, the NIH did not fund studies of cannabidiol or cannabinoids as grant categories until 2015, according to a distribution of expenses on the agency’s website. Although annual research spending has skyrocketed since then – from $9 and $111 million for cannabidiol and cannabinoid research in 2015 to $29 and $184 million in 2021, respectively – funding for this area remains derisory compared to other fields of research. It doesn’t 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 do it”
The journey of Dr. Robin Duncan, a Canadian researcher at the University of Waterloo, Ontario, to discover CBD’s ability to potentially “prime” cells against COVID-19 was smoother, but not without its own “comic” blocks, she said. Although cannabis and research into it are both highly regulated by Health Canada, the country’s federal health agency, the use and possession of cannabis has been federally legal since 2018, sold to consumers through provincial retailers and distributed to researchers for study and growth under 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 United States, endured layers of bureaucracy to do so. Through federal politics, she had to put safety protocols in place around her lab and had to request a research license of the federal health agency for its last paper, what was published in preprint this week when reviewed in the peer-reviewed Life Sciences Journal.
Unlike in the United States, Duncan had the option of purchasing 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 it in my research,” she said. “That would not be considered acceptable. I need a research license for this, although it is available.
“It’s almost comical because it takes months and months to do it,” Duncan said. “It probably takes a week to complete the paperwork. And in the end, I buy, like, a milligram at a time of CBD.
Duncan’s research offers a promising expansion of the global arsenal for preventing and treating COVID-19, but obstacles in the research process, such as those faced by van Breemen, have prevented publication of his findings until now. nearly two years after the start of the pandemic.
In the United States, there is some movement at the federal level to change the conditions that have led to this reality. In recent 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, the law would allow researchers to obtain marijuana for study purposes from dispensaries, dramatically shortening the research approval odyssey. The bill passed the House but died in the Senate when first introduced in 2019-20; a new version of the law has not yet been voted on.
“Cannabis laws in this country are broken, especially those dealing with research,” Blumenaur said on the floor of the house in 2020 after first introducing the bill. “It’s illegal anywhere in America to drive under the influence of alcohol, cannabis or any other substance. But we don’t have a good impairment test because we can’t study it…It’s foolish and we need to change it.
A seemingly small step, passage of the bill could reap huge rewards for the scientific community. But broader policy measures, like ending prohibition altogether (described more recently by the Republican Party States Reform Act and one Rough draft of the Democrat-sponsored Cannabis Administration and Opportunity Act, which has yet to be introduced), would accomplish the same thing.
When asked if ending federal prohibition would open a new frontier of cannabis research, van Breemen didn’t mince words.
“Absolutely,” he said.
This would have been especially helpful during the time crunch the pandemic presented to researchers, many of whom put other studies aside to work on COVID-19 studies. Van Breemen hopes the momentum of his study could change the reality of studying cannabis compounds, not just for COVID-19, but for all diseases.