With marijuana illegal under federal law, the red tape and bureaucratic hurdles facing American scientists who aim to study cannabis render the task nearly impossible. Some, however, like Dr. Sue Sisley from Scottsdale, Arizona, have persevered nonetheless, coming as far as to — almost — reschedule cannabis flower as a prescription medication for patients with posttraumatic stress disorder (PTSD). In partnership with the Multidisciplinary Association for Psychedelic Studies (MAPS), Sisley has secured the FDA's blessing to pursue clinical research on veteran PTSD patients, who smoke cannabis to mitigate their symptoms.
Sisley's pot-for-PTSD research is nothing new; her studies have been going on since 2015. Now she's gearing up for the third and final phase of her research, leading up to FDA approval of a "new drug" (and hence, cannabis rescheduling under the Controlled Substances Act). But, there's a catch: The drug (i.e. the cannabis) Sisley uses in Phase III must be the drug that goes to market, yet she cannot go to market with the cannabis that's available for Phase III because it's not just poor quality, but it's grown for research purposes only.
The National Institute on Drug Abuse (NIDA) is the sole entity licensed by the government to grow cannabis. A far cry from the crop of lush pot farms in places like California, NIDA's cannabis is grown at the University of Mississippi. At times, it's resembled green talcum powder rather than fresh bud, and all the samples have been contaminated with mold, Sisley says. Moreover, the cannabinoid percentages labeled by NIDA have been found inaccurate by third-party testers in Colorado.
Available in high-THC, high-CBD, and 1:1 varieties, NIDA's cannabis has little genetic diversity beyond those three given ratios — and anyone the least bit familiar with cannabis knows just how nuanced and complex the plant can be with regard to its hundreds of cannabinoids and terpenes (aromatic compounds).
Nonetheless, up until now, Sisley could deal. On a regular basis, study subjects — veterans with PTSD — have been given as much cannabis as they needed to smoke in order to feel better. Cannabis isn't a cure for PTSD, although it treats symptoms by suppressing dream and/or nightmare recall, and focusing patients on the present.
While earlier phases of FDA research are more about demonstrating drug safety, Phase III is about measuring efficacy — but Sisley worries that study "results are being sabotaged by low-quality plant material with no genetic diversity." Due to this defect in the study, it's likely Sisley may even need to repeat Phase II. Yet, that still doesn't solve the imminent conundrum facing Phase III.
Even if NIDA grew top-notch bud, it still couldn't be used for commercial purposes. "Whatever study drug is utilized in Phase III is the one that must go to market later, so NIDA cannabis is fundamentally inappropriate or not allowable for Phase III because it's never going to be allowed to go to market," Sisley told to Civilized. "It's only allowed for academic research, meaning it can never be made into a prescription medicine. That's the really clear reason why the NIDA monopoly needs to end."
In an email to Civilized, NIDA confirmed that its role is to produce marijuana for research, not for sales or commercial dissemination: "FDA typically requires Phase III studies to use the product that will actually be marketed, so large scale Phase III studies are usually done by the company that will be marketing the medication, but it is feasible that a commercial enterprise interested in applying for drug approval using government-provided marijuana could produce bioequivalent materials for the market."
According to Sisley, that means the research team would need another "bridging study" after Phase III to prove bioequivalence, which could cost another $30 million. But the question remains: why would the researchers even want a drug that's bioequivalent to anything NIDA's producing?
The NIDA monopoly has been in effect since 1968 — despite that in 2016, the DEA announced it would take applications from those seeking cannabis cultivation licensing. That all came to a screeching halt when ex-Attorney General Jeff Sessions took office.
"Everyone put in their applications, including us, but they took my application fee and never processed my application," said Sisley. "They refused to follow through on the commitment to the public that was made two and a half years ago and basically stole my $3400. Now our research is coming to a complete standstill."
FDA Phase III trials cost anywhere between $30 million and $100 million, depending on how many sites or subjects the study needs. "It takes us years and years to raise $30 million. We're not a Big Pharma company, we're a not-for-profit," Sisley said. "We're not going to spend $40 million to do this twice, to work with NIDA cannabis and then repeat it once the monopoly is done."
No no, instead, MAPS is planning to sue the Department of Justice (DOJ), and potentially the DEA, for "unlawful delay" in issuing licenses for federally approved cannabis cultivation. And MAPS isn't alone in condemning the DOJ for their inaction on licensing new growers: Within the past few weeks, the American Psychological Association (APA) has also called on the attorney general to act immediately in reviewing the more than two dozen grower applications that have been languishing for over two years.
"Without access to an expanded range of cannabis products engineered under FDA-approved Good Manufacturing Practices [GMP], scientific research cannot hope to keep pace with the ever expanding recreational and medicinal cannabis marketplace," APA CEO Dr. Arthur Evans wrote in a letter to Attorney General William Barr. "While NIDA provides a staple catalog of cannabis products and derivatives for research, it cannot keep pace (nor should it be expected to) with the range of products available to consumers in the 10 states that have approved recreational cannabis use or the 34 states distributing cannabis products through medical dispensaries.”
As the cannabis marketplace becomes increasingly sophisticated in legal states, the absurd irony of the conflict between state and federal law manifests in that scientists are left to grapple with a frustratingly limited supply of federally legal, research-approved cannabis — especially when 26 applications to expand that supply have simply been ignored.
"The core idea [of MAPS lawsuit against DOJ] is essentially that an administrative agency can't ignore Congressionally established timelines for its behavior," explained Ismail Ali, policy and advocacy counsel for MAPS. The Administrative Procedure Act binds federal agencies to do what Congress says they have to do, he adds, so if Congress says there's a timeline for something that has to happen and that's been violated or interrupted, then that institution is in violation of Congressional statute.
In this case, the DOJ's failure to allow the DEA to issue licenses after more than two years is in violation of their original 90-day grace period. Jeff Sessions, presumably, had been holding the process up — but now that he's out, there's still been no action. "We're asking for the DOJ to stop delaying the DEA's actions," Ali said. "It's an injunction to ask the court to demand that DEA issue licenses."
But the court likely won't hear the lawsuit until other remedies have been exhausted — so among other strategies, MAPS has asked sitting representatives, like Senator Orrin Hatch, to write letters of support for the idea of licensing growers.
"The conditions are ripe for ending the NIDA monopoly," Rick Doblin, executive director of MAPS, told Civilized. With about 64 percent of Americans in favor of legalizing marijuana, he says, there's little need to propagandize people and block science. "From a strategic point of view, I'm trying to establish the principle that Drug War politics should not impede research into the medical uses of Schedule I drugs," Doblin added.
In the meantime, before cannabis actually becomes prescription medicine, the study's Phase II results are still pending. From there, they'll publish those results in a scientific journal, explore foreign companies that could navigate the red tape around importing cannabis for Phase III, continue to prepare the lawsuit, wait for the DEA to issue licenses, and see how the role of the new Attorney General impacts the whole thing.
Sisley and her team are already in conversation with a few Canadian cannabis companies, which have already opened up a "drug master file" with the FDA. "So once they have both an approved scientific protocol for an FDA Phase II or Phase III trial, and they can prove that their cannabis flower meets GMP criteria, these Canadian LPs will legally be allowed to import flower into the US for these approved clinical trials," she said. "It's painful to me, I want to support our local farmers in the US, but our government is forcing us to go to foreign countries. We have all these talented farmers here in the US that could easily produce GMP-grade cannabis without any difficulty."
With the NIDA monopoly on the cannabis plant, specifically, rather than synthesized formulations of cannabinoids and terpenes, Doblin notes the importance of flower's inexpensive path to medicine. "It will become generic so that from a public good perspective, what we want to do is have a highly effective, low-cost medicine available to people, paid for by insurance," he said. "MAPS would like to build on the study we've done with Sue and eventually make marijuana flower in smoked or vaped form into an FDA-approved medicine for PTSD."