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Meg is the Group Editorial Director for Cannabis Patient Care and Cannabis Science and Technology magazines at MJH Life Sciences.
Dr. Sue Sisley has been pioneering research in the U.S. cannabis industry and fighting for quality cannabis samples to conduct her clinical trials. We recently spoke to her about the challenges she’s faced, what’s ahead for her future research, and more.
The Hippocratic Oath charges medical doctors to uphold specific covenants throughout their career as physicians. One such proclamation is to “respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow” (1). How does this message track when you consider medical cannabis? The medical community is historically not taught about the benefits of cannabis or the overwhelming evidence of an endocannabinoid system. What are doctors to do when their patients come in seeking help or advice about using cannabis as a treatment?
There are a number of doctors and medical professionals trying to answer this call to action by paving the way forward with research and educational efforts. For instance, Dr. Suzanne (Sue) Sisley, MD, is an Arizona-based physician practicing internal medicine and serving as the president and principal investigator of Scottsdale Research Institute (SRI). At SRI, Sisley is conducting controlled trials of smoked and vaporized cannabis, attempting to move whole plant flower through the entire U.S. Food and Drug Administration (FDA) drug development process. The mission statement for SRI states (2):
“The purpose of the Scottsdale Research Institute is to coordinate rigorous, scientific studies to assess the safety and efficacy of cannabis and cannabis compounds for treating medical conditions… Research will focus on the potential medicinal benefits of cannabis for diseases and conditions as specified by the National Academy of Sciences, Institute of Medicine Report (1999 and 2017) and by the Workshop on the Medical Utility of Marijuana, National Institutes of Health (1997). The SRI will strive to conduct high quality, controlled scientific studies intended to ascertain the general medical safety and efficacy of cannabis and cannabis products and examine various forms of cannabis administration. The Institute will be seen as a model resource for health policy planning by virtue of its close collaboration with federal, state, and academic entities. The SRI will also highlight the current barriers to federally-regulated Marijuana Research.”
Sisley is also the Medical Director for medical marijuana (MMJ) license holders in 12 different states in the U.S., from Hawaii to New Jersey. She offers patient education and physician engagement, serves as a faculty member at Colorado State and Humboldt State Universities, and speaks at cannabis conferences all over the country.
It’s clear that Sisley is on a mission to educate the public and her peers about the objective data on medical cannabis, but not without scientific research to guide her. She wants to understand why cannabis is working for so many of her patients and then share that knowledge with the greater medical and scientific communities. Despite her earnest endeavor, Sisley has been met with many obstacles along the way, specifically from the federal government. In the following, we learn more about Sisley’s research efforts, the challenges she has faced, and her plans for the future.
As stated earlier, even today most medical professionals are not taught about cannabis as a treatment option or the endocannabinoid system. Therefore, it should come as no surprise that Sisley was hesitant to take cannabis seriously as a medicine at first. “The only thing I knew about cannabis was from my medical school residency training, which taught me that it was just a dangerous, addictive plant that should be avoided,” said Sisley.
Sisley explained that she kept hearing anecdotes about cannabis use from her patients-mostly military veterans and their families that she’s been treating for more than 20 years-who were reluctantly revealing that cannabis was helping them more than traditional pharmaceuticals. “My thinking was so blocked back then,” she explained. “But what really drew me in was, over the course of years, this continual mountain of anecdotal evidence that kept piling up and even collateral history from all these family members saying how they got their loved one back. I just couldn’t ignore that anymore.”
At the same time, veteran suicide rates were drastically on the rise. Sisley said that she started seeing veterans in her own practice who were ending their lives. “It was then that I realized that we needed to look harder at what this plant has to offer through controlled trials,” she said.
From there Sisley became curious about the barriers to cannabis research in the U.S. and uncovered a road fraught with obstacles. She partnered with the Multidisciplinary Association for Psychedelic Studies (MAPS), which is “a 501(c)(3) nonprofit research and educational organization that develops medical, legal, and cultural contexts for people to benefit from the careful uses of psychedelics and marijuana” (3).
“They [MAPS] were the ones who helped guide me through this-navigating all these regulatory hurdles to be able to get the studies under way,” said Sisley. “It’s been an incredible team to work with. These guys have 30 years of experience doing nonprofit drug development research. So, they really helped shape a lot of my commitment to scientific freedom and to furthering FDA approved clinical trials in this area.”
Sisley’s primary target for research followed suit with what she was witnessing with her patients: she wanted to conduct a clinical trial with veterans suffering from post-traumatic stress disorder (PTSD). The study took 10 years to complete because Sisley was impeded by the government at every turn-so much so that she initiated the lawsuit against the U.S. Drug Enforcement Administration (DEA) (see “Sisley Versus the DEA” further on). However, the study is nearing the finish line now.
“The study we just completed was an FDA phase two trial, so it’s an early phase drug development trial, looking at four different varieties of smoked cannabis flower in these military veterans that have PTSD,” said Sisley.
Unfortunately, the data could not be shared with us at press time because the specifics of the study have not been published yet. “We have to go through peer review to get publication, but we’re hopeful because this is the kind of gold standard research that the medical community really embraces. Randomized controlled trials are what we all demand as physicians, and they have a lot of credibility,” said Sisley.
Sisley said she fully expects a peer-review committee to embrace her research. However, she was able to share that all scientists who strive to study cannabis as a medicine (herself chief among them) are concerned about the quality of the cannabis used in the trial undermining the efficacy of the data. One of the many challenges Sisley faced in conducting her clinical trial was obtaining quality, real-world cannabis. The University of Mississippi, which has a contract through the National Institute of Drug Abuse (NIDA) to grow cannabis, has historically and currently been the only place where researchers in the U.S. could get access to cannabis for their studies.
This is where Sisley’s lawsuit comes into play. The cannabis she received for her clinical trial was moldy and diluted with stem, sticks, and leaves. “It’s not just the flowering tops of the plants. There’s all this extraneous plant material, which may harm these outcomes,” she said. “That’s why we decided to pursue litigation against the DEA because we just feel that this is an abomination the way that the government is enforcing this monopoly at the University of Mississippi for more than 50 years.”
Sisley explained that the University of Mississippi has been the only federally legal drug supply for every cannabis controlled clinical trial in the U.S. “Think about all these other studies that were potentially undermined by this low-quality plant material,” she said. “All we’re asking for is a level playing field. We want to be able to study real-world cannabis and that’s not what we’re getting from our federal government.”
Sisley also explained that cannabis is the only Schedule I drug restricted by such a monopoly. “MAPS, my study sponsor, when they study MDMA [3,4-Methylenedioxymethamphetamine], LSD [Lysergic acid diethylamide], or any other drug in Schedule 1, they don’t go to NIDA to purchase their study drug. They can buy research-grade MDMA or mushrooms from any laboratory in the country or outside of the country. There are no limitations,” she said. “But with cannabis, it’s the only drug in Schedule 1 that has this absurd situation where we only have one federally legal drug supply. That has to change. That must change immediately because if the DEA does not finally move forward to license other growers for drug development research, we will never see rigorous clinical trials progress properly.”
Sisley pointed out that other countries all have multiple growers for research, and they are miles ahead of us now, in terms of clinical trials. “We may never be able to catch up,” she said. “We’re just so far behind on this, it’s going to take years. Even if the DEA finally approved additional growers tomorrow, it would still take them years to get up and running because it’s not like you can just implement some pop-up GMP grow facility.”
Furthermore, a proper pharmaceutical-grade cultivation site would need to eventually meet good manufacturing practice (GMP) criteria from the FDA, and it could take many growth cycles to get to that point. Sisley said that’s why it’s so imperative that the DEA act now. “They promised us in 2016 on the Federal Register that they would license other growers for research, and they have not followed through on that. They happily processed my credit card for over $3000 but never processed our Schedule 1 manufacturer application,” said Sisley. “We’re hoping that this litigation will light a fire under them to finally do the right thing and rebuild their credibility with the public, which has been really harmed by these apparently fake announcements where they have no intention of making good on their pledges to the public.”
In 2016, the DEA announced that it would start accepting applications for other licensed growers to supply cannabis for legitimate research in the U.S. (4,5). However, the applications have not been approved in the time frame outlined in 2016, which stated a 90-day review. In June 2019, Sisley filed a lawsuit against the DEA seeking action on SRI’s application to grow cannabis (6). The petition to the court says in part that the cannabis Sisley received from the University of Mississippi for her PTSD clinical trial with veterans “arrived in near-powdered form, diluted with extraneous material like sticks and seeds, and many samples were excessively moldy.” The petition explains that allowing SRI to grow its own cannabis would improve drug quality and genetic diversity as well as provide them with more options for potency, cannabinoid and terpene profiles, and better prevention of mold and mycotoxin, especially when dealing with immuno suppressed patients in clinical trials. They have been waiting for the DEA to respond for more than three years, which according to the petition is an unlawful and unreasonable delay.
In late August 2019, the DEA announced in a press release (7) that it would be moving forward to facilitate and expand scientific and medical research for cannabis in the U.S. The DEA said they would be providing notice of pending applications from entities applying to be registered to manufacture cannabis for researchers.
Sisley, however, is rightfully skeptical after waiting so long for her own application to be processed, and believes the DEA made that announcement in response to a deadline from her litigation. “There was a panel of judges that ordered the DEA to respond in 30 days, and on the eve of the day that they were required to respond, suddenly they came out with this announcement, which was really the relief that we were seeking,” she said.
“We consider it a victory in some respects, at least theoretically, this is only a minor achievement because it has not resulted in any tangible change. Researchers still have to purchase cannabis solely from University of Mississippi for now and until the day this monopoly is finally dismantled. And the government has not provided any timetable when they will process these applications and approve new growers so this could be years or even decades away,” said Sisley. “The DEA is now admitting that these 33 applications have been sitting on their desk for three years, and they are claiming they will be moving forward. But sadly, for scientists like me that have dealt with federal agencies and the slow and extensive bureaucracy here, I don’t view this as a time to celebrate at all.”
Sisley explained that she views this as just another delay tactic. Her big fear is that the application approvals will be postponed indefinitely. “It’s not a tangible victory until the studies are finally really moving forward with real-world cannabis,” she said.
Assuming one day there is a true victory and Sisley is able to conduct studies with real-world cannabis grown in the U.S., she plans to run another PTSD clinical trial. Until then, Sisley plans to import cannabis from foreign growers to conduct her clinical trials. She can request GMP-grade cannabis flower to be imported into the U.S. for the purpose of a federally-approved clinical trial by opening a drug master file with the FDA. If this flower meets the FDA’s nebulous GMP criteria, then the DEA must allow the flower to be delivered into the U.S. for an FDA institutional review board (IRB) approved protocol.
Sisley has also done some research using cannabis to treat pain and opioid addiction, relating that work with some of her patients that are professional athletes. This branch of her research also began with what she was witnessing with her patients that are veterans. Sisley explained that when the veterans were reporting that they were able to wean themselves off their opioids using cannabis, she was dubious. However, she started to see that those patients no longer needed her to write prescriptions for pain pills.
“I was stunned because you don’t really see that very often, right? Usually patients need more and more. They build up tolerance, and they need their prescriptions to double and triple over years,” said Sisley. “I was so grateful to see these patients seeking out plant-based alternatives, especially cannabis.”
That put Sisley on a path to start asking scientific questions and building studies around cannabis as an alternative to opioids and a treatment option for pain. She began a partnership with the University of Michigan, and they published survey data in the Journal of Pain (8). “Even though it was survey data, the peer-review committees still saw value in it because it was rigorous and demonstrated a real trend that we’re seeing nationwide where patients are choosing cannabis over these much more addictive prescriptions,” said Sisley.
Patients were not just coming off of opioids though-Sisley said they were able to wean off other addictive pharmaceuticals such as benzodiazepines and some of the really addictive sleep aids and anti-anxiety meds. “I’m so eager to find safer alternatives to these drugs because they’re pretty toxic,” said Sisley. “If cannabis-a natural flower-could help patients walk away from these pharmaceuticals, it seems like an ideal situation.”
With this research trend out in the field, Sisley started hearing from athletes seeking help coming off opioids. She explained that initially she was hearing from players in The National Football League (NFL) and The National Basketball Association (NBA), but slowly other athletes from all around the country started contacting her.
“We were getting inquiries from MMA [mixed martial arts] fighters, from hockey and rugby players, who were starting to realize that the league management was pummeling them with all these opioids,” said Sisley. “They were kind of distributed like candy, and they weren’t being provided the proper informed consent.”
Sisley explained that normally in her clinic she tells patients all of the pros and cons of each prescription she writes. However, in these athletic leagues there’s so much pressure to perform or to get back on the field that often athletes are not properly informed. “So, these folks would just get opioids and other, anti-inflammatory injections so they could get back out there, and they weren’t provided the proper profile of the risks and the potential addiction,” said Sisley.
Sisley began treating a lot of these athletes, especially ones who’d retired and realized that they were suddenly completely dependent on these opiates. She explained that they would ask for guidance on how to kind of cross taper off the opioids and onto cannabis, which she was doing successfully with a lot of players. One such player was Mike James, an NFL running back, who was featured in the CNN “Weed 4” documentary with Sanjay Gupta (9). James was injured during a Monday night football game and required surgery, after which he was given opioids to treat his pain.
“James had an opioid dependency and a strong family history of substance abuse,” said Sisley. “He was really vulnerable and almost suicidal-going down a path where he may not have survived. But luckily, I think cannabis saved him and his family.”
Unfortunately, for players like James, the NFL does not support medicinal cannabis use. So, James became an advocate to help change that policy. The CNN documentary put some pressure on the NFL to do something, but James and Sisley took it a step further by filing a therapeutic use exemption (TUE) for his medical use of cannabis.
“James and I were the first doctor–patient team to ever submit a cannabis TUE to the NFL,” said Sisley. “We submitted the TUE to enable him to stay on cannabis because we explained how he successfully got off the opioids and was using cannabis alone to manage his pain. This was working well for him and he was still performing well on the field.”
Despite the pressure from the CNN report and the TUE, the NFL would not approve of cannabis use for James. He ultimately chose to retire early.
“That’s what we see with so many players now-they are either not entering professional leagues or they’re retiring early because they realize that they won’t be able to access cannabis legally while they’re in the league, while they’re active,” said Sisley.
Sisley foresees leagues such as the NFL and NBA struggling down the road if they don’t change their policy on medical cannabis because more and more players are realizing that they don’t want to get these repeated injuries, especially concussions, without being able to use treatments that they know are less addictive and possibly a neuroprotectant to prevent progression of brain injury.
“We have clear peer-reviewed data now showing that cannabis is definitely a neuroprotectant,” said Sisley. “The fact that the leagues won’t allow their players access to this plant is unconscionable really.”
Sisley also explained that during meetings with the NFL they submitted study designs and proposals of how they could do a real controlled trial looking at cannabis in either active players or off-season players, but the NFL wouldn’t respond to that. “The NFL has set aside $100 million to study player wellness as part of the concussion settlement, and they refuse to use any of that money to study cannabis,” said Sisley. “That would be a perfect opportunity for them to at least support the science and to be able to show the public and the players that they really do care about this. There’s a potential for them to uncover a new treatment for pain, and they just won’t invest anything into that.”
On the other hand, Sisley commended the National Hockey League (NHL) and Major League Baseball (MLB) for their friendliness towards cannabis. “They’ve never sanctioned players for testing positive. I think they’re a model for all of the rest of these professional leagues,” said Sisley. “If everyone could behave like them and have more compassion toward players who want to seek out a safer alternative to opioids, I think that would be extremely valuable.”
Sisley noted a few surprises in her cannabis research, such as getting a more balanced perspective and understanding that there are true risks and benefits to cannabis use.
“One of the best things that happened to me was being able to observe patients in the lab every day who were smoking cannabis flower and to see that there are legitimate side effects,” she said.
Sisley explained that it’s easy to get swept up in the enthusiasm of the cannabis movement and start to lose objectivity as a scientist. But when she finally got to really study cannabis day in and day out, she saw tangible-and in some cases concerning-side effects as a physician. “I also balance that with the fact that these side effects are still far more minimal than most of the prescriptions that I write for patients every day in clinic,” she said. “I’m trying to emanate a more balanced approach when I talk to the public to be clear that this is a medicine like any other. There are risks and benefits. There are real side effects. But through good clinical trials, there are ways that we can learn to minimize those side effects and harness the medical potential in a better way.”
Another thing that surprised Sisley was the efficacy of smoking flower, which was something she initially underestimated. She explained that she was very dismissive of smoking flower at first because as a physician she doesn’t want people to smoke anything. Sisley said she spent 10 years of her life fighting for the Smoke Free Workplace Act in Arizona and called it a strange irony that she is now the principal investigator on cannabis smoking studies.
“I have to acknowledge that smoking is a very legitimate delivery mechanism, and it’s incredibly powerful and robust,” said Sisley. “In some cases, pulmonary function testing even improved with smoked cannabis flower, and I was really mystified by that because it seems so paradoxical to what you would expect as a physician.”
Sisley went on to explain that this federal government-funded pulmonary safety research speaks volumes about how much more study and education is needed about this plant. She thinks we can learn a lot from Native Americans and how they’ve learned to harness the medical benefits of cannabis and other plant-based medicines through smoking and ceremony. “We need to stop vilifying smoking and start utilizing it through FDA-controlled trials so that we can really understand more about the risks and benefits of smoking,” said Sisley. “Our research is focused only on smoked and vaporized flower because we are so convinced that this is the best technique for extracting the medicine without chemicals.”
The next study Sisley wants to tackle is late-stage cancer patients. She plans to evaluate smoked cannabis flower for treating cancer patient’s quality of life and pain issues with flower from a Canadian LP.
“There’s such a broad breadth of medical conditions that seem to be responsive to cannabis that it’s almost like a candy store where there’s just too much to choose from and you don’t know where to start,” said Sisley. “So, we’ve chosen to focus our studies on PTSD, cannabis for pain, and cannabis as a substitution for opioid dependence.”
PTSD resonates with Sisley the most because it’s such a complex illness. She explained that because there are so many different target symptoms right now that illness ends up getting treated with many different pharmaceuticals to hit each target symptom. There has not been a new treatment for PTSD in more than 18 years. “That’s why the idea of cannabis is so compelling to me, because it seems like this complex flower can treat the entire constellation of PTSD symptoms with one intervention versus the typical polypharmacy,” said Sisley.
“I’m eager to uncover a new treatment for PTSD, and I hope cannabis will prove to be that,” she added. “But I don’t know. We need to do much more aggressive research and hopefully see government funding come to bear in this because trying to fund nonprofit drug development research through private donors or investors is nearly impossible since they all ask about ROI, return on investment, which is impossible to predict nor guarantee with randomized controlled trials.”
Sisley’s ultimate goal is to one day see cannabis flower on the shelf next to conventional pharmaceuticals with an FDA indication. “Our whole mission is trying to get cannabis on the market with an FDA indication for PTSD, pain, or opioid substitution so that finally insurance companies will have to pay for it,” she said.
For Sisley’s patients and other medical cannabis patients, that day can’t come soon enough.
M. L'Heureux, Cannabis Science and Technology 3(1), 56-62 (2020).
For more with Dr. Sisley, please watch our video interview series:www.cannabissciencetech.com/cannabis-science- conference-videos/dr-sue-sisley-talks-cannabis-and-nfl-ptsd-and-more.
This article was originally published by Cannabis Science and Technology in February 2020. The original story can be found here: https://www.cannabissciencetech.com/view/dr-sue-sisley-advocating-medical-cannabis-research-patients-and-reform