​Dr. Sue Sisley: Can Strain Science in Cannabis Help Doctors Find the Holy Grail of Precision Medicine?

Henry Truc  |

By now, an overwhelming majority of the population and the medical community have agreed that marijuana does have health benefits. As a result, the discussion on the medicinal benefits of cannabis should be shifted from one dwelling on whether or not they actually exist, but to one that focuses on what those benefits actually are for patients. The obstacle there is that there's actually very little research that has been done on the full potential of cannabis, particularly when it comes to the whole plant. In the first part of our interview with award-winning researcher and advocate Dr. Sue Sisley, we discuss a lot of the challenges that the scientific and medical community faces when trying to learn more about the potential of cannabis as a form of medical treatment.

In this interview, we wanted to get a better understanding of why patients and doctors alike are so optimistic and interested in wider legalization for medicinal use. What exactly makes cannabis so effective–even on an anecdotal level–in treating patients' symptoms?

EQ: You’re one of the most recognized figures in the medical community when it comes to cannabis research. Where did your interest in the medical benefits of cannabis, particular in treating PTSD, originate from?

Dr. Sisley: I have been taking care of U.S. military veterans for almost 20 years now, since first working with them at the Phoenix VA hospital, and it provided me a crucial window into understanding the suffering of vets with PTSD. I developed a deep fondness for these veterans and they began teaching me about their experiences. Eventually, they reluctantly began disclosing to me that they were usingcannabis to manage some of their PTSD symptoms. I say reluctantly disclosing because these veterans knew that I was trained in a very conservative medical model where I was never exposed to the notion of the endocannabinoid system nor even the concept of using marijuana as medicine at all during medical school or residency training. So at first, I was highly judgmental and probably even scared off a lot of veterans who wanted to get my feedback. So instead of helping them, I realized I was chastising them for using this plant. It’s something I still regret now.

It took me several years to unblock my thinking and begin to finally listen to their compelling stories–both from the veterans themselves and from their family members describing the life-affirming experiences that they were observing. Over time, you started hearing from spouses and children who were saying, ‘Look, I got my husband back. I got my dad back.’ It was extraordinary to hear. A lot of these veterans had taught themselves how to use marijuana in a way that would enable them to walk away from all of their prescription medications, and no longer be dependent on the VA system.

I was really stunned by this, and eventually I realized that we were going to have to study this plant in a rigorous way. We at least owed it to these veterans to put the plant through the rigors of a serious controlled trial. But instead, the government has stonewalled this research at every turn and it’s really an abomination because what this represents is science being shackled by politics. It’s really given me a bird’s eye view about the myriad ways the US government has systematically impeded marijuana efficacy research in this country.

EQ: PTSD is a very serious problem, but is an issue that often feels like it gets swept under the rug. How has your experience been working with vets dealing with this disorder?

Dr. Sisley: It’s been really tough to see these veterans suffering so profoundly. It’s a public health crisis, and we have veterans that are killing themselves at a horrific rate. The data from the VA estimates 22 suicides per day, but we all know that statistic is a low estimate and doesn't include all of the veterans that end their life but were labeled as accidents rather than by suicide.

The hallmark of PTSD is chronic sleep deprivation that’s associated with these really terrifying nightmares and flashbacks. But it’s a diverse constellation of symptoms, everything from depression, anxiety, insomnia which sometimes makes them agitated/irritable and difficult to be around. Some patients they have hallucinatory psychotic thoughts, paranoia, hypervigilance, in addition to the flashbacks and nightmares. There’s also a broad spectrum: the severity of PTSD can range from people with daily and nightly symptoms, to some who can function relatively normally and are triggered only by certain events.

These guys live with some really dark and gruesome thoughts swirling through their head throughout the day. And that’s why they become so reclusive. They try their hardest to escape from society because it's impossible being around people who cannot empathize with these ghastly thoughts.

Or being around noises reminiscent of past bloodcurdling experiences. All of that can trigger past grisly memories for them. So it’s easier for them to just isolate themselves. A lot of them are completely housebound. And it was really sad for me to struggle with these guys for so many years and watch them incapable of regaining their vibrancy. These were incredibly talented high-functioning people prior to their military service.

A lot of them don’t end up with obvious physical injuries, but then they end up with this very treatment-resistant PTSD. And they don’t even get the sympathy of their family and friends because they don’t see that there’s anything outwardly wrong with them. So on top of everything, they also have to struggle with explaining to people around them what they’re dealing with.

EQ: For those suffering from PTSD, what treatments are currently available to them and why do you feel that they are not sufficiently meeting these patients’ needs?

Dr. Sisley: Clinically, we see that veterans are looking for medications that will target those PTSD symptoms, particularly insomnia, free-floating anxiety associated with the nightmares, and flashbacks. Sadly, the only two medications that have FDA approval for PTSD are Zoloft and Paxil. That’s it, and those are both highly disappointing. When those two meds fail, we’re then allowed to put these guys through the gauntlet of all kinds of other FDA approved meds that were never formally tested/approved for PTSD.

I can use all the antipsychotics. I can use all the mood stabilizers like Lithium and Depakote. I can use all antidepressants from any class, not just SSRIs, but SNRIs, Tricyclic antidepressants, all of these. I can use all of the sleep meds, including addictive benzodiazepines which go on for pages. I can use virtually anything that would treat any mood-anxiety disorder. So you can see why these veterans feel like guinea pigs, and why they call this the “Combat Cocktail”. They come back from service, and they get put on, 10, 12, 15 different medications because the syndrome of PTSD is so complex. Each target symptom gets handed a different prescription, and the piles of pills can snowball quickly.

EQ: What effects of cannabis suggest it can be a better alternative in treating PTSD than what is currently on the market?

Dr. Sisley: So the challenge is that PTSD is a very complex syndrome with multiple target symptoms. But that's why cannabis seems to be able to function as monotherapy for many PTSD suffers. The cannabis plant is also complex, containing over 400 different bioactive molecules. For instance, NIDA just announced they've identified 138 phytocannabinoids. That chance to be able to target multiple receptors is really valuable. We don't fully understand yet how each of these cannabinoids work and which ones are clinically relevant, but we have a mountain of anecdotal evidence from veterans claiming that they are able to use cannabis successfully for symptom control--claiming it's even superior to any of the prescriptions they’ve been given.

A lot of them were able to turn their back on all of these prescription meds and just use the plant alone. I was so stunned by this, but I was intrigued that these veterans would claim that they were able to use cannabis as a single intervention. So it became not just a scientific journey, but a political journey to understand WHY the government is so determined to suppress whole-plant marijuana research. But at the same time they’re willing to patent cannabinoids. They’re willing to allow pharmaceutical companies to isolate individual cannabinoids, but you’re not allowed to study EFFICACY of the green leafy substance -- the natural plant.

EQ: While the medical and scientific community has not been able research cannabis as thoroughly as they may want, what do we know about it currently?

Dr. Sisley: Well, it’s really fascinating in that it seems all of these cannabinoids have some type of clinical bioactivity where they may elicit some clinical response. The most well described cannabinoids that we always refer to are THC and CBD, but the truth is that there’s dozens of other cannabinoids there that could be clinically relevant. What’s so exciting is that it’s not just the cannabinoid content, but there’s all these different potentially bioactive molecules (terpenes, flavonoids etc) within the plant that all seem to work together synergistically to create what we now describe as “The Entourage Effect.”

This is a really compelling case for why marijuana can control a myriad of different symptoms. And it is not just PTSD. A lot of these patients that I take care of in my practice are treating everything from chronic pain to traumatic brain injury, to PTSD, to a variety of G.I. complaints, and managing all of it with one plant. That really speaks to the incredible complexity of the plant. Not a silver bullet but what we call a synergistic shotgun. All of these compounds in the plant working in concert with each other. Certainly, all of these areas need a tremendous amount of research in order to understand and elucidate more fully how the plant can interact with these different disease states.

But it’s really clear that the plant is loaded with therapeutic value, and we just need to figure out how to harness that.

EQ: As you’ve alluded to, there is this intentional ignorance that is keeping cannabis science in the dark ages, preventing a better understanding and more intelligent applications of the plant. It also eliminates the ability to prescribe it in a controlled setting, which leads to a lot of veterans basically resorting to self-medicating themselves. Are there dangers that can result from this?

Sisley: There are definitely concerns about that. Marijuana, just like any medication, has risks and benefits. There are documented side effects to marijuana, and that’s what concerns me. The activist community sometimes tries to portray marijuana as a cure-all, a panacea for everything. I have to really try to caution them to slow down with that language because what happens then is that vulnerable and desperate patients get very overzealous. As a result, people could be going in full bore into certain strains/high potencies of cannabis that might be detrimental to them.

Hopefully, we start to understand which strains may be best for PTSD, and maybe also which strains should be avoided. There are a lot of assertions that a high THC strain could cause more side effects and exacerbate their PTSD. But then again, there’s other conflicting data that came out of ICRS etc suggesting that high THC was the better treatment intervention for PTSD.

Part of this is contingent on whether the veteran is new to marijuana or not. If they’re completely naïve to cannabis, then trying out new strains could be really challenging and could create a lot of side effects for them. We do see a number of veterans who tell me that they never will touch cannabis again because they had one harrowing experience in college where they became psychotic with paranoid delusions, or had a panic attack etc.

This is the concern I have. I believe that the plant does have therapeutic value, but we need to know which strains are best for which illnesses. We need to tailor the phenotype to the patient because even if one patient can tolerate high THC, that same strain given to another veteran–who may have a completely different brain chemistry–could suddenly have a terrible reaction to it.

It’s personalized medicine, now called precision medicine. We’re trying to target the therapy directly to the individual. But it’s going to be really hard to do, and that’s why so much of this work is trial and error. It’s also why the veterans have developed their own sort of Underground Railroad now where they’re teaching each other how to use it and sharing their cannabis knowledge with each other.

EQ: So as a result of the constraints to the medical and scientific community, veterans have taken this upon themselves?

Dr. Sisley: Right. And I think, in some cases, it’s probably better than getting conventional medical advice because the truth is that vast majority of medical doctors (MDs & DOs) don’t know how to counsel patients in this area. There’s only a very select number of physicians in this country that are truly experienced in how to utilize cannabis as medicine. Those physicians are incredible. They are doing crucial work, but they are rare. Most doctors don't have a clue how to talk to patients about cannabis. So it’s imperative that veterans learn from each other and hopefully avoid some of the pitfalls, because a lot of them have had bad experiences and they can teach each other how to avoid this.

EQ: It’s great that veterans have created their own support system for treating PTSD with cannabis, but ultimately there’s still a significant amount of risk because of how little we do know and the limited resources we’re putting in to find out. How has this prevented medical practitioners such as yourself from providing more assistance?

Dr. Sisley: All of it concerns me. I don’t even formally recommend cannabis to my patients because I’m so deeply worried about not knowing what these patients are getting. In Arizona for instance, we don't even mandate lab testing for our medical marijuana. I have no clue what strains these guys are accessing, so I don't write recommendations. I don’t certify patients. But I don't judge them anymore if they’re are using it and I certainly don’t actively discourage them from it. I try to learn from them and hear about their experiences and try to understand what it is they’re using (often urging patients to send their cannabis to a local laboratory voluntarily), and document how they're responding clinically.

So if they find that the strain is working optimally for them, I encourage them to pay the nominal fee to obtain a lab analysis. Figure out what’s in it so that they can pursue phenotypes that have a similar cannabinoid and terpene profile because that’s the key. Once you find that "best fit", you really want to continue with that rather than still experimenting with other strains that might be detrimental.

But it’s important that I point that that I don't recommend cannabis to patients. I don't certify people for their cards because I’m solely focused on the research and I really want to help veterans by getting objective & rigorous data for them. There are a lot of veterans that will never touch cannabis because it hasn’t been put through the FDA process. There’s a lot of veterans that are highly conservative and that have been trained in the D.A.R.E. model that cannabis is dangerous. So they will never be able to view cannabis as medicine until we can provide objective data, free from human bias.

There’s also concern that our research may prove that marijuana is not helpful for PTSD. We have seen other published data that’s already suggested marijuana exacerbates PTSD. Again, these were primarily observational studies and case series.

Having data from a triple blind randomized controlled trial is vital. Unlike pharmaceutical company trials, ALL of our data, the good and the bad will be put into the public domain....for everyone to scrutinize and at least that means we can begin an informed debate based on LEGIT DATA and not purely on emotion/opinion.

The good news is that previous conflicting data are mostly from observational studies. That’s why it’s so critical that these randomized controlled trials get implemented finally-- observational studies are not considered reliable data by the mainstream medical community because they’re still vulnerable to human bias.

EQ: There’s still so much that we don’t understand about the potential of cannabis from its medical efficacy to proper application to the various effects of different phenotypes and so on. What is the most significant misconception you feel that needs to be dispelled for the broader public?

Dr. Sisley: My biggest concern is that the general public still talks about cannabis as if it’s a single plant. We need to explain to the public that the plant is incredibly diverse and there’s all these different phenotypes that all have different clinical effects.

The important thing when you’re talking to the public is having a balanced approach. It’s crucial to acknowledge the risks of marijuana as well as the benefits. Not just to try to make all these exaggerated claims about the vast therapeutic benefits without admitting that this plant does have side effects.

We need to be careful in counseling our young people about this--undoubtedly this will be confusing for some. But I think that’s the main thing to explain. The more education that the public is offered about the diversity of this God-given plant (and how these different phenotypes could potentially be harnessed to be used in a therapeutic modality), then we have true chance of enhancing public health. We need to do a better job of explaining the crucial need to elevate "strain science", because understanding which strains are best for which illnesses will get us closer to the Holy Grail of precision medicine.

You can read more from our special program The Future of Cannabis here. To find out why Equities.com and Viridian Capital Advisors launched this program, be sure to read What is The Future of Cannabis? This program was made possible by the support of our sponsors. Click here for a full list of our sponsors.

DISCLOSURE: The views and opinions expressed in this article are those of the authors, and do not represent the views of equities.com. Readers should not consider statements made by the author as formal recommendations and should consult their financial advisor before making any investment decisions. To read our full disclosure, please go to: http://www.equities.com/disclaimer



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