Well, I want to say thank you so much for doing this. I know it's been so long since I last talked to you. I know. I'm looking towards chatting some more in the future, but thanks so much for doing this. Yeah. Absolutely. Just to catch up with you, it's amazing what you've been up to. You must be really busy but also, obviously, you're super successful, so it's worth it, right? Thanks, Ken. Yeah. It's been really busy, as you can imagine, and I'm sure it's completely the case for you. It's just a busy time but I love what I'm doing. So that makes all the difference in the world. Yeah. That is very cool. It's very cool. Well, so I told you a bit about the class. I'm teaching a class in cannabis and health, and we just talked about chronic pain and I thought about some of the work that you're doing. Especially, I thought it would be great to have you talk because you have a big PCORI grant. The term patient-centered, I think is so important. I thought maybe I could just start off by getting you to chat for a minute about your PCORI grant, and what patient-centered means, and then we take it from there. Yeah. Now, that sounds great. So patient-centered is really interesting. There's been a big push at the National Institutes of Health and also, of course, the PCORI, Patient-Centered Outcomes Research Institute, to really conduct patient-centered research. What that means is that, patients are integrated into all levels of decision-making in the research project. So the expectation is that the investigators are partnering with patients to both design the study, to choose the outcome measures. The ultimate goal is to ensure that we are conducting research that is meaningful to patients, not just the scientists, but the actual recipients of the ultimate products of the research. In the case of what I'm doing and what others are doing in terms of clinical research, it's particularly relevant because then we have confidence that the treatments that we develop and investigate will be more broadly disseminated and adopted by the key stakeholders because they have given us key input at every stage throughout. It makes total sense. So the public health significance obviously is greater with the more you involve the patients, and I think it's interesting to me too because in the cannabis space. Obviously, some advocates out there who were very vocal, I think this is the example of a space where we want more patient involvement, and by the best through across the work also. So we just talk some in the class about different interventions for pain. So maybe you can tell us more about your big PCORI grant. Yeah. So an overriding philosophy and real issue in the country right now is that, we're trying to treat pain at best and at lowest risk, and so de-emphasizing opioids is a huge national focus right now. What we recognize is that some of the lower risk and evidence-based ways to treat pain involves psychological strategies or what we call, behavioral medicine. There's about 30 years of science that really puts forward these treatments like cognitive behavioral therapy for chronic pain as well as self-management. Chronic pain self-management has been effective for pain treatment, but they're not broadly integrated into pain care pathways in the United States. Multiple government agencies like the Institute of Medicine, the CDC, the National Pain Strategy, they have all put forward that in order to reduce opioid prescribing and to treat pain more comprehensively, we should integrate these strategies into pain care pathways that all levels, from the acute pain management to chronic pain management. Even though that imperative is there, we haven't done a good job with implementation. So in my PCORI project, we are endeavoring to conduct some of the first primary science on this topic, very specifically in patients with chronic pain who are taking long-term opioid prescriptions and have agreed to voluntarily taper down on their doses over the one-year period that they will be enrolled in our clinical trial. So our study is called, the Empower Study, its Effective Ways of Managing Pain and Opioid-Free Ways to Enhance Relief. The Empower Study, the title, the logo, and even our outcomes were informed with patient-stakeholder input. Yeah, it's so cool, and they picked the coolest logo too. So if anyone wants to see that, you can go to empower.stanford.edu. You can see the study website and what patients chose for what they wanted to see what was welcoming to them. So fundamentally, this is an interesting project because we're not just testing, we're not just doing a comparative effectiveness study of cognitive behavioral therapy, eight weeks of cognitive behavioral therapy, as well as six weeks of the Chronic Pain Self-Management Program, we are doing that. But we're doing all of this within the context of a patient-centered opioid tapering program. So we are enrolling in total almost 1,400 patients around the United States into our study. Of those, roughly 1,400 patients, about 865 of them are agreeing to reduce their opioid doses. Then once those 865 people come in, they're randomized to one of our three study groups, group CBT, Group Chronic Pain Self-Management, or Taper Only. So even the Taper Only, sometimes people call that usual care, but all three of our study groups are actually getting care. They're getting a taper. But we hypothesize that the patients that receive one of our two evidence-based behavioral treatments for pain will evidence enhanced outcomes in terms of greater opioid dose reduction, greater pain reduction, and also improvement across a range of outcomes that are meaningful to patients such as function and participation in social roles. Patients just want to live better. They actually don't care so much about their opioid doses. They just want less pain, and they want to be able to do more. Sounds right. Absolutely. Well, that's very interesting. So I imagine too because obviously, we're interested in the cannabis also, we must have or I should ask you, how do you treat cannabis use. Is it a screening out, a roll out, you just pour to the data like that? No. So I should tell you that the prequel to Empower Study was a pilot study that we conducted in Colorado, and published in Jama Internal Medicine about this time last year. In this study, we invited patients to participate in a voluntary patient-centered opioid reduction program, and the patients that we enrolled were all on moderate and high dose opioids. So all the way from 60 morphine equivalents per day, all the way up to 1,005. So this was really a clinical sample of moderate and high dose opioids. We found that of the patients who enrolled in our study, 37 percent were also using marijuana. So that was interesting to us that a lot of people taking opioids may also be medicating pain and other symptoms with cannabis. So one of the questions that I was interested in is as these patients were tapered their opioid doses over four months, would we see cannabis use increase? We actually didn't find that, Ken. We found that we didn't have a large enough sample to really test differences. It was a bit like 18 patients were using cannabis. But not only did we find that cannabis use did not increase as patients tapered, there was a slight signal for cannabis cessation, where something on the order of three or four patients reported stopping their cannabis at the same time that they stopped their opioids. That was really interesting to me. So now, in our much larger clinical trial, the Empower Study, we have systems in place to very carefully assess cannabis use, the amount, the type, whether it's prescribed or recreational, and we're tracking them very closely over the course of the year that they're involved in our study, so that we can begin to understand these relationships between pain, opioid use, behavioral pain medicine, opioid use decreasing, and what happens to cannabis use in the context of that. That's fascinating. That is actually going to be amazing data to look at later. I just spoke to another investigators unit who are down at UCLA. She did study approximately five or six months ago. They're looking at the combination of opioids and cannabis and saying that they work so synergistically to produce more effect on pain, basically. Not that one substitutes for the other but that there's something about the combination. But it's interesting because what you're saying is they go up or down together and in some ways that might make some sense based on the seers finding. But, the thing about this is of course we have no idea what's going on. That's right. The science is lagged so far behind what people are doing that we just have to know how it works. That's true and I think that a factor that's really under appreciated is the methods by which you conduct a prescription opioid taper matter greatly. A lot of physicians in the community, almost all of them, lack clear guidance on how to appropriately and compassionately reduce prescription opioid use. The guidelines that exist right now are too aggressive for our patients who are on high doses or patients who have been taking opioids for years or even decades. If we go to aggressively in a prescription opioid taper, it amplifies pain, it amplifies distress and withdrawal symptoms, pain being a primary symptom of that, and it leads to a lot of failed tapers. So in the context of this, I could see that if patients are force-tapered, or if they're engaged in the taper that's too aggressive, that they could increase marijuana use in order to self-medicate the discomfort of the taper, not necessarily their baseline pain at all, but just the taper itself. So this is a big focus nationally right now. I mean, the question of whether you should be on opioids or not on opioids, I care less about that. I am very focused on when we do decide to taper, we must treat patients with compassion. We must be mindful that we are not exposing them to brand new iatrogenic risks caused by an inappropriately aggressive taper that fails to account for the unmasking of some psychological symptoms and the increasing distress. Yeah, totally. I think it makes more sense that with over correction, we'll just have some negatives too. So you've just mentioned our masochism symptoms. I want to pass on a question for my students because they were asking about, is there this energy between or the interaction between the psychological side of things and potentially the [inaudible] therapies in cannabis? I think part of where this questions comes from too is, we just don't know we just don't know if A, how strong is the association between cannabis and changes in opium use and pain? What would the mechanism be too? Because it may not have a direct analgesic effect, it may be as you just mentioned, maybe it's somehow helping people get over withdrawal or maybe some other psychologisms that are unmasked. I think that's what making comments all about and of course you've seen lots of patients from the behavioral side of things. How do you see cannabis playing out? So I'm trying to pass on that question as best as I can then maybe you can help. Yeah. So I think it's helpful first to come into an appreciation of the definition of pain. So the International Association for the Study of Pain, defines pain as being a noxious sensory and emotional experience. So the definition of pain includes psychological dimensions. It's half of the definition. But when we talk about pain, we all pretend as if it's largely sensory, and there's these little cognitive and emotional aspects that we should consider. That's actually baked in. So psychology is integral to the experience of pain and they are inseparable in truth, they truly are. We try to separate them and we can arrive at some estimates of how some very direct psychological experiences can influence what a person reports as a pain score, the number that they tell us. But on balance, when we recognize that pain is really and it's truly a psycho-sensory experience, anything that impacts our psychology, emotional and cognitive functioning, will have impacts on our sensation and what we report to be pain, so yeah. I mean, once we come into that awareness, I would say it's impossible for it not to be a part of the equation, 100 percent. The bigger question is, what are the large-scale effects at a group level? Then we have to be mindful that it's really the individual differences that matter which comes back to the patient-centered research, where we want to focus on each individual and all of their individual characteristics that make them have a disparate response to the average. Yeah, it's super important. I think you also have come now full circle back to the patient center piece, the fact you're so right. We can do all this research and we never look at these averages and across people, but ultimately there are big differences in terms of how people respond to these things, and in terms of all the many factors that influence the outcome. So yeah. I think you did a nice job of really highlighting the emotional, sensory side of things. I mean, obviously cannabis has an impact on those things too. So it's pretty unclear how but definitely multiple possibilities how cannabis might impact the sensation of pain and/or the interpretation of pain, the emotional side of pain. So yeah, and essentially, things are better or worse. I mean, you're still going either way. So it's just a fascinating in a way of sorts. It really is, no question about it. I mean, I'm not a pharmacologist and it's not my area, but I think the cannabinoid line of research, I'm really excited for more of that to come online and inform our understanding about how can cannabinoid products that maybe have some of those psychoactive properties removed, how those could safely treat pain. The interesting thing about people in the community just accessing marijuana, is that that's a whole different ball of wax, where we're definitely engaging all of the psychological aspects and influencing those. We really can't say with any degree of confidence that that is safe or effective or helpful for our patients with pain. In large part, because all of the rules and structures around the research have been so rigid that we haven't been able to conduct much of the primary science. Exactly, you're totally right. We just know our time in cross-talking about that. The barriers and then, what does that mean? That means there's no research, it means that basically, people who were marketing cannabis can fill in that knowledge gap with whatever they want. Of course, there's so many things out there you can ask. That's why it's impossible to know what works and what doesn't work or what has the opposite effect, because people are using all different versions, all different kinds. It's difficult know. But yes. So I just want say thank you so much and I know I've probably kept you a bit long here but it's so nice for you to do this. I really appreciate. I'm looking forward to have a chance to talk with in person. It's been a long time since we had a chance to chat. I know, it's been a real pleasure Ken. I'm really excited with all of the work that you and the group is doing at Colorado. I look forward to seeing all of the results from that. We'll have to have you down here sometime soon. That would be great. All right, Beth. Take care. Thank you so much. You too. Bye. Bye.
