The study is currently recruiting participants in California and if you are suffering from those conditions and wish to try cannabis as a mitigation strategy, then this might be a good way of getting your toes wet.  But as always, it is best to hear from the researchers themselves in their own words what this is all about. So it is my pleasure to share a conversation with you that I had with the refreshingly enthusiastic and knowledgeable principal investigator of the study, Dr. Daniel Kruger, who agreed to tell us all about the motivations behind the project.

But before diving into the weeds of the conversation let me beat the drum for the study a little bit.  Here is what you need to know if you wish to participate:

1. You need to be a California resident
2. You have one of the aforementioned conditions: Fibromyalgia, Rheumatoid Arthritis, or Osteoarthritis of the hip or knee.
3. You will be sent several hundreds of dollars worth of cannabis products over a period of 12-weeks. There is a reimbursable $15 fee that is returned to you if you complete 90% of the study. 
4. Participants who complete the study have a chance to receive an additional $50-$500 in Amazon gift cards. (More info at releaf.at/umpain)

You can find more detailed information and sign-up at the following link:

https://releafapp.com/michigan-research-study/

The Interview

Alexander Schering, PhD
Good afternoon Dr. Kruger, thank you very much for sitting down with me to discuss your wonderful project. 

Daniel Kruger, PhD
Oh, oh, it's nice. It's nice to talk with you. 

Alexander Schering, PhD
Why don‘t we start by having you tell us more about your background and why you do what you do?

Daniel Kruger, PhD
Sure! So, I'm Daniel Kruger, I'm a researcher at the University of Michigan. My research spans the full range from the very theoretical to the applied. I have a research program, where we integrate the theories of evolutionary biology into understanding humans. So understanding human psychology, behavior and evolutionary frameworks. And that's, that's quite an exciting area for me. I also work a lot in applied research on the other end of the spectrum, including research projects that are designed to bring direct benefits to communities, not so much theoretical questions, but rather research that's going to help people, especially locally, understand the health patterns in their community and the effectiveness of interventions, etc. And because of that I have been in the world of public health, and I would be going to public health conferences to present our research which was typically community based health surveys, program evaluations, and such. But I would see a lot of presentations on cannabis. And at that time, all these presentations were pretty firmly in what you could consider  prohibition era thinking.

Even up to five years ago research was following the so-called gateway drug model.

They're about abstinence based programs and research on what all the possible harmful effects of cannabis are. Like, does cannabis use cause intimate partner violence? You know, things like that. Even up to five years ago research was following the so-called gateway drug model. This was a recurring theme. And after California, Oregon and other states in the US legalized cannabis for medical use, I would go up to these presenters, and I would say, okay, I see what you're doing. And there's value, we do want to know what possible harms exist. And maybe we don't want children using mind altering substances, if it's going to cause them harm. However, now there are millions of adults that have legal access to cannabis. And they're using it to treat all sorts of different health and medical conditions. So, what's the public health framework for that? How do we maximize people's benefits and minimize the cost, risks, and harms? This is as you know the true mission of public health! 

I got a lot of funny looks, you know, people were usually stunned and looked at me, like, I was this crazy guy. Right. But sometimes people were a little more responsive, at least considering it and just said, “well, you know, we don't think this is dangerous, or we don't know enough about that.” That's a very true and honest answer, you know, we really don't know enough about it. So my conclusion is, well, why don't we study it? Why don't we research it? 

After just a series of these experiences, I was thinking someone has to do something about this. Someone really has to do something about this. Well, I guess it's us, you know, because nobody else is doing anything about this. And I mean, quite honestly, it's a different world today. There's been a big boom in cannabis research and it includes research from the perspective of “let's take medical cannabis seriously” - So, what would that mean? What would we want to know? I think that since we did get started fairly early on in the current wave, we've been able to push the boundaries of where the research is. 

Let's take medical cannabis seriously!

One of the big questions is, what is cannabis good for? You know?  Because, in the 19th century, mainstream medicine really wasn't that effective. In fact, they had all kinds of pseudo scientific practices, like bleeding and giving people mercury, which was basically poisoning people, and the alternative was these cure-all remedies. You can imagine somebody traveling around the Wild West in a stagecoach and just selling these little tinctures. And they could be anything. It could be really high proof alcohol, opiates, or cannabis. And, you know, people took them and they felt better. Right? Maybe maybe just because they were intoxicated, maybe because they stopped doing those things that were actually bad for them but were the standard remedies at the time. But it was a cure all right.  It was to cure anything and everything. 

But now in the era of scientific medicine, we want it to be empirically based. We really want to make recommendations and implement practices based on what works and what is the best solution. So that's why we're partnering with “MoreBetter, Ltd.”, because we really want to see, what is cannabis really effective at treating? How do you really optimize the therapeutic value of cannabis by using different compositions? Because as you know, there are hundreds of different cannabinoids. And by now, most people have heard about THC and CBD, those are the two most commonly known and well studied, but there are actually hundreds of different ones and in all sorts of different ratios that you could use in combination. So, that's one of the things that we're interested in looking at.  How is the efficacy of therapeutic cannabis affected by the different ratios of THC, CBD, other cannabinoids, terpenes, etc?

In order to maximize effectiveness, if you go online, there's a lot written about, oh, well, you know, here's this terpene, and it does this. And I'd be interested to see the actual research, you know?  Where did these claims come from, because a lot of the time it's just based on experience, like one person tried this, and that, and this worked for me. But we want to be more systematic than that. Because, as you know, anytime you have any kind of intervention, there could be expectancy effects. You could call it placebo effects, which sometimes gets a bad name, but there really is so much that's psychosomatic in the sense that what we believe really does influence what we experience and the outcome. So, you know, that's something we want to look at. 

We are particularly interested in chronic pain, because that's one of the conditions that has already had the gold star. The National Academies of Science, Engineering and Medicine of the United States has determined that cannabis is effective at treating pain. So the official scientific body of the country, and certainly not not a radical institution by any means. Okay, so we know that!  But there are a lot of details that go beyond just, okay, cannabis is effective at treating pain. There are different kinds of pain, there are even different kinds of chronic pain, and they have different physiological mechanisms and systems in the body. Now this is another component of our research.  Since there are actually different kinds of chronic pain that can manifest in the body. 

• How good is cannabis at treating these subtypes of pain? 
• What cannabinoid ratios and the composition? 
• What really works best for each condition? 
• Is there just like an optimal formulation that works best for everyone? 
• Or do different formulations work better for different conditions? 

I mean, these are the kinds of questions you'd want to know, if you're actually serious about using cannabis therapeutically.  Getting the details right in terms of what really works, and what works better. Because it could be that we see improvements in everybody, but what we really want is to identify best practices, so that people can follow up on those.

Alexander Schering, PhD
This is all really interesting to me, because if you look at the cannabis world as a whole, it seems like the way the research is done is kind of backwards. I always bring this up with researchers like yourself. People are using cannabis already. It is quite widely available and people are self-medicating with it.  Normally, it should be the other way around. You would do the research, you discover something that works and then you put it through efficacy and safety testing. Only then does it become medicine. Right? 

Daniel Kruger, PhD
Yeah, yeah, and that's a very big artifact of the legal history of cannabis in the United States and how that legal framework spread out to the rest of the world. So in the early 20th century, you may have read up on all the characters involved, like Anslinger and all these other folks who drove the original criminalization of cannabis. At the time, it really did seem like a grab for political power. Anslinger was in this tax office that was kind of just like a small component of a government agency that didn't have a lot of power or influence, but manufactured a crisis with this marijuana. Nobody knew what it was, because nobody used the term marijuana. In fact, I've talked with colleagues from Latin American countries, Central America and Mexico. They say they didn't even recognize that term. I mean, that's not what Spanish-speaking people used to call cannabis. So it was kind of a manufactured crisis that gave him a mission and more and more funding to rid America of this “terrible”, you know, “demon weed”, right?  

At the same time, the American Medical Association came out with a statement saying: “Hey, wait, wait, hold on here. Wait, you're talking about cannabis? This is not what we understand, there's no reason why you should get so upset and scared about cannabis to prohibit it.” So even the American Medical Association which at the time again, you know, really not a radical organization, said, “Whoa, you're not really basing this on the current evidence!” But unfortunately, you know, cannabis was criminalized, and that basically put a stop to any kind of research in the modern era, where people were moving towards scientifically based medicine. You know, the 20th century is really the time when it actually became better to go to a position in terms of your health outcomes in 1911. And, you know, there are a lot of great developments in scientific medicine, but unfortunately, cannabis was left behind because it was prohibited, it was illegal, and there was certainly a huge propaganda engine that was just keeping it in people's minds. An illegal substance that was bad for you and was just going to corrupt the youth. And there's no benefit. Right?

Prohibition era thinking impaired research for a long time

Honestly, it really is just in recent times, since the turn of the last century, that we have this notion of cannabis being medicinal and not that people were just going overboard, and restricting it, even though it wasn't as dangerous as folks were claiming. Instead the notion that it was actually good for people, in some ways, that it was therapeutic.

I mean, that was kind of a back to the future again. You know, it's not the first time that's happened. But people started to take that seriously again, but it already existed in the underground again. Even though it's illegal, and the tens of thousands of arrests for cannabis, you know, people were growing it in their basement or out in the forest. So people had access to it. People were using it outside of the mainstream healthcare system.

So you're right, it was the opposite of what typically happens with a pharmaceutical product where a company invests in a series of clinical trials, and they perfect the formulas, and then first use it in rodents, and then even just in small samples of people, just to make sure it doesn't kill them, or seriously harm them, before they even investigate, whether it actually creates some benefits. So, in that sense things are sort of happening in reverse. But, I'm glad that this kind of work is being done. Because it's not following the typical pharmaceutical model.

We're not going to try to patent any of these formulas or anything to try to monopolize the market. We have our values and our goals are aligned with finding out what really are the best practices and how we can really help people. As academic researchers, we're not in it for the money, there's not going to be a great financial windfall for those who found that low and behold, look, this works. I don't think I've seen anyone try to patent a particular, you know, THC to CBD ratio and market that.

Alexander Schering, PhD
Don’t give them any ideas !

Daniel Kruger, PhD
Yeah, no, don't don't tell them that! don't tell them that, because that's actually what's happening with psychedelics right now. But, if we can, if we can get our work out there, then this will be prior art. Right? That's fine, then nobody can patent it. Because look, we've already done it. And you know, just like the polio vaccine, this is something that it's too important for us to be greedy about. We're just going to release our results and share them widely.

Alexander Schering, PhD
So then maybe you can tell me a little bit about that study, specifically. I saw on the website that you're working with two groups, one is “level” and one is “overcome”. Can you give me a little bit of information about the partnership? How did that happen? I see that, one of the flyers, I think it's the one with the QR code, was saying that it's for fibromyalgia, rheumatoid arthritis, and osteoarthritis, right? Yes. knee and hip pain? Oh, well, that's very painful. So that would be great. If that worked.

Daniel Kruger, PhD
Yeah, yeah!  So those are three chronic pain conditions that have different manifestations, physiologically. So that's one of the reasons why we picked those. We picked them because they have different mechanisms. And yes it is a partnership. Tyler at “MoreBetter, LtD.” is kind of the convener of this partnership, and has put together the pieces to make a project like this work. Because as academic researchers, we have very tight regulations and restrictions on what we can actually do, and research. 

So I can do survey research, like I can give people surveys and ask them about their experiences, but I can’t give people cannabis. Right. So basically, what this partnership is, we design the research, Tyler sets up the infrastructure, you know, his company produces the releaf app. So they're actually doing all the data collection, through their releaf app. This is going to deliver a dataset to us at the end of the study that's been de-identified. So there's no participant information in it whatsoever, there's no way to track down who's in the study. And all of our results, of course, are reported as aggregate statistics.

We take averages and we look at relationships. It is not the kind of research like, you know, a focus group, or like an individual interview, where we're looking at one specific person. Instead we're looking at the group as a whole, and patterns across hundreds of hundreds of people.  Then, at the end, we will analyze the data, and we will be blind to the conditions. So we won't even know. It’ll be like formulation A vs. formulation B and formulation C, these are the results. And then once the results are known, then the curtain will come up, and we'll say, Oh, well, low and behold, you know, this is what formulation A and formulation B actually are. That's a good way of making sure that the conclusions are airtight and that there aren't any sort of biases that are influencing whether I have a favorite terpene and I really want this terpene to win, right? Well, you can't do that in real research. 

Alexander Schering, PhD
So, what kind of formulations are in play here for the study? Is it isolated CBD extract, is it mixed? Is it full spectrum? What kind of formulations are we talking about?

Daniel Kruger, PhD
All of the above so, you know, folks full spectrum CBD, there are varying levels of THC and different different terpene compositions.

Alexander Schering, PhD
Interesting. So you're looking at THC, CBD, other cannabinoids and then also terpenes as well, that's great! So how many different groups do you have? In the study? Roughly how many different conditions are you looking at?

Daniel Kruger, PhD
Well, we have three different pain conditions. And then we have a few different product compositions that we're trying. So it's a crossover design where we have three different pain conditions and multiple products, and we are making sure that we test all the different possible combinations of conditions.

Alexander Schering, PhD
Are there any obvious exclusion criteria that you would want to avoid? If people sign up? Are there any groups to whom you would say it is probably not a good idea for you to sign up?

Daniel Kruger, PhD
It has to be adults living in California, because that's where they can legally ship people the products. Unfortunately, we can't do it everywhere. And that's just the legal restriction. You know, women who may be pregnant or could get pregnant, that's something we want to be careful about.Then anyone who might have issues with THC, because the product could potentially contain THC. So if somebody knows or might suspect that they're not able to take THC, and it wouldn't be good for them, then it probably wouldn't be a good idea. Lastly, of course, you have to have one of these three conditions, fibromyalgia, rheumatoid arthritis, or osteoarthritis of the knee, or hip.

Alexander Schering, PhD
To wrap things up a little bit. I'd like to ask a number of just general interest questions like, nothing specific about the research, but just in general. So the University of Michigan, how is the ecosystem there for research like this? Is it cannabis friendly? Is there a problem with regulations? Did you have pushback when you suggested a study like this, or was it effortless?

Daniel Kruger, PhD
Well, we're careful to make sure that we're operating within the regulation. So we do have a fairly narrow lane of the kind of research we can actually do. But as long as we stay within those parameters, it hasn't been an issue. We have an institutional review board that reviews all research projects, including this one. We're able to do it, because we don't have any contact with participants directly, and it's all de-identified. So there's no way for us as researchers to know who's in the study.

And that's important because cannabis is still federally illegal. And I don't think there's too much of a risk, especially as a research study. But, you know, right now the federal government is basically taking a hands off approach. Like, okay, so if it is legal within the state then we're not going to intervene. But it is still in the regulations. It's on the books. It's still in the law. So that's always considered a potential risk. And that's why we don't have any kind of way of identifying participants. So, even if something catastrophic happens, and we had a complete change in our government, and they were completely anti cannabis, and they put us on trial. Well, we wouldn't be able to give any names. 

Alexander Schering, PhD
So, personally, have you tried cannabis?

Daniel Kruger, PhD
Oh well! Ha! - I'll tell you when it's federally legal.

Alexander Schering, PhD
Okay. That's fair. Yeah, I think this was a really comprehensive explanation of the motivation behind it all. So, how many participants are you looking for? What's the study size you're aiming for in total

Daniel Kruger, PhD
Well, you know, it would be good to have at least 100 in each condition, and hopefully more because, unfortunately, sometimes people drop out of studies. So we usually start with a little more than we would really need at the end. But we do that because there is individual variation. You wouldn't want to just do a study on six people. Because there could be a whole range of variability due to a person's health background and each combination of conditions, etc, etc. So, you know, we want to have a lot of data. I mean, as a researcher, the more data the better. But, we also have to be pragmatic in terms of just what our research infrastructure could support. So, we would love to have at least 100 people to complete the study in each condition.

We are looking for 100 participants from California. Sign up!

Alexander Schering, PhD
All right. Well, I think that's pretty much all the questions I have for you, today. Thank you very, very much for taking the time to sit down with me. I think what you are doing is very interesting and valuable. Hopefully it will help people. I have a number of friends who suffer from osteoarthritis and wish they didn’t, so work like yours has the potential to tangibly improve their lives and perhaps inspire legalization to move along a little faster.

⁠Daniel Kruger, PhD
Thanks for your help with getting the word out!

https://releafapp.com/michigan-research-study/