WSU researcher Leslie Lundahl, Ph.D., discusses her team's efforts to study the potential therapeutic benefits of cannabis use by veterans

Episode Notes

Recently, the state of Michigan granted WSU $7 million to investigate the potential therapeutic effects of cannabis to improve military veteran patients' quality of life and reduce post-traumatic stress disorder and depressive symptoms that can precede suicide. In this episode, lead researcher Leslie Lundahl, Ph.D., talks with host Darrell Dawsey about her team's research, the grant and the evolution of public opinion about the social acceptability of marijuana.

About

Dr. Lundahl's overall research objective is to advance our understanding of addictive behaviors, with the goal of developing new treatment approaches and improving existing options for individuals who seek help for their substance use disorders. To this end, she has focused her scientific endeavors in several key areas: identifying factors (e.g., personality, environmental, pharmacological) that are potential determinants of drug seeking behavior; developing and refining human laboratory models (e.g., cue-induced and stress-induced craving/use, drug discrimination, subjective effects, choice procedures) to efficiently and rigorously test mechanisms of action that underlie drug-taking behavior and contribute to relapse, as well as test candidate medications for pharmacotherapy; understanding factors that might predict treatment retention and treatment outcomes; and using this knowledge to improve existing treatment options and guide development of new, better-targeted treatment approaches for substance use disorders. Although most of her work involves cannabinoids, she has also conducted studies on alcohol, nicotine, MDMA, cocaine, and opioids.

Additional Resources

Read about the $7 million grant to WSU to study marijuana's potential therapeutic effects on vets

Learn more about the Drug Lab

Follow the Wayne State School of Medicine on Twitter

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Transcript

Announcer:

Welcome to Today @ Wayne, a podcast that engages and informs the Wayne State University campus community. With news, announcements, information, current events and discussions, relevant to the university's goals and mission, Today @ Wayne serves as the perfect forum for our campus to begin a conversation or keep one going. Thanks for joining us.

Darrell Dawsey:

Welcome to the Today @ Wayne podcast, I'm Darrell Dawsey. With a wave of marijuana legalization having swept states throughout the country in recent years, Americans are talking differently and more openly about marijuana use than ever before. While much of the conversation is focused on cultural and criminal justice implications, at WSU the conversation is centered largely on research. In August, the state of Michigan awarded Wayne State University a $7 million grant to investigate in military veterans the potential therapeutic effects of cannabis to improve patient's quality of life and reduce post-traumatic stress disorder and depressive symptoms that can precede suicide. Leading the project is the School of Medicine's Associate Professor of Psychiatry and Behavioral Neurosciences, Leslie Lundahl PhD. Dr. Lundahl is a research educator in the translational neuroscience graduate program in Drug Lab Detroit, a multidisciplinary team at the School of Medicine focused on understanding more about the development and treatment of substance abuse and substance use disorders. She's here with us on the Today @ Wayne podcast to talk about some of the cutting edge work she's doing in cannabis research. Welcome Dr. Lundahl.

Leslie Lundahl:

Thank you so much for having me. I'm really excited to have an opportunity to talk about some of this work. It's pretty exciting.

Darrell Dawsey:

Yeah, it seems like it. A lot of folks, they see marijuana or cannabis and maybe there are a few snickers-

Leslie Lundahl:

Definitely.

Darrell Dawsey:

Because we're still sort of developing an approach to this thing that goes beyond being prohibited in America for so long. So I was wondering if you could talk to us a little bit about some of the research that your lab has been doing. You guys have been doing some stuff on the negative effects of drug abuse, but now you're taking a look at some of the therapeutic effects and what potential it has. Tell us a little bit about what's going on.

Leslie Lundahl:

Sure. So for about the last 20, 25 years, we've been conducting what are called behavioral pharmacology studies in the laboratory with humans. Meaning that we administer different drugs perhaps alone or in combination with other drugs to see how they affect people in terms of subjective effects or cardiovascular effects, physiologic effects, cognitive effects. And so we've done a lot of studies on, well we've looked at MDMA or ecstasy, we've looked at methamphetamine, cocaine, heroin, other opiates, certainly tobacco, alcohol, and of course cannabis.

Leslie Lundahl:

So really what we have focused on has been medications development, looking at ways that we can help people who want to stop or cut down their drug use. So we've been very focused on sort of the negative effects and how we can sort of help people return to a healthier level of functioning. So this is a radical departure for us because now we're looking at one of these substances, cannabis, which not too long ago was sort of viewed as the evil weed or the gateway to harder drugs, or whatever view you might have. We're now looking at this particular substance as a possible therapeutic for folks, and that's kind of a radical departure.

Darrell Dawsey:

Yes, it is. Let me ask you, you're focusing on military-

Leslie Lundahl:

We are.

Darrell Dawsey:

...veterans right now. Why are they sort of your target? Why are they so important to the study?

Leslie Lundahl:

Sure, that's a good question. So one of the reasons that this grant was funded, the funding came about through the Marijuana Regulatory Agency, which is the state of Michigan's regulatory agency for cannabis. And their interest in veterans is that, so first of all, anywhere from 13 to 31% of US combat or military veterans experience PTSD. And that's a far greater rate than you'd see in the general population, which is usually around five to 10%. A lot of veterans who seek treatment for PTSD and trauma related problems report that they use cannabis on their own to self-treat their PTSD and depression related disturbances for things like stress. With PTSD you often see sort of an exaggerated startle, or sort of a hyper arousal, certain panic symptoms. They can have negative mood, pain, oftentimes they don't sleep well. They have nightmares. We also know that more than 6,400 US veterans died by suicide in 2018.

Leslie Lundahl:

And this is a rate that's actually increasing. This is more than 17 suicides every single day. The suicide rate is probably due to untreated or undertreated depression and PTSD symptoms and their related psychological problems. And another point that's important is that in a recent survey, more than 20% of veterans reported that they used cannabis to manage their mood and anxiety symptoms. 75% of them said they would consider cannabis as a treatment option for pain or mental health issues. And 68% believed that the US Department of Veteran Affairs should allow research exploring the use of cannabis as a therapeutic option. Currently they do not. We sort of believe that we owe it to our service people to look outside the box for any kind of treatment that could give any kind of relief, because this is just too high of a cost. There's just too many lives lost.

Darrell Dawsey:

Now, I know you're not an advocate one way or another necessarily, but we know that even as states are legalizing marijuana, it continues to be treated like a Schedule A drug by the federal government. Does that in any way hamper the work that you're trying to do?

Leslie Lundahl:

It doesn't hamper ours so much because we are one of the lucky few laboratories in the country that are allowed to administer cannabis in a smoked route of administration. So, there are FDA regulations, DEA regulations, and NIH regulations. And all three of those agencies sort of have to align in a magical way to get approval and get all the certifications to be able to do this kind of work. So we are fairly lucky. We've been able to do this for about 20 years, like I said. But it did take us a couple of years to get all of those stars aligned, to get the required regulatory things in place.

Darrell Dawsey:

Now, is one aim, there's talk about CBD, which has medicinal effects. THC, which I guess is the main psychoactive ingredient in marijuana.

Leslie Lundahl:

Exactly.

Darrell Dawsey:

Are you guys, does your research involve sort of trying to find a balance between the two of these? How are they dealt with, how are they addressed in the research?

Leslie Lundahl:

Well, so that's actually one of the major goals of our study is, as you probably know like you just said, THC is the psychoactive ingredient in cannabis and CBD is a cannabinoid also found in the plant cannabis that does not have psychoactive effects. And in fact, it looks like CBD might be the ingredient that does have more of the pain relieving or the anti-inflammatory, or the calming effects to when you smoke marijuana. So one of our goals is to look at different ratios. So for example, a lot of folks who say that they use marijuana or cannabis for symptom relief, don't like being high. They don't enjoy that feeling of intoxication. So one thing that could be recommended to them is that they find a product with a lower THC concentration, with a higher CBD concentration.

Leslie Lundahl:

And so we know very little about that. We don't know what kind of concentrations work better for pain, which ones work better for sleep, which ones work better to sort of calm your stress. So one of the things that we're doing is we're looking at the safety and the effectiveness of different combinations. So for example, we'll look at high THC-high CBD, high THC-low CBD, high CBD-low THC, and low CBD-high THC. So those four variations of those two. And really what we're looking for is what's safest. We know that THC raises heart rate. We know that it has cardiovascular effects. And especially if we're looking at older people, this is a concern. So we really want to try to figure out what is the optimal combination of symptom relief that is most safe.

Darrell Dawsey:

Are you also addressing issues such as delivery? You mentioned cardiovascular issues. So is there smoking of the marijuana? Are people consuming edibles? How is this being delivered?

Leslie Lundahl:

For this clinical trial we are looking, we're going to use a vaporizer, a medical grade vaporizer. And the reason for this is with edibles a lot of people find them very unpleasant because there's a very slow onset of action as with any oral drug. And then once it's on board, it stays on board for hours. Whereas a smoked or vaporized drug comes on very quickly and doesn't stay for very long. So that allows us to do our testing in a laboratory without making people have to stay there for hours and hours and hours.

Darrell Dawsey:

Gotcha.

Leslie Lundahl:

But at some point we will have to look at an oral thing, an oral delivery. Because I seriously doubt that a smoked drug is going to be accepted as an actual medication because there's too many risks with smoking.

Darrell Dawsey:

I would imagine. Now you studied the issue of drug abuse for years. We talked at the outset about changing public perceptions around marijuana. Are you surprised at these changes that are taking place and to what degree do these changes make it easier for researchers like you to do your work?

Leslie Lundahl:

You know, I think that's a really interesting question. I'm not sure. I guess I would say yes and no. In some ways to me, I feel like it's been very quick that marijuana has, so remember that movie in the 1920s, what was this called?

Darrell Dawsey:

Reefer madness.

Leslie Lundahl:

Reefer madness, right? So there's this perception that you smoke and you go insane. Then all through the sixties and seventies, when it started to get popular and there were things like just say no and DARE, and if you smoke, you're not going to be able to think. So to me, it seems like it's been sort of quick to go from that to now it's a medication that is therapeutic.

Leslie Lundahl:

But if you think about it in context, cannabis has been used for thousands of years. It has been used for, it can be tracked way back to Egyptian times. So in that context, it really has not been a quick evolution if you think about it. I would say I'm a little concerned that it's being embraced so quickly in popular opinion, because I think that's outpaced the science. So that makes me a little bit nervous. We really don't have well controlled evidence that support these uses yet. And so this is one of the studies that I think is going to help clear that up. And certainly we need many, many more studies that will help clear it up, but they have to be well-controlled, well-designed studies.

Darrell Dawsey:

Do you worry that there's a danger that as we sort of culturally come to embrace and normalize marijuana usage, are you concerned that perhaps in doing that we may be diminishing some of the actual negative physical effects?

Leslie Lundahl:

I think we could. And I guess where my concern would lie there is with adolescents. Because I think we have very clear data that the brain is still developing in very important ways up until when people are 24, 25 years old. And the research is fairly clear that if you start smoking early at 13, 14, 15 years, that there are some changes in brain chemistry and brain structure that may not be reversible. And over time may show up, particularly in middle age, as things like memory decline or difficulty with cognitive functioning. So I am concerned about teenagers thinking that, hey, this is medicine, it's very safe. When really I'd like them to delay. So I think that's one of the things I worry about.

Darrell Dawsey:

Gotcha. Last thing for me.

Leslie Lundahl:

Sure.

Darrell Dawsey:

Tell us a little bit about your team. You guys have a pretty robust team doing some heavy lifting. Just tell me a little bit.

Leslie Lundahl:

Yeah, we've got a pretty big team. And a lot of that is because there are a lot of moving parts to this project. We try to get as much data as we can to inform as many different areas as we can. So we have to bring in experts in all of these different areas. So I am actually a clinical psychologist and a behavioral pharmacologist. And my colleague, Dr. David Ledgerwood is a clinical psychologist. And he and I will be conducting the two clinical trials that are looking at whether THC and CBD reduce PTSD symptoms, severity and suicidal ideation. Dr. Seth Norrholm is a co-principal investigator with me. And he and Dr. Tanja Jovanovic are both experts in neuro behavioral aspects of trauma and PTSD. So they're going to look at individual differences in fear learning and extinction, as well as psychophysiological reactivity to trauma cues.

Leslie Lundahl:

Dr. Norrholm is actually an expert in creating VR environments. And so he is going to be creating a virtual reality environment to expose some of our participants to trauma related cues in the safety of just the trauma, the VR environment rather than actually obviously the real trauma environment. Dr. Hilary Marusak is an expert in the endocannabinoid system. So this is the body's own cannabinoids that are in the brain. She'll be looking at how the effects of THC and CBD interact with the body's own cannabinoids, endocannabinoids. And so that's pretty interesting. And then Dr. Mark Greenwald is a behavioral pharmacologist. He'll be looking at genetic markers that will help us hopefully be able to predict who might have a positive response to THC or CBD, or just as importantly, have a negative response. We also have a chemist and some biostatisticians to help with all the analysis. So we have a pretty broad team, it's a very strong team, and we need every single one of them to pull this off.

Darrell Dawsey:

Sounds like this is going to be some heavy, heavy lifting.

Leslie Lundahl:

Yeah, this is a big project.

Darrell Dawsey:

Qualified people.

Leslie Lundahl:

Absolutely.

Darrell Dawsey:

It's good to know that we're doing this kind of research and we're trying to do what we can to help vulnerable populations, particularly our veterans. Is there anything else that maybe you want to add about this work, something maybe I haven't asked you or something that you would like to emphasize?

Leslie Lundahl:

I guess part of what I'd like to say is that this is a pretty unprecedented project, and I think this is not necessarily something the federal government would fund. And so we're very thankful the state of Michigan for sort of having the vision to see that this is something that's important. Whether we find that cannabinoids are therapeutic or have too many risks, I mean, that's really important for us to know.

Leslie Lundahl:

Our physicians need to know how to discuss whether or not a patient should try a cannabis therapeutic. And I think they need data to really guide those discussions. And people need to be informed, do I really want to try this CBD for my pain? What does the science say? What kind of dose do I need? Do I mix it with THC or not? And I think that's stuff that we just don't have a lot of scientific guidance on yet. So I think this project is really going to move us forward. And I think that's exciting, whether it's our group or other groups who are able to sort of take it further after we get these results. I think that's pretty exciting.

Darrell Dawsey:

Well, we wish you all the very best in this very important research. Dr. Leslie Lundahl, thanks so much for joining us here at the Today @ Wayne podcast.

Leslie Lundahl:

Thanks for inviting me. I really enjoyed it. Thank you.

Darrell Dawsey:

All right. Hope to have you on again soon. Take care.

Leslie Lundahl:

Absolutely. Thanks to you too.

Darrell Dawsey:

Bye Bye.

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