Researching Psychedelics for Potential Therapeutic Use

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Recently, interest in psychedelic research has seen a resurgence, strengthened by better designed and controlled clinical trials and the use of neuroimaging, examining psychedelics' potential therapeutic use for PTSD, addiction, anxiety, and depression. On today’s episode, we talk with Dr. George Mashour, professor of anesthesiology and pharmacology and founder of the Michigan Psychedelic Center about using rigorous scientific methods to unlock the mysteries of psychedelics and investigate their potential as therapeutics. 

Learn more about the Global Psychedelic Survey 2025, launching 5/1/25

Learn more about The Fundamentals

Transcript

Kelly Malcom:

Welcome to The Fundamentals, a podcast where we explore biomedical research here at Michigan Medicine. Research is fundamental to University of Michigan's mission to improve the world. On each episode, we'll meet the people behind the research, learn more about their fields, and the fundamental questions they are trying to answer.

I'm Kelly Malcom, a science writer and communication strategist for the University of Michigan Medical School. This season, we'll start by explaining a little bit of the history behind the questions our experts are asking and get a glimpse into the future of healthcare.

Psychedelics are compounds that change a person's awareness, mood, or perception of time and space. Archeological evidence suggests that humans have used psychedelic plants such as psilocybin, mescaline, ibogaine, ayahuasca DMT, cannabis, and peyote as part of their spiritual and healing rituals for millennia.

The first fully synthesized psychedelic LSD was created in 1938 by Dr. Albert Hoffman, who was studying substances including lysergic acid produced by the fungus ergot. Ergot can grow on grain, and when ingested can cause fever and hallucinations. The story goes that during his work, Hoffman accidentally contaminated himself with a small amount of a lysergic acid derivative and noticed unusual psychic effects. On April 19th, 1943, he purposefully consumed 250 micrograms of LSD and asked his lab assistant to escort him on his bike ride home as the drug took full effect.

Speaker 2:

Kaleidoscopic fantastic images surged in on me, alternating, variegating, opening and then closing themselves in circles and spirals, exploding in colored fountains, rearranging and hybridizing themselves in constant flux.

Kelly Malcom:

April 19th is now known as Bicycle Day. This first trip inspired a wave of investigation of LSD and psilocybin as potential therapeutics for psychological disorders, including anxiety and depression. However, due to increased regulation of pharmaceutical research as a result of unethical protocols, disappointing early clinical trials, and the stigmatization of recreational drug use, LSD was classified under UN Convention Schedule I, meaning drugs with no currently accepted medical use and a high potential for abuse. Psychedelic research all but halted in the early 1970s.

More recently, interest in psychedelic research has seen a resurgence, strengthened by better designed and controlled clinical trials and the use of neuroimaging, examining psychedelics' potential therapeutic use for PTSD, addiction, anxiety, and depression. Researchers like Dr. George Mashour, professor of anesthesiology and pharmacology and founder of the Michigan Psychedelic Center, are using rigorous scientific methods to unlock the mysteries of psychedelics and investigate their potential as therapeutics. Welcome to the show, Dr. Mashour.

Dr. George Mashour:

It's wonderful to be here. Thank you.

Kelly Malcom:

How did you become interested in studying psychedelics as an anesthesiologist and a neuroscientist?

Dr. George Mashour:

My original and foundational interest is in consciousness, and this interest developed when I was an undergraduate student studying philosophy. That interest led me to anesthesiology, led me to neuroscience, and ultimately led me to the University of Michigan where I founded the Center for Consciousness Science. Originally, we were focused more on the level of consciousness, the overall arousal state, being awake, being asleep, being anesthetized. We studied anesthetics and sleep. But then, especially through interactions with our graduate students, we started to get more and more interested in psychedelics as a tool to modulate consciousness. That's what we're doing now at the Michigan Psychedelic Center from the foundational science right up through clinical trials.

Kelly Malcom:

I'm not completely surprised it was graduate students who kind of pushed you in this direction, but really what is the potential connection between psychedelics and consciousness?

Dr. George Mashour:

I mentioned anesthetics before, and anesthetics help us understand the brain mechanisms that control the level of consciousness, that overall state of either being awake or asleep. Psychedelics help us understand what is referred to as the content of consciousness. So why is it that we see this redness of the rose or the blueness of the sky? Because psychedelics don't radically alter our level of consciousness or our arousal state, but they have a profound effect on how we see or hear or perceive the world. And so understanding what happens with the brain before and after the administration of a psychedelic can give us insight into consciousness.

And of course, like anesthetics, psychedelics also have therapeutic potential and are being increasingly explored in psychiatry and neurology and other fields.

Kelly Malcom:

I imagine that it's probably a little more challenging to study psychedelics because they do have a little bit of stigma. Maybe that stigma is reducing over time, but there is still stigma around psychedelics. Is that warranted, and how do you do your research in that environment?

Dr. George Mashour:

There's definitely stigma and there are definitely a lot more regulatory guardrails to studying psychedelics compared to something like studying anesthetics. I wouldn't say the stigma is warranted, but I do think that caution and care are warranted. I think we need to learn a lesson from what went on in the 1960s where experimentation really started to spill over beyond the boundaries of the ethical. So I do think we all need to be cautious and we need to be fully adherent and compliant with these regulatory guidelines so we can ensure safe and ethical study and therapeutic exploration of psychedelics.

Kelly Malcom:

Which are the psychedelics that researchers like yourself and others are really looking at currently?

Dr. George Mashour:

One of the most common compounds is psilocybin, which is the active ingredient in psychedelic mushrooms. That has been tested in a number of different settings, including clinical trials. And in fact, we have studied psilocybin in pre-clinical models of chronic pain. We've had one small proof of principle clinical trial using psilocybin for patients who have fibromyalgia that was conducted through the Chronic Pain and Fatigue Research Center. So that is one drug that's commonly studied. We're also studying DMT dimethyltryptamine, which is a potent psychedelic drug, and we're studying that more in the laboratory model. Other drugs that you don't see in human use as much, such as DOI, which we're studying in the lab. And then there's this interesting class of drugs that can function as anesthetics or psychedelics depending on their dose, and that includes ketamine and nitrous oxide, which we've studied across multiple species.

Kelly Malcom:

I know you mentioned that psychedelics can tell us a little bit about the content of consciousness. Do we really know what is happening in the brain when you are using a psychedelic substance?

Dr. George Mashour:

There's certain things that are known. I wouldn't say that the mechanisms are fully elucidated because we don't yet know what the fundamental mechanism of conscious experience is. And so I think those two are going to move together hand in hand. But we do have a sense of what's happening in terms of molecular targets like the serotonin receptor, where those psychoactive effects seem to be mediated. But there are likely other molecular targets as well. We know what happens at the level of large-scale brain networks, and that's something that is beginning to be elucidated and the literature to which we have contributed in terms of enhancing those functional connections and that communication across the brain and allowing a broader repertoire of brain states to be accessed, enhancing neural complexity and the complexity of neural signals. So there are some fairly consistent findings across a variety of studies. Now the task is how do we connect what's going on at the level of the brain networks to what's going on in experience and the first-person perspective.

Kelly Malcom:

Can you tell us a little bit more about why you founded the Michigan Psychedelic Center?

Dr. George Mashour:

I really wanted to build a community. We're in the midst of what has been referred to as the psychedelic renaissance. Things really shut down after the laws changed in the early 1970s. But really over the past 10 to 15 years, there has been this resurgence in interest in psychedelics, a resurgence in high-level scientific study, in clinical research. There have been changes in policy, in law, and also in cultural attitudes towards psychedelics, probably in part led by the changing perspectives on cannabis. So I think we've been a part of that, and I wanted to ensure that the University of Michigan was a leader in this space and working collaboratively with the other centers and institutes that were being founded. I think we have really remarkable talent across the University of Michigan. Prior to the center, I had started an unofficial collaborative of researchers and just found that there was authentic interest and a lot of people doing interesting things that could contribute. So the goal was to build a community, build a home, and to have that be legitimized by a formal center status.

Kelly Malcom:

Do you have trouble recruiting people who may use psychedelics to participate in research about psychedelics?

Dr. George Mashour:

There's really been widespread interest in the Michigan Psychedelic Center and getting engaged in studies, and I frequently hear, and we hear from people from across the state of Michigan. I think we have to be careful in terms of the types of studies that we're conducting to get very careful inclusion criteria, especially for individuals who have chronic pain which we've studied or psychiatric conditions. And on that note, I want to acknowledge our wonderful partners in the Department of Psychiatry who have been leaders in terms of studying ketamine and psilocybin for depression.

Kelly Malcom:

Can you maybe expand on the ketamine story? I didn't realize that we had a ketamine clinic.

Dr. George Mashour:

Yes. So if I can give you a longer story about ketamine, that story really is rooted here in Detroit and Ann Arbor. Ketamine was first synthesized as an analog to Phencyclidine or PCP, which was used as an anesthetic, but people woke up just flora delirium. So they were looking for analogs that might have the same properties but not be so deliriogenic as it's called. So Ketamine at the time was known as CI-581. It was synthesized at Parke-Davis by an organic chemist named Calvin Stevens, who is a professor at Wayne State. And then it was first studied in humans and in surgical patients by a pair of faculty here at the University of Michigan, Dr. Edward Domino, who is a professor of pharmacology, and Dr. Gunter Corson, who was professor of anesthesiology. That was going on in the '60s, and they published those seminal articles in the mid 1960s.

Ketamine originally was explored as an anesthetic, but in the 1990s it started to become clear that at sub-anesthetic levels it also had antidepressant properties, and importantly it had rapid-acting antidepressant properties, and that's distinct from the more conventional antidepressants which can take four to six weeks before you start experiencing mood changes. And so ketamine ultimately became FDA-approved for certain forms of depression. Our colleagues in the Department of Psychiatry lead a ketamine clinic where people can receive that really important therapy for depression.

Kelly Malcom:

I know that there was recently a Global Psychedelic Survey, and there will be sort of a second part to that coming up. Can you describe your involvement with that survey and what did it find and what does the next iteration hope to accomplish?

Dr. George Mashour:

The Global Psychedelic Survey of 2023 was the inaugural such survey, and the goal was really to get community voices and community engagement. The premise was the people who can offer the most perspective or the best perspective about psychedelic drugs are those who are using psychedelic drugs in a variety of different settings. So I think that was the original goal. I was not involved in that first study, but some of my wonderful colleagues here at the University of Michigan have partnered and collaborated with those who are leading the study and who have published a number of articles. Again, really getting that community voice, which I think is an important complement to the other work that we're doing here in terms of clinical trials or more the foundational laboratory science.

When I heard that there was an opportunity to connect with the principal investigator, Philippe Lucas, who led the first Global Psychedelic Survey, or GPS as it's called, I really was very eager to be involved and to have the Michigan Psychedelic Center as the sole sponsor and the University of Michigan as the home to be the repository for what is going to be a very, very rich data set.

The survey is going to be translated into about 15 languages and disseminated worldwide. It will truly be an unprecedented resource for investigators, for academics, for policy makers, for the community to learn about the perspectives of those who are self-administering psychedelics, and again, in a variety of different settings, or who have experienced the psychedelic experience in the clinical setting to help inform its effects and its potential for research, as well as its potential for clinical care and its adverse effects. We need to be really vigilant about not getting caught up in the hype and recognizing, like any other drug class, psychedelics can have harmful effects. And so again, this will be a great resource.

Kelly Malcom:

What is your hope for the future of psychedelic research?

Dr. George Mashour:

Focusing on the University of Michigan, I want to continue to grow the community across the tripartite mission of research, education, and ultimately clinical care. I hope that we can further engage the community. I think one avenue that will be key for success of the center and also the overall program is to get more NIH-funded research supporting the investigation of psychedelics, both in terms of the basic neuroscience, but also in terms of applicability and translatability to human conditions and psychiatry and neurology and other fields.

So really want to continue to enhance the community, engage our academics across campus, and really across the campuses if I can. And really, again, want to emphasize conducting ourselves with the highest ethical standards, with the highest safety standards. I'm really thinking about the long game. There's a lot of hype and excitement right now, but I'm really interested in what's going to be happening decades from now. I think to really build that foundation, we need rock solid, credible, careful, rigorous scientific evidence, and that's the kind of foundation that I hope we can build at the Michigan Psychedelic Center.

Kelly Malcom:

Dr. Mashour, this has been incredibly fascinating. I do hope that people listening who are interested are able to participate in the Global Psychedelic Survey, GPS as you put it. We will share that information with this episode. So thank you again so much for being on the show.

Dr. George Mashour:

Thank you for having me.

Kelly Malcom:

The Fundamentals is produced by the Michigan Medicine Department of Communication in partnership with the University of Michigan Medical School. Find us and subscribe wherever you listen to podcasts.