Exploring the Magic Mushroom, with Albert Garcia-Romeu (S3, Ep7)

It’s effective against depression, can help you stop smoking, even ease end-of-life distress. It’s non-addictive, naturally occurring, and has been used for thousands of years — but you can’t have it. It’s psilocybin, the compound that creates the “magic” in dozens of species of mushrooms. Johns Hopkins researcher Albert Garcia-Romeu, Ph.D. knows just how magical it is. He’s conducting research on psilocybin’s therapeutic value for everything from persistent Lyme disease to a range of mental health conditions. Find out what this psychedelic drug can do, and why it got such a bad reputation. Plus… revisiting Timothy Leary’s rise and fall as he turned on, tuned out, and dropped out.

Phil Stieg: Hello, and welcome to Dr. Albert Garcia Romeu from the Department of Psychiatry and Behavioral Sciences at Johns Hopkins School of Medicine and the National Institutes of Health. The presence of hallucinogenics  was described in ancient cultures and their use characterized throughout literature. They were studied broadly in the 60s and 70s, but were then outlawed by the government. Today, Dr. Garcia Romeu will explore with us more recent data on the use of psychedelics in the treatment of addictions and the neurobiological relationships between their use with mindfulness, altered states of consciousness and spirituality. 

Albert, thank you for being with us today.

Albert Garcia-Romeu: My pleasure. Thanks for having me.

Phil Stieg: One can’t help but look at the fact that these things were outlawed back in the 60s. Why on God’s Green Earth did you pick this as a subject to base your career on?

Albert Garcia-Romeu: Actually, I did not. It was a sort of a strange turn of events that brought me to be here.  I was studying  spiritual and transformative experiences as my dissertation research to understand what bearing those had on mental health. And for some people, those experiences were set off or triggered by their use of cycle actives like LSD or psilocybin. As a result, there was some crossover between my interest in that area and the work that was being done here at Hopkins by Roland Griffiths and Matt Johnson and others who had been working on this for some time already.

Phil Stieg: Before we get into the psylocibin work that you’ve been doing, can you outline for us what various hallucinogens there are?

Albert Garcia-Romeu: Yeah. There’s lots of different types of hallucinogens. Some of them, we know can be addictive and harmful, like Benocyclidine or PCP. The drugs that we’re studying mainly are what we call these classic psychedelics. And that includes a number of naturally occurring substances, like dimethyltryptamine, which is found in ayahuasca, psilocybin, which is found in about 200 species of mushrooms, mescaline, which is found in cacti like San Pedro and Peyote. So there’s a number of these naturally occurring psychedelic compounds that are of interest for research, therapeutically and neuroscience.  So, yeah, there’s a lot of different types of substances that fall into this broad hallucinogen class. But these classic psychedelics are really the space that we’ve been focusing on here at Hopkins.

Phil Stieg: In that regard, what happened? I mean … LSD was invented in what, 1938 or synthesized. What changed to make you and other individuals say that now is the time to focus on this. What changed?

Albert Garcia-Romeu: Well, I think there’s a change in sort of the zeitgeist or the way that, culturally speaking, people are thinking about these types of substances. And if you sort of take a step back and look at other drugs. So not only were all these classic psychedelics outlawed or placed on schedule one back in 1970 during the Nixon Administration – but so was cannabis.  Obviously, since the 90s, you’ve seen the tide turn in terms of acceptability and interest in use of cannabis, both for recreational purposes, but obviously for medical purposes as well. I think in general, as the pendulums swing back a little bit to where people are interested and curious about whether these types of substances may have a place in terms of medical or therapeutic use. 

I think a lot of people have anxiety and depression and are interested in finding ways to cope with that. There’s been a huge growth of pharmaceutical types of medications to try to help with some of those issues, but those are not always successful, or they may come along with side effects. That sort of sets the stage for looking for alternative methods or means. You know, I like to tell people when they mentioned this, oh, this is sort of becoming closer to mainstream now. What was mainstream really for a long time was that people use these substances, and it was part of Indigenous cultures.

Phil Stieg: So why did you pick psilocybin, of all the choices, what led you to that?

Albert Garcia-Romeu: Well, I didn’t pick it. This work got started here at Hopkins when I was still in high school, as a matter of fact. So I was not around to make those types of …..

Phil Stieg: (laugh) All right, so why did you gravitate to it?

Albert Garcia-Romeu: Well, yeah, I ended up working here with a group of scientists who have been doing behavioral pharmacology research for decades and who decided that psilocybin was a good target.  And it’s got a number of attractive properties. So first of all, it’s very nontoxic, so you can have a very high dose of psilocybin without putting any of your major organ systems at risk.

Phil Stieg: Is it addicting?

Albert Garcia-Romeu: It is not addictive. None of these classic psychedelics are what we consider addictive in the traditional sense, meaning that they don’t create a sort of compulsive drug seeking type behavior, neither in animals nor in humans. But one of my old professors used to joke the reason that we’re studying psilocybin is because it’s not spelled LSD. 

And so because of all the cultural baggage around that, psilocybin sort of flies under the radar a bit more when you’re talking about it and talking about it as a naturally occurring product that comes from mushrooms, it sort of helps to disarm some of the stigma that can come with these psychedelic compounds.

Phil Stieg: And what are the therapeutic uses that you anticipate might come from your research?

Albert Garcia-Romeu: So the main areas that have shown what I would say is the most substantial promise is in treating major depression and mood disorders.  We’ve seen good evidence that it can help people with these conditions as well as substance use disorders. Or what we often talk about is addictions. And that’s a long-standing  area of investigation where people have studied that since the 60s. 

I think the other kind of overlapping area that’s been very much of interest is in palliative care. So people end of life, people who are dealing with existential issues and have things like cancer related distress.  You know, whatever we can do to help those people improve their quality of life and enjoy the time that they do have left, I think is really important. And there was great research back in the earlier era showing that there is good potential there. And since then, that’s also been one of the most studied areas here at Hopkins, at UCLA, at NYU, all those labs found very positive findings using psilocybin in cancer patients who had anxiety and depression related to their diagnosis.

Phil Stieg: So you said that psilocybin is not addicting in the usual sense. Can it become addictive in the sense that you like the effect that it has on you so much that you repeatedly use it and have to get it?

Albert Garcia-Romeu: Yes. So people can become more sort of psychologically dependent on the effects.  But there’s an interesting sort of self-limiting factor in terms of the pharmacology of these drugs, which is that they build a very rapid tolerance. And so let’s say you took psilocybin today, and then you take it again tomorrow, and then you take it again the day after that. By the third or the fourth day, you wouldn’t really be feeling anything anymore because your receptors are down regulated to the point where you’re no longer getting the drug effect. 

Phil Stieg: At some point it’s not effective at all, 

Albert Garcia-Romeu: Correct.

Phil Stieg: Or you have to keep increasing the dose?

Albert Garcia-Romeu: Even if you increase the dose, at some point you’re going to stop getting that drug effect.

Phil Stieg: Well, I was impressed in reading through some of your literature that it seems to have some neuroplastic benefits. So what does it do – turn on our stem cells and induce brain regeneration?

Albert Garcia-Romeu: So it seems as though (and this is largely evidence from preclinical research with animals) but even a single exposure to a drug like psilocybin can change the way that the brain is wiring itself, meaning that you’re seeing more arterization, more synapse formation, more connections. And sometimes that’s good, and sometimes that’s not good, depending on where it’s happening and how. But this is seeming to happen in very important regions, including prefrontal cortex and hippocampus, that could lead to ability to more optimally control your behavior in a way or change your behavior in ways that would be consistent with things like antidepressant effects in humans.

Phil Stieg: So I’m interested you kind of outlined a rather rapid assimilation to the drug, and we know that it improves mood and decreases anxiety and decreases craving. But addictions or use disorders are a long-term issue. So where do you see psilocybin fitting in terms of intervening in those conditions?

Albert Garcia-Romeu: The way that we’ve inherited from an earlier era of research is this model of a sort of brief intervention. You’re usually kind of providing a wraparound treatment which includes counseling before and after the drug.

Phil Stieg: So it’s part of a comprehensive, integrated treatment program. And what you use the psilocybin in the acute phase?

Albert Garcia-Romeu: Yes, absolutely. So I’ll talk about smoking because that’s why I spent the majority of my time working. With our smokers, for instance, what we would do is we would have about a three-month window where we’re working with them therapeutically, and we’re seeing them usually about weekly during that time, For the first month as a sort of preparatory phase where there’s no drug administered. They continue to smoke as normal. And we really just go into the regular counseling process that you would do in a talk therapy. We talk about why they smoke, why they would like to stop smoking, learn more about the person in their life and their background, build a sense of rapport so that there’s a good working relationship that you then go into the high-dose sessions with. Usually we do is set a target quit date to stop smoking on a particular day, which also coincides with the first high dose psilocybin session. And so the person smokes as normal until that day, and then on that day, we give them a high dose of the drug, and then they stop. And then we kind of continue to provide care for a month or two afterwards on a regular basis, really just trying to encourage them to maintain abstinence, but also troubleshoot if they run into any problems along the way.  And this seems to be a really effective model for treatment.

Phil Stieg: Is this generally available to people now or only in your research trial?

Albert Garcia-Romeu: Oh, no. Yeah. This is still super illegal, pretty much outside of a clinical trial. And my goodness, let me tell you the amount of paperwork we have to do. I just got approval to start a new study and people with persistent Lyme disease. You know I started the paperwork on that last March of last year, and I finally got the approval to start it just this week. 

Phil Stieg: I bet they measure every picogram of psilocybin. You have to make sure it doesn’t disappear.

Albert Garcia-Romeu: Oh, yeah.

Interstitial Theme Music

NarratorFor what it was worth, the history of psychedelic drug research in America was dominated by one figure charismatic figure with his famous catch phrase…

Timothy Leary (archive recording): “Turn On, Tune In,  Drop Out…”

NarratorIn this edition of “This Is Your Brain, The Guided Tour” we take a look back at the most famous  – and least understood – figures of 1960’s counterculture, Dr. Timothy Leary. 

A veteran of World War two, Leary completed a doctorate in clinical psychology at UC Berkley in 1950. He spent a decade as a promising journeyman researcher and part time therapist in California and Europe.  Becoming an instructor at Harvard 1959,   Leary oversaw the Harvard Psilocybin Project. The project used LSD and psilocybin (both legal at the time) to treat alcoholics and help former convicts stay out of prison.  

In a move that is still considered controversial, Leary began to take the drugs along with his subjects.  In August 1960 he consumed psilocybin mushrooms for the first time, an experience that drastically altered the course of his life.  

Leary commented that he had “learned more about his brain and its possibilities and more about psychology in the five hours after taking these mushrooms than in the preceding 15 years of studying and doing research”.

After being fired from Harvard (for failing to show up to teach his classes) Leary became famous as an evangelist for the use of consciousness altering substances.  Testifying before a congressional committee in 1966,  Leary was asked by Senator Ted Kennedy if LSD usage was “extremely dangerous.” 

Leary replied, “Sir, the motor car is dangerous if used improperly…Human stupidity and ignorance is the only danger human beings face in this world.”  He advocated for legislation so adults could be trained and licensed in the use of LSD “for serious purposes, such as spiritual growth, pursuit of knowledge, or their own personal development.”

His proposal fell on deaf ears.  Before the end of the decade laws were passed to make psychedelic drug use illegal in all fifty states.  

Leary’s later career was increasingly colorful.  Imprisoned on drug charges in 1970, Leary escaped after a few months and lived most of the decade as a fugitive.  Eventually re-settling in California, Leary managed to earn a living in later years as a self-styled  “stand-up philosopher” giving lectures and touring college campuses with a series of debates opposite convicted Watergate felon G. Gordon Liddy. 

Following his death in 1996, a  small portion of his cremated remains were launched into orbit.  A poetic end for the “ultimate drop out”.

Music Fade Out

Phil Stieg: When you take psilocybin, do you have a mystical or a transcendental experience, or is that related to other hallucinogens?

Albert Garcia-Romeu: Psilocybin definitely can occasion those types of experiences fairly reliably, but not in everyone. And we still don’t know why.

Phil Stieg: And explain that to me – What is that mystical or transcendental experience that a person would describe to you with the drug? 

Albert Garcia-Romeu: Sure.  And you know. people have been having these types of experiences as long as humans have been around, and drugs are just one way of getting there. 

There seem to be some people who are more or less prone to having these types of experiences even without the drugs. The reason I got interested in this in large part was a lot of time I spent when I was working in the US Forest Service, living in Montana. It was living in the woods and basically being outdoors for extended periods of time that led me to have these very strong feelings of connectedness and awe – in natural settings people can have those experiences. But the classic experiences that have been described both in religious traditions but also in these psychedelic research studies is really a sense of unity. Usually we walk around very much with a sense of I’m me and I’m inside here, this “meat bag” that I’m walking around in, and everything out there is other.  That’s the universe, if you will. And there’s a sort of separateness there and the sense of unity that can come through either these drug experiences or otherwise are largely mediated by this sense of “Everything is one.” 

I’m connected to the air around me. I’m connected to the walls and other stuff, other people, other cultures. It’s not just in space, too, but it can also be in time, meaning this moment is touching eternity in a way all the way forward and all the way backwards. So when you have that type of sense of self-dissolution or ego dissolution, that can also be very profoundly powerful for people who are struggling with mental health conditions because it can also sort of loosen the shackles, if you will, of some of those repetitive patterns of thinking or behavior that they may have been stuck in, whether that be smoking or negative thinking from depression. And so that’s what seems to be happening for some people when they have these high dose experiences.

Phil Stieg: That was my next question is, like we said, this has been around for a long time, centuries. And why all of a sudden the positive results? Are we using different doses? Are we asking different questions? Are you doing the science any differently so you’re getting these positive results because I’m surprised they didn’t get any back in the 50s and 60s when they were doing this. They didn’t get this. What changed?

Albert Garcia-Romeu: Well, actually they did, but the results were all over the place at the time because the way people were studying these drugs were very variable. And so somebody in one laboratory who may have been a skeptic about these drugs might take an in-patient with alcohol problem and strap them to a hospital bed and give them an extremely high dose of LSD, and then let them go and say, well, see, it didn’t do anything. They’re feeling better. They’re not feeling any better.

Phil Stieg: They’re asking different questions. And they didn’t certainly it sounds like they didn’t go about it in a scientific fashion either.

Albert Garcia-Romeu: But also we have new standards in place of how to do science.  So really, a lot of what we’re doing now is just going back to what was done in the 60s and doing it again and showing that indeed, this was correct, that, yes, we can use these to treat palliative care patients or people with substance use issues.

Phil Stieg: And I was curious about the fact that you use Psilocybin in conjunction with cognitive behavioral therapy for smoking cessation. So is it the CBT that stops smoking, or is it the Psilocybin that kind of takes the edge off. I’m trying to get my arms around what it’s really doing, other than making you feel a little bit happier, I guess, since it’s like a serotonin drug. Right?

Albert Garcia-Romeu: Well, in terms of what it’s doing. We just don’t know in terms of how it’s exerting these anti addictive effects, which is why I’ve been spending a lot of time doing these brain scans and what have you. But there’s something about the drug experience that seems to shut down or interrupt the normal addictive process, which then allows the brain to sort of almost “reboot” itself and restart without that operating in the background. And so that seems to be very helpful for some people.  For instance, our initial study with psilocybin for smoking cessation. The program, the CBT alone would usually get something like 20 – 25% of people who quit, the people who got the CBT with high dose psilocybin. We had 80% of those people quit smoking.

Phil Stieg: I’m sorry, 80%? And how durable is that?

Albert Garcia-Romeu: We kept following those people out for about two and a half years, and at that point, 60% were still not smoking, which is the majority of them.

Phil Stieg: That’s marvelous. These are people that have been smoking for more than ten years.

Albert Garcia-Romeu: On average, about 40 years, actually.

Phil Stieg: Wow, so they were addicted.

Albert Garcia-Romeu: They were smoking longer than I was alive when I started working with many of them.

Phil Stieg: I understand you’re also starting to use this for the treatment of Alzheimer’s. Is it the memory component or is it the other symptoms that go with Alzheimer’s that you’re treating with psilocybin?

Albert Garcia-Romeu: Well, we’re looking at the whole package, meaning we are going to examine the effects on memory. Really, we’re starting with the low hanging fruit, which is we’ve seen antidepressant effects in people with major depression. We’ve seen antidepressant effects in people with cancer- related distress. And many people with Alzheimer’s disease or related dementias are also struggling with comorbid, depressed mood, which obviously detracts from quality of life. And so that’s our main target is just looking at this is improving mood and quality of life. But of course, while they’re in here, we’re doing good batteries of memory and cognitive function and seeing if that’s going to be changed or altered in any beneficial way. And that would be also consistent with some animal literature showing that these psychedelics, again, even a single dose can enhance and boost certain memory processes, certain types of learning object, memory consolidation, that after you expose animals to these drugs, they actually do better. So again, that’s a working hypothesis that we’re studying in those folks now.

Phil Stieg: At the clinical level, has there been just one case where we all said, my God, I can’t believe this happened, this is such a great thing?

Albert Garcia-Romeu: I mean, I work with dozens of people in over 100 of these high dose sessions. And so you see a lot of really interesting stuff.  I think one anecdote that I always found really interesting is this one gentleman that I work with, who he was in the 70s. He was a career military man, a high ranking, very clean-cut fellow. And obviously, as you’d imagine, never any sort of history of drug use at all whatsoever. But he had a big experience here at the lab quitting smoking, which is great, of course. But in addition to that, he said that his experience – and this is not that unusual, honestly – but he said that his experience was really characterized by this encounter with a higher power or God if you will. This is not a person that is particularly spiritual coming into this. He’s very what you might think of as more of a pragmatic type. And when he left, I gave him a list of books because he asked me, ‘I want to learn more and I want to read and understand this experience more.’ And so became quite enmeshed in reading about spirituality and trying to learn more about that area and developing that part of himself, which for somebody to do that after so many years of not really delving into that at all, I think it just really struck me as that was very powerful.

Phil Stieg: Were you a spiritual person? Is that why you’re interested in this? When you all got going.

Albert Garcia-Romeu: I would imagine I was a bit of more of an atheist until I had some pretty powerful experiences that really kind of shifted the way that I thought about these things. And I think I’ve always been a seeker, I guess so. I started reading a lot when I was little, and then. Yeah. So I’ve eventually kind of landed what you might consider in a spiritual camp.

Phil Stieg: Well, that’s why I asked whether these experiences with the patients have changed your view of spirituality. It sounds like it has.

Albert Garcia-RomeuIn a way. It sort of confirmed what I thought, which is we all have a sort of direct link to the source or higher power within us. And in order for us to be healthy, we just need to tap into that. And so helping people do that is sort of what I see is my role here.

Phil Stieg: So my final question is, number one, why do you think that we should embrace this and should we legalize it? And then how available is this?

Albert Garcia-Romeu: Yeah. So I’ll start with the second question. So right now it’s not that available, meaning that you have to go to clinicaltrials.gov or our website, HopkinsPsychedelic.org, and find a clinical trial if you want to do this, at least in legal, above-board fashion. Otherwise, you’re putting in yourself at risk of either getting some drugs that could be dangerous, black-market substances that you don’t know what they are, you don’t know the dosage. And obviously there’s legal peril there as well. However, work is being done now, particularly with depression, and psilocybin is moving towards an FDA granted breakthrough treatment designation because it is being seriously studied as medication that could be approved as a treatment for depression, in which case then the drug would have to be rescheduled, removed from schedule one, and then it would become accessible at clinics for wider accessibility to treatment.

Phil Stieg: So to get information now, they should go to what website? Can you reiterate that, please? 

Albert Garcia-Romeu: Yeah. So clinicaltrials.gov is a place where you can find all sorts of clinical research and put your location in. And you can also use keywords like Psilocybin or MDMA or whatever you’re interested in and then try to point you in the direction of what’s available.

Phil Stieg: Dr. Albert Garcia Romeo. Thank you so much for enlightening us and bringing us back to where Hallucinogenics and in particular psilocybin might be of benefit to us for the treatment of depression, for addictions and mood disorders. I look forward to reading your research in the future. Thank you so much for being with us.

Albert Garcia-Romeu: My pleasure.