Learn what’s to come in psychedelic therapy research including risk mitigation, contraindications, and treatment purposes as Andrew Penn explores this important subject.
Episode Summary
In this conversation, Andrew Penn, co-founder of the Organization of Psychedelic and Entheogenic Nurses (OPENurses), discusses the use of psychedelics in therapy and the challenges and concerns surrounding this emerging field. He addresses psychedelic misconceptions and hype, emphasizing the need for more research and caution. He also explores the potential benefits and risks of psychedelic retreats as well as the importance of psychedelic harm reduction.
Penn highlights the specific considerations for using psychedelics in individuals with bipolar disorder and the need for further study in this area. Additionally, he discusses the potential impact of hormonal factors on psychedelic therapy and the recent approval of a treatment for postpartum depression. This conversation explores the manifestation of depression, contraindications for psychedelic use, serotonin syndrome, and the future of psychedelics.
Discussed in this episode:
The need for psychedelic therapy research to separate the hype from the reality
Harm reduction strategies, such as safe spaces and support, in the use of psychedelics
Risks of bipolar disorder and psychedelics and the careful considerations to understand
Interactions between psychedelics and hormones and the need for more research
The recent approval of a treatment for postpartum depression in mental health care
Contraindications for psychedelic use, including a history of psychosis, cardiovascular disorders, and certain medications
The dangers of serotonin syndrome that can occur from the over-use of psychedelics
The use of psychedelics in clinical vs. non-clinical settings
"One myth to unpack is this idea that [psychedelic use] is ‘one and done’ and ‘curative.’ And frankly, I was part of that hype at the beginning, too, because in our very early studies, that's what we were starting to see." - Andrew Penn
Related to this episode:
Resources for Mental Health
Listen to the series on Psychedelic-Assisted Therapy
Learn more about the Organization of Psychedelic and Entheogenic Nurses
Check out Unseen Women in Psychedelic History by Maria Mangini
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Guest Bio
Andrew Penn, MS, PMHNP is a psychiatric nurse practitioner, clinical professor at the UC San Francisco School of Nursing, and a researcher on psychedelic therapies at the UCSF Translational Psychedelic Research Program (TrPR). He has been an investigator in studies examining MDMA-assisted therapy for PTSD, on psilocybin-assisted therapy for people with Parkinson’s disease and depression, and was a co-PI on the phase 2 study of psilocybin-assisted therapy for major depression, recently published in JAMA.
An internationally invited speaker, he has taught at SXSW, TEDx, Aspen Institute, and the Singapore Ministry of Health. Additionally, he has published widely on psychedelic therapies and their intersections with nursing and is the co-founder of the Organization of Psychedelic and Entheogenic Nurses. He can be found at AndrewPennNP.com.
Transcript
Georgie Kovacs:
Andrew, I'm so honestly, in all seriousness, I'm so excited to connect with you. I know you're a very busy, in demand person. I was I'm just really appreciative that Lynn Marie had introduced us. You've came highly recommended by a bunch of sources. And, Honestly, I I got into I had decided to do an episode on psychedelics, and then I started talking to some folks, and I realized there's no way that I could cover this, with justice in 1 episode. And so it's turned into a 3 part series, and honestly, it could probably be a 20 part series. But For the purposes of of femme power health, I think 3 parts should be sufficient. And if, of course, there's more questions, we could do follow-up.
Georgie Kovacs:
So I really appreciate You're making time. Why don't you tell us about yourself and and you how you got into this field And what you're doing within it. Because I do think it's so unique and interesting. So please share that with us.
Andrew Penn:
Yeah. Sure. My name is Andrew Penn, and I'm a clinical professor at UC San Francisco and the School of Nursing, I'm trained as a psychiatric nurse practitioner. Did that 20 years ago now. And I divide my time between teaching. In the school of nursing, I teach, advanced practice nursing students, so people that are gonna going to become psychiatric nurse practitioners. I work at San Francisco VA doing clinical work and overseeing residents there. And I also spend part of my time doing research on psychedelics.
Andrew Penn:
So that's a a very interesting and very robust area right now. Worked in the past on the, the MAPS sponsored study of MDMA assisted therapy for PTSD and also on the, USONDA sponsored study of psilocybin for major depression, a single dose of psilocybin for major depression. And more recently have been working on some small trials that we're doing in our lab, looking at people with bipolar 2 disorder, who have depression, treating them with a psilocybin intervention, also recently completed a small trial of people with depression and Parkinson's disease. These 2 the 2 studies I just mentioned, the bipolar study and the Parkinson's study are important. Even though they're small studies, those are 2 groups of people that have largely been excluded from trials to date. And so we wanna see if we can begin to, see if there's evidence for safety in those in those populations as well. And then we're getting rolling on a study of people with, chronic low back pain, and are gearing up to do a study of, young adults with anorexia nervosa, all of which we're we're addressing with a psilocybin assisted therapy intervention.
Georgie Kovacs:
I mean, this is honestly just such a fascinating topic for me. I know that Michael poll Pollan has written about, Psychedelics, which I think has helped people, I guess, make it feel more mainstream, so to speak.
Andrew Penn:
There's a lot of hope and a lot of hype around this space right now. And part of the challenge, especially for somebody who is new to it, is is sort of separating the wheat from the chaff. But even for those of us who've been in it for a while, it's we're finding that, you know, many of the subjects who come into our lab, have have real big hopes for this, which I understand because we don't have, the treatments that we have right now for a lot of mental health conditions are not as effective as we would like. So I I fully understand they the need for better treatments, it's just we're still in a very early stage of this. So there's a lot of things that we just don't yet know. And that's just the nature of science. That's okay. You know, that's why you do science is to try and try and answer those questions.
Andrew Penn:
But, in the absence of data to answer these questions, we're finding that a lot of people are engaging in kind of rampant speculation. And that's creating a lot of challenge and a lot of a lot of sort of noise in the space that's difficult to cut through sometimes.
Georgie Kovacs:
When things are out there, especially now with social media, People pick up on it, and we're in this quick fix society where we're not really diving deep into things, and we're making a lot of assumptions. And let's face it. I mean, I know when I was going through my 4 years of fertility treatments, you kinda get in the underground because you're trying to find an answer. And so, you know, in light of Kind of that tone. What is it that you want people to know that we're not discussing, especially for those who are more on the open minded, I'll try anything decide perhaps because of fear and desperation in trying to get help. Mhmm.
Andrew Penn:
Yeah. I certainly understand the motivations for for being interested in this, as was mentioning a minute ago, the shortcomings of the current mental health system leave a lot of people either untreated or undertreated, you know, they're partially treated, and they they, you know, they might feel better, but not well. And that's an important distinction. And I think where where there's some challenges in the messaging around psychedelics, I think there there was this early notion that this could be sort of a one and done treatment. That, you know, you hear this phrase, oh, it was like 10 years of therapy in one day. And I really think that's over promised on a number of different levels. The data that we're seeing right now as towards, as to the regards to the durability of the effects of the treatment, they vary. But, you know, the reality is probably this is something, you know, if we look at something like psilocybin for major depression.
Andrew Penn:
The the durability might be 6 months to a couple of years, and and then person would probably need to be retreated. And in the early studies that we saw of this, we were seeing people who, you would go several years out and still say they didn't feel depressed, which is great. And there will be people like that, but I'm not sure that's going to be, that's gonna be the average response. So so I think one sort of myth to unpack is this idea that this is one and done and curative. And and, you know, frankly, I was part of that hype at the beginning too. Because in our very early studies, that's what we were starting to see. But the nature of of of doing clinical trials is that you are, you start with a very kind of cherry picked group of subjects who are, are, you know, likely to be able to that you can treat them safely and, you know, that they're they're kind of ideal patients in some ways. And then as you get into larger studies, what we call phase 3 studies, there's, there's, it's more representative of what real patients look like.
Andrew Penn:
It, it's still not perfect because there's a lot of things that we exclude people from that have complexities like other medical conditions, other psychiatric conditions, comorbid substance abuse that so we exclude those people from phase 3 studies usually, but that's who represents our real world patients. And so there's always this challenge in sort of translation of, are you going to get the same benefits with, the people in real life that you got in the clinical trials. And, you know, we've seen this time and time again in psychiatry. We, when SSRIs first came out in the 1980s, you know, people talked about curing depression. Because in clinical trials, they they were so robust. And then we bring them out into the real world, and we give them to people who have, you know, medical issues, or they have an alcohol use disorder, or what have you. And they don't work as well. I think, not because they're not going to work, but I don't think they're going to work as well as they are sort of currently promised.
Andrew Penn:
And they and and the way that they will work is going to be different than what we're used to. And I think this is an important thing to understand is that a lot of our treatments that that we use right now, say common antidepressants, they are effective for some people. You know, there's it's it's very fashionable in the psychedelic space to kinda make a straw man argument about SSRIs and talk about how, you know, there's not many of them and they don't work very well. And and there's certainly some truth to that, but they do work very well for some people, and we're gonna need both. We don't need to we don't need to eliminate 1 with the other. We what we need is more treatments, not fewer treatments in in psychiatry. And so, this will be another option, hopefully. But the way that they work, the way they affect this change appears to be somewhat different in that things like SSRIs generally tend to kind of blunt negative emotions.
Andrew Penn:
And they sort of turn down the volume on anxiety or depression. The downside is they have, they they tend to turn down the volume on other emotional experiences as well. So people on SSRIs will say, well, you know, I don't feel as depressed, but I just don't feel as much of anything. You know? I used to cry in sad movies. Now I'm just finding myself not feeling it. And so there is this this, challenge with them is that they they sort of dampen people's emotional experience, which if you're depressed is is not necessarily a bad thing, but it's different than how psychedelics work. So psychedelics tend to be, you know, sometimes the term is nonspecific amplifiers. And so they turn up whatever happens to be present right now for the person.
Andrew Penn:
And so they they tend to, take somebody's emotional experience. And when they're done in this when they're used in this more therapeutic setting, they they often are really will con that that person will be confronted with whatever that is they're dealing with. And that often gives them an opportunity to to work through that, to feel more confidence in feeling those feelings. Because, you know, we spend a lot of time as human beings trying to avoid feeling what we are feeling. Something called experiential avoidance in the psychology literature. And psychedelics are really counter to that. So they really tend to amplify whatever emotional experience the person is having. And this is one of the reasons why, good preparation is so important.
Andrew Penn:
So before you know, just to be clear for people that have not heard of this work before, you know, sometimes people ask me, will I just go down to, Walgreens and get LSD? No. No. No. No. So the what so what we're looking at here is is a model where this is really a psychotherapy model that is catalyzed, amplified, if you will, with, the judicious use of a drug 1, 2, maybe 3 times. So instead of taking a drug every day, you're having this preparatory psychotherapy process with the therapist, sometimes 2 therapists. Those same 2 people are gonna be in the room with you when you take the drug, and you have all day kind of carved out for that. So, you know, nothing else going on that day.
Andrew Penn:
And really during that dosing day, we encourage people to go inward. So the other misconception a lot of people have is that we're sitting there doing, you know, cognitive behavioral therapy for those whole 8 hours or something. No. Most of the time, when people are under the influence of the psychedelic, they're not really talking much. In fact, we encourage them to have this kind of inward experience. We provide eye shades, and we have a preselected set of music that people can listen to to really direct their attention inward. The drug will wear off after 5, 6, 7 hours. And then starting the next day, we begin doing this thing called integration, where we talk about the experience that the person had, try and unpack that, look for opportunities possibly for them to change something about the way that they're engaging in their life, their the way they're thinking about themselves or thinking about their, their circumstances.
Andrew Penn:
And we might repeat this process depending on the study protocol. In the MAP study, we did that 3 times. The USONA study, we did it just once. So there are these different models of doing this. But, it's just important to understand that sometimes that psychedelic experience, it's not all rainbows and unicorns. It often can be quite challenging. It can sometimes be it can be quite beautiful, but it can also be dark. It can be scary, you know, in you know, something like a PTSD study, we get the agreement of the the subject.
Andrew Penn:
We we this is part of the preparation of if your trauma doesn't come up during the session, can we bring it up? Because we're gonna spend some time talking about that. And that's really, really important because a lot of times people with PTSD spend an inordinate amount of energy trying not to think and feel about the traumatic experience. And so we want to make space for that, in this therapy specifically. So the so those are some of the so the differences. The other thing that I think people need to understand is that, while psychedelics are largely physiologically safe, you know, compared to say something like an opioid, which in large enough doses repress suppresses breathing and and you can die from psychedelics generally have a high margin of physiologic safety, but they can be psychologically challenging. And especially if they are used in settings where people don't have the support of somebody who knows what they're doing when that person is in that state. Especially when somebody is taking this in a societal context in which these are, against the law, where people can lose their their job over this, for example. So that engenders a kind of fear around this, where, people who are having a difficult experience might be apprehensive about seeking help for that.
Andrew Penn:
You know? And so so this idea that these are without any potentially negative side effects, I think is untrue. And it's it's misleading people. I think about that recent case of the airline pilot who had ingested psilocybin a couple of days before. And then, you know, when he was on the the plane, had this experience of what we call in psychiatry, derealization, that things weren't real, and that that's that was his rationale for for pulling the fuel cutoff switch switches on the on the on the plane. You know, that was somebody who was clearly having a challenging psychiatric experience that was likely secondary to recent ingestion of of psilocybin. Was he on psilocybin at the time? No. Because psilocybin doesn't last that long. But he was experiencing some challenging effects following that.
Andrew Penn:
And I wonder had that might that situation been different, had that person had more support and the place where he could talk about those experiences before he had to go back to work. So so the the the I think the the misconception I wanna clear up is that, you know, while these are relatively safe physiologically, they do come with some potential attendant psychological challenges that can be mitigated with good support and a good structure to support that person in. And that's so you can't necessarily replicate these things by finding somebody who grows mushrooms and taking this on your own. That you might. I mean, we don't we haven't tested that. We haven't studied that, to compare if the 2 are comparable. But, you know, there's there's a lot of people who are kind of charging ahead of the science. The culture is charging ahead of the science.
Andrew Penn:
Laws are starting to charge ahead of the science. And, you know, as a scientist, that concerns me.
Georgie Kovacs:
Like, which which laws, that are charging ahead, are most concerning to you.
Andrew Penn:
Well, I see a lot of well intentioned laws around decriminalization. So to be clear from the outset, I think drug prohibition is a totally failed public policy. The idea of putting people in prison for changing their consciousness is bad policy. It doesn't work. That said, sort of letting the floodgates open and letting the commercial sector come you know, or even the sort of de facto commercial sector come in and offer, say, something very powerful like psilocybin widely without much guidance or without without a culture that has an ability to absorb that. You know, we don't have good messaging around what is a safe setting to use psychedelics in? What is an appropriate dose? How long should you plan for? Those are all public health messages that we need to have out there to go along with something like decriminalization. And there's this kind of urgency to get this stuff out there, in part to correct the wrongs of the past, which I fully support and appreciate. You know, I do think that we, as a culture, can develop an adult relationship with this in much the same way we have with cannabis.
Andrew Penn:
So, you know, 25 years ago in can in the US, if cannabis was still this largely prohibited substance, you know, a lot of people went to jail for it. People still go to jail for it, you know, particularly people of color, particularly marginalized communities, it's often used as this kind of cudgel to, to to harm people with, you know, with with legal repercussions. But I think in the last you know, now I turn on my social media and I'm getting ads, you know, for cannabis, and not just CBD. You know? I'm seeing THC and delta 9 and delta 8 and delta 10, THC being sold, you know, in social media ads. So, you know, clearly, we've we've come to a different relationship with that. And I think we can do the same thing with psychedelics, but it's very early days still.
Georgie Kovacs:
Okay. Interesting. So you mentioned that you're looking at bipolar 2. I have a particular interest in this because, And Lynn Marie and I were talking. I was like, should I say this? She's like, well, when you share, that's when you open the door for others to to feel comfortable. So I will share. So I have bipolar 2, and, it sucks, like, really bad. I have to, like, monitor So many things.
Georgie Kovacs:
Like, the biggest one is sleep, like, what time I go to bed, how much sleep I get. And sometimes I can't control it because I've hit menopause, and so it's just like all these layers. And, you know, I actually, had done an episode on cannabis, and someone sent if some to me. And I tried it, and I don't know if it was COVID, perimenopause, you know, having my son and No one around to help. During COVID or if it was the the cannabis, I went nuts. And I was like, I am not touching this. It's set on my shelf and expired. And so I think about, like, this study.
Georgie Kovacs:
And so one, I'm like, how in the world do you do it? What is the risk? Like, can someone have a Psychiatric break because I've been on all sides of the stream of mental health having this. And so I'm I'm so curious about, Like, the precautions, what you're seeing, that you're allowed to share. Like, how would someone in these States where it's like, I would so want a solution, but I also see when it's bad, it's scary that I'm like, no way. So I'd love to hear about that.
Andrew Penn:
Yeah. For sure. Yeah. You know, for your listeners, it it might be worth just briefly differentiating out these different bipolar numbers.
Georgie Kovacs:
What do they mean?
Andrew Penn:
So, you know, when peep bipolar disorder is historically something called manic depression. And bipolar one disorder is where people have periods of depression, and they also have periods of what we call full mania. So in in full mania, somebody for for many days at a time, you know, often sometimes several weeks at a time, will have periods of a very elevated energy. Sometimes it can have kind of a euphoric or grandiose quality. People get lots of ideas, and and they'll often be talking very fast. They they might sleep, you know, an hour a day, maybe even not sleep at all. And after a while, it really starts to, people's judgment becomes impaired, they can become impulsive. And and and it often ends with a a really rough depression, which can go on much longer than than the the manic episodes.
Andrew Penn:
So these manic episodes are usually kind of, infrequent visitors, but people spend a lot of time being depressed. So that's bipolar one. Bipolar 2, which you're talking about, Georgie, is where, somebody it's really a condition of chronic depression with kind of a cyclical quality. So the depression will come and kinda come and go. And and we differentiate this from depression, which is is sort of a response to outside events. So people with bipolar disorder often will have they'll fall into a depression, and they'll have no idea as to why. Because there is it's not reacting to something in the outside world. It's more a reflection of their internal, biology.
Andrew Penn:
And, and they spend a lot of time being depressed. And the reason it's still it's not just called major depression, which is what most people think of when they think of depression, is because of these periods so there's a cyclical pattern to it, but then there are these brief periods that we call hypomania. Then hypomania is where somebody for maybe a day or 2 has an increase of energy, you know, maybe a week, an increase of energy. But it's often not very pleasant. It often can feel kinda restless and agitated and anxious. Am I am I describing this accurately? Yes. Georgie? Okay.
Georgie Kovacs:
Yes.
Andrew Penn:
You know, you're not able to sleep, but you you but you're exhausted. You know, it's kinda wired, but tired. It's not it's not a good feeling at all. There's there's not a lot of enjoyment in those those periods at all. And so the reason why we're we've been cautious in the trials to date around bipolar disorder is that there are case reports. I've I've written one, that's in the literature, myself, that people getting getting either having mania or having psychosis type symptoms. When I say psychosis, you know, feeling paranoid, feeling like maybe things aren't real, feeling, like, people are trying to harm you, those sort of, distortions of reality, if you will, consensual reality. And, there are reports of people with bipolar disorder having these episodes elicited by, psilocybin and other psychedelics.
Andrew Penn:
And so when you start doing clinical trials, you're you're exceedingly cautious in who you allow into the trials in order to maximize safety. And then as you begin to develop, some knowledge base around for whom this is safe and whom it's not safe, which is just as important as knowing for whom it is safe is knowing who who can be harmed by a treatment is then then you can start to kind of, work on those edges. Right? And so so the reason why we chose bipolar 2 instead of bipolar one is that, you know, we want to make sure that we don't, we don't make people worse. You know? It's really the short answer. Ideally, we wanna help people feel better. So in a pilot study, which is what we're doing, you don't have a placebo control, so we know what we're giving everyone. Everyone knows what they're getting. And we're looking more at the safety signal then the efficacy.
Andrew Penn:
If we we'll look at both. But really, the first question to answer is, can we do this with a small number of people without making them worse? And we're very early in the study, so we haven't we haven't actually, analyzed the data yet. But it'll be interesting to see if we can do this safely. So that's that's the question that we're working on right now. And if we can do it safely, then that creates a sort of foundation of of evidence that we can then go on to do larger studies, with more people, maybe with the placebo control, to try and control for some of those expectancy effects that we talked about around like Paul and and and then really start to see if this can be something that helps. So, you know, these sort of insights help people understand, like, why does this take so long? This is why.
Georgie Kovacs:
Yeah. No. It's true. And, you know, I mean, I hope you you find something because you're right. It's like I, I even talked to my therapist, and I'm like, today, I'm, like, on it. And so this is the day where I am, like, tackling my list because I don't know how long it's going to last. And I'm still very productive. I've luckily, I've never, like, Sat down and, like, had to, like, crawl into bed for 3 day.
Georgie Kovacs:
I've never been like that, but I'll struggle to, like, do Things the way I normally do, and I used to never be like this. And so it's incredibly irritating because I literally have no idea. So I just I'm like, control sleep, control what I eat, and I hope for the best each and every day.
Andrew Penn:
Yeah. No. It's you know? And and and, you know, you're certainly not alone in that. And I for people that struggle with that or or any really, you know, kind of chronic episodic illness, which affects your ability to function, part of the burden of that is that unpredictability. You know? What's tomorrow gonna bring? I don't know. You know? Will I be able to do these things that I planned tomorrow? I don't know. You know? We'll see what tomorrow brings, but it it's it it definitely is part of the challenge for sure.
Georgie Kovacs:
Do you have either anecdotal or Data, anecdotal evidence or data around menstrual cycle timing or even phase of life because, Like, for example, when a woman is in perimenopause within a given day, the hormones are all over the place, much less over a given if Menstrual cycle, however long that menstrual cycle chooses to be at that point in time. You know, and then, obviously, when, there's all these added layers. Like, now a lot of women are undergoing Utility treatments. You're given additional hormones. So there's all these, like, hormone related activities that are happening. Like Lynn Marie even said, is there a certain time of the month where someone is on a regular cycle? It's better to give it than not. So What what do we know so far about that?
Andrew Penn:
I think the short answer is not enough. Not a lot. Not enough. And and some of that is it's not willful neglect. I think it's it's just a artifact of the relatively small sizes of these studies so far and and that mostly studies are focused primarily on, creating the evidence that would be necessary for getting this to the FDA and having FDA approval. Once you have that approval, it becomes a lot easier to do studies of of of different populations. Right? And so, you know, if you just if so, if we were to look at something, so one of the larger studies, that was done recently has been 2, what we call phase 2, studies of psilocybin for major depression. The one I worked on, I think we had a 108 subjects, something like that.
Andrew Penn:
And the one that was done in the UK had a little over 200. So if we say, you know, roughly half that population is, identified female at birth, you know, we've got a 100 people, were 50 people and where, you know, that question of where they are hormonally at any given moment, is another large variable. And so this is definitely data that we need to start looking at. You know, I think it's it's definitely needed to understand this. Because we know, you know, that women, for example, experience mental illnesses some mental illnesses such as anxiety and depression and PTSD disproportionately to to males. And so that's that's one big challenge, and one one area that we, you know, this is another underscoring why we need better treatments for this, for these conditions is that that, women suffer from them proportionately, and we need better treatments. As and we also know that biologically, there are these these closely tied relationships, say, between estrogen and mood, progesterone and mood, serotonin and estrogen tend to kinda track each other. And so, you know, there are these fairly, predictable, mood experiences that that people have, you know, in the premenstrual phase, for example, or postpartum.
Andrew Penn:
And so there's a there's a huge need for this for sure. And then understanding I mean, there was, I do believe in the MDMA study phase 3 that female sex did predict a better outcome for people that were randomized to the the MDMA group. I'm not sure what to make of that, but, you know, that that I think is encouraging news, especially given that that women are, over twice as likely to experience PTSD in their lives so, you know, and then there's there's a whole another subset of of understanding that we need to to gather around, are on transgender, patients, you know, and and how does hormone replacement therapy impact the effects of these? And and are there or should we be thinking around timing? You know, I think your point is well taken that that the effects of these may may be attenuated by where somebody is in their menstrual cycle. There is Natalie Goukasian at, at Hopkins did a interesting case series of of of 3 women talking about changes in their menstrual cycle, following psychedelics. And so there may very well be a signal there. But, you know, we are really just in very early days with this. There's you know, we need better funding to do the research so we can really begin to explore these questions, on on a large scale.
Georgie Kovacs:
And I know it's harder, More expensive and takes longer for women, but, like, they're half of our population.
Andrew Penn:
There are there are reasons to be hopeful around this. You know, so So psychedelic therapies could be included under a broader umbrella of what we might call rapidly acting antidepressants. And so this would also include things such as Ketamine, but also, you know, a drug called Zeranolone, which is a, it's a oral version of of a drug called Brexanolone, which was, FDA approved maybe about 4 or 5 years ago, which if Brexanolone was a, was an IV, infusion, rather kind of cumbersome to to give and to obtain for postpartum depression. But isoran alone recently was given FDA approval, as a a treatment for postpartum depression. And it's it's not an SSRI. It works on something called GABA receptors. And, you know, it has a rapidly acting antidepressant effect. And so so that is I think things such as that are really promising, because that because postpartum depression has has really been an area that that we don't, you know, like many areas of in mental health, we don't have treatments that are as as rapidly acting and as robust as we would like.
Georgie Kovacs:
I'm curious, you know, in the recent trial where the PPD drug was approved, I'm curious if you had any thoughts based on your research and experience With these different, mental health conditions about why perhaps the, major depressive disorder wasn't approved, but Partum depression was.
Andrew Penn:
So just the back backstory for those who are unfamiliar. So zuranolone was was simultaneously being investigated before, both postpartum depression, but also, major depression. You know? So not not necessarily related to childbirth. And, it did not have, it did not succeed in the in the major depression study, whereas it did in the the postpartum study. So the FDA approved it for postpartum depression, but not for major depression. It's it's difficult to know. You know? It it, you know, maybe that, that the hormonal changes that are, attended to postpartum depression were, were better addressed with, this drug, which is essentially a version of allopregnanolone. And, you know, that may have been why it was it was more robust.
Andrew Penn:
I mean, I think I'm just really kind of, engaging in a lot of speculation here. But but, you know, unfortunately, the data did not support that it it worked in major depression. You know, that that may be an artifact of the way the study was designed. You know, sometimes when when you, have these sort of disappointing results, you go back to the drawing board and you say, okay, was there did we do something wrong here? You know, was the dose insufficient? Was the treatment not long enough? Do we need to look at those kind of things? You know, do we need to you start looking at at various populations in your in your study and see if there's a if 1 group did better than another, you know, so sometimes you see, sex difference in in the the the data. And so those would, I think, all be the things that you go back and look at after after study is unsuccessful.
Georgie Kovacs:
So are there any known contraindications For psychedelic use that people should be aware of. So we know you we talked about bipolar 2. Being studied or for bipolar, generally. But what about any other known contraindications, which is, hey. You know, I heard this. I'm fascinated. I'm going to one of these retreats, you know, or I have a a place where I know to use it safely, And I know x, y, z about myself, therefore, I definitely should not be using it. Like, who who would that be?
Andrew Penn:
Yeah. Well, you know, I don't I don't want to give medical advice to people that I I don't know. But I can tell you what we the things that we, some of the things that we exclude in our in our studies. Definitely people that have a personal history of psychotic of any psychotic illness. So somebody who's had a history of schizophrenia or by, you know, bipolar one, particularly with psychosis, or has a first degree relative with so a mom, dad, brother, or sister with, with psychosis, in any form, we would be very cautious about and and often exclude. So, you know, that's because there is a genetic component to, many of these conditions, and and sometimes people can have some of the, the the genes which are associated for risk for that condition, and so we I would be we'd be very careful around that. The other area where where we're very cautious around is people with cardiovascular disorders. So things such as psilocybin and MDMA do cause transient increases in blood pressure and heart rate, when the drugs are, are in effect.
Andrew Penn:
And so, we're very careful with people that have uncontrolled high blood pressure, have congestive heart failure, have arrhythmias, cardiac arrhythmias, have heart valve problems. Those are other areas. And then the other thing that we control for in these studies is that, in many studies, medications are discontinued. And sometimes that's because they directly interfere with the effects of the drugs. So for example, we haven't gotten too much into the weeds of the neurobiology here. But, classical psychedelics, which is sometimes referred to as LSD, psilocybin, DMT, which is the active ingredient in Ayahuasca. Those are, those have part of their effects are mitigated by something called the serotonin 2A receptor. And so the a a drug that blocks a serotonin 2A receptor.
Andrew Penn:
So something, such as like trazodone or a whole class of medications called atypical antipsychotics. So this includes things like, Seroquel, Zyprexa, Risperidone. Those all block the serotonin 2A receptor and would likely, mitigate the effects of a psychedelic that works on serotonin 2 a. So it would it would probably dampen the effects of that. There are other drugs that we, have that are contraindicated, which means that that we we take people off them before they ingest the drug for safety reasons. The sort of the most, important one probably in that area would be most, antidepressants should not be combined with something called Ayahuasca. So Ayahuasca is a is a a brew that originates from the, the Amazon, and it contains at least 2 different plants. One of which contains the drug, Dimethyltryptamine or DMT, and the other contains something called an MAO inhibitor.
Andrew Penn:
And so MAO is an enzyme that breaks down, things like serotonin and Norepinephrine eat dopamine in your body. And the reason why this brew has, both the psychoactive plant and the MAO inhibiting plant is to prevent the Ayahuasca from being broken down in the the DMT, and the Ayahuasca from being broken down in the gut before it has a gets to the brain. But that creates a potential risk for something called serotonin syndrome, if they're taken with, an antidepressant that works on serotonin, Prozac, Lexapro, Zoloft, something like that. And so generally, people need to be off of those medications for some time, and it varies from medication to medication, depending on how long the med stays in your body generally, for for some period of time before they were to ingest Ayahuasca, that's a really important safety, precaution.
Georgie Kovacs:
Wow. Wow. So what is serotonin syndrome?
Andrew Penn:
Serotonin syndrome is essentially when you have too much serotonergic activity, serotonin activity, in your central nervous system. And so people, it can manifest, in the form of like jaw clenching, teeth grinding, shivering, difficulty, monitoring your, your body temperature, which is the the biggie the big risky thing here, is that people can get hyperthermic, so called malignant hyperthermia, where people's body temperature gets very hot, and they have difficulty cooling it down. Serotonin syndrome can result in in seizures. It it it can actually be life threatening. So it's something that that you have to be careful with, particularly with these drugs that work on serotonin. And, you know, you can see serotonin syndrome like symptoms in people that use, excessive amounts of MDMA in 1 in one setting. That's a that's a known risk with MDMA. It can also disrupt, things such as your sodium levels in your blood, which can lead to swelling in the brain.
Andrew Penn:
This is these are uncommon side effects to be clear. But it's also one of the reasons why, you know, back in the the old rave days, you know, there were there were issues with hyperthermia because people were often dancing in hot settings, you know, we don't see that happening in our clinical trials because we're we're monitoring people's temperature. So that doesn't seem to happen when people are not ingesting this in a in a hot environment and then exercising in the form of dancing. But one of the things that was sometimes happened back then is people drink excessive amounts of water, which can lead to something called hyponatremia, which is where you sort of flush out a lot of the sodium in your your bloodstream. And that causes all sorts of disruptions, including, swelling in the brain. So, you know, while people want to you certainly want to remain hydrated under something like MDMA. You don't you shouldn't be drinking, you know, gallons and gallons of water. That's not a good practice.
Georgie Kovacs:
I would love to summarize, like, what people who are curious should do if if they're Truly interested. And then I wanna conclude with, like, what you're excited about in the near future. We've we've had a cautionary tale In this discussion, you know, it hasn't been psychedelics are the best thing around. Everyone should be on them all the time. Forget pharmaceutical medications. And I really appreciate that because I I do think, with the way media clickbait, you know, all these things, people, I think, Take things to a certain level. And look. I'm one who will try anything.
Georgie Kovacs:
But even I'm listening I've, you know, I've interviewed 3 experts know. And I'm like, wow. I'm kinda sold on being really careful.
Andrew Penn:
I think there's sort of a both and answer to that question. Right? So, you know, I'm I'm obviously very interested in psychedelics. I spend a lot of my waking hours thinking about it, talking about it, and writing about it. So I wouldn't do that if I didn't think there was promise. That said, I want this to succeed, and I wanna follow the data. And and, you know, the the the thing about science is that, you know, you have to follow the data no matter where it takes you, even if it's not where you thought it was gonna take you or if you're disappointed by it. So, you know, in sort of descending order of probably safety and containment, the the the more difficult way to have one of these experiences, but probably the safest way to have one of these experiences is to enroll in a clinical trial. Because it's important to remember that, with the exception of Ketamine, which is we haven't they talked about, but, certainly can have very psychedelic like effects and is also a rapidly acting antidepressant drug.
Andrew Penn:
That these the the compounds we're talking about today, MDMA, psilocybin, LSD, these are all schedule 1 drugs. So they're, you know, they are, as of right now, federally illegal to, to possess or use. And so the only place where that can be done legally is in a clinical trial. The best way to find clinical trials for anything is something called clinical trials .gov. This is a government sponsored website, it's not sponsored by a drug company. It's just National Institutes of Health. And it is a directory of all clinical trials. It's as simple to use as Google.
Andrew Penn:
You know, you could type in there depression and psilocybin. And it will show you all the trials that are, going on right now that are about to start or that, you know, you can limit the you can filter the results, by geography. And at least gives you an idea of if there are studies going on that that might be of interest to you. So that's that's this that's probably the, the safest way to do it you know, now some states like Oregon are developing these, what they call adult access programs, adult use programs. It's a supervised use, not necessarily for a clinical indication. In fact, in Oregon, they specifically cannot say that they're gonna treat your depression. So you you go to one of these experiences and it's kind of like, I guess, you know, like going to a yoga retreat. Right? You don't need a you don't need a doctor's prescription to go to a yoga retreat.
Andrew Penn:
And your, your work there is largely self directed. And so a place like Oregon has, passed a law that that allows for adults to have a psilocybin experience in a supervised setting, which they unpoetically call a psilocybin service center, but but that's so that that is available to adults going to the state of Oregon. Colorado is also in the middle of a of a bill that will allow some degree of access. And many states and local, areas are starting to to kinda dip the toes in water of of various forms of either adult access or decriminalization. And then there are other countries where this is available, you know, Jamaica, Mexico, Peru, Holland, where there is some some form of legal access. And as I mentioned before, the the the, those kind of settings vary considerably. So, you know, I would really strongly suggest somebody do do their research before, and and talk to people that have been to those settings before going into that. And also understand that we can't necessarily say with certainty at this point that we can replicate these clinical findings in these nonclinical trial settings.
Andrew Penn:
So if somebody says, well, you know, you can go to Oregon and take psilocybin for your depression, and it'll work just as well as what we're doing at UCSF or at Johns Hopkins, we don't have evidence to support that as of right now. We haven't done that study. It's a study that really needs to be done. You know, we we have seen from survey data that people that use psychedelics in a what we call naturalistic setting or maybe recreational self directed settings, you know, often do report, they self report benefit. And they also they also report a small portion of harm. So, you know, these are not without some degree of risk, but the vast majority of people report, you know, some benefit from them as well. So, you know, that has always been and probably will forevermore be one route that people experience psychedelics. And, you know, they certainly people are within their rights to do that.
Andrew Penn:
It's just a little less predictable, perhaps. But if they are going to do that, you know, to really be thoughtful about how, where, are and with whom they do that. You know, to have a place set up where you are away from the distractions of the everyday world. You do not want to be get your phone notifications while on a high dose of psilocybin. You don't want to be you don't wanna be in a place where you could fall down and get hurt in that state because, you know, you may not be fully, attuned to your body. You you ideally want somebody there who can be with you and an eye on you and and reassure you if you get scared. So these are all sort of harm reduction measures that that people can think about, you know, if they are going to pursue this sort of thing on their own, to to be really thoughtful about how they do it. That that while, you know, certainly many people have had, delightful experiences at, you know, a concert or Burning Man or something like that.
Andrew Penn:
People also have really challenging experiences out there too. You know, anybody who's worked at a place like Xendo or RockMed at a at a concert, you know, knows that that people have challenging experiences. It can be very just sincerely overwhelming to be in a concert with lots of people. Lots of noise, lots of lights, you know, when you're when when your brain and your emotions are in a very raw place. And, you know, the thing with psychedelics is kind of a old adage that you don't always get the trip you want, but you get the trip you need. Yep. Somebody who goes to, you know, some place like Coachella, you know, and decides to, you know, enhance their music experience with with a psychedelic, may get that experience. They might also end up thinking about when their mom died when they were 10 years old, and that's gonna be a very different experience.
Andrew Penn:
And and it's not to say that thinking about when your mom died when you were 10, it can't be is is necessarily harmful. But Coachella might not be the spot where you wanna have that experience.
Georgie Kovacs:
So what are you excited about in the near future? What are you, hopeful for or excited about?
Andrew Penn:
I'm really excited to see, the end of well, so MAPS is is will soon be submitting something called an NDA, a new drug application to the FDA for the, for the approval of of MDMA assisted therapy for PTSD. And assuming that is that is approved, that's when things are gonna get really interesting. Right? So and really complicated because, we don't really have a healthcare system that's set up for this right now. I mean, we have we barely have a healthcare system that's functioning as it is. So, you know, to add this layer of complexity, is going to create some brand new challenges, which I think create exciting opportunities, but also are gonna are gonna be challenging to navigate. But I'm really excited at the idea that, you know I'll I'll share with you a story. You know? So when, last time I had to take antibiotics, you know, some crowd. I don't remember what it was.
Andrew Penn:
But, you know, I remember, like, a day and a half later, feeling like myself again. You know? And I thought, damn. I wish the meds I prescribed for people for psychiatric conditions worked this well. Right? You know, so the idea of actually I've been working in mental health for 30 years, you know, and I've seen a lot of people who I have great admiration for who are really struggling. You know? And I really would love, as a clinician, to be able to offer more robust treatments that actually work better and that sustain that benefit over time. And that help people develop a different relationship with these parts of themselves that are, you know, that have depression, that have anxiety, that have trauma, that that maybe, you know, what we're what we're doing here is not necessarily eliminating those things. It's not this kind of, you know, like, we're gonna cut that out of you sort of idea, but that you you develop a different relationship with that aspect of yourself in a way that that reduces the amount of suffering. And I think that's that's something that's so important.
Andrew Penn:
I'm also really excited as a nurse to see how, nursing is going to play a central role in this. I mean, the I think nurses bring to this work a a sort of a natural, skill set and a native sensibility for sitting with people, for making room for, for healing, that's really excited. I I cofounded an organization called the Organization For Psychedelic and Theogenic Nurses, open nurses. And I I think nurses are gonna be a really important part of, delivering this care and also scaling it. Because, you know, one of the challenges we're gonna have is we don't have enough clinicians to deliver this therapy, who've been trained in this. And so I have a vision where where many nurses learn how to do this work and and can sit with people while they they go through these these experiences, keep them safe and and help them heal.
Georgie Kovacs:
I did read about about the nurses program that you started, and it sounds wonderful. And I agree. Jordana and Jacqueline and I, which will be the 1st episode in this series. We talked about, okay. So now we have these approvals. Now what?
Andrew Penn:
The history of psychedelics is yeah. And the history of plant medicines in general for which meant some psychedelics derived from, is really one that was largely occupied by women through much of history. And and the the people who have carried this knowledge forward and endured a lot of persecution for doing so have largely been women. And so, you know, I think it's just worth acknowledging that debt of gratitude that that we will all if these if we are successful in this, that we will owe to those to those women who have very bravely carried this forward.
Georgie Kovacs:
Oh, thank you. Maybe there'll be a, documentary on that. Because the now there's you see all these documentaries where they're bringing forth, like, oh, there was actually all these women behind the scenes that helped with all these grand moments in the world. So thank you for acknowledging that.
Andrew Penn:
Next year, my I'm hoping to go to Saskatchewan, Canada, because there is a nurse there named Kay Parley who worked with, a psychiatrist back in the late 19 fifties, early 19 sixties, a guy named Humphrey Osman Humphrey Osman has did many things. But one of the things that he also did was coined the term psychedelic along with his friend Aldous Huxley. And so Kaye Parley worked in a large state psychiatric hospital there in Saskatchewan, Canada using LSD with patients who had alcohol use disorder, in the early 19 fifties and in late in beginning of 19 sixties, well before this ever became known to the youth movement and Timothy Leary and all the stuff that happened later, there's a a period of history starting with the synthesis of LSD in in 1938, going up until 1970 when the Controlled Substance Act was written of research similar to what we're doing now. Perhaps not as rigorous as the research we're doing now, but but there was a lot of interest and a lot of what you might, you know, call sort of above ground scientific work looking at this. And so Kate Parley, she is now 100 years old. Every time we correspond, she reminds me that she she says, well, I am a limited time offer. But I've spoken to her on on Zoom, and and she's she's sharp as a tack and has some amazing stories to tell about this. So so, yeah, we wanna contribute to the the history of this that focusing, some of these these women that my my friend and colleague, Maria Mangini, highlighted in a really fantastic paper called Unseen Women in Psychedelic History, which I can't recommend highly enough.
Andrew Penn:
Yeah. And she talks about she talks about Kaye Parley and a number of other women who have been really instrumental in holding this, but don't always get the, the recognition that they deserve.
Georgie Kovacs:
And wasn't LSD even discovered in a lab with the scientists with from Sandoz was actually trying to, discover something for post RM?
Andrew Penn:
Well, not for postpartum. So the interesting thing, indulge me this for a second, is that so l LSD was derived from, ergotamine, which is a a fungus that grows on rye and other grains. And interesting thing is that midwives have known about ergotamine for centuries because ergotamine used as a uterine tonic, so it causes the uterus to contract. And so it was used, by midwives in, so quickening of of of, of labor so, you know, some people that were struggling to labor and also in postpartum hemorrhage to get the uterus to clamp down and and and cut off the the bleeding from where the the placenta detaches. And they were Sandoz was looking at this as a possibility, or ergonomines is a possibility as for something they called analeptic. And analeptic was a drug that you it was a respiratory and cardiac stimulant that you would give to people, maybe as they're coming out of anesthesia, which if you remember, you know, it was fairly new invention. Thank God for anesthesia. But, you know, we didn't really have anesthesia until the turn of the the the 18th, 18th century.
Andrew Penn:
1800 into 1900. And and also to reverse barbiturate overdoses. So barbiturates, which were the the previous drug before Benzodiazepines, were much more dangerous an overdose, it's probably a barbiturate overdose that that, that caused, Marilyn Monroe's death, for example. And so this idea of developing a drug that would keep people breathing and their heart beating, if they were in an overdose situation was the other thing that they were interested in in developing, they had no idea it had these psychoactive effects that it does. And as the story goes that that Albert Hoffman, who was the the chemist working on this, accidentally ingested some tiny amount, you know, on his fingertips, you know, probably touched his mouth, and thought he'd poisoned himself, actually. And it was actually his young, lab assistant, Susie Ramstein, who got him home on a bicycle. That's where the the expression bicycle day comes from. It's acknowledgment of the the day that LSD was was discovered to have psychoactive effects
Georgie Kovacs:
No way.
Andrew Penn:
She got them home. It was 1943. So it's the middle of the war in in in Basel, Switzerland, and they didn't have gasoline was rationed, so they were on bicycles. So they got home on their bicycles. He he asked that she call his his doctor who examined him and found there's nothing physiologically wrong with the mother, then his pupils were very dilated. But, you know, he went on to have this rather fantastical experience that that, you know, I think he was frankly partially quite scared of. You know, he didn't quite know what he what he stumbled into. After that, you know, Sandoz sort of had a had a solution looking for a problem. You know? And they started to to try it, through sort of crowdsourcing, if you will, to to ask psychiatrists to to if they wanted to, work with it and to report back what they they discovered.
Andrew Penn:
And so that's how that's how we got LSD, which is really a a wild accidental discovery, like a lot of things in science. You know?
Georgie Kovacs:
Thank you so much for making time and for your dedication and for, you know, giving us the the truth about this because we want people to be safe. And, look, I'm all for trying new things, but we wanna make sure that We we tread with caution when necessary. So thank you so much for for sharing the facts and your perspective.
Andrew Penn:
Thanks for having me, Georgie. I appreciate it there. Enjoyed our talk.
Disclaimer
The information shared by Fempower Health is not medical advice but for informational purposes to enable you to have more effective conversations with your doctor. Always talk to your doctor before making health-related decisions. Additionally, the views expressed by the Fempower Health podcast guests are their own and their appearance on the program does not imply an endorsement of them or any entity they represent.