Ben Malcolm, PharmD, MPH, BCPP received his bachelor's degree in pharmacology at the University of California, Santa Barbara, and then continued to earn his doctorate of pharmacy and master's in public health at Touro University, California. He completed two years of post-graduate residency training: the first in general pharmacy practice and the second in psychiatric pharmacy. After residency training, he began his career as an academic at Western University of Health Sciences College of Pharmacy and obtained his board certification in psychiatric pharmacy. Ben envisions a society in which access to psychedelic drugs in a variety of safe and supported settings is available for purposes of psycho-spiritual well-being,
personal development, ceremonial sacraments, and treatment of mental illness. And to serve this vision, he began a psychopharmacology consulting practice and educational website, spiritpharmacist.com to help people understand the interactions between traditional psychiatric medications and alternative psychedelic medicines.
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0:03:44.6 PA: Hey listeners, welcome back to Third Waves podcast. So, one of the recurring questions that we get from our audience and generally from the wider community is questions around the pharmacology of SSRIs and how they interact with psychedelics and just general psychotropic medication. So, today we are interviewing Ben Malcom, and Ben also goes by the Spirit Pharmacist, which is his website and platform, exploring these interactions between more typical psychotropic medications and the classic psychedelics.
0:04:23.9 PA: Ben received his Bachelor's Degree in Pharmacology at the University of California, Santa Barbara, and then continued and got his Doctorate of Pharmacy and Masters in Public Health at Touro University, California. He completed two years of post-graduate residency training, the first in general pharmacy practice and the second in psychiatric pharmacy and after residency training, he began his career as an academic at Western University of Health Sciences, College of Pharmacy and obtained his board certification in psychiatric pharmacy. Ben envisions a society in which access to psychedelic drugs in a variety of safe and supported settings is available for purposes of psycho-spiritual well-being, personal development, ceremonial sacraments and treatment of mental illness. And to serve this vision, he began a psychopharmacology consulting practice, an educational website spiritpharmacist.com to help people understand the interactions between potential and optimal clinical approaches to psychedelic therapies when persons are taking traditional psychiatric medications. Ben, welcome to the show. It's good to have you.
0:05:31.7 Ben Malcolm: It's so great to be here. Paul, thank you so much for having me on.
0:05:35.5 PA: You're in Costa Rica right now, right? You're in Tamarindo.
0:05:39.4 BM: That is correct.
0:05:40.3 PA: How is it? What inspired you to move down to paradise and experience some of that pura vida?
0:05:49.5 BM: Really just kind of a perfect storm of circumstances. I'll say that the consulting I was doing from Spirit Pharmacist was kind of taking over more and more of my life to the point I was really working two jobs between academia, and that was just not sustainable for me.
0:06:08.0 BM: My wife also works in this space, she's a... The Psyched Soul is her platform. She was doing pretty well, so there was a chance to reinvent myself, and then I think just the pandemic in general has given a lot of people a license to rearrange their lives in a way that feels more aligned with who they wanna be and the kind of lifestyle that they wanna live. And we have a almost-4-year-old, so we felt like we had a couple years before she really needs to settle into a grade school type of environment, and all these things were just a license to have an adventure. So I heard a lot of great things about Costa Rica, and it hasn't disappointed so far. Just a lush, wonderful country, really friendly people, and we're enjoying our time down here in Tamarindo immensely so far.
0:07:04.8 PA: And I'm just curious on that note, what's the general vibe as it relates to psychedelics and plant medicine in Costa Rica?
0:07:15.5 BM: I think that there's definitely a level of openness. I think that there are certain pockets in the country that are really organized around psychedelic medicine work, or retreats. I wouldn't say Tamarindo is a huge hotspot for all of that, but certainly there are retreat centers fairly close by. There's a guy that's selling psilocybin mushrooms and honey for micro-dosing at the farmers market, right? So that's a little bit different than what you may come across in the United States, so that's kind of what I've observed so far.
0:07:55.1 PA: Yeah. And from what I understand, most of these plant medicines, ayahuasca and psilocybin in particular, are decriminalized. So we've had a couple guests on the show in the past, from Soltara, from Rythmia, from 1heart, which is doing ayahuasca retreats. I'm actually, at the time of this recording, I'm gonna be in Costa Rica next week to have a psilocybin ceremony with our coaches that we're training. So there seems to be almost... Costa Rica is very laid back and chill. And they're very open to this, but it's not necessarily regulated, and it's not like there's a ton of oversight from the government itself. It's just sort of live and let live, has been my sort of impression.
0:08:38.2 BM: Yeah. I would concur with that, yeah. There's not a whole lot of rules, except for don't hurt yourself or other people. Beyond that, then I think people tend to either accept it and be open to it, or at least kind of look the other way.
0:08:51.3 PA: Yeah. There's just not a lot of energy spent on worrying about it, I guess. Which was helpful. The United States could maybe use some more of that energy. And one statistic I saw recently was super, I guess, validating or affirming, and that's 65% of Americans now support psychedelic assisted therapy, so the medical use of psychedelics. And I feel like what your work and what you've brought as your gift to this space is so central to that, because a significant percentage of those people are likely on, or have been on, maybe SSRIs or other sort of classic psychiatric medications. So I'd love if you could just sort of set the scene for our audience before we dive in deeper. What inspired you to start Spirit Pharmacist and be such a sort of well-known figure as it relates to the interaction of more traditional medications and these sort of spirit medicines, plant medicines that we know and love and find to be so helpful?
0:09:56.3 BM: Yeah. So I could tell the long and winding, kind of convoluted personal story about how I got here, but I think I'm going to just set the stage a little bit more between this kind of psychedelic and psychotropic, as I like to call it. Psychotropic to me means traditional psychiatric medications, so this kind of interface between them. Because you have these trials now with psychedelic assisted psychotherapy that are showing just wonderful, unprecedented sorts of benefits for the treatment of several types of mental illnesses, and oftentimes mental illnesses that are refractory to the standard types of treatments, or aren't responding to the level that people are after from the standard types of treatments. Or addressing illnesses like PTSD or obsessive-compulsive disorder, where those first-line anti-depressants, that get a lot of use for depression and anxiety, don't even work as well for those kinds of conditions. So there's really psychedelics kind of coming in to the mental health scene to treat refractory types of illnesses, or to kind of just fill gaps in unmet treatment needs where traditional psychotropics just fall short. But all of these studies, at least with MDMA and psilocybin, have excluded almost all types of psychotropic medications.
0:11:27.9 BM: And there's probably a couple different reasons for these. One is there could be some type of interaction that is dangerous between them, or, and probably more likely in most cases, it's about confounding the experiment. It's like when you're conducting a trial, you only wanna have one experimental variable. So if you have all of these people on psychiatric medications that could either introduce risks or change the benefits in some way, right? Maybe even improve outcomes, 'cause we don't know, we haven't really done formal studies combining them, then you essentially kinda shoot yourself in the foot. So the precedent for research has been to exclude almost all of these medications, whereas that's not how psychiatry is practiced in the real world. And it's essentially not gonna be feasible, probably, for everyone to replicate a clinical trial environment or protocol around their medications when these things are... In my mind, I think the train has left the station and are going to be medically approved in the pretty near future.
0:12:36.0 BM: So, stopping psychiatric medications can inherently be a pretty tumultuous, challenging, and even dangerous thing to do. There is not a whole lot of incentives for the companies that are producing those psychotropics to really research best practices in discontinuing them, and you can imagine scenarios where persons either abruptly stop or taper off too quickly and become unstable because of medication withdrawal and then your psychedelics have a poor outcome, and then the headline reads "Psychedelics mess people up," where it is really related to their preparation and what they were doing with their psychiatric medications or vice versa, people that don't know enough about their medications and their potential for interactions and don't stop them or change them perhaps when they should, and either get very lackluster or diminished types of effects that leave them kind of confused and scratching their head and being kind of like what a joke, like people were telling me this was gonna be profound, mystical, and life-changing and almost nothing happened and I wasted a lot of my time and resources doing this, and I was already feeling kind of hopeless and now I've just... Like what options are there now?
0:13:50.9 BM: So, I think that, inherently, this sort of interface between psychotropics and psychedelics is going to be incredibly important to the safety and efficacy of psychedelic-assisted therapies, and believe it is now, but it's really only gonna increase in importance the more people that are coming to this, the more people that wanna try it, the more you see expansion of retreat centers and jurisdictions where those things are legal, it's gonna become, I don't know, at least, you know [chuckle] of course, to me [Unclear speech] the most important thing about it all, right, from the angle that you're sitting in, it seems like it to me.
0:14:31.9 PA: Well, especially in a US-centric way, if we're looking at Europe, let's say there's... I would say less widespread use of SSRIs and Wellbutrin and some of these classic medications. This is in many ways, not a strictly American phenomenon, but it's by and large, specific to Americans. And of course, as a population, there's over 350 million Americans and a significant percentage of those Americans are on these medications and could benefit from that, and I'd love, before we go deeper into sort of the maybe contraindications and sort of the interactions between ketamine, MDMA, psilocybin and some of these medications, I'd love if you could just sort of set the scene for us in terms of, how did we get to this point in time with SSRIs and these classic psychotropic medications. Why have they been prescribed so much? Why had they been utilized so much over the last 40 years? And what have we now learned about their efficacy or lack thereof?
0:15:41.5 BM: In the 20th century, the first, probably half of the 20th century, a lot of mental health-related care was therapy and particular types of therapy, like depth therapy, like Freudian psychotherapy or Jungian types of psychotherapy. So that was really what's historically referred to as the kind of psycho-analytic paradigm, like the idea that mental health is ultimately rooted in unconscious places of the psyche, and with enough analysis, you could uncover or unearth those types of places and bring about healing. Through the '40s '50s, early '60s, these are things when Lithium as a mood stabilizer for bipolar conditions, the first antipsychotic, Thorazine or chlorpromazine came on the market. And these offered benefits in people with bipolar conditions and psychosis where there'd never really been any treatments or the treatments had been truly barbaric like lobotomy types of treatments and things like that.
0:16:54.1 BM: And so, the advent of particularly mood stabilizers and antipsychotics kind of brought about the downfall of the asylum area, and it was kind of, we're gonna treat mental health in the community now, but the kind of community hubs for treating mental health never truly materialized, and then with the kind of Controlled Substance Act and declaration of the war on drugs that happened in the late '60s and 1970, we saw a lot of mental health treatment being passed along to incarceration settings. So, in the United States today, the prison system is the largest "provider" of mental health treatments in the country, and the idea that cycle analytic methods for treating illness kind of was pushed aside and went out the window and was replaced by this idea that structure determines function; a very biologically physicalist type of perspective or world view where, "Oh, mental illnesses are a result of imbalanced neurotransmitters, and all we need to do is give some type of substance that balances the neuro-transmitters," and that's how we're going to see improvements in mental illness.
0:18:12.8 BM: So the pendulum swung all the way from the psychoanalytic paradigm, all the way to a biologic paradigm. And so, we see a lot of biologic-related treatments for mental illness today and just kind of increased prescribing of things like anti-depressants and, you know, psychedelics are somewhere in the middle, in that, sure, you can find plenty of research about potential neurochemical effects that could be beneficial, things like diminishment of the default mode network, things like upregulation of neurotrophic factors.
0:18:50.5 BM: So I think it's kind of undeniable that there is some neurochemical or biological basis to the improvements that you see with psychedelics yet subjectively they offer this kind of phenomenologic experience where people are feeling that parts of their subconscious or unconscious are becoming unearthed. And they can kind of see old problems in new light or perhaps have insights into negative events of the past, traumatic types of events that also are really associated and correlated with kind of improved types of treatment outcomes. So there's probably some forms of mental illness out there that are predominantly biological, things like schizophrenia, for example, there's a fairly defined like age range. The clinical course can be rather textbook for some people, there's a whole variety of other reasons that people can be psychotic, but schizophrenia as an illness has kind of a textbook definition and you will see cases that fit that arc pretty well.
0:19:56.0 BM: And then you have things like depressions and anxieties, which are probably more psychosocial spiritual types of illnesses that are a result of different cultural or lifestyle related factors and probably throwing purely biological treatments at illnesses like depressions, anxieties that are oftentimes heavily in the psychosocial or spiritual types of domains may not be the most effective methods or treatments. So this idea of psychedelics and the types of talk therapies that come with it, and the biological effects really seem to me to be progress in the treatment of mental health, because I really think it balances kind of some theories about mental illness in the first half of the 20th century with some of the more cutting edge type of neuroscience that's been coming out in the last 50 to 75 years.
0:20:57.9 PA: Yeah. That's a brilliant overview. And I'm glad you mentioned the sort of biological or reductionist or physicalist approach versus the psychoanalytic or the sort of depth even gestalt therapeutic approach, right? Because it... From my understanding of it, I read this book called the Anatomy of An Epidemic by Robert Whitaker, which is a phenomenal book about how these medications were so over-prescribed and essentially they took the model of penicillin and penicillin and how it could target specific issues in the gut, let's say, and they replicated that model for the brain to target specific neurotransmitters. And what we've been discovering is that we're much more complicated or things tend to be much more complex than just, "Okay, we gotta pick that one target and then it'll change everything." Now when it comes to sort of your work in this space then, with running Spirit Pharmacist, with being at the intersection of these two, what are some common stories that you hear from people who have maybe been on medications and are looking to work with psychedelics? What... How, yeah, just kind of give us a sense or a feel anecdotally of who is trying to make this leap in this transition, what medications are they trying to sort of cycle off of and how are psychedelics helping with that process?
0:22:37.5 BM: Yeah. Now I've talked to a lot of different people with a lot of different types of things and stories going on. So I'm just pausing here to kind of like think like, okay, is there some sort of amalgamation that is like most typical? And I would say that the kind of standard person that I'm speaking with is in their 30s, 40s, 50s, or 60s. So it's usually not very young people. And I do talk with people in their 70s and 80s, but they're not the majority of folks. Most of the time they have a kind of an extensive history of antidepressant use. And most of the time, their kind of identified struggles with mental health started in their teens or early 20s. So they're usually longstanding types of things. Sometimes they've tried to take breaks from antidepressants in the past and had some success with that.
0:23:34.1 BM: Sometimes it's been more or less continuous use for years to even even decades. And most of the time they've done quite a bit of introspection and self work already. So most of the time they have some type of support with a therapist or have done extensive amounts of therapy in the past, they've tried various types of medications and usually found some of it to be a benefit, but not really quite gotten them to the place that they want. I'll also say that there's something sort of timely about psychedelics for them in most of the cases in that, "Well, I managed my depression in my 30s, 40s, 50s, but now that I'm in my 60s, I'm retiring and a lot of things in my life are changing and I'm looking to understand who am I now and how do I want to spend the last 20 or 30 years of my life, or I got on antidepressants, because I was having such a rough time. I was in graduate school. I was going through a divorce, but I graduated and it's been a few years since then. And I'm in a slightly better place, and I'm interested in what these things can do for me and how they can kind of transform my life."
0:25:02.3 BM: So it's usually not the most severe and acute types of symptoms. There's usually some relative level of stability that they're experiencing. Usually they've tried other modalities and usually both Western and Eastern types of things. Things like acupuncture, yoga, meditation are not foreign concepts for most of the people that I'm talking with, and are kind of seeking the next piece in their path to recovery or wellness or self knowledge or self learning.
0:25:37.7 PA: I think that's kind of the standard case I guess I would be talking to, but it really is a huge variety. Lots of people with Bipolar II types of conditions or things that... Some sources on the Internet may say, "No way, that's strictly contraindicated and it's gonna be horribly dangerous." And then, they're getting anecdotes from other people with bipolar conditions as like, "Yeah, but in my case, it was pretty helpful." So kinda reviewing histories for the severity of the illness, what the red flags that they have are and how can we minimize those or just make it as safe as it can be if they really wanna proceed with this type of thing. And I guess I'll say that some people are sort of ambivalent and that they're looking for reassurance. But I think a lot of people have already decided, like, "I'm gonna try this in some way, shape or form. And now I just... I'm looking for the information on how to do it safely." So it keeps going on and on.
0:26:41.0 BM: Yeah, it's a multifaceted... There's tons of matrices here and I think it would be helpful for our audience and our listeners just to go a bit more into some of the specifics. One of the recent papers that was published out of, I think Switzerland in combination with MindMed, was about psilocybin and SSRIs. And as you mentioned before, most if not all of the clinical research, we're now seeing a little bit more, that's not the case. But most, if not all of the clinical research has been on people taking psilocybin who were totally off their medications, this one that was published out of Switzerland, that was not the case. Now, the sort of... I think, conservative public talking point is don't ever mix these two. Don't ever mix psilocybin and SSRIs. And yet, from what I understand about the research, it says, actually it's quite safe. So I'd love if you could just talk through that nuance a little bit.
0:27:38.2 PA: If someone is on SSRIs, Prozac or Zoloft or other SSRIs and they're considering psilocybin in particular will stick with now. I know it's different for MDMA and ketamine and ayahuasca, psilocybin in particular. How do you approach that? Is it okay for someone to microdose to help wean off those SSRI medications? Do you typically say, "Hey, first wean off all of the SSRI medications before touching any psychedelics whatsoever?" I know there are plenty of people who do high doses of psilocybin when they're still on SSRIs as a way to sort of break out of it. So I'm just curious from a pharmacist perspective, how do you approach that sort of dilemma?
0:28:20.7 BM: Yeah. Well, my approach is never like a one size fits all thing. The whole idea of the consulting service is that, I'm trying to figure out what is your level of attachment to these antidepressants? Do you get benefit out of it? Do you even want to stop or taper off a bit? And I think sort of beyond goals and intentions with the psychedelic that they're using, what are the goals and intentions around the types of standard medications? And you do meet people that are, "I don't know if I'm getting much out of my antidepressant. I'm not really sure. It's been a couple of years and I would really like to understand who I am without this substance or without this kinda chemical filter on my life. And I've tapered off a couple of times in the past and it's gone okay but four or five months down the road, things do get kinda dark and rocky and then I go back on them."
0:29:22.9 BM: "So for me, I feel like I wanna taper off my antidepressants and see if I can use psychedelics as an alternative to keep me well and hopefully result in a better outcome than my antidepressants." And it's kinda like, "Okay." It sounds like you are pretty motivated to stop your antidepressant and understand that there could be some challenges or a rockier path in the months ahead because of that. But you sort of have the time and space in your life and you're up for it at that particular point. "Okay, let's go ahead and try to taper off here." versus, "Well, I just started this a few months ago and it's sort of working for me and I tried to taper off once or twice before and it was just awful for me. I had horrible neurological types of brain zaps and paresthesias. The suicidal thoughts came back immediately. And overall, I'm just not... I don't think this thing is working. I'm not in a good place at all, but tapering is gonna put me in a worse place."
0:30:38.0 BM: And it's kinda like, "Okay, well, I don't know if you really have the sort of emotional cushion to get through a sort of taper process." And it also sounds like maybe there is some benefit to the antidepressant or maybe you're not really sure if your goal is to actually stop it, because there's a lot of fear around discontinuing and maybe we should be thinking about doing a course of ketamine or trying some type of psychedelic that may still have some positive effect for you. And maybe we can get you feeling better. And that may be a better time to try to see what's going on with the antidepressant or if we can live life without it and that kinda thing. So I'll say there's no kinda cookie cutter approach unless it's truly dangerous or adverse. And for the most part, I kinda think of ayahuasca and ibogaine sort of being in the league of their own as far as risks in combination with these antidepressants.
0:31:39.2 BM: For things, like you brought up the Liechti study through MindMed recently with psilocybin, and the SSRI they're using was Lexapro or escitalopram. I will say from my knowledge, experience and reading and... Published an article on serotonergic psychedelics and serotonin toxicity this past year, I cannot find a lick of evidence that SSRIs and things like the classic psychedelic tryptamines, so LSD, psilocybin, N, N-DMT, in combination are dangerous or really increase the risks of a serotonin toxicity. And to me, a serotonin toxicity is a life-threatening toxidrome characterized by myoclonic seizures and severe hyperthermia, whereas some of the other serotonergic things that can happen, dilated pupils, upset stomach, agitation, panic, maybe even like a paranoia type of a thing, mild hyper-reflexia or some kinda volitional shaking, these can come up when people combine SSRIs and psilocybin, but they can come up with just psilocybin by itself. These sort of serotonergic somatic effects of psychedelics are not uncommon. So I get that sometimes people combine them, and really unpleasant psychological or physical things occur but with the absence of myoclonic seizures or severe hyperthermia, I cannot convincingly think that it's really a serotonin type of toxicity.
0:33:17.1 BM: I'll say the Liechti study... It leaves a lot to be desired [chuckle] for me, in that essentially the methodology was that they gave people two weeks of the SSRI escitalopram or a placebo, and then they randomized them to psilocybin essentially. And what they found was that the positive mystical types of effects of psilocybin were preserved. Some of the sort of more challenging or negative aspects of the psilocybin experience didn't seem as prominent actually in the people that were taking the escitalopram or the Lexapro. So the author's kinda conclusion is that, "Well, psilocybin still works, and people still get the positive effects." But there could actually be something about like, "Maybe SSRIs actually improve the tolerability of psilocybin and doesn't take them to such the negative or challenging places." And I think that the big flaw with this is that they only gave them two weeks of Lexapro use, while these SSRI drugs, it's the number-one, most standard, basic counseling point about them, is that they take at least four weeks, and maybe six to eight weeks to produce the types of genetic or neuro-adaptive changes that ultimately result in people feeling better. So giving it after two weeks, you really didn't give it long enough for the kinds of receptor downregulation events that someone that had been taking SSRIs for months or years would probably experience.
0:34:52.5 BM: And so whatever data you're getting there is not really gonna be very generalizable to people that are actually taking these SSRIs in the real world. And it may very well be that... Well, they say like, "Well, they... We didn't find a diminishing of effects," and it's like, "But you did, some of the negative aspects of the psilocybin experience were actually diminished. And maybe if you would have extended that study for another four weeks, you would have seen more of a global diminishment in the type of effects." So I'll say that from my practice, it is really variable. I have some people that are taking SSRIs and will say, "I tried five grams of psilocybin mushrooms. My friends were on a different planet, and I was just kinda wondering what's going on and felt like taking a nap." I'm kind of like, "Okay, well, that doesn't really sound like what should happen." And then you have other people that get plenty potent effects of psilocybin while taking anti-depressants, while taking pretty solid doses of those anti-depressants and/or claim they get a lot of mood benefit even from very small doses or microdoses of their anti-depressant.
0:36:05.8 BM: So I think to summarize all that, I'll say that the data that has been generated around this is inconclusive and leaves a lot to be desired from a methodological standpoint for me. And that it really seems quite variable as whether people will respond to psilocybin while taking an SSRI or an SNRI versus not. However, I can't find much out there that would suggest that it's contraindicated from a physical safety type of standpoint or perspective. And I think that the last part of your question was around microdosing and tapering. And I usually encourage people to try to start the taper and get as far as they can with it without having to introduce a microdose. If they run... If they get 50% of the way, and they start running into more bothersome types of withdrawal, and they want to try a microdose or few to see if that helps or sort of staves off some of the withdrawal symptoms, I'm generally okay with that kind of self-experiment.
0:37:19.3 BM: And I've found that indeed some people really feel like, "Wow, this was so helpful. It's like my withdrawal symptoms really improved after I did that, and it helped me continue with the taper." I have other people where I suspect either maybe their microdose was too high, or they're just sensitive in general, and it sort of feels like the microdose amplified some of the withdrawal effects. So it's like, "Ah, I was feeling some level of anxiety, I think associated with either my anxiety or medication withdrawal, and then microdosing seemed to just really take it through the roof where I was almost like panicking now."
0:37:54.7 BM: So again, I don't have a great like... "Oh yeah, microdosing really helps all people taper off of their anti-depressant." I do get people reporting that, and sometimes the results or their anecdotes are resoundingly positive, but I've also had people that it just didn't work out for them, and I tend to also caution people against chronic use of microdosing, I'm concerned about valvular heart disease and the potential risks of chronic uses of serotonergic psychedelics, so this is another reason why... Well just get as far as you can before you introduce some microdose 'cause you probably wanna limit your course of microdosing to one, two months max. So once you start micro... You don't wanna like, Okay, we're gonna start micro-dosing at the get-go, it's gonna take you three months to taper and then you need two months of microdosing and now we're in this position of, "Well, do I stop microdosing as I finish the taper, even though I feel like it's been helping me all along 'cause of this possible risk?" I'd rather kinda be like, Okay, let's save the round of microdosing to when it gets difficult and you're probably within two months of stopping or getting off the medication, because then if it does work for you, if it does work for you, then you've kind of aligned it so that it's helping you through the most challenging part of it, and really going from some drug to no drug for the most part is the most challenging step for people.
0:39:27.0 PA: Just to go into that a little bit more Ben... And thank you for the response. I asked you a big question that had many parts, and you really did a great job navigating that. What... And I'm curious how well you know this, I don't know, in terms of your background in neurobiology, I know you're not necessarily a psychiatrist, but let's say someone has been on SSRIs for 10, 20 years, what is that doing to their serotonin systems, to the receptors, to the brain, and how is it different than, let's say, a classic psychedelic and what that might be doing and how that interacts with serotonin and the system there.
0:40:10.2 BM: As far as real long, long-term effects of most psychoactive drugs, there's not a ton of really great data out there as far as... Does an SSRI do something different when someone takes it for one year versus taking it for 10 years? That's something that I have not found much in the way of data that would inform a person. SSRIs block the serotonin reuptake plumb, so acutely, they increase the amount of serotonin that you have in the synapse or the space between two neurons, but that doesn't result in people feeling better immediately. So whatever is happening there, takes some period of time. So I always say that, well, anti-depressants are really slow-moving drugs because they tend to produce changes over a period of weeks to months, and the types of changes that have been associated with benefit is down regulation of serotonin receptors, and specifically, there's a lot of literature about the serotonin 1A receptor, and the types of coping mechanisms that could be associated with that, so things like passive coping mechanisms, so things like... The analogy I use is being able to weather the storm.
0:41:33.0 BM: When antidepressants are working well, people will oftentimes say things like, I feel better. My mood is in a much more even keel, and the things that used to really agitate or irritate me or cause a lot of anxiety, there's a softness to that edge or the littlest thing would get me down and cause me to cry at work, it was very embarrassing, it was happening on like an almost every day basis, and now I don't get triggered in that way, and break down emotionally in environments where that may not be so acceptable." So it seems that it sort of gives people an emotional jacket. When it's not working well, people will report stuff like, "Well, this emotional jacket numbed me, it zombified me, my emotional range become way too narrow, I kinda felt like a robot, it's like I wasn't so sad but I wasn't happy either. I couldn't experience joy to the fullest extent." So I'll say down-regulation of serotonin receptors, specifically serotonin 1A receptors and being linked to more symptomatic reductions, functional improvements and being associated with passive sorts of coping mechanisms. Psychedelics also down-regulate serotonin receptors. They do so rapidly, and it's mostly the serotonin 2A receptor that is the focus with at least serotonergic types of psychedelics.
0:43:09.2 BM: It seems that the serotonin 2A receptor may be associated with more active types of coping mechanism, so essentially people being like, Well, these circumstances of my life are what is leading me to feel not so great, so how am I gonna get better? I have to change the circumstances of my life in order to do that, so it's more active and perhaps more adaptive from a transformational or lifestyle type of thing, and the psychedelic is known to be a psychoplastogen or a neuroplastogen. So it makes a person emotionally vulnerable and suggestible like in the experience, but part of this is they're more moldable.
0:43:57.2 BM: Like, there's an opportunity for learning, and/or unlearning and re-learning to occur more readily in the psychedelic experience, and probably for the 48 to 72 hours afterwards, is probably a time where neuroplasticity is high, and they tend to sensitize people to emotions. Acutely in the psychedelic experience, the emotional range is oftentimes way expanded, where they're feeling really extreme versions of feelings, either positively or negatively, anxiety or things like bliss or mystical types of effects. And then almost with microdosing too, it seems like people are like, "How does microdosing work?" And it's like, "Well, I felt a little bit more present perhaps." But oftentimes people are going through their lives and they're noticing things differently. That, "Oh well, I usually eat these sorts of junky foods, I tried to eat the junky food on my microdose day and it didn't taste right, so I didn't do that that day. And then I did that for a few weeks and all of a sudden I started to feel somewhat better." So I think of psychedelics as active coping and emotional sensitizers, right?
0:45:20.9 BM: So some people may be not feeling enough. They're numb, they're anhedonic, they're depressed, they're in a rut. Brightening the effect with something activating and expansive of the emotional range, like a psychedelic, could be quite helpful for them. You can also imagine people that are maybe quite empathic and that are sort of already overloaded with a lot of feelings, they're sort of hyper-sensitive to feelings at baseline, and perhaps adding psychedelics in those situations can break down the walls almost too much for them.
0:45:58.5 PA: Which goes back to your point about...
0:46:00.1 BM: This is kind of my... Yeah.
0:46:00.3 PA: This is all... What I always say with our students is, it depends. Right? The context always depends.
0:46:07.6 BM: Yeah, exactly.
0:46:08.8 PA: And I'm glad you...
0:46:10.0 BM: But I guess like... Yeah, yeah. Yeah. 1A/2A receptors, like, you know... So basically, serotonin receptor down regulation is what SSRIs and psychedelics have in common. Different serotonin receptors, over different periods of time, and different sorts of emotional effects, but they're both serotonergic things that down-regulate serotonin receptors.
0:46:31.2 PA: It's the commonality. Beautiful. Okay, so I wanna go into some more specific stuff. Let's talk a little bit about ketamine and MDMA. Ketamine, as we all know, is now a legal option. There are a lot of people... It's incredibly efficacious for suicidal ideation, as well as for depression treatment, resistant depression, major depressive disorder. It's, I would say, legally the most widely used substance that has psychedelic-like properties that's currently being used. And then MDMA, it looks like, will be the first medicalized psychedelic for PTSD, thanks to MAPS and all of their work, so looking by the end of 2023. It's not quite as available at this point in time, but a lot of people are paying attention and once it becomes legal will wanna use it. So I'm just curious for... Those are... Ketamine and MDMA themselves are two very different substances and drugs. And obviously they're both very different from the classic psychedelics, the tryptamines and lysergamides and even phenethylamines. When you're looking at SSRI use, or the use of Wellbutrin or SNRIs, what is contraindicated for ketamine? Let's just start there. What are those... That relationship between ketamine and some of the more classic psychotropic medications?
0:47:47.9 BM: Ketamine has a couple of real big upsides, or advantages, from perhaps like a treatment of different types of illness perspective, and then from a compatibility with psychiatric medications perspective. So ketamine primarily is a glutamate antagonist, so it's not a serotonergic type of substance and it doesn't work on really norepinephrine or dopamine too strongly either. So as far as its ability to really interact with a lot of the first line or standard types of antidepressants that you see out there, like SSRIs, SNRIs, Bupropion, Mirtazapine, it's really great. It's clean. It's compatible with these types of things. And to one of the points like earlier in the conversation, when ketamine was being studied in the early 2000s for things like treatment-resistant depression, they would wash everyone's medications out. Now that esketamine, or Spravato, is approved on the market, the actual FDA indication is treatment-resistant depression in conjunction with the standard type of first-line antidepressant.
0:49:03.9 BM: So ketamine is an option for people that are on SSRIs, SNRIs, Bupropion, Mirtazapine. The effects are preserved. It still can have some really wonderful types of antidepressants there. So for people that are not ready to attempt tapering their antidepressant or are gravitated towards a more legalized medical model of psychedelic use at this point in time, ketamine is a real clear winner.
0:49:35.4 BM: Similarly, ketamine has been studied and shown to be safe and effective for persons that are having depressed episodes with bipolar conditions. Whereas things like MDMA and psilocybin, there's not much data or the data that's out there suggests that there could be risks of precipitating manic episodes. So for the person with bipolar depression, ketamine is also probably a safer and perhaps even more effective option at this point in time. And along with the bipolar conditions, the mood stabilizer lithium is one that is known to increase the risks of seizures with serotonergic psychedelics like psilocybin or MDMA, whereas lithium has been studied in conjunction with ketamine and demonstrated that it is safe. So for the person with a bipolar condition that's depressed that's taking lithium, it's like home-run ketamine for the win, because it's safer, they don't have to change their medications, and for a lot of people that just have standard types of depression that just are not ready to attempt or try stepping off their antidepressant for whatever reason, it's gonna be a really great place to start or begin.
0:50:55.4 BM: Downsides of Ketamine is that people often need to get several treatments in a fairly short period of time, there's sort of an induction round to it and all, there's... I would say in the kind of controlled clinical settings, the risk of addiction. It depends with Ketamine, are not high, but it is a habituating and reinforcing type of substance. And people have developed substance use disorders with Ketamine, or things like lower urinary tract symptoms or bladder problems from over-use of Ketamine, so there are some downsides to it there as well.
0:51:32.7 PA: I'm just curious, are there any contraindications for Ketamine? Are there things that people just should be weary of when it comes to potential use of Ketamine?
0:51:40.6 BM: Yeah. Yeah. Yeah. So from the efficacy perspective, things that are highly GABAergic like the Benzodiazepines, really tend to take the edge off of some of the dissociative or psychedelic effects of Ketamine, but they also tend to really water down the antidepressant effects of Ketamine as well. So this is somewhat dose-dependent, it seems like an equivalent of maybe Valium, Diazepam, something like eight milligrams a day or more seems to really interfere. Whereas your person that's half a milligram over Azepam twice a week, 'cause insomnia is bad... Like... Okay, that's not gonna be a deal breaker for Ketamine. But the person that's using high doses of Benzos or Benzodiazepines multiple times daily use, they're gonna get a whole lot less out of Ketamine than some others.
0:52:33.4 BM: There are some other kind of glutamatergic types of drugs out there, or GABAergic types of things. Things like Lamotrigine or Lamictal, where it's sort of controversial. Like some data suggests, okay, the effects are relatively preserved, some data suggests, well, there could be a reduction in antidepressant effects. The unfortunate part about Lamictal and Ketamine, is Lamictal is just not a good drug to be holding temporarily. And it has to be titrated where people start it extremely slowly and even giving short breaks of it can increase the risk of things like really severe types of rashes, they call it like Stevens-Johnson Syndrome. It's essentially a rash that affects mucus membranes, so eyeballs, mouths, large areas of the body. If you really get Stevens-Johnson Syndrome, you're probably gonna end up in an intensive care unit made for burn victims, 'cause there's so much skin sloughing off. So you're gonna do Ketamine, you're taking Lamotrigine... Unless you have a good rationale for stopping the Lamotrigine and trying to stay off of it, I really would recommend starting and stopping it for that reason.
0:53:47.6 BM: But you may notice that the effects aren't quite as strong. Yeah. But for a lot of the first line things like just the SSRIs and whatever, Ketamine's great and compatible.
0:54:00.5 PA: That's phenomenal. So let's go into MDMA. And while we were talking, I pulled up a little study that was recently published about how previous antidepressant use may blunt the effectiveness of MDMA assisted psychotherapy. It was published in the Journal of Psychopharmacology. I think these were some of the first findings that were published on that relationship between SSRIs and MDMA. And I'd love if we could just... I'll just sort of keep it as open as possible for you. What are we looking at in terms of relationship between MDMA and the classic psychotropic medications? What should people be mindful of if they're considering MDMA assisted psychotherapy now or in the future?
0:54:39.4 BM: I think of MDMA as being a serotonergic amphetamine, meaning that its primary mechanism is probably to release serotonin and it releases serotonin by reversing neurotransmitter flow through the serotonin reuptake pump. The serotonin reuptake pump is a critical piece of MDMA's mechanism of action. So if you have drugs like SSRIs or SNRIs that are blocking the serotonin reuptake pump, it really tends to block the effects of MDMA. So there's really good reason to think that there's just a direct pharmacodynamic type of drug, drug interaction between SSRIs or SNRIs, or any drug that really strongly blinds the serotonin reuptake pump and MDMA, and you would predict that the effects of MDMA are gonna be diminished.
0:55:34.6 BM: We mentioned the Psilocybin and Escitalopram study, this was out of Matthias Liechti's lab, and Liechti's lab has been studying this question with MDMA and antidepressants for a couple of decades now. So there's actually quite a few sort of Phase one clinical drug interaction studies, where similarly they only give people a few days of SSRI types of antidepressants and then MDMA or placebo. But they notice that the effects of MDMA are decreased, something like 40% to 70%. So it's pretty well documented with a number of different types of antidepressants that the effects can be acutely diminished in combination.
0:56:16.1 BM: This other article that you mentioned, I think it's Alli Feduccia's study that kind of looked at some of MAPS Phase two data that dealt with people that needed to taper an SSRI antidepressant to be enrolled in the clinical trial, versus persons that had a much more remote history of antidepressant use and did not need to taper them to be enrolled in a Phase two trial. And what they found in that study, is essentially that even with two MDMA treatments spaced a month apart and a three week washout period between stopping antidepressant use and the time that they started the MDMA assisted therapy, they still weren't getting the same type of decreases in their PTSD scores a month after that second treatment. So it really seems that there's also some refractory period of time between when they stop an antidepressant and when MDMA will really start to exhibit its full effects. And this may have to do with this sort of serotonin receptor down-regulation that long-term antidepressant use can cause. Or maybe even serotonin reuptake pump down-regulation, that's another feature of long-term antidepressant use. So...
0:57:40.2 BM: Big problems for MDMA assisted therapy and people that are taking SSRIs or SNRI types of anti-depressants. The phase three data so far with MDMA hasn't really found this kind of signal for reduced anti-depressant effects, but they... The methodology that they've used to analyze the phase three data is different than the methodology that Feduccia and her colleagues used for the study that you mentioned. And the phase three trials give people three MDMA sessions instead of two.
0:58:19.6 BM: So my kind of counseling for people that are tapering an anti-depressant and wanting to move towards MDMA-assisted therapy is one... Is like, you probably really do need to taper and wash it out if you want this to work for you. You probably just really can't be on an SSRI or an SNRI antidepressant and get the types of subjective effects and trauma... Reduction in trauma symptoms while you're taking it.
0:58:49.9 BM: And even if we wash it out for... I'm gonna say a minimum of two weeks, but ideally, maybe more like four to six weeks ahead of time you can expect that first session to kinda be a toss up as far as whether you're gonna get strong effects of MDMA and symptom reductions there or not. However, you should really think of MDMA-assisted psychotherapy as a large intervention that happens over six months where you're gonna do... At least two, ideally, three sessions in that period of time. And each session is likely gonna build on the last one. MDMA is probably gonna become more potent the longer that you're off of your antidepressant. And essentially just don't do one and give up. That first one could be really tempting to give up afterwards, 'cause like, "Man, I went through all of this hard work. I tapered off this thing. It didn't really work very well for me." And... Or it was unpleasant. It was just like, "Okay... " People say like, this is ecstasy. What was ecstatic about it? I just felt nauseous and there was some strange physical energy in my body. And this lasted for a few hours, and that was it. Like, "What am I supposed to make out of that?"
1:00:13.2 BM: And it's like, well, probably that you're still experiencing withdrawal and that the med was still sort of interfering. Is probably what you're supposed to make out of it. But there's a real temptation because of the sort of time and resources that go into this thing. You wanna make the most out of each session and when the first one doesn't work well it can be challenging to be motivated to continue to invest as much as they invested into it. But I think with enough persistence they really can. So that's the SSRIs and SNRIs.
1:00:48.3 PA: And what about the others? Are there other sort of like...
1:00:50.8 BM: Yes, I really wanna specifically mention Wellbutrin or Bupropion and MDMA 'cause it's a different ball of wax. So Wellbutrin is not... It doesn't work on the serotonergic nervous system. It's not a serotonin re-uptake inhibitor. It's a dopamine norepinephrine re-uptake inhibitor. And structurally, Bupropion is a cathinone. So it's a Phenylethylamine. It's a mild stimulant, is what Wellbutrin actually is. It's a non-controlled substance. So that's nice compared to other stimulants.
1:01:24.4 BM: But it's essentially a mild stimulant and it blocks a couple of the enzymes that MDMA relies on for metabolism. So when Wellbutrin or Bupropion and MDMA are administered together you get higher concentrations of MDMA and higher concentrations of Bupropion. Bupropion is a medication that is contraindicated in people with seizures or epilepsy because it lowers the seizure threshold. MDMA causes the central nervous system excitation. It can cause a release of antidiuretic hormone, which can drop serum sodium levels. And in recreational environments, people taking perhaps an overdose, perhaps being in very hot environment with lots of visual stimulation and being dehydrated or maybe physically exhausted from dancing, seizures can occur with MDMA, or Ecstasy. There's some... I'll say observational data through the FDA's Adverse Event Reporting System, suggesting that out of all of the anti-depressants out there, persons that are ingesting Wellbutrin and MDMA tend to have a higher chance of death or mortality.
1:02:51.8 BM: So I'm kind of thinking... Well, Wellbutrin and MDMA sounds dangerous. It increases the effect of MDMA. It prolongs the effect of MDMA and you're giving essentially two stimulants at the same time that both have some risk of seizures to it. So opposed to the SSRIs, SNRIs where it's like, "Oh, it's contraindicated 'cause it just won't work for you."... I think Wellbutrin is one of this kind of... I would say like sketchy types of combinations where the risks of adverse effects could actually be increased.
1:03:26.2 BM: The good news about Wellbutrin is it tends not to have the same type of really bothersome neurological types of withdrawal syndromes that the SSRIs or SNRIs do. So it's not really characterized by the sorts of brain zaps or paresthesias or flu-like symptoms. It's a stimulant, so it's usually a mild type of stimulant withdrawal. Lower mood, fatigue, feeling more tired, but not necessarily the same sort of... It's just really awful for weeks and weeks and weeks. So typically, Wellbutrin is the type of substance that persons could miss a few days off and the world wouldn't end for them. And they could go through with an MDMA experience safely that way. But I would caution people in combining them. And everything is dose-dependent in this world. Using 450 milligrams of Wellbutrin and 250 milligrams of MDMA, that sounds a lot more dangerous to me than someone that's on 150 milligrams of Wellbutrin and wants to use 75 milligrams of MDMA with a booster of 35. So there's some nuance and gray area and maybe it depends on what your level of risk tolerance is and things like that, but it is a combination that's flagged as sketchy in my mind.
1:04:50.4 PA: One last thing that I wanna touch on is Ayahuasca. And you had mentioned it earlier, that Ayahuasca was sort of in a league of its own compared to psilocybin, ketamine, MDMA. And I think it's because of the MAOI in the Ayahuasca, right, that adds additional complications. So what, if someone is interested in looking at Ayahuasca, and most reputable if not all reputable retreat centers will know this very well in terms of the contraindications, but just what are we looking at in terms of potential risks and contraindications for Ayahuasca and some of the classic psychotropic medications?
1:05:29.9 BM: So Ayahuasca essentially has the Ayahuasca vine which have harmala alkaloids or ß-carbolines in it, things like harmine, Harmelin, Tetrahydroharmine, and the psychedelic component of Ayahuasca is an DMT. So the thing that really changes or modulates the risks with Ayahuasca compared to the other sort of classic psychedelics like psilocybin or LSD, is, like you said, the Ayahuasca Vine, or the harmala alkaloids. The harmala alkaloids block monoamine oxidase, which is an enzyme that is critically important for the metabolism of many neurotransmitters, but particularly and specifically serotonin. So when you have drugs that increase intrasynaptic serotonin, like SSRIs, like MDMA, MDMA releases serotonin.hese are the ones that are truly the highest risk in combination with MAOIs as far as precipitating a serotonin toxicity. Which is, again, severe, life-threatening hyperthermia and myoclonic seizures, is gonna be the sorts of hallmarks for that. However, the harmala alkaloids in the Ayahuasca Vine also block other liver enzymes. They block one called CYP2D6. They also block one called CYP3A4. So there's many other different types of psychiatric medications that rely on those enzymes for metabolism. So beyond the sorts of serotonin toxicities that could be possible, and are really just black and white in my mind, just like, don't mix the two.
1:07:13.8 BM: It's just not a good idea. Even a microdose is kinda like... There's no defined microdose of the Ayahuasca Vine that's out there. And yeah, you can find people that are getting away with it and saying that it's helpful, but some people can get away with playing with fire and others can't, but the reality is that playing with fire is just not really the safest idea at all, unless you're sort of a poi fire spinner person, you probably have no business really kind of doing that type of a thing. But yeah, like Wellbutrin. Okay, that's a dopamine norepinephrine reuptake inhibitor, that's not serotonergic, so am I gonna get Serotonin Syndrome mixing it with Ayahuasca? No, you're not. But you may get increased concentrations of Wellbutrin, and maybe that does increase the risk of things like seizures, or just kind of unpleasant types of experiences that are characterized by sort of breakthrough side effects of psychiatric medications, rather than the types of deep spiritual states that you're really aiming for or perhaps hoping for with something like Ayahuasca.
1:08:21.8 BM: So those harmala alkaloids, wonderful precipitating the oral bioavailability of DMT, but they really do have the potential for a lot of different types of drug interactions to occur. So the serotonin-releasing, serotonin reuptake blockers are by far probably the most dangerous in combination, but there's probably a host of others that I would at least put in the sort of yellow light, right? It just kind of like, Okay, it's not red, it's not green, but it's sort of in the realm of, "Yeah, we should probably be cautious there and think about at least temporarily holding and suspending, if not really attempting a taper and wash out." And all that just goes back to the sort of intentions of the user that we talked about earlier.
1:09:08.0 PA: So what I'm hearing is ketamine and psilocybin are the safest across the board in terms of with the classic psychotropic. MDMA's efficacy may be blunted by recent SSRI use, so a lot of people are looking at first a wash out, a tapering and then a wash out, to get the full efficacy of MDMA. Wellbutrin is a bit of an exception. There's some special things there with Wellbutrin and MDMA. And then with Ayahuasca, what I'm also hearing is, and this is what I've seen with retreat centers as well, basically a full tapering and wash out of all medications is likely ideal to really fully go into an Ayahuasca ceremony, to have that experience that is often spoken about. Is that...
1:09:58.8 BM: I think that's a pretty fair... That's a pretty fair summary.
1:10:02.3 PA: Completely fair. Great. Great. Well, Ben, this has been so helpful. Even just an hour of your time to go deep into SSRIs, SNRIs versus psychedelics, the different type of psychedelic medicines, and contraindications or a lack of contraindications, serotonin toxicity, the different substances, the different research we discussed, and this is really just, I would say a primer or a warm-up in terms of what you do with Spirit Pharmacist. So, just before we wrap up, I'd love if you could just tell our audience a little bit about... If they're interested in learning more, if they're interested in diving deeper into this, how can you help them through your platform, Spirit Pharmacist.
1:10:48.9 BM: So, a few different things in offering, is one... Hopefully, I think I gave you a link for it, I have an anti-depressant and psychedelic drug interaction and tapering guide that really kind of spells out the types of interactions that we talked the hour about here, as well as gives a lot of just guidance about how to go about tapering your anti-depressant and even provides like a monitoring tool so you can kind of track yourself as you go and understand, "Am I feeling withdrawal right now? Am I feeling sort of return of my original illness or symptoms?" And how may those things inform my plan for subsequent taper, so that guide is available just as kind of a free, like no cost type of resource, and I think you have a link for it, but it's also available through just the blog, on my website, spiritpharmacist.com.
1:11:45.6 BM: The other things that I offer are courses, so I have a course in tapering anti-depressants, kind of a logical extension of the free guide. Our course in the foundation to psychedelic pharmacology as well as psychedelic pharmacology by substance. So if you're really interested in taking a deep dive into the pharmacology of these different compounds, how they differ from one another, particularly the psychedelic pharmacology by substance course, you're probably gonna enjoy that a lot. I offer consultations, so just with individual types of situations and lots of patients, clients, retreat center applicants, people like that in the consultation service, but I also talk with therapists, psychiatrists, providers of these types of things that just want to maybe go through a number of cases or some of their FAQ types of things, and finally I offer a member resource and support program, which combines these two things. So you get all of the courses and written drug interactions guides I have, so it's kind of like a course and webinar, written drug interaction guide like Netflix, if you will, that kinda comes along with the member resource and support program, and then you get support services.
1:13:02.2 BM: So, we do email-based Q&A as well as discounts on the private consulting and for providers, I allow them to extend those discounts to their clientele. So, oftentimes, patients will be using the member program 'cause they're tapering and/or starting to use psychedelics and they want to bounce psychopharm questions off of me as they go, learn more about their anti-depressant tapering or the substances that they're thinking of getting into. And then providers are using it to essentially, "Well, I have this person on these meds, what do you think?" Well, I think A, B, C, but I think these things need to be clarified, which we could do in a consultation." "Okay, great, let's go ahead and get a consultation for that person", or sometimes things just get resolved through email Q&A, and it's kind of like, "Do I need a consultation?" It's like, "No, you don't," 'cause we figured it out through the email. So, in my mind, the member resource and support program is definitely the best value that I offer. It definitely has the most resources to it and it features the most interaction or support from me personally, and that's spiritpharmacist.com in a nutshell.
1:14:16.1 PA: Beautiful. Well, it's an incredible offering, and so needed in this sort of emerging gray market space as more people take their health into their own hands, because a lot of people don't have medical professionals who really know a lot about psychedelics, and so to have a resource like yours and the support that you offer for this really critical juncture of psychotropic medications and these spirit plant medicines is so, so important. So, I just wanna thank you for creating all of that and amplifying the importance of this... It's a really important topic as these substances crest in the mainstream, and to have a resource like yours has been and will remain very valuable for both, practitioners and individuals alike.
1:15:09.4 BM: Thank you again for having me on the show. It's been... It's been a real pleasure talking with you.
1:15:12.9 PA: Thank you, Ben.
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