1 00:00:00,000 --> 00:00:08,920 Welcome to the Psychedelic Passage Podcast. My name is Jimmy Nguyen. I'm joined here by my 2 00:00:08,920 --> 00:00:16,920 co-host, Nick Levitch. We have a very exciting topic for you all today, as well as a wonderful 3 00:00:16,920 --> 00:00:25,680 guest on our episode. I'd like to take a moment to introduce Dr. James Giordano. He's a PhD and 4 00:00:25,680 --> 00:00:30,480 a master's of philosophy, is a professor in the Department of Neurology and Biochemistry, 5 00:00:31,240 --> 00:00:38,100 chief of the Neuroethics Studies Program, leads a sub-program on military medical ethics at the 6 00:00:38,100 --> 00:00:44,800 Pellegrino Center for Clinical Bioethics, special advisor to the Brain Bank, co-director of the O'Neill 7 00:00:44,800 --> 00:00:50,940 Pellegrino Program in Brain Science and Global Health, law and policy at Georgetown University 8 00:00:50,940 --> 00:01:01,160 Medical Center in Washington, D.C. And Dr. Giordano is also a veteran, serving in the past as a U.S. 9 00:01:01,220 --> 00:01:08,300 Naval flight surgeon, serving with the United States Marine Corps. And so thank you for joining us 10 00:01:08,300 --> 00:01:13,700 here, Dr. Giordano. Thank you for having me. I really appreciate it. Yeah, you have quite a list 11 00:01:13,700 --> 00:01:21,980 of things on your accolades. And so we're really grateful to have the opportunity to pick your brain 12 00:01:21,980 --> 00:01:30,960 and have a dialogue that we feel may be helpful to our listeners. And today's topic will revolve 13 00:01:30,960 --> 00:01:37,660 around how to go about choosing the right psychedelic substance for you. And so Nick and I get this 14 00:01:37,660 --> 00:01:44,420 question so often. Pretty much every consultation call. Yeah, pretty much every interaction that we 15 00:01:44,420 --> 00:01:50,960 have with folks, given that we mostly talk to more psychedelic curious folks, folks who are newer to 16 00:01:50,960 --> 00:01:58,540 psychedelics. And oftentimes Nick and I find ourselves being able to talk anecdotally about some of these 17 00:01:58,540 --> 00:02:06,620 factors. And so I'm really excited to have a scientific background and some some why around these 18 00:02:06,620 --> 00:02:12,020 things. But before we get into that, I'd love to just learn a little bit more about you, Dr. Giordano, 19 00:02:12,400 --> 00:02:21,200 and and and how given your history and your resume, what got you into this intersection with 20 00:02:21,200 --> 00:02:25,280 psychedelics? So curious. I was 10 years old and a cousin brought me to Woodstock. 21 00:02:28,140 --> 00:02:34,180 I usually use that as sort of a personal introduction. But truth be known, I was I'm trained as a 22 00:02:34,180 --> 00:02:38,600 neuroscientist and a molecular and biochemical neuroscientist and as a neuropathologist. 23 00:02:38,960 --> 00:02:43,380 And a lot of the work that I had done, both my doctoral work and some of the clinical work and 24 00:02:43,380 --> 00:02:50,040 subsequent work I've done, examines various types of neurochemical networks, processes, 25 00:02:50,660 --> 00:02:56,820 specifically the serotonin system of the brain and dopamine system together with the opioid system. 26 00:02:57,360 --> 00:03:02,360 And these systems are rather labile in some of their effects to a variety of different substances, 27 00:03:02,360 --> 00:03:07,820 most notably the psychedelic drugs that have been known to act directly through the serotonin system, 28 00:03:08,280 --> 00:03:12,360 but then also affect a number of things, if you will, downstream. And of course, 29 00:03:12,400 --> 00:03:16,040 we recognize that there are other drugs that have been used both recreationally as well as 30 00:03:16,040 --> 00:03:21,280 therapeutically, and in some cases illicitly, that engage the same systems and the amphetamine 31 00:03:21,280 --> 00:03:25,180 drugs and the stimulant drugs working through the brain's dopamine and norepinephrine system. 32 00:03:25,700 --> 00:03:28,240 And certainly, I mean, unless someone's been living under a rock, 33 00:03:28,240 --> 00:03:33,880 we understand that we're in the midst of an opioid crisis, most notably the tragedy of fentanyl, 34 00:03:34,120 --> 00:03:38,960 and those drugs work through the brain's opioid system, which then also engages other mechanisms 35 00:03:38,960 --> 00:03:46,000 in the body. But we were very interested early on in the brain's serotonin system. It's a rather old 36 00:03:46,000 --> 00:03:50,640 evolutionary system. So it's not only present in humans, it's present in a lot of other animals. 37 00:03:50,640 --> 00:03:56,800 But what's important about the serotonin system in humans, as we came to learn, literally as I was 38 00:03:56,800 --> 00:04:01,580 going through the academic ranks and engaging my research and sort of going up the, if you will, 39 00:04:01,640 --> 00:04:07,680 scholastic ladder, associate, professor, et cetera, is that there is a lot of diversity in the system. 40 00:04:07,900 --> 00:04:13,560 And the way the system works is really parsimonious. I mean, it really keeps its system and very simple. 41 00:04:13,560 --> 00:04:19,640 You've got one brain chemical called serotonin, and it's capable of interacting with a whole bunch 42 00:04:19,640 --> 00:04:24,640 of post and pre-synaptic receptors. And let me make that easy for the listener. That's sort of 43 00:04:24,640 --> 00:04:30,420 like saying you have a single key that can turn a whole bunch of different locks. And those locks 44 00:04:30,420 --> 00:04:38,560 are on very different doors. And those doors are nodes and networks within the brain that open us up 45 00:04:38,560 --> 00:04:46,920 into various rooms of thought, emotion, experience, capability of imagination, memory, 46 00:04:46,920 --> 00:04:51,920 and a whole host of behaviors very often that go along with them, both in health and disease. 47 00:04:52,540 --> 00:04:59,720 So harnessing, if you will, that key and understanding those locks is really a very 48 00:04:59,720 --> 00:05:06,980 important aspect of medical neuroscience, but also it interfaces, as we know, with social neuroscience, 49 00:05:06,980 --> 00:05:10,140 legal neuroscience, and there are ethical issues that arise in and therefrom. 50 00:05:11,300 --> 00:05:18,280 So which came first? It sounds like the excitement and curiosity around neuroscience 51 00:05:18,280 --> 00:05:26,180 maybe was the foundation. And then at some point you had come across these psychedelic 52 00:05:26,180 --> 00:05:31,680 compounds and substances and maybe saw that interconnectedness there. Am I understanding that, 53 00:05:31,800 --> 00:05:31,960 right? 54 00:05:32,180 --> 00:05:36,320 I mean, a bit of both. I grew up during the 60s. I was a kid of the early 60s. 55 00:05:36,320 --> 00:05:42,140 And I remember growing up and vividly watching those first rocket shots, the Mercury program, 56 00:05:42,260 --> 00:05:47,160 the Gemini program. I remember watching on television when Neil Armstrong took that first 57 00:05:47,160 --> 00:05:52,540 step on the moon. So this was an age of exploration. And I think that it was always a question of 58 00:05:52,540 --> 00:05:57,140 exploring the next frontier. I mean, if you recall during the 1960s, there were some very innovative 59 00:05:57,140 --> 00:06:02,700 exploratory approaches to the highest reaches of the Himalayas and other mountain ranges. We're going 60 00:06:02,700 --> 00:06:07,320 to the depths of the ocean. I mean, if you recall during the 1960s, the Jacques Cousteau series was 61 00:06:07,320 --> 00:06:13,620 huge. The bathysphere and the bath escape, the Trieste going down to the depths of the Mariana 62 00:06:13,620 --> 00:06:19,400 trenches. But then also there are a tremendous amount of scientific and biomedical discoveries that 63 00:06:19,400 --> 00:06:26,680 turn that lens inward so that now, if you will, the exploratory frontier was the body. And probably at 64 00:06:26,680 --> 00:06:32,860 the cutting edge of that frontier was the brain. And so that iterative knowledge of the brain was 65 00:06:32,860 --> 00:06:36,780 very, very influential while I was growing up. And I'll tell you a true story. I've said it before 66 00:06:36,780 --> 00:06:42,520 in other lectures. I don't mean to sound redundant. But when I was about six or seven years old, my dad 67 00:06:42,520 --> 00:06:48,600 took me to see the movie Fantastic Voyage with the now recently deceased late Raquel Welch, Stephen Boyd. 68 00:06:48,960 --> 00:06:54,260 And the premise was that they use a military technology, a miniaturization technology to 69 00:06:54,260 --> 00:06:59,780 miniaturize equipment. And what they did is they miniaturized a submarine with the crew that they 70 00:06:59,780 --> 00:07:05,560 inject into the human body to then travel into this diplomat's brain to be able to then use a new 71 00:07:05,560 --> 00:07:11,080 weapon at that time, which was a laser beam. I'm not kidding. To be able to dissolve a blood clot and 72 00:07:11,080 --> 00:07:17,180 therefore get this individual well to be able to then transmit these secrets to the United States 73 00:07:17,180 --> 00:07:23,120 from what would essentially be a Cold War country. Well, I saw that movie with my dad and I was about 74 00:07:23,120 --> 00:07:28,200 six or seven at the time. It came out in 1966. I guess it was about seven. And I thought it was 75 00:07:28,200 --> 00:07:32,640 the best thing I've ever seen. I mean, the whole idea of this going into the brain. And they were 76 00:07:32,640 --> 00:07:36,940 waxing very philosophical in the movie that this is the basis of our thoughts and our memories and 77 00:07:36,940 --> 00:07:40,740 our essence. Well, I just thought it was the coolest thing I'd ever seen. Plus, all the glow 78 00:07:40,740 --> 00:07:45,320 winking gizmo toys that they were using. I thought, this is what I want to do. And it didn't hurt that 79 00:07:45,320 --> 00:07:49,680 I'm six years old, seven years old, seeing Raquel Welch in a wetsuit. I was like, yeah, this is cool. 80 00:07:49,680 --> 00:07:56,660 So here I am now in my middle sixties. And in fact, this is really what I've been doing for 81 00:07:56,660 --> 00:08:02,620 the past 40 years, not necessarily being injected into the body per se, but being able to take those 82 00:08:02,620 --> 00:08:07,240 exploratory journeys into different areas of the brain through the different tools that we have, 83 00:08:07,280 --> 00:08:12,380 we have at our disposal. And it's been for me, a fantastic voyage ever since. So yeah. 84 00:08:13,480 --> 00:08:17,400 Except you didn't need a miniaturized submarine. It turns out there's 85 00:08:17,400 --> 00:08:24,180 some naturally occurring medicine, substances, fungi out there that are essentially doing the 86 00:08:24,180 --> 00:08:28,560 same thing. And I really appreciate what you said about the era of the sixties being this 87 00:08:28,560 --> 00:08:37,920 sentiment on how far can the human go? Like how far can human potential go? And it seems like a lot of 88 00:08:37,920 --> 00:08:46,060 that was directed internal as well. And so I'm curious, you know, and getting into our dialogue 89 00:08:46,060 --> 00:08:56,740 and our conversation about how this affects the modern day psychedelic curious person. So we have 90 00:08:56,740 --> 00:09:09,720 a resurgence of information, of social acceptance, of anecdotal experiences. And in our, you know, 91 00:09:09,720 --> 00:09:18,360 society in the United States, there's likely a handful of psychedelics that folks will come across more of 92 00:09:18,360 --> 00:09:23,480 the classic, quote unquote, serotonergic psychedelics. We're talking about, you know, 93 00:09:23,560 --> 00:09:32,980 psilocybin containing mushrooms, LSD, DMT and ayahuasca, maybe a handful of others. There are a couple of 94 00:09:32,980 --> 00:09:41,280 other classes, MTMA, ketamine. And so what would you start by sharing with folks? You know, because 95 00:09:41,280 --> 00:09:45,980 when Nick and I have these conversations, we're talking about effect, we're talking about duration, 96 00:09:46,200 --> 00:09:52,660 we're talking about intention. We can't get too, too far into mechanism of action. So can you give 97 00:09:52,660 --> 00:09:57,900 the audience a little bit of a primer on what you would share with folks when they're trying to 98 00:09:57,900 --> 00:10:03,320 determine what the right psychedelic substance is for them? I mean, I think absolutely it's also 99 00:10:03,320 --> 00:10:07,860 important to discuss a bit of the history and historicity because they speak to the current 100 00:10:07,860 --> 00:10:13,460 attitudes, both medically as well as socially, right? I mean, as you recall, many of these drugs 101 00:10:13,460 --> 00:10:21,340 began, if you will, their trip, no pun intended, or maybe a little one, as potentially therapeutic 102 00:10:21,340 --> 00:10:26,700 agents. I mean, many of them had been developed because they had the potential to be able to alter 103 00:10:26,700 --> 00:10:33,060 cognition and emotion and behavior with at least an eye towards some tangible therapeutic application 104 00:10:33,060 --> 00:10:38,120 or benefit, number one. Number two, they were very, very effective at doing what it was they were 105 00:10:38,120 --> 00:10:42,700 doing. I mean, if you actually follow some of the work in psychiatry during the 60s, which again, 106 00:10:42,700 --> 00:10:47,460 was in many ways limited by the toolkit it had, particularly the investigative toolkit, what we 107 00:10:47,460 --> 00:10:52,460 knew about the brain in the 60s is discriminably different than what we know about the brain now 108 00:10:52,460 --> 00:10:59,780 in 2023, primarily based upon the tools that we had at our disposal. But clearly, these things worked 109 00:10:59,780 --> 00:11:07,380 to do something. And so coming out of the 1950s into the 1960s, absent some of the more garish 110 00:11:07,380 --> 00:11:12,540 experiments, the one that probably comes to mind for most folks is the military one called MKUltra. 111 00:11:12,960 --> 00:11:18,600 But here too, the goal was, look, these are very effective drugs. Could they expand the cognitive 112 00:11:18,600 --> 00:11:25,700 performance capabilities of either our own personnel or could they be used at a variety of doses where 113 00:11:25,700 --> 00:11:31,240 dose may be impendent here to sort of say, all right, could they affect negatively affect the 114 00:11:31,240 --> 00:11:36,340 cognitive, emotional, and behavioral activities of opposing forces? In other words, could they be 115 00:11:36,340 --> 00:11:43,100 weaponized? And that idea still comes up from time to time. But I think what happened is that the relative 116 00:11:43,100 --> 00:11:48,940 success of the outcomes gained with these drugs in that they did produce literally psychedelesis, 117 00:11:49,080 --> 00:11:53,540 in other words, the ability to be somewhat mind-expanding, changing patterns of cognition, 118 00:11:54,120 --> 00:11:59,740 changing existing patterns of emotionality and various aspects of emotional fixature, etc. 119 00:12:00,320 --> 00:12:04,740 And then in some cases, the resultant behaviors that went along with that, both acutely and then 120 00:12:04,740 --> 00:12:09,920 more durably, well, like anything else, the cat gets out of the bag. And if you follow some of the 121 00:12:09,920 --> 00:12:16,200 the literature of LSD particularly, and look at some of those early experimental trials, for example, 122 00:12:16,260 --> 00:12:22,760 with Dr. Leary, the success of those investigations and experiments was such that things get out there. 123 00:12:23,020 --> 00:12:29,720 And then at that point, they became socially used and then perhaps misused. And then what tended to 124 00:12:29,720 --> 00:12:36,460 happen during the late 60s and early 70s is there was a conflation, a social, legal, and therefore at 125 00:12:36,460 --> 00:12:41,600 least publicly ethical conflation, that all of these things represented heinous drugs of abuse. 126 00:12:42,020 --> 00:12:48,040 Well, let's face it. One of the more destructive drugs on the market is acetaminophen, Tylenol. 127 00:12:48,380 --> 00:12:54,880 You can overdose on that like that. And if you're susceptible to any kind of liver dysfunction, 128 00:12:55,240 --> 00:13:01,400 you're sort of walking a thin line. So it's not necessarily that the drug is dangerous or not, 129 00:13:01,400 --> 00:13:07,280 but it has to do with dose, understood mechanisms, patterns of use, and is it being gatekept 130 00:13:07,280 --> 00:13:12,600 effectively? And is it really being usurped for its therapeutic benefit? Or has it just sort of 131 00:13:12,600 --> 00:13:18,120 gotten, quote, out there? And therefore, these patterns of social use and potential misuse have 132 00:13:18,120 --> 00:13:25,380 become de rigueur. So here we are in 2023. Let's look back on the 60s and 70s and some of the strictures, 133 00:13:25,380 --> 00:13:31,240 the legal strictures and social strictures of the 70s. Come through the 80s, the 90s we had here in 134 00:13:31,240 --> 00:13:36,240 the United States, a congressionally declared decade of the brain. Fast forward, for example, 135 00:13:36,320 --> 00:13:40,940 to most more recently, the Brain Initiative, Brain Research to Advancing Innovative Neurotechnologies, 136 00:13:41,240 --> 00:13:48,280 launched by former President Barack Obama in 2013, that spent a lot of government money developing 137 00:13:48,280 --> 00:13:55,240 tools and technologies to be able to assess the brain so as to more accurately access and effectively 138 00:13:55,240 --> 00:14:01,160 affect the brain in those ways that were therapeutic on one hand, but there were also 139 00:14:01,160 --> 00:14:07,700 enabling on another occupationally, for lifestyle purposes, and to just get a better understanding 140 00:14:07,700 --> 00:14:13,100 of what constitutes brain health, inclusive of preventive brain health. So now we revisit 141 00:14:13,100 --> 00:14:20,400 the psychedelics in that light of new science with new tools, a better understanding both of 142 00:14:20,400 --> 00:14:25,800 the brain and a far more granular approach to the way these drugs can be used, which then 143 00:14:25,800 --> 00:14:28,600 affords us insights to how perhaps they should be used. 144 00:14:30,100 --> 00:14:36,860 And so how do these new tools and this new understanding of the brain, how do they intersect 145 00:14:36,860 --> 00:14:44,460 with psychedelics? Like what has been the backbone of your work as it relates to the brain and 146 00:14:44,460 --> 00:14:45,340 psychedelics? 147 00:14:45,340 --> 00:14:52,040 I think there have really been three. Certainly coming out of the early 90s and through the 90s, 148 00:14:52,040 --> 00:14:57,180 we have the Human Genome Project. And part of the mission of the Human Genome Project was to help 149 00:14:57,180 --> 00:15:03,640 to define and in that way establish what might be our neuropsychogenome. In other words, what genes 150 00:15:03,640 --> 00:15:10,220 were at least contributory, if not directly responsible, for those structures that ultimately 151 00:15:10,220 --> 00:15:15,460 had functions in our neurological and cognitive capabilities and our psychological capabilities. 152 00:15:15,460 --> 00:15:22,180 And also what genes were responsible for the development, execution, activity, and patterns 153 00:15:22,180 --> 00:15:26,960 of activity, as well as susceptibility of these various neurochemical systems in the brain, inclusive 154 00:15:26,960 --> 00:15:34,020 of the brain serotonin system, functioning not only in health, but also in disease and injury patterns, 155 00:15:34,800 --> 00:15:40,380 as well getting some understanding how various substances, both potentially therapeutic substances 156 00:15:40,380 --> 00:15:46,320 and others interact with individuals based upon their genetics and based upon the physiological 157 00:15:46,320 --> 00:15:52,480 expression of their genetics called their bodily phenotype. What that really led to is the idea of 158 00:15:52,480 --> 00:15:57,740 personalized precision medicine. But personalized precision medicine, I think, is a very important 159 00:15:57,740 --> 00:16:04,720 facet of a larger lens that seeks to understand that the more we know about the structure and function 160 00:16:04,720 --> 00:16:10,560 of the body, the more we're able to assess when things are going right, when things not only are going 161 00:16:10,560 --> 00:16:15,260 wrong, but they may have some bias or predisposition for going wrong under a variety of different 162 00:16:15,260 --> 00:16:20,480 environmental conditions, and what things work on what people at what time for what reasons. 163 00:16:21,360 --> 00:16:27,200 So the idea is dialing in that level of precision. So we're not taking the buckshot approach, 164 00:16:27,280 --> 00:16:30,920 but now we're taking a much more stringent sharpshot approach. 165 00:16:30,920 --> 00:16:37,320 So that's a very, very different orientation to understanding how brains work, literally from 166 00:16:37,320 --> 00:16:43,680 the genes up. That's number one. Number two is the idea of being able to create far more selective 167 00:16:43,680 --> 00:16:48,840 compounds. Now here we're looking at various areas of bioengineering, and we may be able to use 168 00:16:48,840 --> 00:16:55,240 much more selective compounds, number one, and certainly lower doses if we can develop pharmaceutical 169 00:16:55,240 --> 00:17:00,020 preparations that get these compounds into the brain more effectively and don't necessarily 170 00:17:00,020 --> 00:17:04,880 distribute their effects more widely in the brain and the body, but once again, see that 171 00:17:04,880 --> 00:17:07,540 sharpshot. So here we're looking at the technologies. 172 00:17:08,180 --> 00:17:17,180 Yeah, I think this is like, I hear this around a lot of the pharmacological experiments to try to, 173 00:17:17,280 --> 00:17:24,380 let's say, like shorten the duration of an LSD experience, or maybe create psilocybin analogs that are 174 00:17:24,380 --> 00:17:33,900 more visually laden or maybe have a two to three hour arc of duration or even try to affect some of 175 00:17:33,900 --> 00:17:39,740 the common after effects or during effects such as like nausea or headache or some of those things. 176 00:17:39,740 --> 00:17:43,720 Is that related to what you're talking about around this bioengineering? 177 00:17:43,720 --> 00:17:49,460 So if you think of the fact that any drug will produce sort of a menu of effects, well, 178 00:17:49,480 --> 00:17:53,180 there are certain things on the menu you want, and there'll be certain things on the menu you don't 179 00:17:53,180 --> 00:17:58,180 want. And if you know the structures and processes that are involved in those things you want and you 180 00:17:58,180 --> 00:18:02,980 don't, you can augment certain things you want, and you can mitigate certain things you don't. 181 00:18:03,720 --> 00:18:09,320 Well, to some extent, we have that capability. The other issue then becomes, well, okay, we now also 182 00:18:09,320 --> 00:18:14,800 have synthetic biology. We have gene editing. So for those things that are plant derivatives, 183 00:18:15,280 --> 00:18:21,940 could we literally make these things brand new or modify existing substances that come from fungi, 184 00:18:22,100 --> 00:18:27,240 most notably, for example, psilocybin, but also certain plant derivatives that we know are important 185 00:18:27,240 --> 00:18:35,660 to the activity of a hybrid mixture like ayahuasca. So as to literally create a cocktail that maximizes 186 00:18:35,660 --> 00:18:42,440 the effect, optimizes its beneficial and or what individuals would feel enjoyable or literally 187 00:18:42,440 --> 00:18:47,660 mind-expanding capabilities, and minimize the potential and reality of those side effects that 188 00:18:47,660 --> 00:18:54,120 individuals find burdensome or, in some cases, risky or harmful. The last point, the last technology, 189 00:18:54,200 --> 00:18:59,020 and this is huge, is that there was a revolution in and around the middle 80s that allowed us to 190 00:18:59,020 --> 00:19:05,600 essentially peer into the living brain, utilizing ever more and iteratively, increasingly sophisticated 191 00:19:05,600 --> 00:19:12,140 and capable types of brain imaging. Now, what we can do with brain imaging, again, casting all limitations 192 00:19:12,140 --> 00:19:18,340 aside, and there are some, but we understand those working in the field, is it allows us to peer into the 193 00:19:18,340 --> 00:19:25,480 living brain to see where certain substances are working and gaining an effect, and also to seeing how the 194 00:19:25,480 --> 00:19:31,500 connectivities, the interactions, the real-time areas of nodes and networks that are communicating and 195 00:19:31,500 --> 00:19:38,540 talking to each other or not talking to each other in the brain are engaged, are modified, and may actually 196 00:19:38,540 --> 00:19:44,900 be sustainably changed even after a particular pharmacological experience. So that's given us some 197 00:19:44,900 --> 00:19:50,740 real mechanistic and anatomical insight of what these things do and where they do it, and we can apply 198 00:19:50,740 --> 00:19:58,360 that in some cases very generally. But I think part of the mission is using these tools far more 199 00:19:58,360 --> 00:20:03,920 specifically on a personalized level to be able to determine who should get what, how it works, and 200 00:20:03,920 --> 00:20:11,700 what they shouldn't get. So I think we should dive into that question, because to the average listener of 201 00:20:11,700 --> 00:20:19,380 our show, either psychedelic curious or psychedelic interested, how do they navigate all of these various 202 00:20:19,380 --> 00:20:25,380 substances? Like, how do they choose what's best for them? I mean, Jimmy and I give our spiel when we 203 00:20:25,380 --> 00:20:31,520 chat with folks from our perspective as facilitators, but I'm curious from your perspective as a researcher 204 00:20:31,520 --> 00:20:37,660 and a scientist, how do you determine? I'll tell you, one of the reasons I'm actually on this program is 205 00:20:37,660 --> 00:20:42,640 because what you do provide to your listeners and to those who you mentor and you counsel is a prudent, 206 00:20:42,900 --> 00:20:48,660 pragmatic approach to that type of guidance. And I think that's important, because what you're doing is 207 00:20:48,660 --> 00:20:54,160 you're translating the science that I and colleagues who do what I do and like what I do 208 00:20:54,160 --> 00:20:59,580 then provide to give your people the best information they can. And if we sort of, if we distill that, 209 00:20:59,660 --> 00:21:06,800 essentially, as we started the conversation, I mean, we really have about three major true psychedelics 210 00:21:06,800 --> 00:21:11,500 and some derivatives, and they all have slightly different effects. Certainly, we have one of the 211 00:21:11,500 --> 00:21:17,480 older substances, which is psilocybin, derivatized from mushrooms, both the dry mushrooms, as well as 212 00:21:17,480 --> 00:21:23,940 other preparations, as well as the extract. We have lysergic acid diethylamide, LSD, and we have 213 00:21:23,940 --> 00:21:28,840 dimethyltryptamine, most characteristically as part of an ayahuasca preparation that's multi-componential. 214 00:21:29,540 --> 00:21:33,740 Let's just take a look at those three first, and then let's take a look at some of the others. And there 215 00:21:33,740 --> 00:21:37,820 are really only two that we really want to deal with here, which is the methylated amphetamines, 216 00:21:37,820 --> 00:21:43,500 methylated oxy, methamphetamine, ecstasy, or other preparations, moly, and ketamine, which is a 217 00:21:43,500 --> 00:21:46,760 completely different animal, but we'll leave that for a little later. 218 00:21:47,340 --> 00:21:50,820 And what about mescaline? Do you guys look at that at all? 219 00:21:51,300 --> 00:21:55,000 Yeah, we have. But I mean, I think one of the problems here with mescaline is that the dosing 220 00:21:55,000 --> 00:21:59,720 of mescaline is highly variable. And then of course, the other issue is the mescaline preparations have 221 00:21:59,720 --> 00:22:04,380 been highly variable to date. So I think one of the things we're seeing from the mescaline research is 222 00:22:04,380 --> 00:22:08,600 that there's a need for standardization of mescaline preparations so that the individual 223 00:22:08,600 --> 00:22:13,100 who obtains mescaline, inclusive of the clinician who may look to use mescaline therapeutically, 224 00:22:13,480 --> 00:22:17,760 can get a preparation, number one, that has high purity and good quality, and number two, 225 00:22:18,280 --> 00:22:23,200 are therefore able to dose that appropriately without worry about contamination of either dose 226 00:22:23,200 --> 00:22:28,360 level in terms of the actual level or other substances. So some of the other stuff, 227 00:22:28,360 --> 00:22:36,380 with psilocybin and or LSD and or DMT, most people from the scientific side would advise 228 00:22:36,380 --> 00:22:43,480 a relative engagement just along that pathway. So psilocybin might be for those individuals who 229 00:22:43,480 --> 00:22:48,860 are totally psychedelically naive, who may have some experience with other drugs, but are looking 230 00:22:48,860 --> 00:22:55,280 for a psychedelic experience that number one is very strongly dose dependent, not only on the extent of 231 00:22:55,280 --> 00:23:01,760 the experience, but on its manifestations, that doesn't really engage at least at the lower doses 232 00:23:01,760 --> 00:23:08,100 such a high level of situational and circumstantial derealization and or sort of a discontinuity of 233 00:23:08,100 --> 00:23:14,140 one's sense of self, but certainly could. But that also allows a sort of iterative psychedilesis where 234 00:23:14,140 --> 00:23:20,660 you do feel the mind expanding capabilities very, very visually, at least at first, that also involves 235 00:23:20,660 --> 00:23:25,640 certain changes in cognitive patterns. And what one can find when dealing with psilocybin is that 236 00:23:25,640 --> 00:23:31,340 low doses of psilocybin can be very effective for the psychedelically naive. And then mid-level doses, 237 00:23:31,340 --> 00:23:37,200 after someone achieves what is the right dose for them to do what they want the drug to do, 238 00:23:37,640 --> 00:23:44,080 can be persistent over a fairly long period of time without any tolerance. So again, sort of determining 239 00:23:44,080 --> 00:23:49,360 what is the best for you, we like to always say, start with something that you're most going to be 240 00:23:49,360 --> 00:23:55,180 comfortable with. And for most people, that's psilocybin. Start low with a dose, go slowly 241 00:23:55,180 --> 00:23:59,980 with using that dose and sort of feeling out the parameters on the different circumstances and 242 00:23:59,980 --> 00:24:04,420 situations in which you're tripping and always have someone who's there reliable for you. 243 00:24:05,160 --> 00:24:10,180 And then at that point, when you're comfortable, you ask the question, is that enough? Is that providing 244 00:24:10,180 --> 00:24:15,800 for me that level of psychedilesis, whatever that means to me, cognitive expansion, emotional release, 245 00:24:15,800 --> 00:24:22,540 re-identification? And I'm good with that. If it ain't broke, don't fix it. However, for those 246 00:24:22,540 --> 00:24:26,920 individuals who've had some experience with the psychedelics, what they may find is that there 247 00:24:26,920 --> 00:24:32,700 are certain psychedelics that are literally more viable for them. For example, there are some folks 248 00:24:32,700 --> 00:24:40,780 who will swear by LSD. Yeah, psilocybin works for them, but LSD does what they want it to do. It gets 249 00:24:40,780 --> 00:24:48,000 them to that point of mind expansion. Openness, creativity perhaps also allows some level of 250 00:24:48,000 --> 00:24:53,120 sort of defiliation with the self that allows them to sort of ground their emotionality and gain 251 00:24:53,120 --> 00:24:59,640 reperspectives on things. Psilocybin for them just didn't do it. But again, here too, if one is 252 00:24:59,640 --> 00:25:04,980 psilocybin experience and now one is going to go over to using some other compound, whether it's LSD or 253 00:25:04,980 --> 00:25:12,340 let's talk about DMT in a moment, start low, go slow. Interestingly, when we look at something like 254 00:25:12,340 --> 00:25:18,420 dimethyltryptamine, the potency of the dimethyltryptamine, as well as some of its ancillary 255 00:25:18,420 --> 00:25:25,600 neurochemical effects creates a bit of a more potent experience. It's far more of a transcendental 256 00:25:25,600 --> 00:25:29,740 experience for most people. I mean, you know, colloquially it's been referred to as the God 257 00:25:29,740 --> 00:25:35,220 molecule. And the issue there is that what you're seeing with dimethyltryptamine are three things. 258 00:25:35,360 --> 00:25:41,100 Number one, it binds very quickly and very hard. Number two, it stays bound for a while. 259 00:25:41,840 --> 00:25:47,180 And the fact that it stays bound changes the node network activities of a number of those involved 260 00:25:47,180 --> 00:25:51,980 networks in the brain that utilize serotonin. So what people are getting are sort of compound 261 00:25:51,980 --> 00:25:58,020 experiences in the first person, the phenomenological first person that for them can very, very quickly 262 00:25:58,020 --> 00:26:04,740 take on spiritual transcendent and existential characteristics. So that's a little more 263 00:26:04,740 --> 00:26:11,000 potent. The other issue is that it's pretty rare to find individuals just doing DMT as a standalone. 264 00:26:11,680 --> 00:26:16,720 Most DMT is delivered as part of the ayahuasca preparation. And as you know, there's a whole 265 00:26:16,720 --> 00:26:21,420 ceremony that goes along with the ayahuasca preparation. And indeed, part of that is purgative. 266 00:26:22,040 --> 00:26:27,080 People feel like they want to purge, they want to throw up. And there's a change in individuals, 267 00:26:27,080 --> 00:26:32,880 both physiology as a consequence of multiple ayahuasca inductions, as well as their cognitive 268 00:26:32,880 --> 00:26:37,560 appreciation of what's happened to them. But again, the ritual, the circumstance, and the 269 00:26:37,560 --> 00:26:43,760 engagement of the other activities and preparations in ayahuasca other than DMT are important to that 270 00:26:43,760 --> 00:26:46,180 experience. So you can categorize those three. 271 00:26:46,180 --> 00:26:50,640 If I can jump in here really quickly, just to give a little bit of context for our listeners. 272 00:26:52,160 --> 00:27:02,780 For DMT, there's typically two formats that most folks will encounter. One is a smokable version 273 00:27:02,780 --> 00:27:11,300 of DMT or vaporized version of DMT, which is usually synthesized. There's also another smokable version, 274 00:27:11,300 --> 00:27:19,780 which is called chenga, which is a combination of different DMT containing herbs, plants, and then 275 00:27:19,780 --> 00:27:27,680 also combined with MAOIs, which are monoamine oxidase inhibitors. And so what many folks find is 276 00:27:27,680 --> 00:27:36,500 that if you're vaporizing or inhaling DMT, that duration is very short and very intense because of 277 00:27:36,500 --> 00:27:44,080 the way that your body metabolizes that. But then in combination with an MAOI and then ingested, that 278 00:27:44,080 --> 00:27:51,220 typically then follows the format of more traditional ayahuasca experiences where you have a longer 279 00:27:51,220 --> 00:28:02,880 experience. And so those are very different. And even with LSD, we're typically sharing with folks 280 00:28:02,880 --> 00:28:11,240 that that's a longer experience. You know, you're strapping in for 8, 10, 12, sometimes 16 hours. 281 00:28:11,800 --> 00:28:19,660 Something that you said in an article that I read in the past, possibly mentioned that it's the way 282 00:28:19,660 --> 00:28:28,800 that that specific chemical compound binds to our serotonin receptors and the way that it fits exactly 283 00:28:28,800 --> 00:28:36,220 allows for a longer mechanism of action. And I think it's really interesting what you said between 284 00:28:36,220 --> 00:28:42,320 psilocybin and those other two, because very practically, like not scientifically related is 285 00:28:42,320 --> 00:28:48,280 it's about how you receive the medicine and you receive the compounds. So psilocybin just happens to be 286 00:28:48,280 --> 00:28:58,260 one of those psychedelic medicines that proliferates quite easily in your local area. 287 00:28:58,260 --> 00:29:04,420 And so it's one of the few places where you can get the direct medicine as opposed to LSD, 288 00:29:04,420 --> 00:29:11,920 where maybe it's in a vial, maybe it's sprayed onto blotter paper with DMT, also hard to gauge dosage. 289 00:29:12,060 --> 00:29:18,620 And so I'm just sensing that there's both the neurological functioning that you're talking about 290 00:29:18,620 --> 00:29:26,340 here, then also in practicality on how you receive it and your dosage and how you're intaking these 291 00:29:26,340 --> 00:29:27,540 medicines as well. 292 00:29:27,560 --> 00:29:31,620 They're one and the same. So if we take a look at any drug, any substance, there are really two 293 00:29:31,620 --> 00:29:34,400 things we have to consider when we're looking at how the way it's going to work at the body. Number 294 00:29:34,400 --> 00:29:38,860 one, it's called, it's pharmacokinetics. How does it get around to where it's got to go? 295 00:29:39,420 --> 00:29:43,160 So if you're smoking something, you're rapidly taking in through the mucous membranes and 296 00:29:43,160 --> 00:29:48,800 characteristically getting very rapid penetration into the circulation, circulatory system that 297 00:29:48,800 --> 00:29:54,160 delivers it directly to the brain very quickly. Very often what you're going to then get is very 298 00:29:54,160 --> 00:29:59,120 strong, we call a pharmacodynamic effect. It gets where it's got to go. It hits its target keys, 299 00:29:59,300 --> 00:30:05,020 so to speak. Key goes in lock, turns that lock. But what you're seeing is very often the dosing of 300 00:30:05,020 --> 00:30:10,940 the way you would take that in is relatively short. And it comes, you're not really huffing on this and 301 00:30:10,940 --> 00:30:15,040 huffing on this. So what you're getting is a rapid dose very, very quickly into where it's got to 302 00:30:15,040 --> 00:30:19,140 go. You get a spike effect and characteristically you're going to come down as that then wears off 303 00:30:19,140 --> 00:30:23,740 pharmacologically. In other words, it dissociates with its, if you will, that key comes out of the lock, 304 00:30:24,160 --> 00:30:30,580 things fall back to normal. Once you start to ingest something, what happens then is now it 305 00:30:30,580 --> 00:30:34,500 takes a little bit longer to get where it has to go. But characteristically, you're going to be 306 00:30:34,500 --> 00:30:39,200 absorbing it over a longer period of time as it goes to that area of your GI tract that absorbs it. 307 00:30:39,740 --> 00:30:44,100 And then once it gets into that compartment, you're getting it not only initially, but you're getting 308 00:30:44,100 --> 00:30:49,480 it throughout this full time period of its absorption, its distribution, and its use. That's 309 00:30:49,480 --> 00:30:53,560 going to last longer. This is what happens with things like LSD or if you take things by mouth, 310 00:30:53,560 --> 00:30:58,720 like DMT by mouth. The other issue is in the preparations of DMT that do include a monoamine 311 00:30:58,720 --> 00:31:04,000 oxidase inhibitor, what you're getting is a double whammy. So now what you're doing is you're 312 00:31:04,000 --> 00:31:11,140 breaking down one of the principal enzymes that is necessary to break down the principal chemical 313 00:31:11,140 --> 00:31:17,440 through which the drug works. So you're elongating the effect of the chemical because you're making 314 00:31:17,440 --> 00:31:24,500 more serotonin available in the synapse. You're also making more dopamine and norepinephrine 315 00:31:24,500 --> 00:31:30,100 available, which then downstream augment this effect. Now, there are some caveats that go along 316 00:31:30,100 --> 00:31:34,480 with that. I mean, obviously, one of the things you see with the monoamine oxidase inhibitors is those 317 00:31:34,480 --> 00:31:40,380 drugs have also been used psychotherapeutically. And one of the risks of using monoamine oxidase 318 00:31:40,380 --> 00:31:45,800 inhibitors is that it works not only on the brain's monoamine oxidase, but also on monoamine oxidase 319 00:31:45,800 --> 00:31:51,500 wherever it's found in the body. And this can lead to a whole bunch of problems with blood pressure, 320 00:31:51,900 --> 00:31:58,700 the possibility of cardiac and cardiovascular effects. It might be pretty robust and burdensome. 321 00:31:58,940 --> 00:32:03,860 And you're also looking for interactive effects. So we know some individuals, for example, are very 322 00:32:03,860 --> 00:32:08,840 sensitive to monoamines when they're taken, monoamine oxidase inhibitors, when they're taken 323 00:32:08,840 --> 00:32:15,280 with cheese products, pickled foods, dried meats, pickled meats, smoked meats. 324 00:32:15,440 --> 00:32:17,260 Yeah, the presence of tyramine, I believe. 325 00:32:17,660 --> 00:32:18,000 I'm sorry? 326 00:32:18,280 --> 00:32:20,260 The presence of tyramine, I believe. 327 00:32:20,360 --> 00:32:23,340 Correct. Correct. So that's what it's called is a tyramine, 328 00:32:23,480 --> 00:32:28,360 characteristically a hypertensive crisis, because what then happens is your body metabolizes tyramine 329 00:32:28,360 --> 00:32:35,760 the way it would perhaps other forms of viable precursors. And those precursors then feed into 330 00:32:35,760 --> 00:32:40,440 that system and blow your neurochemistry. So we have to be somewhat cautious with that. 331 00:32:41,080 --> 00:32:48,400 One of the interesting parts of LSD is, as you mentioned, LSD fits into that lock very tightly. 332 00:32:48,880 --> 00:32:55,000 And once it's in there, it hangs out. So what we see is that it's not only rapid binding to serotonin 333 00:32:55,000 --> 00:33:02,320 receptors, but it's rapid tight binding to those receptors that turns that lock, opens that lock, 334 00:33:02,320 --> 00:33:06,880 and then stays in there for a while. So that's going to be a fairly elongated trip, as you say, 335 00:33:06,940 --> 00:33:14,240 which can last anywhere from eight to 20, 25, 30 hours, depending both on dose and susceptibility 336 00:33:14,240 --> 00:33:14,880 of the individual. 337 00:33:15,520 --> 00:33:17,100 I've approached those hours before. 338 00:33:17,480 --> 00:33:26,500 Same, same. That's the reason where candidly, we give like a warning label associated with folks 339 00:33:26,500 --> 00:33:31,700 who are seeking LSD experiences. It's like, this can be a really powerful experience. Don't get me 340 00:33:31,700 --> 00:33:36,360 wrong. I've had my fair share personally. But there's a lot of times where you get to hour 341 00:33:36,360 --> 00:33:43,420 eight, hour 10, hour 12, and you're like, ready for it to be done. And there is no off button. And 342 00:33:43,420 --> 00:33:50,240 it's so person and dose and situation dependent. And that's one of the challenges I think with LSD 343 00:33:50,240 --> 00:33:55,080 that not many people talk about is, when you have a tab or a piece of blotter paper, gel tab, 344 00:33:55,140 --> 00:33:59,900 whatever it is, you don't know the density with which that was laid. And so you can test to make 345 00:33:59,900 --> 00:34:05,180 sure that it's LSD, but determining dosage is actually really, really challenging. 346 00:34:06,000 --> 00:34:09,640 And there's a number of factors. I mean, how you're taking it in, are you taking it sublingually 347 00:34:09,640 --> 00:34:14,080 or actually swallowing it? How much is actually there? Do you know what you're getting? And then 348 00:34:14,080 --> 00:34:18,420 it's also very, what we call ecologically dependent. What's going on in your body that's 349 00:34:18,420 --> 00:34:22,440 going to predispose the way that drug is distributed and bound. And then what's going on 350 00:34:22,440 --> 00:34:26,540 in the actual environment, the trip environment. And so what a number of people find is, yeah, 351 00:34:26,540 --> 00:34:31,120 they get to like hour eight or nine and think, this is good. I'm coming down only to then get 352 00:34:31,120 --> 00:34:36,900 a re-trip occurrence around hour 12 or hour 13, not necessarily as a flashback, because what's 353 00:34:36,900 --> 00:34:41,300 happening is the kinetics or the dynamics of the drug are altered in that person. So you 354 00:34:41,300 --> 00:34:44,960 essentially get a rebound effect, which can then be problematic for some folks. 355 00:34:45,500 --> 00:34:46,980 That key is still in that lock. 356 00:34:47,500 --> 00:34:50,640 Yeah. In other words, they think they're down, but- 357 00:34:50,640 --> 00:34:55,760 Well, and often that's worse. Often that's worse is thinking you're done and then finding out you're 358 00:34:55,760 --> 00:35:00,800 not because you've like crossed the finish line in your mind, only you're not actually there. 359 00:35:00,800 --> 00:35:06,260 Yeah. I love this by the way, because one of the nicknames that I have for our podcast is the 360 00:35:06,260 --> 00:35:12,780 It Depends podcast. And what I'm hearing is that not only is there the, what you call the 361 00:35:12,780 --> 00:35:20,240 pharmacokinetics and the pharmacodynamics around these medicines and substances, their mechanism of 362 00:35:20,240 --> 00:35:26,940 action, but then it's also your own physiology, your own body chemistry, your own neurochemistry. 363 00:35:27,440 --> 00:35:35,320 And so it depends. And so one of the takeaways that I hear from you is you got to know how the 364 00:35:35,320 --> 00:35:43,680 locks and doors in your own system somewhat operate. And, and, and it seems like one of the 365 00:35:43,680 --> 00:35:52,800 really only viable ways to do that is this low and slow experimenting, testing at low dosages, 366 00:35:52,800 --> 00:35:57,500 just to get some parameters on how these medicines work with your body. 367 00:35:57,840 --> 00:36:01,640 I mean, so a couple of adages that I think go a long way, and I'll give you actually three. 368 00:36:02,440 --> 00:36:06,560 First is the saying we throw around frequently in the brain sciences, which is see one brain, 369 00:36:07,140 --> 00:36:11,980 see one brain. Brains have a lot of things structurally in common, but as I said earlier, 370 00:36:11,980 --> 00:36:16,640 the devils and the deities lie in the details. If we think about the fact that brain cells that 371 00:36:16,640 --> 00:36:23,100 fire together tend to wire together, and I'm being metaphorical, what happens is that individuals 372 00:36:23,100 --> 00:36:28,060 develop node and network patterns that are just that they're individual. And of course, 373 00:36:28,160 --> 00:36:34,040 although the generalized function is going to be pretty much ubiquitous and universal, it's the 374 00:36:34,040 --> 00:36:38,320 specifics. And those are specifics that are very susceptible to these types of drugs, right? 375 00:36:38,320 --> 00:36:43,940 Point number one. Point number two, I mean, it's the oldest adage of wisdom from antiquity. 376 00:36:44,320 --> 00:36:49,600 Know thyself and know thy limits. I mean, it was the inscription on the pillars of Delphi. 377 00:36:50,280 --> 00:36:54,720 Know thyself. What are you looking to do with these drugs? Know your limits. Have you taken them 378 00:36:54,720 --> 00:36:59,080 before? What effects have you had before? Have you not taken them before? And given that, 379 00:36:59,360 --> 00:37:04,080 what are your limits in terms of experience and what things might you need to have on board 380 00:37:04,080 --> 00:37:10,500 to stay safe environmentally, a friend, a tripping buddy, so to speak, as well as a safe spot, 381 00:37:10,620 --> 00:37:15,740 a safe spot that for you is environmentally secure, but that also has the necessary resources 382 00:37:15,740 --> 00:37:21,160 if in fact you feel, I need medical help here. And the third, and I think this is most important, 383 00:37:21,700 --> 00:37:26,000 and we're talking about start low and go slow, correct? And this brings us into sort of what 384 00:37:26,000 --> 00:37:31,180 sometimes we call a research dilemma called the Collingridge dilemma. In other words, you sometimes 385 00:37:31,180 --> 00:37:38,440 won't know unless you go, but you have to be prepared to take the trip. So the best way to be 386 00:37:38,440 --> 00:37:43,040 prepared is to gain as much information as you possibly can. Again, the beauty of podcasts like 387 00:37:43,040 --> 00:37:47,200 yours is that it not only provides that information in general, but it also provides a resource to the 388 00:37:47,200 --> 00:37:52,600 listener to be guided or at least to be mentored to some extent, but also understanding the literature. 389 00:37:53,060 --> 00:37:58,380 And again, your podcast is a good resource for that, but know yourself. What have been your 390 00:37:58,380 --> 00:38:03,200 experiences, not only with psychedelic drugs, but with other drugs? What have your experiences been 391 00:38:03,200 --> 00:38:08,980 with alcohol? Are you using other substances at this time? Prescription drugs, illicit drugs, 392 00:38:09,380 --> 00:38:14,960 alcohol? Do you have medical conditions that might in some way be affected by the mechanism or process 393 00:38:14,960 --> 00:38:22,700 of these drugs? So again, knowing thyself and knowing thy limits is the best stance of preparation 394 00:38:22,700 --> 00:38:27,300 to then engage, start low and go slow because you won't know unless you go. 395 00:38:28,700 --> 00:38:36,200 So this has been a really, really engaging and interesting topic of conversation, I think, for this 396 00:38:36,200 --> 00:38:44,680 episode. And I can already tell that we have a lot more that we want to discuss and dive into with Dr. Giordano. 397 00:38:44,680 --> 00:38:52,940 And so this might be a good time for us to pause this part of the dialogue. And then we'll continue 398 00:38:52,940 --> 00:39:00,700 on with an episode two, a part two, let's say, of this dialogue so that we can dive deeper into not 399 00:39:00,700 --> 00:39:06,260 only the mind of Dr. Giordano, but the mind of all, you know, psychedelic curious folks. So that'll wrap 400 00:39:06,260 --> 00:39:13,640 it up for part one of our episode with Dr. Giordano. Thank you for listening to this portion of the 401 00:39:13,640 --> 00:39:19,460 episode. You can download episodes of the Psychedelic Passage podcast anywhere you find your 402 00:39:19,460 --> 00:39:26,820 podcast, whether that's Apple Music, Amazon, Spotify, iHeartRadio. If you like the show, please give us a 403 00:39:26,820 --> 00:39:34,240 rating or review. We're always open to feedback and comments from our community so that we can continue 404 00:39:34,240 --> 00:39:39,140 to provide this thought provoking dialogue. So thanks for joining us this week.