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The Ethics of Psychedelic Medicine ft. Neuroscientist Dr. Giordano

“The Ethics of Psychedelic Medicine ft. Neuroscientist Dr. Giordano” explores a conversation on ethical programs regarding the brain and psychedelics. Our hosts analyze the precision of personalized medicine and how it is being applied to intentional psychedelic use.

Giordano stresses the importance of aligning expectations and knowing oneself before experimenting with psychedelic substances. Jimmy Nguyen and Nicholas Levich discuss how MDMA and ketamine differ from classic psychedelics and their potential effects. 

What privacy and security-related concerns arise with the need for increased precision in medicine? What responsibilities does the individual undertake as a result of personalizing their medication regime?

Later, our hosts touch on the potential role of genomic markers in determining an individual’s response to psychedelic medicine. Is the intentional ceremonial model equipped to support individuals with biomedical conditions seeking to use psychedelic medicine?

Episode 38: The Ethics of Psychedelic Medicine ft. Neuroscientist Dr. Giordano

Jimmy: Welcome to the Psychedelic Passage podcast. My name is Jimmy Nguyen. I am joined here by my co-host and best friend, Nick Levich. 

Last week we had a really engaging conversation with Dr. Giordano who is a neuroscientist and a professor at Georgetown University. He is involved in ethical programs around a lot of different areas of study regarding the brain and a former veteran with the United States Marines. 

We got into such an engaging conversation that we realized that it was going to span two episodes and so we wanted to give you a little bit of a summary or a breakdown of our conversation so far, and then segue that into Part 2 of our conversation. Nick, what were your biggest takeaways or thoughts from that first half of the conversation with Dr. Giordano?

Nick: I think one of the main things that he made very clear to me is that it’s very important that we as journeyers or psychedelic curious folks, align our expectations of what we’re seeking, this medicine or this drug to do with what the potential outcomes or effects are of each substance.

It’s basically the acknowledgment of like, “Okay, well, I’m looking for this particular effect which medicines, if any, have the possibility of providing that effect.” Even if they do have the possibility, we have to sign ourselves up for the full range. 

And so, we have to have a willingness to go all the way in, so to speak, with a new medicine because we simply don’t know how our unique body chemistry will respond. That kind of creates this interesting environment where we as a journeyer have to do our best to choose what’s best for us, knowing that there’s still not this 100% certainty in how we’re going to respond.

Jimmy: Aligning of expectations, stepping into the unknown, having that courage to be able to do so– [crosstalk] 

Nick: And [crosstalk] the base-level research and education of what’s what? Like what does MDMA do versus what does psilocybin do?

Jimmy: Yeah. I love it when our world in the ceremonial space kind of lines up with the scientific world. And so I really appreciated that from our conversation with Dr. Giordano. Without further ado, we’ll jump into Part 2 of our conversation and dialogue with Dr. Giordano.

Nick: It’s funny because we have some people that reach out to us and will say things like, “Hey, I know that I’m really sensitive to drugs and alcohol or I know that when I go under for anesthesia, I need a very little bit and I’m gone.”

To your point of knowing thyself, we do have these very interesting barometers as we go through life and try inputting different substances into our system, we start to get a roadmap of how we respond. 

I’m notoriously sensitive and so for me like– I can have a full-blown journey on two grams of mushrooms and for some people, they’re totally lucid and just getting warmed up at that amount.

Jimmy: I’m usually about triple the dosage that–


Jimmy: So, we end up having a lot of efficiency in our co-sharing of dosage there.

Giordano: But, let’s face it, I mean, this is not anathema to what you see with other things. If you ever spent an evening at a bar, a cocktail lounge, or other couple of people after a single drink, wow, they’re like a 16-year-old schoolgirl who’s never tasted alcohol, or a 16-year-old schoolboy who’s never tasted alcohol. No genderism implied. 

There are other people who, quite frankly, they’re four, five, six down and they’re just racking and stacking. They’re good to go. There are a lot of things inclusive as a set of experience, which can build pharmacological tolerance in some cases. 

All of these things figure into this quasi-calculus realistically, very often, as we say, the best person to be able to estimate and navigate that: yourself.

Jimmy: Yeah. I talk about the “know thyself,” as far as, like, emotional content, usually about knowing what may come up or what things may be buried deep within your psyche. But I really appreciate this physiological lens of knowing thyself as well. 

We’re approaching our time here with our episode. I want to make sure that we cover a couple of important things. We may not be able to go as in-depth as I know you want to, but I know that you had a comment about potentially MDMA and ketamine. Do you have maybe just some quick important things to share with our listeners about those two?

MDMA & Ketamine: Managing Expectations

Giordano: Absolutely. MDMA is a slightly different drug. There are those who really would not classify that drug as a true psychedelic, although I think there is some mind-opening to it. I mean it’s very often referred to as an affiliate. 

Even as you know, the general experience when one does MDMA is just that. There’s a very strong sense of affiliation. We see that because of the actual mechanism of the drug. Very often people will feel loving and amorous. But what happens is a lot of that connectivity is very strongly vested within what people already feel is their in group. 

So, for some individuals, yeah, they may feel very strongly and very amorous and very loving and very bonded to individuals that they may like or think they like or feel that they like. But they may also get certain feelings of sort of separatism and maybe even paranoia where people who just rub them the wrong way.

I think that’s one of those things that is not well explained because, again, the colloquial word on the street is, you drop ecstasy and that’s what you get. You get this ecstatic experience and that’s true, but everything carries a bit of a price. 

The other issue is that MDMA effects characteristically are very, very dose-dependent, but they’re kind of short-lived so what you tend to find is that people will multiple stack their eggs over a period of a night. 

They’re out, they’re jamming, they’re in a club, they’re in a rage, whatever, that’s fine. But what ends up happening there is the more you take, the MDMA, the more you take and or the more frequently you take it, the greater the potential for the MDMA crash. 

And the MDMA crash can be profound and you have to be ready for that. Again, very dose-related, both in terms of the actual amount and the frequency of taking the drug over a period of time. Now let’s shift over to ketamine, completely different animal. 

Ketamine is a dissociative. What can happen at even moderate doses of the drug is that you get a complete experiential dissociation because what it does is scatter the node network activities of the brain based upon its neurochemical action. 

And individuals literally feel completely disconnected. For some individuals, they go into a place that is so disconnected, that is so isolated, that is so perceptually sparse, that’s what’s called a k-hole, or a black hole for them.

Some individuals find that to be a positive experience because it’s purgative, it allows them to get in touch with themselves, it’s very isolating and as a consequence, they come out of the other way feeling reconstituted. But it can also be terribly frightening. 

With ketamine, probably as much as with DMT or with LSD, it’s very, very important to understand the selectivity of the agent. And it’s also very important to understand what the agent could do, because it is almost impossible beforehand to determine what type of trip the individual will have on ketamine. 

And what their first person’s subjective experience of that trip will be relative to things like positivity or negativity. Their experiences of the ketamine trip itself, the induction of the k-hole effect. So here too for ketamine, very, very important. Start low, go slow, and have a safety mechanism on board.

Jimmy: Interesting. The same mechanisms for ketamine, but the way that an individual might experience that subjectively may dictate the context around it. For myself, it took me a lot of just testing and almost internal training to realize that k-holes can actually be quite comforting and therapeutic. But the first kind of incidental k-holes that I found myself in were really scary. 

I really hear that in what you’re sharing. Nick and I are always proponents of preparation and integration and hands-on support emotionally during ketamine experiences, which I think is just so overlooked in that subset of psychedelics. 

I have to know, what causes that MDMA crash? Like from a neurological or neuroscience standpoint. I’m just so curious because this is something that we find folks with. But I’m just so curious, from your lens, what causes that?

Giordano: Sort of three things that are interactive. We know that MDMA interacts very strongly, once again with the brain’s serotonin system. One of the things that it does is it causes a very, very robust release of that chemical from a nerve, that can then work within those pathways. Well, a single dose of MDMA is going to cause a rather robust release. 

But you can imagine that if you increase the dose, in other words, the actual quantity per dosing, or you more frequently take the drug, in other words, repeated dosing, you’re getting that whammy effect over and over and over again. 

There is a relative depletion of your brain’s ability to actually make that chemical. I mean, there’s a metabolic pathway that’s involved, what you sort of do is you kind of run out, so to speak. You have to make some more. 

But at the same time, what you’re doing is the postsynaptic effect and the overall effect of the MDMA when you’re doing this is very energizing. You’re literally utilizing energy stores in the brain.

The third is that very often what you tend to find is that individuals who are doing MDMA also are doing MDMA and they’re engaging in those activities that whatever they’ll be doing, interacting with others or rage, whatever, it’s fine. 

They’ll be a little neglectful of other what I’ll call physiological hygienic and or metabolic needs and they become very dehydrated. What will tend to happen is those three things taken together, literally a reduction in your brain’s serotonin and availability. Your brain has to essentially remake that almost from scratch and that takes some time.

Number two, the fact that you’ve used a lot of those energy molecules and you have to reboot to literally re-substantiate the chemistry of energetics in the brain and that’s going to make you fatigued when that’s gone. 

And third, you’re dehydrated. We’re talking about a nosedive, and of course, that can last anywhere from a few hours to an individual who may be susceptible to forms of psychiatric conditions like anxiety, dysthymia, or depression. It can be far more durable.

Nick: I mean, I know it for myself, I have definitely overdone it with MDMA in my younger years and have crashed hard to the point where, like, for a week after, I was basically just in a deep depression and not very functional. 

And I came out of it, but I was ruined for a good 7 to 10 days after that. I was like, “Okay, that’s my limit. Now I know what this looks and feels like if I overdo it.” For those who are listening, that’s what happens when you don’t use a scale and measure your dose and you’re in a more, what I’ll call like, club environment where there’s no way to monitor that.

Jimmy: [crosstalk] -or just a recreational setting.

Nick: Right.

Giordano: Yeah, here too. For the person who let’s say raving and raging, the two R’s of MDMA use, which is what you usually see socially. They’re at the rave and they’re raging with this. “This is great, I’m feeling good.” 

What we find is when you take MDMA, single dosing, it gets in there pretty quickly, does what it’s got to do, and then you begin to come down off of that. And you begin to feel “normal again.”

Well, let’s face it, whenever you’re taking the MDMA and you want to preserve that along the length of that social experience, very often people will drop another hit, and maybe another hit or what they’re doing, Nick, is exactly what you’ve said. 

They’re not quite certain as to what they’re actually getting per hit. And as a consequence, what they’re looking to do is get the most bang for their buck, which is then take more per unit hit.

Both of those experiences, both of those events, are going to result in some kind of super dosing, which is then going to cause those effects, the serotonergic depletion, the energetic depletion, the dehydration, and you crash. And you crash hard.

Nick: Hard, really hard.

Jimmy: Yeah. I find that with MDMA and ketamine both being what I call like short-acting drugs. Typically, those have a come up, a peak, and a comedown. What I hear you saying about the redosing, especially in recreational environments around MDMA and ketamine, is you’re trying to achieve this plateauing effect by intervals of redosing.

When you look at the standard dosage of MDMA, probably being around 120 milligrams there, then 80 to 100, though that obviously ranges, as we’ve talked about, depending on physiology and depending on setting in context-

Then when you’re out in an environment where, let’s say, you’re ingesting another pill, or you are ingesting another portion of powder, then it’s unknown what your dosage is. In the name of what you are sharing about the going low and slow, I want to provide somewhat of a public service announcement to folks, that low and slow only matters if you can document it. 

Like if you go low and slow with MDMA or ketamine, but you’re not in an environment where you can track that second, maybe third dose, or maybe you just do your initial dose, and let it run its course, then it doesn’t actually help [laughs] there.

As we approach the end of our conversation, I want to make sure that we have space for each of you to be able to cover everything that you wanted to cover on this episode. So, Nick, do you have other questions for Dr. Giordano while we have his time that are burning or at the surface for you that you want to cover here?

The Challenges of Standardizing Psychedelic Effects

Nick: Well, I’ll share my takeaway and then my question. My takeaway from this discussion is that what you’re describing, Dr. Giordano, is that we have to align our expectations, what we’re hoping this drug, this substance, this medicine will do with what the possible effects of that substance are. 

And we have to be willing to get some of those perhaps unwanted side effects along the way, knowing that we have a very individualistic way of responding to these medicines that may have themes or trends.

My question is, in regards to– you’re talking about kind of this trend of personalizing medicine, can we give you the one thing that you need for your genome and your particular brain chemistry that will give you the effect that you want? 

How close are we to that with something like psilocybin? Because from my perspective, I have seen the same dose and setting of psilocybin go in wildly different trajectories based on the journeyer. And so, for me, the biggest variable is always the journeyer. 

What I’m curious about from your perspective, is there a world where we can standardize these effects. So, that regardless of your brain chemistry or your particular genome that you get the same effects as the person next to you?

Giordano: You’re invoking my radio voice, where I have to go “where psychedelics are illegal”. [Nick laughs] I think that ideally, what you’d want to see is that the trajectory of biomedical science aligns with its capability in any and all of its settings of application. 

So, if what we’re talking about is increased precision in medicine, well, that’s a very, very good thing. But wait, there’s more. Here too, I think there’s a caveat. What does that precision mean? How do you get it? Well, I’ll tell you how you get it. 

You get it through data, which means that the more we know about each other, the more I know about you, the way even more you know about you through various tests, and that information is available not only to you. Well, that information is also pretty labile and very liable, and you have to worry about who gets that information. 

We have to then ask the question, are our civic institutions ready to be able to support and protect the security that’s needed to get that level of personalized medicine? And that’s just in the four walls of the clinic. 

Once we let this out, and we put responsibility into the hand of the journey person, the user, now they become their own gatekeeper with responsibility for what it is they’re getting, how it is they’re taking it, what they know about themselves and who else knows about them.

Now what we see is some of the parameters of security and safety and control rest on the individual shoulders, which is a very, very different set of obligations. So, yeah, I think that technology would certainly capabilize clinical settings of use, of psilocybin, LSD, DMT, certainly MDMA. We’re already seeing that. I mean, as you know I work with a number of military and veteran personnel. 

And the utility of some of these drugs and treating individuals who had resistant PTSD, depression, etc. Has in some cases been absolutely astounding. But that’s within the four walls of the clinic and even there we’re bounded by, constrained as well as capabilized, by the tools we have at our disposal.

Once it comes out of the clinic. And now we’re moving into a broader set of populations with, again individualized use. In some ways that’s for lifestyle enhancement and in other ways that may be, what they consider to be therapeutic. All bets are off. 

The caveat goes along here, is if you are thinking of using these psychedelic drugs for what would be an identified therapeutic purpose, you’re depressed, you have post-traumatic stress disorder, your debilitating anxiety disorder, or other issues that you feel are sort of neurocognitive, psychological.

My suggestion would be to seek clinical intervention and do not try to self-medicate it with these molecules because you do have an existing biomedical condition-And the way your brain responds to these might be quite, quite different than someone who doesn’t. This is a case where not only guidance but direct clinical supervision is absolutely necessary.

Jimmy: Yeah, absolutely. I share with folks that the clinical medical model will really apply and help a lot of folks. In parallel, a private-use, intentional ceremonial model, will help and support a lot of folks and there’s somewhat of an overlap. 

I think a lot of the conversation in psychedelia today is like one or the other. But there’s a contextual component to this. The other thing that I hear you saying, I actually find it really fascinating that two things come up for me. 

One is the mechanism of action of these psychedelic compounds, but the other is as we’ve been chatting about your own physiology and your own makeup. I’d be curious to see if there is some type of genomic marker or some type of a trend in neurochemistry that may indicate certain things with other folks. 

I also just want to quickly just take a moment to just express– I love it when science– I guess maybe the more woo-woo parts of psychedelics come together, because what you’re describing as far as my takeaway with what you just said around the scientific component is-

“Okay, we may have the tools, we may have the technology, we may have the capability, but it really depends on what you do with that and the ethics and the care around that that actually impact people’s experiences.”

I can’t help but think that is so in line with a lot of ceremonial and indigenous approaches to this, because there are many people who learn from hundreds of thousands of years that these are tools and technologies-

And the context in which you use them and how you use them actually dictate and indicate the types of experiences that you have, the meaningfulness of those experiences, the significance of those experiences. And so, I just think it’s a wonderful parallel that you’re describing that.

Parallels in Clinical & Ceremonial Psychedelic Therapy

Giordano: Let me speak to that if I could because you raised a very interesting point about the intersection, the interdigitation between the medical model and then I’ll call the ceremonial ritualistic model. 

I think more and more in medicine, we’re recognizing that intersection can be very, very important. There are groups and organizations, and I can tell you one, it’s a non-subsidized plug, if you will. 

There’s a group called Veterans of War, and they cater to individuals who’ve had treatment-resistant depression PTSD, who may be seeking the psychedelic experience for both of those particular venues. 

Certainly, something that is clinically supervised, but also a clinically mentored experience of the whole ritualistic and shamanistic engagement, which includes literally a trip, and not just a drug-induced trip. But a trip, a journey, a voyage to be able to experience the richness of that in a highly supervised, very, very safe and secure, not only model but milieu and framework. 

For those of your listeners who may be veterans, who are having these issues and may be seeking this type of therapeutic, I strongly recommend that, again, and not as any sort of a paid endorsement at all. But because, realistically, it does represent the potential venue by which these individuals can vector into the care that they may need.

Jimmy: Yeah. I love that. We are all about providing tangible resources to folks. In that regard, I’ll also point out Veterans Exploring Treatment Solutions so that’s

And probably Nick and I’s favorite organization is the Heroic Hearts Project held up by Jesse Gould, who– they have this experiential component to it, but they’re also participating in a lot of study and research with organizations around data and things like that. So, I think it’s really amazing. 

Dr. Giordano, I want to give you some space as well. Are there any things that are important to this dialogue that you want to bring forth to our listeners or anything that you have this burning desire or calling to share while we’re in this conversation?

Giordano: A couple of things really. We’ve hit on so many good things. The conversation has been so rich, and I’ve been really very grateful that you guys have asked these great questions for me and it’s been fun. 

To reiterate just a few points that I think are really good bottom line up front and really good bookends on the back end. Number one, know yourself, know your limits. Start low and go slow, if this is something you wish to experience. 

Again, if what you’re looking to do is to seek using these compounds for therapeutic reasons, then realistically, the medical model is the model to engage and it becomes important to seek those resources that provide that level of clinical supervision, guidance, security, and safety.

In other words, don’t do this yourself. If there’s an underlying medical problem that requires the use of these for therapeutic purposes, use that experiential engagement within the clinic, what it’s intended to do.

Jimmy: Yeah. Thanks for sharing that. What comes up for me is the empowerment of the journeyer or the psychedelic curious person to know that they have a say in their process, in their experience. 

I know that there’s a lot of folks out there who feel like, “Man, I’m at my brink, I’m at my edge. I don’t know if I can wait a few years for, let’s say, a clinical medical model to come up.” What I hear you saying is maybe positing this question of what’s more important, an experience now that has maybe percent chance of helping you get to your intentions-

Or maybe down the road, there is a program or a psychedelic compound or a psychedelic medicine that like you said, has that precision, that exact fit into what you need. We’re starting to see that with psilocybin analogs like 4-AcO-DMT and different tryptamine derivatives and super LSD, and all of these things. Thank you so much for joining us here.

Giordano: Pleasure. Thank you.

Jimmy: It’s been a really, really eye-opening. Interesting. I like nerding out on anything psychedelic as well and I’m just really grateful that we were able to weave in, I think, a lot of the different components in the psychedelic space-

And speak about it from a neuroscience lens, from a practical lens, from a culture and community lens. So, I really appreciate that. So, thank you, Dr. Giordano. Where can people follow your work and find you? I know that you’re pretty regular on news articles and podcasts and things like that, but where can folks find more of you?

Giordano: If they’d like to reach me, they can reach me directly by my Georgetown website. They can reach me at james.giordano. G-I-O-R-D as in delta, A, N as in November, O 

And just put in the subject line, “psychedelics” so we’ll know that it’s referential to this podcast. Again, I’ll get back to them as soon as I possibly can. I can’t promise that I’ll get back to them that day or depending on what the week is, but I certainly will make every effort to get back in touch with them.

If what they’re looking for are those resources, again, I’m going to be a bit of a hard a** about this if I may. If there are individuals who actually have an existing medical psychiatric issue that they truly believe has been completely nonresponsive to other forms of therapies-

And psychedelic therapy is what they’re seeking, my real strong recommendation, and I would go one step further, my urging here, my prompt, is to seek clinical attention. It may very well be that working together, sir, you and I and Nick, can actually help to have these people find what they need that’s out there.

Because there are those programs for those individuals that provide that level of clinical supervision, and will provide that level of clinical oversight in the administration of these compounds for therapeutic means.

Jimmy: Yeah, thank you. Listen, to the man. Get the care that you need that is specific for you, not just who’s first available and who’s around. [chuckles] So, thank you for that. 

That wraps up this episode. You can download episodes of the Psychedelic Passage podcast by looking for our podcasts anywhere that you get podcasts, Apple Podcast, Amazon, Spotify, IHeartRadio. If you like the show, please rate and review us. 

We are always open and welcome to feedback, comments, ideas, just to allow us to continue to provide engaging, informational, relevant, actionable content for our listeners. So, thanks again to Dr. Giordano and we will see you all next week.

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