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Okay. So again, I'm gonna go ahead and get started.

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So welcome everyone. We have a wonderful train today with Doctor presentation for a psychedelic assistant psycho therapy before we get started.

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Evaluations and certificates of attendance will be emailed to you within 5 business days following this training. And now, to get things started, I'll go ahead and pass things off to Dr. Nyak.

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Okay, thank you so much. Nyla, and thank you to the raw center for inviting me.

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And very pleased to always happy to talk about this topic, especially to people who treat patients.

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I will share my screen.

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Is that working? Okay? Are you seeing the the slides? Okay?

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Yes, we could see it's a lie!

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Yeah.

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So, yeah, I am a psychiatrist, and I work at the Johns Hopkins Center for Psychedelic research.

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I do clinical work, but majority of what I do is clinical research on psychedelics for various psychiatric conditions.

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And let me.

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We've covered this.

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And covered this so let's just dive into what are we gonna be talking about today?

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So like it, Alex, are obviously this hot button exciting new topic.

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That is being researched for clinical use. However, there's a very broad and wide, a deep history of psychedelics for other uses, as well.

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So we're gonna start by taking about 30 min to cover the back background.

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The history and different models of psychedelic use prior to even getting into what are we trying to do with it now?

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Clinically, simply because on like other psychiatric or it's like a therapeutic treatment.

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There is this whole big other context. This is a long webinar and kind of between each of these sections.

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There's time to pause and talk about about 20 min of questions disperse throughout, not including some time.

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At the end, so I will also try to monitor the thing during.

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And if people have questions that are while I'm talking and I can weave it in, I will.

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But otherwise, between each of these sections will have some time to discuss.

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Then I'll get into what is the actual clinical trial evidence of various psychedelics for therapeutic purposes.

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And we're gonna focus on depression tobacco smoking and tell you of care.

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There are, of course, others, but these are some of the most compelling use cases where we have good evidence that I'd like to show.

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And I'm gonna cover kind of most of what's there.

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Then we'll set that up 40 min. Then we'll talk through.

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You know, how is this actually delivered? What is actually done in psychedelic?

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Therapy. And I wanna remind us that this is a experimental treatment that is not approved.

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It is purely expensiveal at this point, and I'm gonna be describing essentially, what is research?

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So how is it used in terms of the delivery of the psychedelic therapy?

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Take about 20 min for that then I'm gonna introduce this idea that like a delic therapy, is psychotherapy.

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And we'll talk through some justification for why, I feel that way, and we'll also just talk about cases.

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Couple of cases that I think devinstrate. What actually happens to patients.

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What does this look like? And finally, we'll get into clinical issues, future studies, just the future in general.

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And well, we can move on and dive right in. I'm sorry this is.

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Okay, so in this section, we are going to be talking about the background, the history different ways that it's used.

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So first off, what is a cyedelic talk about the history I keep using this phrase models of use.

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So I will explain that it will be clearer.

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Classic psychedelics are drugs that are found from a very wide variety of natural and synthetic sources all over the world, and they all act on the serotonin.

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Twoa. Receptor. So here's an example. We have psilocybin mushrooms, and this is found in like 200 species of mushroom.

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Pretty much all over the world, anywhere they have been looked for.

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They have basically been found. Lsd or Acid, which is, of course, famous.

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This is synthetic, but ultimately fungally derived mescaline, which is found in Peyote San Pedro cacti.

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This doesn't really get talked about a lot, but it's a like a dalek that has been used for thousands of years in South America, and there's Dmt.

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That is used also widely throughout South America in the form of ayahuasca.

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And it's also smoked recreationally by the meo.

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Dmt, there, there's just. There's just many, many like iedelics, and all of these are found in nature except for Lsd.

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Here is a very outdated distribution of where in the world psilocybin mushrooms are found.

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And again, I wanna emphasize, it's actually pretty much been found anywhere.

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Anyone has looked. These are widely distributed throughout nature, and we've kind of covered this, this here, these seeds, these are a probably the oldest psychedelic in you it's called Yoppo, and it contains this but all of these and these drugs.

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Are all different. They have different effects, and only some of these are being studied therapeutically.

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These are not. Dmt. Is 5 amo is, but despite being different, having different effect, they are much more similar than they are different.

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All of these drugs, mimic serotonin in the neurotransmitter, and they act specifically on the serotonin.

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Two-way receptor. So any drug which is which blocks that receptor, such as certain antipsychotics respected on their prerequisite, they will block the effects of psychedelic.

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So all of these different different drugs. Are ultimately acting on this one receptor and causing their effects with some caveats.

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I think it's useful to actually look at the molecule.

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So this is what dmt looks like. It's a fairly simple molecule dimethyl trip to me.

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And this is a one that is being studied therapeutically.

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That also has a long history of indigenous use, and you can number these different positions on the molecule 2, 3, 4, position, etc.

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And you add a little molecular structure to the 4 position now you have 4 hydroxydnt different drug.

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This is the drug from mushrooms that is active.

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You add this to a different position. The 5 hydrax, you know you have 5 hydraxy. Dmt, you've got different drug.

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Then literally, by mythoxydmt. These are.

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Very, very similar drugs, with flight, difference changes. And you have, you know you can span the gamut of the different drugs that are being researched.

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There's also this is just sort of trivia.

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But small religious group has figured out that if you feed the this particular drug 5 meo dmt.

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2 psilocybin mushrooms.

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It makes this intermediate compound, which is not found in nature, and is not really being studied, and is arguably not illegal, and they have formed some church where members can sign up and be mailed.

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This drug highly do not recommend this, but I just wanna convey a bit of the wild world that is going on around these substances.

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So? What effects to psychedelics have. And again, these are different drugs.

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They have different effects, but they are more sensitive. So first off, there are visual effect.

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This is what everyone talks about. You have enhancement, brightening of colors, illusions, hallucinations, close-light visuals, geometric patterns.

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These are not the effects that we tend to think of as being therapeutic.

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You also have a profound enhancement of meaning.

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People often describe these experiences as being among the most meaningful of their lives.

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Broadening of emotional range, including states of rapture or terror.

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The whole gamut also altered sense of time, altered sense of self, and mystical type.

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Experiences which I'll describe in a bit. One thing to note is that in terms of physical toxicity these are remarkably safe drugs.

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This is about as good a definition as you'll get about what it's like.

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A delicate Thank you. Delic drug is one which has small likelihood of causing physical addiction, craving delirium, disorientation, amnesia, and produces thought, mood, and perceptual changes otherwise rarely experienced, except perhaps in dreams contemplative and religious exaltation, et

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cetera mystery experiences. I wanna touch on this because it is described so frequently with these experiences, and it happens like even in the clinical trials, these are operationalized as experiences that with sense of unity, transcendence of time and space positive

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mood, ineffability sense that it cannot be conveyed in words and selflessness.

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I will!

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I will!

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Post up here. This is description by eldest Huxley about what the non self experiences like while you read that.

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Actually, I'll just check the.

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Okay, so and yeah, so in in the definition that I provide answering one of the questions in the definition, I provided there are certain things that are not considered psychedelics, ketamine in this definition is not a classic psychedelic it is a different drug.

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With different effects. Mdma also, not a psychedelic.

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It is a different drug with different effects. Happy to talk more about that in the questions adverse effects there are adverse effects, acute adverse effects.

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There's cardiovascular. It increases blood pressure, heart rate.

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This can be dangerous for people with cardiac conditions mile to moderate headaches, nausea vomiting, neither of which is particularly problematic.

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Usually people who are taking psychedelics regularly. Many of these drugs have.

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Serotonin 2 b. Activity which has LED to certain drugs being pulled off the market for causing cardiac valve problems.

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We don't know if this is actually a problem with psychedelics.

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But this is quite possible. Cardiac valueopathy with chronic use.

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You really do not see the kind of pattern of disordered use characteristic of addiction with psychedelics.

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It doesn't seem to lead to recurrent escalating use in the faces, mounting consequences.

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The way that cocaine, or benzos, or other drugs do.

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The main risks are cycological distress and behavioral.

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Just regulation. Somebody walks into traffic while they're intoxicated.

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That's very bad. There are also people who are at risk of exacerbation, of existing mental illnesses, such as hypothesis or bipolar.

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Most of our studies do not allow people with psychotic or bipolar histories or family histories.

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There have been remarkably few debts when it comes to overdose, including massive, massive overdose of psychedelics generally.

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And again there are caveats, but generally are quite safe.

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So there is this idea, that psilocybin must well sorry all psychedelics have this long standing pedigree of ancient use, and this is true to an extent still live and mushrooms have been used for at least hundreds of years, in central America though really there's no clear evidence.

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That they've been used elsewhere. The feeds I showed you Yoppo, have been used for millennia ayahuasca for at least hundreds of years.

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This is a combination of Dmt. And another drug.

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Peyote, possibly for thousands of years. So like italics, have been used anciently by certain groups.

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However, there is this idea that they've been used kind of across the entire globe.

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That is very like, not true. This is a very popular narrative, though you have this bestselling book.

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You have this cave painting from Algeria, which has actually been doctored, but is taken to mean that there is some psychedelic traumaism going on there thousands of years ago.

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You had this picture of the the stone toape theory. That may be.

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Phillip and mushrooms had some important role in the evolution of human consciousness, and I will not get too much into the weeds of this.

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But my basic point here is, I think there's not a lot of good evidence for this, and it's more wishful thinking.

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Like. I like to really, only convincingly used in a relatively small area.

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The Americas. You don't have, and even then I'll show you again this worldwide distribution of 5 and mushrooms despite them being found in all of these places.

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It's really only here that you have clear. Well-documented use of psilocybin mushrooms.

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Other people knew about them. The ancient Chinese wrote about these mushrooms, but they were regarded as poison, which is probably how anyone who didn't know what they were would think if they took them.

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I will!

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Sorry, having trouble juggling the chat, but I'm not gonna read all this, but there is this idea that psychedelics are also as used indigenously, using a very specific, circumscribed way by shamans that that kind of approximates sort of medical use that we are

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now doing clinical trials, and that is a I, in my opinion, a misleading statement in indigenous groups that have used this like people anywhere, are diverse, and they have used these substances in all kinds of ways.

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There is shamanic use for healing ceremonies, but it doesn't really approximate what we do in clinical trials.

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Generally a shaman takes it not the patient and the shaman will deal with unseen forces, or spirits, or what have you to at enact a cure?

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Is also used for witchcraft or divination, there's also a frank, recreational use in indigenous groups, but there's a huge range of indigenous Us.

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Of psychedelics, a small sliver of which might approximate stuff that we do in clinical trials.

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But I think there is a narrative that the clinical trials are continuing the longstanding tradition of indigenous view, and I do not.

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Know if I believe that I there is actually quite a lot of different ways that these substances are used.

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Again. Happy to talk more about that in Q. And A. People are interested.

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So we are in the psychedelic Renaissance. The call.

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But there have been 2 previous ways of research, one was in the late 18 hundreds, and it kind of continued into the it kind of didn't really stop.

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Actually. But this is following discovery of, and they did a lot of research on this.

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There are some scientific findings, but there is really no clinical use of it.

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And it sort of petered out. The second wave was after the discovery of Ellsd.

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So Lsd is the enormously potent psychedelic it it acts in microgrammed doses.

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So it's in as opposed to many drugs acting in milligrams or grams thousands of times more.

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So it was discovered serendipitously by this guy, Albert Hoffman, who somehow he act accidentally, adjusted it in 1943, had the experiences, and then Drug company that he worked for sendos began mailing it around the world and that LED to a whole line of

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research which eventually got shut down. Cool. Let's just talk about yeah.

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What was done during that. So people didn't know what to do with psychedelics, with Lsd.

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In particular. The CIA tried to weaponize it use it as a truth period that didn't really work bit of work on gay conversion therapy didn't really work.

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Of course, people thought, Oh, here's a great. We can understand the experiences of our psychotic patients.

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Which was a line of research that the academic, that is also petered out.

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Then there's what was called the chemotherapeutic approach, just giving the drug as a drug and trying to affect some kind of therapeutic benefit.

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That also does not work that well. What emerged out of the second wave of research, though, was the psychedelic model which tries to operate the experience, optimize the surrounding context in a way that leads to these kind of mystical or peak or transcendent experience characterized

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by profound sense of meaning, positive mood, subjective unit of self and other.

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But in that era it was kind of let a 1,000 flowers bloom just.

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They tried all kinds of stuff, and the psychedelic model is what is now being used in modern trials.

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But there was a lot that was learned from the second wave, and many of it was learned in the form of mistakes of things not to do so.

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One is the importance of context of set and settings.

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It's not just the drug. It's the drug, plus how it is delivered.

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Some of these trials would just wrap people into a bed.

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They would dose them without telling them they're gonna get a drug, and they'd be under harsh, fluorescent hospital life with people with clip boards passing them questions versus a kind of nice warm interpersonal relationship contexts and you know, nice living room like environment.

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But but also basic clinical ethics. I mean lots of bad actions were taken.

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People kind of felt that because of the unique treatment we can do unique things.

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And this LED to all kinds of boundary violations.

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So I think one of the lessons like regular basic clinical ethics applied do not do weird stuff with your patients. Therapy shouldn't take the drug, maintain good boundaries.

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I wanna talk about the context dependency, though this is kind of termed set and setting.

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So the this is like a quote from a researcher in the fifties, the responses described in clinical experiments on whites are so different from those described by Indian peyotis.

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People who take pay. That's to fall into completely different categories.

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They do not seem to be talking about the same thing, and Sarah White, participants who took payout in research settings had experiences characterized by the station net meeting with net.

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Distress and idiosyncratic hallucination which we're devoid of context and general lack of therapeutic benefit.

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In contrast, American Indian payotes who took the cactus in the ceremonial setting.

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With this presumption of meaningful, beneficial experience had therapeutic benefits and welcome feelings of contact with new, more meaningful reality.

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Prefigured and doctrinal knowledge, and the group that they're talking about here is the native American church which legally consumes payote as a sacrament in group settings and produces this these beneficial effects which are different the key here though is that the context.

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the drugs are highly responsive to the context.

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And the other lesson learned from the second wave is, and this is part of the same thing.

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The context is the need for extensions, psychological support.

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Again. Some of these trials had people strapped to a bed, and just kind of left there, or or just in a rather harsh, hostile environment.

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And again. They didn't have basic clinical ethics back then many of these trials actually just those people who are.

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We're not aware they're going to get a drug that produces very different effects than, Hey?

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Well, we'll talk more about how we actually do it.

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Now I I do want to touch on a bit of how the psychedelic model was discovered.

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So this guy is Humphrey. Osman. He's a Canadian.

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Lsd. Researcher in it was one of the more prolific people of the previous era of psychedelic research, and they were initially using Lsd.

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In patients with alcohol use, disorder, and the thought was to use the psychotomometic model.

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So let's let's the observation was that some people have delirium tremens.

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Very terrifying. Difficult experience of alcohol withdrawal that includes hallucination.

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Sometimes they kind of hit rock bottom, and then they improve, they turn their life around somehow. So that was the context.

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That was the model that he had in his mind when he began dosing people with Lsd.

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With alcohol. Use disorder. Let's create these 10 terrifying experiences of hitting rock bottom that will mimic that.

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And people will improve, and some fraction of people ended up having these highly meaningful cell phones, transcendent experiences that LED them to reevaluate their lives and Yadda Yadda Yadda, and paying attention to that Osman began to modify how they were administering

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the drug to optimize that it was a pivot.

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But this is going on in other places, too, and they were learning from each other.

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And this psychedelic model kind of evolved over time, and it included.

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Other factors. Some music ended up becoming a very important element that was sort of discovered.

00:26:43.000 --> 00:26:49.000
Incidentally, music is also mostly used in indigenous context with psychedelics as well, but also this attitude of experiential acceptance.

00:26:49.000 --> 00:26:50.000
The motto is, trust, let go and be open.

00:26:50.000 --> 00:27:06.000
Do all things that were kind of stumbled upon in the second era of psychedelic research that directly informed how we use them.

00:27:06.000 --> 00:27:21.000
Now, I wanna also just harp on this idea that many people in this work believe that psychedelics are not necessarily inrinsically therapeutic.

00:27:21.000 --> 00:27:33.000
In other words, this Lsd. For example, may help with help people quitting alcohol that does not mean that Lsd is intrinsically anti alcohol.

00:27:33.000 --> 00:27:39.000
If that makes sense and I don't see. Don't remember where I got this quote from.

00:27:39.000 --> 00:27:44.000
But this is from the seventies, virtually all double blind control trials of Lsd.

00:27:44.000 --> 00:27:51.000
In the treatment of alcoholism have shown that the drug by itself has no specific anti-alcoholism effects.

00:27:51.000 --> 00:28:12.000
However, these studies have largely tended to evaluate the drug in a relative vacuum by separating drug effects from the expectations and preconception or set mindset of the patients toward the drug experience and by performing the experiment in such sterile settings as hospitals so the the lessons

00:28:12.000 --> 00:28:13.000
that were learned from that era included positive lessons like this, works and negative lessons.

00:28:13.000 --> 00:28:39.000
This does not work. And so the kind of psychedelic therapeutic research that's going on now is much more in some ways narrower, because there is largely one model that is being studied versus this whole proliferation of everybody trying something different and i'm all yours i'm only really describing the us I mean

00:28:39.000 --> 00:28:47.000
psychedelic research in other parts of the world, doing all kinds of different stuff.

00:28:47.000 --> 00:28:53.000
I think of touched on that. So, yeah, we that's kind of the end of that section. Actually.

00:28:53.000 --> 00:28:59.000
So happy to take any questions on any aspect of the history.

00:28:59.000 --> 00:29:09.000
Thank you. Alex.

00:29:09.000 --> 00:29:12.000
She cannot see the.

00:29:12.000 --> 00:29:18.000
There's one in the that says, did you say that Ssris blocked the effects of psychedelics?

00:29:18.000 --> 00:29:30.000
I did not say that, but I will say that there's caveats there, but we have data on that that I will talk about cut towards the end.

00:29:30.000 --> 00:29:32.000
Okay. And if you can't see them, I'll just read and have to. Yeah.

00:29:32.000 --> 00:29:36.000
Yeah, yeah, mdma, being considered a psychedelic.

00:29:36.000 --> 00:29:48.000
So and so. The definition of psychedelic I'm using is a pharmacological one, and that is drugs that produce that set of objective effect.

00:29:48.000 --> 00:30:02.000
Highly meaningful, visual, reevaluating experience, etc., that acts primarily through the serotonin to a receptor, and mdma actually does do that in part.

00:30:02.000 --> 00:30:03.000
So I would actually say to complicate what I said earlier.

00:30:03.000 --> 00:30:09.000
That mdma partially fits the definition, but, like it does.

00:30:09.000 --> 00:30:12.000
However, the bulk of the effects of Mdma.

00:30:12.000 --> 00:30:16.000
It's creates. It's an impact. And it creates these feelings of emotional safety.

00:30:16.000 --> 00:30:21.000
It creates feelings of connectedness, but it's also a stimulus.

00:30:21.000 --> 00:30:25.000
3, 4, methylene, dioxide, methamphetamine.

00:30:25.000 --> 00:30:27.000
It is an amphetamine drug, so it has effects of stimulants.

00:30:27.000 --> 00:30:33.000
It has some effect of psychedelics, but it has this unique effect.

00:30:33.000 --> 00:30:44.000
Generating empathy, feelings of connectedness and emotional safety, and it is used in a similar way.

00:30:44.000 --> 00:30:50.000
So it. Mdma is often classified as a psychedelic, but it's certainly a very different one.

00:30:50.000 --> 00:31:00.000
So I'm not gonna quibble if somebody wants to define them in the psychedelic, I think that's fine, but it is doing something very different than these and unique.

00:31:00.000 --> 00:31:05.000
Any of these substances available to general practitioners to prescribe.

00:31:05.000 --> 00:31:17.000
So all all of these drugs I'm talking about are not legal to prescribe by general practitioner.

00:31:17.000 --> 00:31:20.000
Kadamine, as I said, is not a psychedelic.

00:31:20.000 --> 00:31:26.000
According to this definition, it's the of anesthetic, and it's FDA approved.

00:31:26.000 --> 00:31:28.000
It's used all the time everywhere in emergency rooms, surgical settings.

00:31:28.000 --> 00:31:29.000
But now it's also being used for depression treatment.

00:31:29.000 --> 00:31:38.000
It has an FDA approval of the form S. Ketamine.

00:31:38.000 --> 00:31:44.000
The FDA approval and the initial trials of ketamine use the chemotherapeutic approach.

00:31:44.000 --> 00:31:51.000
Let's just give the drug to somebody that's in a bed sharing a glowing exit.

00:31:51.000 --> 00:32:00.000
Fine, and it seemed to work. In other words, the drug seemed to work without the psycho like a delic model.

00:32:00.000 --> 00:32:11.000
But now you are increasingly seeing ketamine being used in the psychedelic therapy model, and the frankly, is not something I know a lot about.

00:32:11.000 --> 00:32:15.000
This is partly something that maybe it actually works a lot better.

00:32:15.000 --> 00:32:31.000
Nobody has studied that it clearly works without it. I would not be surprised if it works better, but I also do think that some of this is trying to catch in on the cultural cache of psychedelics which are drugs that cannot be prescribed whereas ketamine can and so there is a

00:32:31.000 --> 00:32:37.000
modeletary incentive for people who give ketamine therapy to describe ketamine as likeedelic.

00:32:37.000 --> 00:32:45.000
I wanna be very clear. This is my perspective. On this. I think a lot of other people would say, this is, of course, ketamine is psychedelic.

00:32:45.000 --> 00:32:50.000
Of course mdma is a psychedelic, but that's fine.

00:32:50.000 --> 00:32:53.000
If people wanna use that definition. But it's a very different drug.

00:32:53.000 --> 00:33:01.000
Regardless, it has very different effects, and as long as we're being clear about what we mean, I think it's fine to call things psychedelics.

00:33:01.000 --> 00:33:11.000
But the term classics, psychedelic. I think everyone would agree, does not include ketamine does not include Mdma.

00:33:11.000 --> 00:33:20.000
Other questions.

00:33:20.000 --> 00:33:33.000
Not the same as mdma again. It's a very, very different drug, and this is partly why I think the words matter, if we call everything a psychedelic, then what are we talking about?

00:33:33.000 --> 00:33:42.000
Ketamine is not the same as mdma is not the same as Lsd.

00:33:42.000 --> 00:33:48.000
I'm not saying it's the same drug. They're not, but they're much, much, much more similar than they are different.

00:33:48.000 --> 00:33:54.000
So using a pharmacological definition, I find to be the most helpful in having people clear about.

00:33:54.000 --> 00:34:03.000
What are we talking about? Especially when there are direct financial incentives to conflate things, confused things?

00:34:03.000 --> 00:34:04.000
Is there any research suggesting? That psychedelics can help people?

00:34:04.000 --> 00:34:17.000
Ptsd, so there is very, very good research that Mdma, which again, in this context, I'm partitioning off from psychedelics.

00:34:17.000 --> 00:34:24.000
The mdma is quite helpful, and and I wanna apologize.

00:34:24.000 --> 00:34:28.000
That's something I'm not really talking about today.

00:34:28.000 --> 00:34:32.000
It's also something that I don't do. But there have been 2.

00:34:32.000 --> 00:34:38.000
Phase, 3 trials that have been completed that have been positive of Mdma.

00:34:38.000 --> 00:34:46.000
For Ptsd. And so that is a that's what you need for FDA. Approval.

00:34:46.000 --> 00:34:51.000
So they're gonna apply for FDA approval. And that could be available early next year.

00:34:51.000 --> 00:34:57.000
It's so. Keep that in mind. Much of what I'm talking about in terms of how psychedelic therapy is delivered.

00:34:57.000 --> 00:35:05.000
Apply to mdma. In practice it ends up looking different because the drugs are different, but the model is actually kind of similar.

00:35:05.000 --> 00:35:12.000
So there has been no research whatsoever. Yet on classic psychedelics for Ptsd.

00:35:12.000 --> 00:35:19.000
Though a number of people are going to be doing that research, including including us.

00:35:19.000 --> 00:35:28.000
Okay, I think we've kinda reached our time there, because time for one more question.

00:35:28.000 --> 00:35:34.000
We can do that, otherwise we'll move on.

00:35:34.000 --> 00:35:38.000
Thank you like therapy. With anxiety.

00:35:38.000 --> 00:35:42.000
Yeah, we we can talk about the next section. Then.

00:35:42.000 --> 00:35:48.000
So let's talk about the empirical results.

00:35:48.000 --> 00:35:54.000
And we've got about 4, 3 min here. And first, I want to introduce the idea of effect sizes.

00:35:54.000 --> 00:35:57.000
I'm not actually quite clear I'm not clear on how familiar people are with that.

00:35:57.000 --> 00:36:05.000
So explain it. Then we'll talk about depression tobacco, smoking, and palliative care.

00:36:05.000 --> 00:36:19.000
There are other things that are being studied that I'm not gonna be talking about, including alcohol use, disorder, including anorexia, including also there's like physical ailment like a headache.

00:36:19.000 --> 00:36:26.000
But the general theme here is that these are different indications of psychedelic that are being studied.

00:36:26.000 --> 00:36:34.000
These are the ones that kind of have the most research on where they're being used in very similar ways, but for different conditions.

00:36:34.000 --> 00:36:41.000
So let's first discuss the notion of effect. Sizes. So an effect.

00:36:41.000 --> 00:36:50.000
Size is a way of comparing the effect of an intervention.

00:36:50.000 --> 00:36:56.000
Like, if you wanna compare here, let me just give you an example.

00:36:56.000 --> 00:36:58.000
Ssris for depression, stimulants for adhd, Metformin for blood, sugar.

00:36:58.000 --> 00:37:09.000
These are very different effect. But there is a way of boiling it down to what is a standardized difference between groups.

00:37:09.000 --> 00:37:14.000
So you can kind of compare Apple and oranges to each other in terms of the magnitude of effects.

00:37:14.000 --> 00:37:19.000
The size sizes can be described as either within group.

00:37:19.000 --> 00:37:26.000
In other words, what is the effect of, or between group?

00:37:26.000 --> 00:37:29.000
What is the effect of silicon versus placebo?

00:37:29.000 --> 00:37:32.000
So this is very important detail that people get mixed up.

00:37:32.000 --> 00:37:37.000
But they within group effects. Size is always going to be larger.

00:37:37.000 --> 00:37:42.000
Than in between group effects, size, because the placebo effect itself has an effect.

00:37:42.000 --> 00:37:43.000
So you wanna look at the between group effect size, if you're looking at just within group.

00:37:43.000 --> 00:37:54.000
And that's gonna include your intervention, plus all the non-specific effects of placebo.

00:37:54.000 --> 00:38:01.000
Now the effect. Size is a common commonly prescribed Med.

00:38:01.000 --> 00:38:07.000
So etherize for depression, barely point 3 to point 4.

00:38:07.000 --> 00:38:13.000
Contract stimulants for Adhd is 1. One is an absolutely massive effect.

00:38:13.000 --> 00:38:22.000
Size. You know, things like for acid reflux is 1.4 highly effective drug.

00:38:22.000 --> 00:38:29.000
So just keep those numbers in mind like point 3.4 fairly small, but something there, one absolutely massive.

00:38:29.000 --> 00:38:37.000
And we're talking about comparing it to something comparing it to December.

00:38:37.000 --> 00:38:38.000
So this is something it doesn't get discussed a lot.

00:38:38.000 --> 00:38:50.000
But what is the effect? Size of the placebo group in a depression trial so there's a big meta analysis that shows that it's quite large.

00:38:50.000 --> 00:39:05.000
The effect. Size of placebo in depression trails is 1.6, and that means that if you do a trial without a placebo group and for depression, and you get an effect size of 1.6 that sounds massive.

00:39:05.000 --> 00:39:12.000
But if you're not comparing it to anything, then doesn't really mean a lot treatment, resistant depression.

00:39:12.000 --> 00:39:13.000
It is lower, which makes sense, but it's 1.1.

00:39:13.000 --> 00:39:33.000
It's still pretty big if there's any confusion about what I've just said, please drop it in the and I'll clarify that this is kind of important, but it gives us a common language to talk about like what are these effects actually compared to something else now in terms

00:39:33.000 --> 00:39:34.000
of controlled trial, of a psychedelic for depression.

00:39:34.000 --> 00:39:41.000
So I'm leaving off some of these studies without a control group.

00:39:41.000 --> 00:39:44.000
We've superseded them. There have been. What is this?

00:39:44.000 --> 00:39:50.000
1, 2, 3, 4, 5, published. So, okay, confused about effect.

00:39:50.000 --> 00:40:08.000
Sizes to basically, let's say I do a trial of Prozac versus Defoe and my Placebo group improves by point 6 and Prozac, improved by one.

00:40:08.000 --> 00:40:12.000
The between group effect size is gonna be like within group. It's gonna be.

00:40:12.000 --> 00:40:22.000
Prozac has one Placebo has point 6, but the difference between those is what you care about how much better is project than a sugar pill.

00:40:22.000 --> 00:40:24.000
That would be like point 4. If you're not comparing it to something you don't.

00:40:24.000 --> 00:40:30.000
You're not really getting like, what is the actual intervention doing?

00:40:30.000 --> 00:40:34.000
You're getting. What is the intervention doing? Put everything that a placebo would do.

00:40:34.000 --> 00:40:42.000
But the main point here is really just the number itself, and the magnitude.

00:40:42.000 --> 00:40:58.000
Just keep in mind, like Ssris point 3 or so, but more effective Meds are like one, and that'll just be helpful contact for looking at what are the psychedelics doing?

00:40:58.000 --> 00:41:05.000
So yeah, number of trials for depression. We, John's Hopkins, had a trial.

00:41:05.000 --> 00:41:12.000
If I've been. All of these are still asylum except for this one, this Brazilian child, ayahuasca, which is it's Dmt.

00:41:12.000 --> 00:41:22.000
And it's legal there. Imperial College had a trial compass, largest drug company in the psychedelic space had a big phase, 2 trial.

00:41:22.000 --> 00:41:23.000
Whatever. We'll just go through the so I'm gonna convey to you all the evidence there is from controlled trial.

00:41:23.000 --> 00:41:31.000
There's also one that has not been completed and not published yet.

00:41:31.000 --> 00:41:37.000
So lot of stuff coming out, and every time I do this aspect of the talk I have to update it.

00:41:37.000 --> 00:41:40.000
So here's the trial at Johns Hopkins.

00:41:40.000 --> 00:41:47.000
That was a wait list control, meaning people got randomized. Either get psilocybin and again, I haven't actually talked about how we deliver this yet.

00:41:47.000 --> 00:41:52.000
I'm gonna talk about that later. They're randomized.

00:41:52.000 --> 00:41:59.000
Try to get, in the usual way. We deliver it psychologically supported contexts, or wait.

00:41:59.000 --> 00:42:06.000
And they got 2 doses here here, I'm showing you trajectories of every single patient in this trial.

00:42:06.000 --> 00:42:10.000
The blue is people who got silicide immediately. The red is people that are on wait lists.

00:42:10.000 --> 00:42:17.000
No intervention, and you can see that. And this is just the grid, hem, depression, scale.

00:42:17.000 --> 00:42:19.000
People who are on the wait list. They didn't improve at all.

00:42:19.000 --> 00:42:25.000
People who excuse me got psilocybin immediately.

00:42:25.000 --> 00:42:28.000
Their depression, scores plummeted this dotted line represents threshold.

00:42:28.000 --> 00:42:31.000
Per mission, and stayed that way for at least a week.

00:42:31.000 --> 00:42:51.000
Sorry a month, and in terms of remission rates and the Philippine group 45%, about half wonder mission, whereas the 0 did and wait list and the between group effect size.

00:42:51.000 --> 00:42:59.000
Remember I told you one is massive was 2.6, which is truly, you know.

00:42:59.000 --> 00:43:08.000
Gob smacking. However, this is the Wait List control trial, and generally a placebo group has the placebo effect, and in this it was basically nothing.

00:43:08.000 --> 00:43:17.000
So it's not the most fair comparison, because, remember, the average placebo effect.

00:43:17.000 --> 00:43:28.000
Size is 1.6, whereas this is basically 0. But even taking that new account you're still seeing a pretty large effect.

00:43:28.000 --> 00:43:35.000
Everyone in this trial got still Simon eventually, and they follow them up to a year, and the effect size is quite large.

00:43:35.000 --> 00:43:46.000
Though big effect, not the best control group, but even accounting for that, you're seeing a large effect on depression that it appears to be durable.

00:43:46.000 --> 00:43:53.000
There are caveats. To this, I think about a third of people went back on antidepressants.

00:43:53.000 --> 00:43:57.000
Our next trial is.

00:43:57.000 --> 00:44:08.000
Brazilian trial. This took 30 people with treatment, resistant depression, so not different from the previous one, moderate to severe 80% of them had personal disorder diagnoses.

00:44:08.000 --> 00:44:09.000
They're mostly clinician, referred. This is actually important.

00:44:09.000 --> 00:44:23.000
There's a difference between a clinician referring somebody to a trial or somebody who's a psychedelic enthusiast showing up that maybe minimizes some of the effects of expectancy.

00:44:23.000 --> 00:44:26.000
Oh, this is a miracle treatment that's really gonna help me.

00:44:26.000 --> 00:44:32.000
And they used a placebo which was actually, I mean, I was as if beverage that includes the psychedelic.

00:44:32.000 --> 00:44:41.000
That's kind of nasty, I think, and then they had this sham Ioasket tasted like ayahuasca.

00:44:41.000 --> 00:44:45.000
That also caused nausea. The way I Wasasca does.

00:44:45.000 --> 00:44:49.000
And you know, these are just 2 different depression scores.

00:44:49.000 --> 00:44:57.000
But the just a week out you are seeing a statistically significant imp improvement on ayahuasca versus placebo.

00:44:57.000 --> 00:45:03.000
Little hard to interpret that. Let's look at something more meaningful.

00:45:03.000 --> 00:45:07.000
Remission rates, so 36% who got Ios?

00:45:07.000 --> 00:45:18.000
And remember, this is treatment, resistant depression. So the response is going to be not as good personality sort of diagnoses. Somebody asks.

00:45:18.000 --> 00:45:27.000
They were mostly Cluster B. With some anti social personality disorder as well.

00:45:27.000 --> 00:45:37.000
I can pull that up actually, later. But I don't remember off the top of my head, but that's the gist of it mostly mostly cluster B, with some anti social personality disorder.

00:45:37.000 --> 00:45:43.000
So!

00:45:43.000 --> 00:45:48.000
The between group effect size was one which, again, that's like very big.

00:45:48.000 --> 00:45:54.000
But the within group effect size of the placebo, and I keep harping on this, because that tells you like, well, did the placebo group do about as well as possible?

00:45:54.000 --> 00:46:08.000
Groups are supposed to do, and the answer is, no the the placebo group should have done like point 5.6 points better.

00:46:08.000 --> 00:46:18.000
But even taking that into account, you are seeing an effect. So this is kind of a theme that, like our control groups, are difficult to control.

00:46:18.000 --> 00:46:22.000
They're difficult because people can kind of figure out what they're getting, which is left.

00:46:22.000 --> 00:46:26.000
The case with the blood pressure pill versus placebo.

00:46:26.000 --> 00:46:27.000
So there are ways of still gleaning important information, even though our control groups are not perfect.

00:46:27.000 --> 00:46:37.000
But the gist here is that there is an effect. Unfortunately they do not follow these people for more than a week.

00:46:37.000 --> 00:46:50.000
That was not only statistically significant, but clinically meaningful, but the effect is probably inflated because the control group is not perfect, but even accounting for that, you still see something.

00:46:50.000 --> 00:46:51.000
Okay. Here's a very interesting trial out of Imperial College, London.

00:46:51.000 --> 00:46:59.000
So this one took people they're not treatment resistant.

00:46:59.000 --> 00:47:09.000
So you know, depression and randomize them to receive either at the Teleprem lexa pro common commonly used.

00:47:09.000 --> 00:47:19.000
Second, or silicon, and it was double dummy, meaning the people who were getting S Telepm.

00:47:19.000 --> 00:47:27.000
Daily pills had sham psilocybin sessions, where they got tiny, tiny, tiny minuscule dos and silicon.

00:47:27.000 --> 00:47:31.000
Likewise the people who got they'll dive in.

00:47:31.000 --> 00:47:34.000
They active dose for taking a daily placebo, and what you can see here, they follow them over 6 weeks.

00:47:34.000 --> 00:47:40.000
They're getting, you know, 20 milligrams of that's the telegram.

00:47:40.000 --> 00:47:46.000
2 doses of py dosilocybin, and there is still 7, appears to be doing better.

00:47:46.000 --> 00:47:53.000
But it is not to a degree that is statistically significant and depending on how you connect it.

00:47:53.000 --> 00:47:58.000
The effect size around point 4. But remember, it's being compared not to a placebo.

00:47:58.000 --> 00:48:04.000
It's being compared to a Fsri, something that we expect to be doing something.

00:48:04.000 --> 00:48:08.000
And you so not a statistically significant difference.

00:48:08.000 --> 00:48:16.000
And yet you look at the remission rates 60% in Philadelphia and 30% in the telegram.

00:48:16.000 --> 00:48:17.000
That's pretty confusing. It's not a statistically significant difference.

00:48:17.000 --> 00:48:38.000
It, but it's a clinically significant, different and this is likely because it's a small trial it's possible that they're detecting an effect that if the trial was larger and interestingly, all of the other, they use 3 other depression scales and all of those were statistically

00:48:38.000 --> 00:48:46.000
significant. This is getting kind of into the details of how clinical trials are run, but you have to pick one and say, this is what we're going to use.

00:48:46.000 --> 00:48:51.000
And they were not really able to use the other ones, but that creates a lot of confusion about him.

00:48:51.000 --> 00:48:57.000
Interpret this trial. Some say it's positive and say it's negative.

00:48:57.000 --> 00:49:01.000
Some say it's indeterminate I don't think I'm gonna get in the weeds of how this analysis was done.

00:49:01.000 --> 00:49:11.000
But this is a a statistical analysis that is able to look at all of the depression scales that were used.

00:49:11.000 --> 00:49:21.000
This is the quiz, the primary one, the handy, the Madrid, etc., and these purple distribution are representing the difference between.

00:49:21.000 --> 00:49:42.000
If I've been, and as the teleprom, with positive numbers favoring, and you can see that mostly these are favoring psilocybin, this one, the one they happen to pick, it's much more.

00:49:42.000 --> 00:49:46.000
Take. But the nice thing about this kind of analysis is that you can.

00:49:46.000 --> 00:49:52.000
You can boil this down into like supporting different evidence.

00:49:52.000 --> 00:49:57.000
Criteria so let me just make that more concrete.

00:49:57.000 --> 00:50:10.000
You can look at various hypotheses, for example, is Phillipin superior to at the teleprom by any amount at all, and quantify the strength of evidence for that hypothesis.

00:50:10.000 --> 00:50:16.000
So here I'm showing it. You graphically. Red is stronger evidence that fsilosiven is superior.

00:50:16.000 --> 00:50:21.000
Blue is stronger evidence that it's not superior.

00:50:21.000 --> 00:50:25.000
Green is just kind of indeterminate. You can't really say one way or another.

00:50:25.000 --> 00:50:30.000
And for this question of is silicide and superior in this trial.

00:50:30.000 --> 00:50:43.000
Extremely strong evidence from this Gail. Strong evidence from these 2, indeterminate from the one that they picked for their primary outcome.

00:50:43.000 --> 00:50:45.000
Point is the bulk of the evidence suggests that probably.

00:50:45.000 --> 00:50:50.000
Yes, it is superior. Is it superior to a clinically meaningful degree?

00:50:50.000 --> 00:50:55.000
And these are, like literature defined. What is there?

00:50:55.000 --> 00:50:57.000
What is the threshold for clinically meaningful, different?

00:50:57.000 --> 00:51:01.000
And here it's much more mixed. I mean, this scales does.

00:51:01.000 --> 00:51:05.000
No, the scale says, yes, these 2 are interminent.

00:51:05.000 --> 00:51:13.000
And yeah, is still saving, at least not worse than at the telegram.

00:51:13.000 --> 00:51:16.000
The evidence is overwhelming that that seems to be the case.

00:51:16.000 --> 00:51:33.000
So my take-home point is that here, as administered in this trial and as measured by these depression, scale those type in probably outperforms as the telephone, not to degree. That is clearly clinically meaningful. But it's certainly not worse.

00:51:33.000 --> 00:51:37.000
Okay. Let's see, had some questions here. What is their mission?

00:51:37.000 --> 00:51:41.000
Right, time people report being. This is a big question.

00:51:41.000 --> 00:51:46.000
The Hopkins trial. On average, people were in remission per year.

00:51:46.000 --> 00:51:56.000
I don't remember the exact numbers off the top of my head, what the percentage breakdown was, but on average, most people in remission, the other 2 trials I've shown you don't show long term data yet.

00:51:56.000 --> 00:52:09.000
So it's it's a question for the field.

00:52:09.000 --> 00:52:18.000
Problem with Carhart. That's the teleprime dosing.

00:52:18.000 --> 00:52:25.000
Yeah, let's we. Let's talk about other questions. I don't fully understand what you mean.

00:52:25.000 --> 00:52:28.000
Okay, so this is the compass phase, 2 trials.

00:52:28.000 --> 00:52:33.000
This is the biggest like Itelle trial that has ever been performed in the modern era.

00:52:33.000 --> 00:52:44.000
Probably ever actually. And this took people with treatment, resistant depression, who, you know, they'd multiple treatments in, not work for them.

00:52:44.000 --> 00:52:48.000
And they had 3 groups. One group got 25 milligram.

00:52:48.000 --> 00:52:49.000
That's the high dose. Another group got one milligram.

00:52:49.000 --> 00:52:54.000
So that's a placebo essentially does nothing.

00:52:54.000 --> 00:52:58.000
Almost but interestingly, another third group got 10. Milligram.

00:52:58.000 --> 00:53:10.000
That's a dose that we don't really expect necessarily to be therapeutic, but would cause effects, and to the idea there to let people feel that they got Filibin.

00:53:10.000 --> 00:53:15.000
But and see what the effect is of that.

00:53:15.000 --> 00:53:16.000
But the bottom line here. This is 233 people divided across 3 groups.

00:53:16.000 --> 00:53:26.000
So it's big is that you do see a significant benefit.

00:53:26.000 --> 00:53:34.000
And this is not only statistically meaningful, but to clinically meaningful difference on the mattress.

00:53:34.000 --> 00:53:45.000
Up to 12 weeks out for the highest desk group, but not for the one milligram or 10 milligram let's look at that in more intuitive terms.

00:53:45.000 --> 00:53:55.000
Remission. So about 30% of participants in the high dose group were in remission at 3 weeks and 12 weeks.

00:53:55.000 --> 00:53:58.000
Yeah, also, I just wanna acknowledge you can look at that and say, 30%.

00:53:58.000 --> 00:54:03.000
That's not very good at all. But the question is always compared to what?

00:54:03.000 --> 00:54:13.000
And so 10% of participants patients in the one milligram and 10 milligram groups, we're in permission.

00:54:13.000 --> 00:54:17.000
Well, there's some great questions shown up we'll address those later.

00:54:17.000 --> 00:54:30.000
Keep them coming, though. So about a 20% difference in remission rates, the effect side, I'm showing it to you over time up to 6 weeks, which was their primary outcome, I think, was point 6.

00:54:30.000 --> 00:54:35.000
And this is compared to the placebo. And so again you can compare that to etherize point 3.4 maybe point 5.

00:54:35.000 --> 00:54:59.000
That's a meaningful different. It's not as big as people hoped, and so despite this being a positive trial, this company stock tanked after these results, came out it's not just because it's I actually kind of I think it's a positive trial. It's a good. Development.

00:54:59.000 --> 00:55:15.000
They're showing that it has an effect. But it's not a miracle, but more concerningly, there were some serious adverse events in the groups that got Phillocybin, and in particular Dave divided this up somewhat confusingly.

00:55:15.000 --> 00:55:22.000
Into 2 time periods. After filming up to week, 3 after week, 3 up to week, 12.

00:55:22.000 --> 00:55:27.000
We're looking at. Hi, doth medium doth placebo.

00:55:27.000 --> 00:55:32.000
So 5 people in both of the groups that got, you know, high dose and medium does.

00:55:32.000 --> 00:55:33.000
Silicon had some serious adverse event compared to nobody.

00:55:33.000 --> 00:55:36.000
It got the placebo, 5 people and 4 people got had some serious adverse event.

00:55:36.000 --> 00:55:47.000
In the second, compared to only one. So you're seeing it sounds like small numbers, but that is quite a lot more serious.

00:55:47.000 --> 00:55:55.000
Adverse events in the groups that got like still, assign that they could feel, and most concerningly, though 3.

00:55:55.000 --> 00:55:59.000
No. Sorry. 4.

00:55:59.000 --> 00:56:13.000
3 participants had suicidal behavior in the high dose group, and so these are all people who did not respond to the treatment one had an aborted suicide.

00:56:13.000 --> 00:56:17.000
Attempts with a past history of non-suicidal self in injury.

00:56:17.000 --> 00:56:21.000
Another had a board, and she suicide attempt ditto.

00:56:21.000 --> 00:56:30.000
They had prior non suicidal self injuries, behaviour through that attempt, and another acquired materials for suicide, attempt past history to the third attempt.

00:56:30.000 --> 00:56:37.000
So this is concerning, and it's something that really needs to be watched and addressed.

00:56:37.000 --> 00:56:44.000
If we're having this high amounts of. But fortunately nobody attempt like I.

00:56:44.000 --> 00:56:50.000
Nobody committed suicide. Nobody died in this trial, but we need to be very careful.

00:56:50.000 --> 00:56:55.000
There is possibility for harm here. And again I wanna emphasize that we shouldn't just understand.

00:56:55.000 --> 00:57:06.000
This is. This is what the drug does. This is what the drug does in context, this trial in particular, actually had less support.

00:57:06.000 --> 00:57:13.000
Than other trials. I think, after the do if people have 2 meetings with their study therapist, and then they're done.

00:57:13.000 --> 00:57:14.000
No follow ups where they're getting measures done.

00:57:14.000 --> 00:57:20.000
But there's not ongoing psychological support.

00:57:20.000 --> 00:57:25.000
And also these are people with perhaps certain risk factors that should be better understood.

00:57:25.000 --> 00:57:35.000
But this is sort of an open question. Of how much are people going to be having these kinds of adverse events moving forward?

00:57:35.000 --> 00:57:41.000
Also possibly a reason why they're stock tank. But ultimately positive trial.

00:57:41.000 --> 00:57:47.000
Okay. This was just published. This is out of Switzerland.

00:57:47.000 --> 00:57:51.000
This is the trial. 50 people with major depressive disorder.

00:57:51.000 --> 00:57:53.000
They used 15 milligrams. It's weight base. So if you're heavier, you get more lighter, you get less.

00:57:53.000 --> 00:58:00.000
But on average about 15 milligrams, which is the not a super high dose.

00:58:00.000 --> 00:58:05.000
The moderate dose, and they looked at 14 day primary outcome.

00:58:05.000 --> 00:58:10.000
Sorry I should mention the compass trial. They looked up to 3 months.

00:58:10.000 --> 00:58:16.000
They have not. There's no, there's no long term data yet, but they're gonna collect that I'm sure this is a 14 day primary outcome.

00:58:16.000 --> 00:58:26.000
There's a result. Phil Thibbon is doing quite a bit better than placebo at 2 weeks.

00:58:26.000 --> 00:58:34.000
Between group effect size is one. Again, that's big. That's a big as far as psychiatric treatments for depression. You know.

00:58:34.000 --> 00:58:36.000
That's a pretty big effect. Remission rates.

00:58:36.000 --> 00:58:42.000
We've got 54% in the filming group.

00:58:42.000 --> 00:58:48.000
And again, this is a pretty modest versus 12%.

00:58:48.000 --> 00:58:55.000
So you know this is a confusing slide. And I think that's just because this is confusing.

00:58:55.000 --> 00:58:56.000
All of these are all the different studies I've shown you.

00:58:56.000 --> 00:59:01.000
They're all looking at different follow up Time point, you know.

00:59:01.000 --> 00:59:09.000
This is a month. This is 7 days, 6 weeks. This is 3 weeks, 2 weeks, and here are the effect sizes.

00:59:09.000 --> 00:59:12.000
They're coming caveats here, though I mean that.

00:59:12.000 --> 00:59:15.000
Okay.

00:59:15.000 --> 00:59:22.000
This is massive, but they're comparing it to perhaps an unfair control group.

00:59:22.000 --> 00:59:34.000
This is massive, but only 7 days. This is little, but it's being compared to at the Teleprem, you know, but the gist is that these are all seem to be trending in similar direction with the caveat.

00:59:34.000 --> 00:59:42.000
There seems to be a signal that something is happening.

00:59:42.000 --> 00:59:45.000
Same studies. Here's your emission rate across the board.

00:59:45.000 --> 00:59:52.000
Here's your mission rates from the control group. Most importantly, though, what's the difference between provision rate?

00:59:52.000 --> 00:59:59.000
The group that got the drug and the group that got the and it's substantial at least 20 like 20 to 40% difference in remission rate.

00:59:59.000 --> 01:00:16.000
And different trials, different different methods. But you're seeing what I would term a clinically meaningful effect from treatments that are administered once or twice.

01:00:16.000 --> 01:00:17.000
Again, this point is just to drive home. These trials are doing all kinds of different things.

01:00:17.000 --> 01:00:20.000
They're looking at different time points. They're giving different drugs.

01:00:20.000 --> 01:00:28.000
They're giving a different time. This has 2 doses.

01:00:28.000 --> 01:00:35.000
So it's a little hard to to sum it all up, but.

01:00:35.000 --> 01:00:43.000
They? They are trending in a similar direction.

01:00:43.000 --> 01:00:52.000
So that's it. Those are all of the published trials of a psychedelic for major depressing disorder.

01:00:52.000 --> 01:01:01.000
This is all. There is 5 trials there is, I said, before, a another large phase, 2 trial that has been completed, but not yet published.

01:01:01.000 --> 01:01:04.000
I'm involved with that, but we can't really say anything about that.

01:01:04.000 --> 01:01:07.000
Hopefully. We'll have that up.

01:01:07.000 --> 01:01:11.000
Within the next several months.

01:01:11.000 --> 01:01:18.000
So one thing I haven't really said is that all of these studies, those Ivan Ayahuasca?

01:01:18.000 --> 01:01:28.000
These drugs last for hours, 6, 8 h, and that's a long time.

01:01:28.000 --> 01:01:36.000
And so there's been this open question. I'm a little reluctant to show this, because it's a press release from a drug company that they haven't published anything.

01:01:36.000 --> 01:01:44.000
But it drives home an important point. This question of well, there are other psychedelics that are much shorter acting.

01:01:44.000 --> 01:01:52.000
For example, Dmt, if it's administered intravenously, can last for 2030 min.

01:01:52.000 --> 01:01:54.000
And I'm not gonna get in the details of this.

01:01:54.000 --> 01:02:04.000
The gist of it is that they gave Dmte in circumstances that are typical for administration, likeedelics, meaning psychologically supported context.

01:02:04.000 --> 01:02:07.000
We will discuss that in the next section. What that looks like.

01:02:07.000 --> 01:02:08.000
And they showed with a 30 min psychedelic experience.

01:02:08.000 --> 01:02:17.000
There is a benefit. Again. They haven't published this.

01:02:17.000 --> 01:02:22.000
This is a press release. So the small trial wouldn't read too much into this.

01:02:22.000 --> 01:02:23.000
But just kind of this is an inkling of things to come.

01:02:23.000 --> 01:02:36.000
People are going to be trying to figure out. What exactly can we modify about this?

01:02:36.000 --> 01:02:39.000
And there's just loads of studies I've mentioned.

01:02:39.000 --> 01:02:45.000
There's this other phase, 2 study that's going to be coming out completed can't really say much about it.

01:02:45.000 --> 01:02:48.000
There's a very large study going on in Germany.

01:02:48.000 --> 01:02:54.000
Hopkins is doing a study where it's people who have major depressive disorder plus alcohol use disorder.

01:02:54.000 --> 01:03:00.000
So, and the field is getting so big at this point that I'm sure I've missed.

01:03:00.000 --> 01:03:05.000
I missed studies. But the point is, the trials have largely been positive.

01:03:05.000 --> 01:03:08.000
So far!

01:03:08.000 --> 01:03:18.000
And there's gonna be Zoomie more.

01:03:18.000 --> 01:03:22.000
There's a lot of critiques of psychedelic clinical trials.

01:03:22.000 --> 01:03:28.000
So one is that you're saying these trials are blinded, but they're not.

01:03:28.000 --> 01:03:40.000
And that's true. If you give a placebo the point of a placebo is for somebody to think that they're getting the active treatment. But.

01:03:40.000 --> 01:03:53.000
It doesn't really work people by and large. Upwards of 80 90% of people can figure out what they got which sort of defeat the point of placebo critique.

01:03:53.000 --> 01:04:05.000
One critique 2 is that maybe a lot of these effects are driven by expectations you have enthusiastic participants who are gonna get better if they feel like they got the active drug.

01:04:05.000 --> 01:04:16.000
And you have people in Placebo group who are gonna be disappointed, and they demoralized if they get the with the context being that most people can actually figure that out.

01:04:16.000 --> 01:04:21.000
But not all. So this is an example. I wanna be very clear.

01:04:21.000 --> 01:04:25.000
Those are very valid critiques, that's partly why I showed the data on are the placebo groups actually performing up to snuff.

01:04:25.000 --> 01:04:35.000
And the answer is, no, they're not so. The effects are inflated but I think they're still there.

01:04:35.000 --> 01:04:40.000
But I like to look at the example of tobacco cessation.

01:04:40.000 --> 01:04:47.000
Cool. Put aside psychedelics for a moment what I'm showing you right now are 3 figures that look at.

01:04:47.000 --> 01:04:56.000
How well do you existing? FDA approved treatments for tobacco, cessation, work, and these are all treatments that are time limited.

01:04:56.000 --> 01:05:03.000
They last up to 12 weeks, and then they're stopped, and then we've we're followed up in long term.

01:05:03.000 --> 01:05:09.000
Follow up. So here they y-axis, for these you have percent abstinence.

01:05:09.000 --> 01:05:13.000
The X-axis. You have, you know, in long term, follow up.

01:05:13.000 --> 01:05:21.000
How was, people are abstinent? Curious. You got Meta propion versus placebo.

01:05:21.000 --> 01:05:26.000
Here you've got nicotine patch Brennan Klein, nicotine, patch, placebo.

01:05:26.000 --> 01:05:35.000
But the gist is that, and all these treatments, none of these in long-term follow-up processes, 40% abstinence.

01:05:35.000 --> 01:05:47.000
So we have a feeling we have a very good sense of about how well can a short term treatment for smoking cessation do in the long term?

01:05:47.000 --> 01:06:09.000
Right enter still assignment. So this is an ongoing study that compares Bill Sivin single high to nicotine Patch with both groups getting Cbt for smoking vacation. And there's no blinding people know what they're getting.

01:06:09.000 --> 01:06:14.000
So everyone gets 4 weeks of Cbt.

01:06:14.000 --> 01:06:19.000
The randomized. Then they either get still a cybin or nicotine patch and that's kind of administered typical clinical fashion.

01:06:19.000 --> 01:06:28.000
Depends on how much the smoking, start on the Nic team pack, and you're kind of tapered off.

01:06:28.000 --> 01:06:32.000
Both groups are getting substantial, psychological support in the form of Cbt.

01:06:32.000 --> 01:06:49.000
During this time, but then, week 13, it's done. Intervention is done, and they're followed up at 3, 6 and 12 months. And they're not only asked if they're smoking, they're also, you know, there's ways of biologically verifying that.

01:06:49.000 --> 01:06:59.000
These patients were smoking about a pack a day for nearly 30 years, with on average 7 prior, but attempts.

01:06:59.000 --> 01:07:03.000
This is data on 60 participants. But we've had about 20 more.

01:07:03.000 --> 01:07:08.000
The trail is actually almost done.

01:07:08.000 --> 01:07:13.000
So there is your data from Hopkins. I'm showing you on the left.

01:07:13.000 --> 01:07:17.000
This is something already showed you appropriate on something you've already shown.

01:07:17.000 --> 01:07:26.000
You, but here's your 40% feeling. Here's the appointment rate in the Philippines group at 3, 6, and 12 months.

01:07:26.000 --> 01:07:35.000
The next thing patch Group reassuringly, is doing about as well as nicotine patch groups do so to me.

01:07:35.000 --> 01:07:46.000
That means that this is probably a fair comparison. Our thumb is not on the scale, but this is a to me, even though it's not unblinded trial.

01:07:46.000 --> 01:07:51.000
People know exactly what they're getting to me. This is probably the most compelling evidence there is in the field of psychedelics.

01:07:51.000 --> 01:07:55.000
There's the trial I'm not involved with. By the way.

01:07:55.000 --> 01:08:01.000
But yeah, you're seeing more than a 20% difference in abstinence rate.

01:08:01.000 --> 01:08:10.000
You compare that? To what typical you know, it's more than 10, maybe about 10.

01:08:10.000 --> 01:08:18.000
But but this is clearly clearing the ceiling of, and it's not going down over time, which is more typical.

01:08:18.000 --> 01:08:22.000
So there's any number of ways to further refine it.

01:08:22.000 --> 01:08:25.000
This is only one dose. What about 2? What about?

01:08:25.000 --> 01:08:31.000
Some kind of ongoing support. What about combining this with other treatments?

01:08:31.000 --> 01:08:43.000
So to me this is a very promising signal that I think directly addresses a lot of the critiques that are level, that the the field of psychedelic research, they're ballot.

01:08:43.000 --> 01:08:49.000
Take a pause and look at the chat. No!

01:08:49.000 --> 01:08:57.000
Okay. So, and I mentioned there's things I'm not talking about, you know.

01:08:57.000 --> 01:08:58.000
There's a trial, Phillip, for alcohol use disorder that was recently published.

01:08:58.000 --> 01:09:06.000
That was positive, and in terms of substance use disorders.

01:09:06.000 --> 01:09:12.000
There's like others, trial starting. But this is kind of the main.

01:09:12.000 --> 01:09:16.000
The main.

01:09:16.000 --> 01:09:19.000
Strong evidence.

01:09:19.000 --> 01:09:29.000
Okay. One of the main use cases of of psychedelics in the previous era was for palliative care indications.

01:09:29.000 --> 01:09:36.000
In other words, people that are dying terminally ill and are having psychological distress associated with that.

01:09:36.000 --> 01:09:41.000
There were many, many studies on that in the previous era, and I'm not gonna talk about these studies.

01:09:41.000 --> 01:09:54.000
I'm gonna talk about modern studies. There have been 4 that I'm aware of our Cts of a psychedelic for palliative or care cancer.

01:09:54.000 --> 01:09:55.000
And I'll just kinda go through these more briefly.

01:09:55.000 --> 01:10:03.000
Than the previous stuff. This grove, 2011. Well, participant.

01:10:03.000 --> 01:10:10.000
They had an advanced stage terminal, canter with a life expectancy of a 6 month to a year.

01:10:10.000 --> 01:10:15.000
What this is. Kind of. Heterogeneous, vague, but plot.

01:10:15.000 --> 01:10:25.000
One of these diagnoses cute justice, order, Tad adjustment, disorder, and they got this fairly modest dose.

01:10:25.000 --> 01:10:31.000
So small. Study Modesto people that have cancer. One of these diagnoses.

01:10:31.000 --> 01:10:37.000
Basically, it showed it's safe. But there's no significant difference in anxiety and follow up.

01:10:37.000 --> 01:10:43.000
Oh, people with cancer people with some kind of anxiety, disorder, modest as it feels.

01:10:43.000 --> 01:10:49.000
I've been safe. No adverse events, but no difference in the Id.

01:10:49.000 --> 01:10:55.000
Similarly small study and from Switzerland, this time with Lsd.

01:10:55.000 --> 01:11:17.000
And very similar inclusion. Criteria, 12 people, cancer or life, threatening illness and survival greater than 6 months these are these are not people that are imminently dying, which is actually what the previous era mostly studied, and they have some form of anxiety hi dose ld versus very low

01:11:17.000 --> 01:11:24.000
do. This time they showed that it was safe, or most importantly, but also significant decreases in anxiety.

01:11:24.000 --> 01:11:29.000
Up to 2 months the large effect size of 1.1 again.

01:11:29.000 --> 01:11:38.000
Keep harping on this, but one is like fairly massive effect. Size for psychiatry.

01:11:38.000 --> 01:11:48.000
And this is also kind of unusual. I mean, you don't normally have clinical trials where all kinds of different diagnosis for are allowed.

01:11:48.000 --> 01:11:53.000
But this is sort of one of the unique aspects of.

01:11:53.000 --> 01:12:00.000
So many people have psychological distress in dealing with terminal cancer or life, threatening illness.

01:12:00.000 --> 01:12:03.000
And I guess that was kind of the rationale.

01:12:03.000 --> 01:12:06.000
They don't wanna limit it.

01:12:06.000 --> 01:12:12.000
This is from Hopkins Griffith, 2015 50 people with a life threatening cancer diagnosis.

01:12:12.000 --> 01:12:18.000
It's active with 4 pregnancies, such as stage 3 or 4, or recurrence, or the possibility of recurrence.

01:12:18.000 --> 01:12:24.000
So again, these studies often get touted in the media as like psychedelics for people that are dying.

01:12:24.000 --> 01:12:38.000
But these people are really not dying. In truth, they have life threatening illnesses, but they have some possibility of some of these people are actually in, you know, remission with the possibility of recurrence.

01:12:38.000 --> 01:12:45.000
Again, very very heterogeneous set of diagnoses, all pointing to some form of depression or anxiety.

01:12:45.000 --> 01:13:02.000
The time it was pretty high dose of silicon, and there were substantial improvements in well-being, anxiety, depression that persisted for 6 months in the majority of people so enduring effects that we're positive beneficial.

01:13:02.000 --> 01:13:05.000
There is a sort of a sister study that was very similar.

01:13:05.000 --> 01:13:12.000
That was performed at Nyu. At the same time, this time had 30 people, and they say it's a life threatening cancer diagnosis.

01:13:12.000 --> 01:13:17.000
But initially it was terminally ill. Stage 4 cancer.

01:13:17.000 --> 01:13:20.000
But this is broaden to include people who are in remission from cancer.

01:13:20.000 --> 01:13:27.000
So this is truly not a study of people that are dying, that people have had cancer.

01:13:27.000 --> 01:13:34.000
And again pretty broad set of criteria that mostly includes people with anxiety disorders one kind or another.

01:13:34.000 --> 01:13:42.000
90% had adjustment disorder and remaining 10 heads generalized anxiety. Hi!

01:13:42.000 --> 01:13:46.000
Does. Silicon versus.

01:13:46.000 --> 01:13:54.000
And they should fairly substantial, reduced anxiety, depression, and demolition.

01:13:54.000 --> 01:13:56.000
And you know again, these are not people that are dying.

01:13:56.000 --> 01:14:04.000
They actually were able to do a 5 year. Follow up study on on this, and most of the people, enduring benefits.

01:14:04.000 --> 01:14:10.000
So. One thing I haven't harped on in this particular study.

01:14:10.000 --> 01:14:17.000
About 6 months afterwards the majority of patients stated that 70% of patients dated that this was among the top 5.

01:14:17.000 --> 01:14:26.000
Most meaningful experiences of their life, so I have not really talked about how this is done.

01:14:26.000 --> 01:14:30.000
That's the next section. That's the end of our kind.

01:14:30.000 --> 01:14:36.000
Of what did the study show? So happy to answer any questions now?

01:14:36.000 --> 01:14:43.000
Which I'm having a lot of trouble seeing. Oh, there we go!

01:14:43.000 --> 01:14:56.000
Alright. So let's take a look. Are there any studies to show it's easier for people to come up to Cybin versus an Ssri when they want to stop Meds?

01:14:56.000 --> 01:15:06.000
So this question is a good one, but it also kind of doesn't make sense and this is an important thing to people are not really coming up till I've been.

01:15:06.000 --> 01:15:14.000
That's kind of one of the nice things about this in the treatment at the right I'm not knocking at the right, and I'm not knocking conventional psychiatric treatment.

01:15:14.000 --> 01:15:23.000
I use them, and I think they work. They are treatments that have to be taken every single day, and you do. Have I?

01:15:23.000 --> 01:15:24.000
People call it Discontinuation, syndrome.

01:15:24.000 --> 01:15:28.000
I think it's fine. They call it withdrawal.

01:15:28.000 --> 01:15:30.000
People do have difficulty coming up at the thread.

01:15:30.000 --> 01:15:34.000
It's not everyone, but it's a substantial number of people.

01:15:34.000 --> 01:15:37.000
But still it's a treatment that's administered.

01:15:37.000 --> 01:15:47.000
Once or twice. There is no coming off it. If that makes sense, if not, and this is where you know you look at Ketamine a lot murkier.

01:15:47.000 --> 01:16:08.000
Some people end up taking ketamine regularly, and have difficulty coming off, but if I've been not being used in a model of like regular administration, I guess I should say, and I haven't really talked too much about this there's also micro dosing where people take tiny tiny tiny doses

01:16:08.000 --> 01:16:15.000
of hey psychedelic, or whatever reason I'm not talking about that in part, because there have not really been any clinical studies on that.

01:16:15.000 --> 01:16:29.000
The studies have mostly been done in healthy people. When you do a properly controlled trials of micro dose, we're talking tiny doses, some of which don't have subjective effect.

01:16:29.000 --> 01:16:30.000
It's very hard to show that it's doing anything compared to a placebo.

01:16:30.000 --> 01:16:37.000
Easy to show that it's doing something, but it's doing something that will be both you, too.

01:16:37.000 --> 01:16:38.000
So I haven't talked about that simply because there's not enough research.

01:16:38.000 --> 01:16:47.000
But that you know people are taking it frequently, and that's kind of actually where you get.

01:16:47.000 --> 01:16:51.000
When I talked about cardiac valve. Issue. That's where you wonder could this cause a problem that people are taking this regularly?

01:16:51.000 --> 01:16:56.000
But no, generally speaking, as administered news trials.

01:16:56.000 --> 01:17:01.000
People are taking the second Alex. Once or twice spread out over weeks, and then not repeatedly.

01:17:01.000 --> 01:17:07.000
After that, and we don't see that people that enter these trials to take get the active drug.

01:17:07.000 --> 01:17:08.000
We don't see that they're going out and then doing it.

01:17:08.000 --> 01:17:15.000
A bunch at home. Oh, which I think I inadvertently answered.

01:17:15.000 --> 01:17:22.000
Another question of studies involving Microdosing. So, yeah, there are a bunch of studies.

01:17:22.000 --> 01:17:26.000
But in terms of beneficial effects. It's not.

01:17:26.000 --> 01:17:30.000
Really, we're not really seeing much that's better than placebo.

01:17:30.000 --> 01:17:34.000
But again we've not seen any studies yet in a clinical population.

01:17:34.000 --> 01:17:41.000
I'm personally not so interested in doing those studies because.

01:17:41.000 --> 01:17:47.000
I mean, there's so much still to do with the macroosing that's where we are seeing kind of strong.

01:17:47.000 --> 01:17:56.000
And during effects. So Doctor Lahay, so not enough back to the Philippine versus as the telegram.

01:17:56.000 --> 01:18:01.000
Not enough weeks on Lexopomax dose. Yeah, this is a 6 week study.

01:18:01.000 --> 01:18:07.000
So!

01:18:07.000 --> 01:18:10.000
Your point was that this study was biased towards Philip Dibin.

01:18:10.000 --> 01:18:15.000
Is that correct?

01:18:15.000 --> 01:18:21.000
I guess you can't really talk.

01:18:21.000 --> 01:18:23.000
But I mean, that's true. Yeah, I mean, that's not.

01:18:23.000 --> 01:18:27.000
They run. It's a 6 week study they're on left to per 6 weeks.

01:18:27.000 --> 01:18:31.000
They were not on 20 milligrams for 6 weeks the dust is bumps from 10.

01:18:31.000 --> 01:18:36.000
I forget exactly when. So, yeah, I mean, it's I'm glad that they compared it to an active treatment but there's clearly more to be done.

01:18:36.000 --> 01:18:43.000
There!

01:18:43.000 --> 01:18:51.000
Do I believe that the effects are primarily due to the administration of the drug, or what occurs in the setting?

01:18:51.000 --> 01:18:55.000
This is a a nice segue, then to talk about.

01:18:55.000 --> 01:19:07.000
Well what is actually happening during the dove. So I will address that in the coming section.

01:19:07.000 --> 01:19:08.000
Yeah, I think we're doing good on time with 40 min.

01:19:08.000 --> 01:19:13.000
Section 43 min.

01:19:13.000 --> 01:19:16.000
With the.

01:19:16.000 --> 01:19:25.000
Any other questions, actually, probably take one more and then move on.

01:19:25.000 --> 01:19:30.000
Yes, some questions in the chat. I can read.

01:19:30.000 --> 01:19:35.000
Alicia asks, is ketamine the same as in Dma?

01:19:35.000 --> 01:19:41.000
Oh, I think, I answered, that it's not. It's a very different drug.

01:19:41.000 --> 01:19:47.000
Oh, there's one also by Alisha, psychedelic direct with anxiety.

01:19:47.000 --> 01:19:54.000
So the the main studies that have been done on anxiety up to this point are the ones that have just shown you.

01:19:54.000 --> 01:20:07.000
It is anxiety in the setting of cancer, and there does not seem, it seems, to help.

01:20:07.000 --> 01:20:08.000
There is a study that is going to launch. That is Lsd.

01:20:08.000 --> 01:20:14.000
For generalized anxiety, disorder. These cancer studies are a little hard to make sense of, because there's like a lot going on.

01:20:14.000 --> 01:20:22.000
They have cancer. They might have Ptsd, they might have Ptsd, they might have adjustment disorder, but they're anxious.

01:20:22.000 --> 01:20:31.000
But and large, and so it doesn't seem that people are having adverse events, and there does seem to be some benefits.

01:20:31.000 --> 01:20:36.000
So really, just need. And there is actually another trial that I left out.

01:20:36.000 --> 01:20:43.000
That was in people that were at anxiety.

01:20:43.000 --> 01:20:44.000
So, yeah, there has actually been some research on that.

01:20:44.000 --> 01:20:55.000
But it's still pretty preliminary, and there's not as much evidence, but compared to say, depression.

01:20:55.000 --> 01:21:00.000
Alisha in the imperial study the higher relapse rate meant more.

01:21:00.000 --> 01:21:03.000
People relapsed after psilocybin.

01:21:03.000 --> 01:21:10.000
No, no, no! The higher relapse. Route relapse right? No!

01:21:10.000 --> 01:21:19.000
The remission rate was higher. I may have misspoke, but the remission rate in the Silicon group was double that of, and again, you can talk about like.

01:21:19.000 --> 01:21:23.000
Is, is that really a fair comparison or not?

01:21:23.000 --> 01:21:29.000
But the remission rate was about 60% compared to 30%.

01:21:29.000 --> 01:21:35.000
All right. One more.

01:21:35.000 --> 01:21:39.000
And yeah, the other point I'll make is that you know one of the reasons why people are excited about people are excited about psychedelics for all kinds of reasons.

01:21:39.000 --> 01:21:46.000
They think it's gonna change the world. I think it's gonna fix it.

01:21:46.000 --> 01:22:05.000
I I I don't think that's particularly likely, but as a treatment for psychiatric disorders, the promise of it is that when it works and it does not always work, but when it works it seems to work fast and there's caveats, to that but that is

01:22:05.000 --> 01:22:17.000
kind of one reason why people are excited, and the other is that it doesn't require daily administration of anything.

01:22:17.000 --> 01:22:24.000
So let's talk about, what do we actually do? This is a 20 min section.

01:22:24.000 --> 01:22:28.000
We're probably not gonna need that much time. So we can we can talk more about this.

01:22:28.000 --> 01:22:36.000
But this is a model of directly imported from the prior wave of psychedelic research.

01:22:36.000 --> 01:22:53.000
I talked about all the different models that are used, including the CIA dropping some Lsd and somebody's coffee and seeing what happens, including treating it as a model psychosis, including giving it to people that are strapped down in the bed.

01:22:53.000 --> 01:23:06.000
But we now do across all trials, with some exceptions, is the psychedelic model, and the hallmark of the psychedelic model is, and attention to context.

01:23:06.000 --> 01:23:12.000
And that starts with preparatory sessions. So I can speak about our trials.

01:23:12.000 --> 01:23:26.000
There are differences across trials and other places, but we typically do at Hopkins roughly, 6 to 8 h of of meetings prior to there being any drug.

01:23:26.000 --> 01:23:38.000
And those those meetings are done with. 2 study therapist, and you know, 1, one of at least one of whom is like a license mental help.

01:23:38.000 --> 01:23:47.000
Practitioner from kind, the other. You know, that could be a research assistance, or that could be another psychotherapist or psychiatrist.

01:23:47.000 --> 01:23:53.000
But there's 6 to 8 h of meetings before they're the dose.

01:23:53.000 --> 01:23:58.000
Then there's the dose, and then there's a follow-up meeting, so let's stick with the prep.

01:23:58.000 --> 01:24:03.000
For now, though so what are what is the point of the preparatory session?

01:24:03.000 --> 01:24:12.000
The one is to get to know the patient, the participant in a very well, in a broad sense, report building.

01:24:12.000 --> 01:24:22.000
You really AIM to build a sense of familiarity and comfort, and that's one thing to, though, is that you want to get their life story.

01:24:22.000 --> 01:24:35.000
You want to begin to develop some kind of narrative about what is the problem they've been dealing with, and what's their understanding of it?

01:24:35.000 --> 01:24:50.000
In what ways they feel stuck. Just you're trying to get a clear sense of the story, and many people kind of in this doing this process, they'll say, Wow, nobody's ever asked me all this before, or they'll start to get some head of clarity just from that alone of what

01:24:50.000 --> 01:24:57.000
has been going on in your life. That's pretty similar whether it's a trial for alcohol use, disorder, depression, anorexia.

01:24:57.000 --> 01:25:01.000
So far we're talking about fairly similar things now.

01:25:01.000 --> 01:25:09.000
There can be condition-specific components. So, for example, some trials have used motivational interviewing.

01:25:09.000 --> 01:25:22.000
I mentioned Cbt. For smoking cessation. So far, that's been a minority of trials that are using a specific, defined, concurrent psychotherapy during these.

01:25:22.000 --> 01:25:34.000
Another component, though, of the preparatory sessions, is to prepare the person for the drug session, and so.

01:25:34.000 --> 01:25:49.000
The drug I've mentioned can cause all kinds of effects, including experiences of terror, including experiences of ecstasy, of rapture, mystical experiences.

01:25:49.000 --> 01:25:58.000
People may feel like they are dying. People may feel like they're they're going insane that they're never going to come back. And it's so.

01:25:58.000 --> 01:26:11.000
It's very important that they feel like they can trust the people that they're in the room with, because if the people the facilitators, we call them are trying to reassure them.

01:26:11.000 --> 01:26:14.000
Look, you're actually safe. You're okay. It's really important that they believe that.

01:26:14.000 --> 01:26:20.000
And they're not gonna really believe that coming from strangers.

01:26:20.000 --> 01:26:32.000
But there is also preparation on what to do, and so these again, these are directly imported from the second wave of psychedelic research.

01:26:32.000 --> 01:26:38.000
So an attitude of experiential acceptance appears to be most helpful.

01:26:38.000 --> 01:26:39.000
I can't say that there's been clear research.

01:26:39.000 --> 01:26:45.000
That's demonstrating that versus people being primed in the opposite direction.

01:26:45.000 --> 01:26:53.000
But people are encouraged to, you know. Trust. Let go, be open to try to move towards whatever content.

01:26:53.000 --> 01:27:01.000
They are experiencing rather than away from it. And they're also encouraged that whatever happens, good, bad, ugly.

01:27:01.000 --> 01:27:07.000
They will be safe, and the facilitators are going to be ensuring that they will be safe.

01:27:07.000 --> 01:27:20.000
They're present the entire time, both of them, except for bathroom break for lunch, which is why there's 2 of them, and so.

01:27:20.000 --> 01:27:24.000
You know. There's also gonna be monitoring of blood pressure, etc.

01:27:24.000 --> 01:27:32.000
But they are, they are gonna be monitored, and and that all happens in in the preparatory session.

01:27:32.000 --> 01:27:49.000
And so, yeah, I keep harping on this, but that actually ends up looking pretty similar, no matter what the trial actually is, I think as the field develops, we may start to see these, they become more and more specific to the condition being studied.

01:27:49.000 --> 01:27:59.000
But but so far it's using a fairly generic model of prep.

01:27:59.000 --> 01:28:08.000
The dosing session, so comfortable living room, like environment, you have the 2 facilitators that have.

01:28:08.000 --> 01:28:11.000
They've gotten to know records of 8 cumulative hours.

01:28:11.000 --> 01:28:12.000
You can see a Buddha in the background.

01:28:12.000 --> 01:28:20.000
We've now removed any references to religious iconography.

01:28:20.000 --> 01:28:27.000
And one thing that I think surprised me is that this is not an active talk.

01:28:27.000 --> 01:28:35.000
Like therapy. People are not being. These are often colloquially called guides.

01:28:35.000 --> 01:28:41.000
People are not being guided. This is a very internal, you know.

01:28:41.000 --> 01:28:50.000
Personal experience. Where they're not really being ushered through in any particular way, participants are apps to lie on the couch.

01:28:50.000 --> 01:29:04.000
They were eyeshades and headphones, and nowadays that as as well, and they listen to music, the music is intentionally selected.

01:29:04.000 --> 01:29:08.000
It's not necessarily the kind of music that people wanna listen to.

01:29:08.000 --> 01:29:13.000
Outside of a psychedelic experience. I won't go into the details about the music unless people really wanna know.

01:29:13.000 --> 01:29:34.000
But the idea is that the music is supposed to in route emotions, but also provide a sense of continuity on something they can pay attention to, to hold on to people typically feel that the music is very very important for guiding the experience and they're encouraged to focus their attention inward

01:29:34.000 --> 01:29:39.000
so there are other ways that people can take, clicked Alex. Right?

01:29:39.000 --> 01:29:44.000
They can be sitting up. They can be talking. They can be walking around.

01:29:44.000 --> 01:29:53.000
But this is a model which is very, very inwardly focused, and it is a moderate to high dose of silicon.

01:29:53.000 --> 01:29:59.000
People often think that oh, this is being done in research. Maybe it's like a little dove.

01:29:59.000 --> 01:30:10.000
No, these are in some cases very high doses of fill in that very well approximate, and go beyond what is being used recreationally by people.

01:30:10.000 --> 01:30:11.000
Any good, attitude of acceptance and curiosity to trust.

01:30:11.000 --> 01:30:14.000
Let go and be open. These experiences have a very odd way of rewarding experience to acceptance and punishing.

01:30:14.000 --> 01:30:34.000
Financial avoidance. So people will often find that something difficult will happen in that they are sort of reflexively try to engage with it with their normal way of engaging with difficulty, perhaps avoiding, perhaps turning away.

01:30:34.000 --> 01:30:39.000
Perhaps intellectualizing, whatever it might be, and they find that it doesn't work.

01:30:39.000 --> 01:30:45.000
And then they will try something else, and they'll find that they're able to navigate the experience.

01:30:45.000 --> 01:30:57.000
So there is a learning that is happening. During this, let me just pause and look at all these questions that are coming in.

01:30:57.000 --> 01:31:10.000
Any reason for using a living room like environment versus another setting. So the living room, like environment, is in contrast to a hospital room.

01:31:10.000 --> 01:31:14.000
And then we kind of got stuck there. There's probably ways to optimize it further.

01:31:14.000 --> 01:31:22.000
A nature setting many. I suspect that that would be better.

01:31:22.000 --> 01:31:36.000
However, you know again, people are. People are largely kind of underneath eyeshades in an internal experience, where, even in a nature setting, they would be not really paying attention to nature.

01:31:36.000 --> 01:31:40.000
But that's something it's nobody studied yet, and somebody should.

01:31:40.000 --> 01:31:44.000
If Clinician referred it the clinician part of the treatment.

01:31:44.000 --> 01:31:57.000
No questions are part of the study team. Also a question there, right like, if this is rolled out to legal, I mean, should people's own clinicians be doing this?

01:31:57.000 --> 01:32:00.000
I'm curious about the music choice vibrational tones.

01:32:00.000 --> 01:32:07.000
So this is a this is one of the interesting things about.

01:32:07.000 --> 01:32:17.000
Takeedelic research. You don't normally have you're not normally researching a new treatment that is already being used by millions of people across the world.

01:32:17.000 --> 01:32:37.000
And so there are a lot of opinion, including that there are people who believe that overtone music gongs trying in some ways you could consider not really music, but sort of sounds with lots of different range of tones are are the ideal form of psychedelic music.

01:32:37.000 --> 01:32:45.000
Lots of people have feel they have discovered the ideal form of psychedelic music, but that is actually a component of it is also in the Hopkins playlist.

01:32:45.000 --> 01:32:52.000
Lots of classical music, lots of world music, chanting, drumming, etc.

01:32:52.000 --> 01:32:53.000
There is a playlist. It's on spotify.

01:32:53.000 --> 01:32:54.000
I can share it afterward, and I can all define it quickly right now.

01:32:54.000 --> 01:33:05.000
It's actually kind of old, but you know what I'll share like a bunch of playlists if people are interested.

01:33:05.000 --> 01:33:11.000
And this is one thing I will say, that is quite different about Mdma.

01:33:11.000 --> 01:33:17.000
This sort of looks like what happened with mdma. Everything I've described is also what they do with Mdma.

01:33:17.000 --> 01:33:23.000
However, the nature of the drug it's a stimulant at some point.

01:33:23.000 --> 01:33:32.000
I've never done Mdm. Therapy, but my understanding talking to people who do is that it actually ends up becoming actual talks like a therapy.

01:33:32.000 --> 01:33:37.000
People sit up and they're talking about the trauma, and there, you know, it's much more familiar to.

01:33:37.000 --> 01:33:45.000
Where is here? Oftentimes, if things are going well, people are silent for hours, and you may not know it's happening you're checking in with them periodically.

01:33:45.000 --> 01:33:54.000
And if people are getting stuck, if they're having to stress, that's when you need to start helping them figure it out.

01:33:54.000 --> 01:33:58.000
But the goal is usually to help them get through that, and then back in.

01:33:58.000 --> 01:34:07.000
So mdma is much more hockey, whereas this is not talk about the ketamine stuff after.

01:34:07.000 --> 01:34:19.000
But but this is kind of the beginning. Really, the meat of this is the follow-up, which is are called integration, session.

01:34:19.000 --> 01:34:23.000
And these are meetings with both facilitators in the days and weeks following.

01:34:23.000 --> 01:34:26.000
I say both, but that's the compass trial. I think.

01:34:26.000 --> 01:34:36.000
Only use one afterward. So you, this is kind of subject to change, and they review the experience on the session day as well as interim events.

01:34:36.000 --> 01:34:40.000
The goal is to try to turn, maybe they had a very confusing experience.

01:34:40.000 --> 01:34:55.000
Maybe had a very meaningful experience, but the goal is to try to help the participant understand and incorporate it in a way that can useful, and I actually view this as being fundamentally psychotherapy.

01:34:55.000 --> 01:35:12.000
The next section is about that. But this is kind of, in my opinion, the most fun part as a clinician, but perhaps the most important part because we're saying that these experiences can be helpful in an enduring way.

01:35:12.000 --> 01:35:16.000
But why like why should the experience of a single day have any impact later on?

01:35:16.000 --> 01:35:28.000
I I don't think we have trouble understanding that in a negative sense, right? If somebody has a severe trauma I don't think any of us have a great deal of difficulty understanding why that can have a positive impact on the road.

01:35:28.000 --> 01:35:29.000
But when done well. These experiences can be the opposite of that.

01:35:29.000 --> 01:35:38.000
A highly meaningful experience that can have a positive impact on the road.

01:35:38.000 --> 01:35:54.000
But that doesn't happen on its own and so there is some interpretation and also a behavioral translation that have to happen to turn these experiences useful sometimes.

01:35:54.000 --> 01:36:03.000
That's easier sometimes. That's more difficult. Let's see.

01:36:03.000 --> 01:36:11.000
Take some of these we're kind of at the end of the section. So.

01:36:11.000 --> 01:36:16.000
Nothing in the chat. Okay?

01:36:16.000 --> 01:36:17.000
Question. I am very interested in varying effectiveness.

01:36:17.000 --> 01:36:22.000
The Ketamine treatments for Trd is the data in this presentation transferable at least in part, Academy.

01:36:22.000 --> 01:36:38.000
I don't know, and this is why I don't know the studies on Ketamine that have been done have just administered ketamine as a drug without any attention to.

01:36:38.000 --> 01:36:46.000
Well, I've heard that some of the earlier Academies studies there were more I don't know.

01:36:46.000 --> 01:36:51.000
Touchy-feely. I guess you could call, but that I don't actually know what that means.

01:36:51.000 --> 01:37:10.000
Bye and large, the study on ketamine have just administered the drug to somebody in a medical setting in a way that was probably not so different from somebody getting any getting chemo, for example, and so, whether all of this other stuff the thing is all this other stuff like being in the company

01:37:10.000 --> 01:37:12.000
of 2, and empathetic, born people who've gotten to know you that in itself does have a beneficial effect.

01:37:12.000 --> 01:37:19.000
So I imagine. Of course, you would mix that with ketamine.

01:37:19.000 --> 01:37:22.000
The question is, does it really help? Is it synergize?

01:37:22.000 --> 01:37:31.000
It could actually help but make the treatment better than just the sum of the 2 parts, and that is what people, when people say ketamine is a psychedelic, that is what they are implying.

01:37:31.000 --> 01:37:39.000
If ketamine is a psychedelic, then all of the things that I'm talking about that pertain to classic psychedelics, applied Academy I don't know if that's true.

01:37:39.000 --> 01:37:48.000
Somebody should do the study, though, and it's again a little difficult to know, because Ketamine is now FDA approved, and not now.

01:37:48.000 --> 01:37:50.000
It's been FDA approved since the fiftys.

01:37:50.000 --> 01:37:53.000
I think, and you can use it. However, you want off label.

01:37:53.000 --> 01:37:57.000
People are using ketamine assisted psychedelic therapy.

01:37:57.000 --> 01:38:02.000
So!

01:38:02.000 --> 01:38:03.000
I just don't know. It seems like sure.

01:38:03.000 --> 01:38:10.000
Maybe it could work. Maybe it does work, but nobody is really researched in a systematic way.

01:38:10.000 --> 01:38:17.000
It's doing something that is necessary, that beyond the drug itself.

01:38:17.000 --> 01:38:19.000
Is this covered by medical insurance? No, this is not an approved drug.

01:38:19.000 --> 01:38:27.000
I mean ketamine is, and at Ketamine is at the approved.

01:38:27.000 --> 01:38:37.000
But you know it's none of none of these classic psychedelics are are approved.

01:38:37.000 --> 01:38:41.000
Mdma actually does have what is called expanded access.

01:38:41.000 --> 01:38:48.000
And so there are patients getting. It's a handful, I'm sure it's less than 5.

01:38:48.000 --> 01:38:52.000
But there are patients who have received an mdma for Ptsd.

01:38:52.000 --> 01:38:59.000
Not in a research study and it's, you know, a question of like, will that happen with psilocybin?

01:38:59.000 --> 01:39:03.000
But basically by and large. This is all highly regulated research.

01:39:03.000 --> 01:39:13.000
None of this is being done out in the community. None of this is standard for treatment, but is being done in the community, though, and we can talk more about this.

01:39:13.000 --> 01:39:25.000
I mean, people. Large chunk of Americans are taking these drugs. But in terms of therapeutic use, it's not really.

01:39:25.000 --> 01:39:28.000
So yeah, hard to answer the question of what are the costs involved?

01:39:28.000 --> 01:39:43.000
It's not a treatment that, but the main cost here is I just said they're spending multiple hours with 2 facilitators, at least one of whom is a highly skilled psychotherapist.

01:39:43.000 --> 01:39:48.000
So that's a lot of money.

01:39:48.000 --> 01:39:53.000
Okay. Can I have a bathroom break before the next session?

01:39:53.000 --> 01:39:59.000
I'm gonna just do that and be right back.

01:39:59.000 --> 01:40:03.000
Yup, that sounds great. Why don't we take like?

01:40:03.000 --> 01:40:04.000
Oh, sure! That is!

01:40:04.000 --> 01:40:08.000
Does a 10 min break sound good, Dr. Nyak, and we could just let everyone go to the bathroom and refill coffee if we need.

01:40:08.000 --> 01:40:11.000
Yeah, yeah, yeah. Okay. I'll get some tea. Then.

01:40:11.000 --> 01:40:17.000
Okay. So yeah, why don't we take a 10 min break and come back about 1050, or so?

01:40:17.000 --> 01:40:18.000
Sounds, great.

01:40:18.000 --> 01:40:48.000
Does that sound good? Excellent? All right.

01:50:02.000 --> 01:50:07.000
Oh, sorry! I can start when ready. All right. We are back.

01:50:07.000 --> 01:50:10.000
Everyone has gone to the bathroom, got in your tea, coffee?

01:50:10.000 --> 01:50:13.000
So our next 20 min section is psychedelic therapy.

01:50:13.000 --> 01:50:24.000
As psychotherapy. The first I'm gonna talk more about the actual subjective effect.

01:50:24.000 --> 01:50:34.000
And then this idea of the common factors of psychotherapy, which I'll explain, and then one or 2 cases.

01:50:34.000 --> 01:50:36.000
So why do I say psychedelic therapy is like a therapy.

01:50:36.000 --> 01:50:59.000
Well, one is that like psychotherapy, it's seems to enact some of the therapeutic effects via an experiential basis, and also like psychotherapy, it can have kind of an enduring impact after it is stop which is not so much the case for there's not really

01:50:59.000 --> 01:51:00.000
a good model of well, we'll put that aside.

01:51:00.000 --> 01:51:10.000
I've mentioned now mystical experience, and ultimately in research, things are boiled down to questionnaires.

01:51:10.000 --> 01:51:27.000
And this mystical experience. Questionnaire, is one that meters these different elements of experience during the session people are responding to it afterwards when they're sober, but they're talking about their experience, and it assesses things like unity.

01:51:27.000 --> 01:51:38.000
Sense of unity with the world. Positive mood, transcendence and space and time, ineffability means inability to communicate the experience in words that's the reverence.

01:51:38.000 --> 01:51:48.000
And there is a dose dependent effect of both dive in 5 milligrams, 15 milligrams, 20 milligrams on the mystical experience.

01:51:48.000 --> 01:51:51.000
Questionnaire, and it's called mystical experience.

01:51:51.000 --> 01:52:00.000
Because it sort of approximates the kinds of classical descriptions of my experience that have occurred in sort of religious literature throughout history.

01:52:00.000 --> 01:52:10.000
Who cares? Well, we care because the mystical experience on the session day predicts later therapeutic outcomes.

01:52:10.000 --> 01:52:15.000
So this is, you know, bottom is mystical experience.

01:52:15.000 --> 01:52:25.000
Going all the way up to 100, which is Max correlation with smoking, creating correlation, with depression, change, correlation with anxiety, change.

01:52:25.000 --> 01:52:31.000
And they're like meaningful correlation. It's not like nothing.

01:52:31.000 --> 01:52:34.000
And lots of so it's correlated with enduring improvements in quality of life, meaningfulness of the experience.

01:52:34.000 --> 01:52:45.000
Various clinical outcomes. A lot of these defects are most strong in healthy participants, but they're correlated with various kind of outcomes as well.

01:52:45.000 --> 01:52:54.000
People, really quibble about the term mystical. Perhaps it's not the best word for marketing reasons, or any reason whatever.

01:52:54.000 --> 01:52:58.000
But the basic point is that you can call it different things.

01:52:58.000 --> 01:53:03.000
A correlation of one means that 2 questionnaires are perfectly. They're identical.

01:53:03.000 --> 01:53:14.000
Basically, they're measuring the same thing, a correlation of point 8 or point 9 means that they're basically the same thing.

01:53:14.000 --> 01:53:19.000
And the mystical experience. Questionnaire roselates with the near-death experience.

01:53:19.000 --> 01:53:23.000
Questionnaire, it correlates with the all experienced questionnaire correlates.

01:53:23.000 --> 01:53:31.000
This is with this questionnaire called oceanic boundlessness, and they're all kind of the same thing.

01:53:31.000 --> 01:53:32.000
I'm not saying that any questionnaire you use is going to be the same thing.

01:53:32.000 --> 01:53:40.000
I mean, these are pretty similar. Just a couple of examples of the All experience questionnaire.

01:53:40.000 --> 01:53:44.000
I felt closely connected to humanity. I felt in the presence of greatness.

01:53:44.000 --> 01:53:56.000
I felt myself, of self change, I experienced something greater than myself that any of these kind of self-transcendent positively valence type questionnaires are probably going to be getting at the same thing.

01:53:56.000 --> 01:54:05.000
Now, whatever you wanna call it, though I said that this correlates with their therapeutic benefits, and so what's the meeting of that?

01:54:05.000 --> 01:54:10.000
Is it the case that these experiences are causing therapeutic benefit?

01:54:10.000 --> 01:54:14.000
Do you have most psychedelic researchers? That is what they will say.

01:54:14.000 --> 01:54:27.000
And here's like an opinion piece on that from 2 of my colleagues titled the thesis in the title, the subjective effects of that are necessary or they're enduring therapeutic effect.

01:54:27.000 --> 01:54:34.000
And there's the dueling opinion, though summed up by no, they're not.

01:54:34.000 --> 01:54:43.000
And this, this is like they were 2 opinion pieces published simultaneously, and you can read it basically.

01:54:43.000 --> 01:54:51.000
No, the subjective effect might not be necessary, or they're enduring therapeutic effects.

01:54:51.000 --> 01:54:54.000
It's helpful to look at a causal diagram.

01:54:54.000 --> 01:55:07.000
So I think both of these camp would agree that both of these pathways exist, meaning let's take Philip Ivin has a therapeutic effect via subjective effects.

01:55:07.000 --> 01:55:14.000
For example, mystical experience, or psychologically insightful experiences, or something.

01:55:14.000 --> 01:55:25.000
Pathway, one pathway, 2 is is causing therapeutic effect, and any of the other stuff is maybe just extra or relevant, or a distractor.

01:55:25.000 --> 01:55:35.000
I think both of these camps would acknowledge that both of these pathways exist it's more of a question of which is the stronger one which is dictating most of the effect.

01:55:35.000 --> 01:55:54.000
That's where the controversy lies, I think, and regardless though my argument is that what is done in psychedelic therapy as currently delivered, is kind of like psychotherapy, or, in fact, is psychotherapy, which does definitely have effect through subjective effect so let's

01:55:54.000 --> 01:55:59.000
talk about why I say that so I don't know.

01:55:59.000 --> 01:56:03.000
I'm actually a little unclear on whether this is controversial or not.

01:56:03.000 --> 01:56:11.000
But there is like a very, very longstanding and well established literature on something called the common feature.

01:56:11.000 --> 01:56:30.000
It's like a therapy. And the basic idea of the common factors of psychotherapy is that different types of psychotherapy totally different modalities, the active ingredients, the things that are doing the bulk of the work there are shared between those and the things that differentiate

01:56:30.000 --> 01:56:44.000
them are actually doing relatively, much less of the work. Basically just is that it is the shared or common factors between psychotherapies that are doing most of the heavy lifting versus the things that differentiate them.

01:56:44.000 --> 01:56:49.000
And this is the Dodo in Alice in Wonderland.

01:56:49.000 --> 01:56:53.000
The Common factors theory is often called the dodo bird verdict.

01:56:53.000 --> 01:56:57.000
After switching around, and Alice's pool of tears.

01:56:57.000 --> 01:57:04.000
The animals in this book they needed to dry off and the dodo suggested a race, and everyone runs in different directions.

01:57:04.000 --> 01:57:17.000
There's no rules, and at the end the dota verdict is, everybody has one, and all must have prizes, and so that's the Dona Ver verdict is applied to the research on empirical research on psychotherapy.

01:57:17.000 --> 01:57:29.000
And they do. And this is true, that when you compare to psychotherapy head-to-head it is actually quite hard to show that one therapy is consistently better.

01:57:29.000 --> 01:57:38.000
In another, and also the specific ingredients that differentiate the type of therapies explain much less of the benefit.

01:57:38.000 --> 01:57:44.000
Then the common factors that they're shared. What are the common factors, though?

01:57:44.000 --> 01:57:51.000
Well, sorry. This is a bit more detail on that.

01:57:51.000 --> 01:57:56.000
Well, I'm not gonna actually get into this.

01:57:56.000 --> 01:58:07.000
So Jerome, Frank, there's many different categories of common factor, like I therapy. I like to run, Frank, though, because it kind of explains relatively well.

01:58:07.000 --> 01:58:14.000
But he, it was like a therapist, and he viewed like a therapy as a cell or demoralization, repairing.

01:58:14.000 --> 01:58:21.000
One has tempted world, this is the that enduring, cognitive, affecting, and behavioral functions that guide perception and action.

01:58:21.000 --> 01:58:37.000
He said, that patient speak help not in response to the symptoms themselves, but because their efforts to cope with them have failed, and he described the effect of like a therapy is on the pathogenic meanings that patients attribute to things in their life.

01:58:37.000 --> 01:58:44.000
And according to Jerome Frank, there are again, there are other common factors, the but they all are relatively similar.

01:58:44.000 --> 01:59:02.000
And the message, basically, he stated that all bona fide second therapies will have these elements an emotionally charged confiding relationship with an expert who is believed to have jurisdiction over psychological feelings, a healing setting like a framework of place we're

01:59:02.000 --> 01:59:21.000
healing is expected to happen. Hey, rationale, conceptual scheme, or myth that can explain the patient, the origin, or the genesis of the patient's problems, as well as providing a plausible means of of how to fix it, and then a therapeutic ritual that is engaged in

01:59:21.000 --> 01:59:27.000
by both the patient and therapist, which is believed by both to be effective and all bona fide psychotherapy should also allow for corrective emotional experiences.

01:59:27.000 --> 01:59:37.000
Some kind of skill building, as well as the ability to rescript at pathogenic meaning.

01:59:37.000 --> 01:59:44.000
It is very hard to see how psychedelic, therapy, S delivered does not fit with these criteria.

01:59:44.000 --> 01:59:52.000
But yeah, the overall take a therapeutic change, according to Frank, is rescripting a pathogenic meetings.

01:59:52.000 --> 01:59:57.000
What is this? Provide? Yeah, I've kind of said this.

01:59:57.000 --> 02:00:04.000
I'll take a sip of water and allow you to read.

02:00:04.000 --> 02:00:11.000
And actually get my tea.

02:00:11.000 --> 02:00:14.000
Now!

02:00:14.000 --> 02:00:26.000
This, I think, is maybe controversial, the even though the literature you can take this very literally if you want that all psychotherapy are the same not exactly what this body of literature is suggesting.

02:00:26.000 --> 02:00:31.000
It's suggesting that like other countries, are more similar than they are different.

02:00:31.000 --> 02:00:40.000
And when you study them in a form that is done in empirical research, it's very hard to show that one is doing something fundamentally different than the other.

02:00:40.000 --> 02:00:48.000
I find that a little hard to stomach when it comes to it's use an actual clinical practice, which is kind of hard to actually study.

02:00:48.000 --> 02:00:57.000
But when it when it comes to psychedelic therapy, I think there is a tendency for that.

02:00:57.000 --> 02:01:12.000
This is like a researcher from the sixties. There's a tendency for psychotherapists who are using psychedelic therapy to feel like their modality is the one that is most perfectly suited I'm gonna read this in full.

02:01:12.000 --> 02:01:24.000
I just curious how under Lsd, the fondest theories of the therapist are confirmed by his patient Rhydian symbols come out of the males with patients with analysts, those who have young gee therapists still with the collective and conscious archetypal

02:01:24.000 --> 02:01:30.000
images, the patient fences, the frame of reference to be employed, and his association can dream they're molded to it.

02:01:30.000 --> 02:01:36.000
Therefore, the validity of any school healing should not be based upon the productions of the patient, especially Lsd.

02:01:36.000 --> 02:01:55.000
Patient there is a Lsd psychotherapist called Dennis Loft, and one of his genuine beliefs about how psychedelics work is by recalling and repairing birth trauma, in other words, the trauma that occurs when people pass from the womb into the world

02:01:55.000 --> 02:02:02.000
during their birth, and here's the description that I'll also read in full from one of his patient.

02:02:02.000 --> 02:02:07.000
I relived my own conception in various stages of my embryological development.

02:02:07.000 --> 02:02:20.000
While I was experiencing all this complexities of the embryo Genesis with details of surpassed the best medical handbooks I was flashing back to an even more remote past, visualizing biogenetic messages from the life of my animal ancestors the

02:02:20.000 --> 02:02:26.000
scientist in me was struck by another riddle. Can the genetic code?

02:02:26.000 --> 02:02:35.000
I'm not gonna read all this actually, but he says I reached a new feeling of harmony and self-acceptance and global understanding of existence that is difficult to define.

02:02:35.000 --> 02:02:44.000
One way of looking at this, assuming that episodic memories from the womb are not possible, which is pretty reasonable.

02:02:44.000 --> 02:02:51.000
Assumption is that these are false memories that LED to therapeutic effects.

02:02:51.000 --> 02:03:03.000
And these are experiences that are fully in line with Stanislav growth treatment method, which is to generate an interpret.

02:03:03.000 --> 02:03:11.000
Birth. Trauma, so!

02:03:11.000 --> 02:03:20.000
I'm just gonna not interpret that. But there's an analogy, I think, to be made with other kinds of therapies as their administered with psychedelics.

02:03:20.000 --> 02:03:38.000
And I think that there are many ways in which this is done, particularly once you get out of the research setting just because something works doesn't mean that it's necessarily the only way, or that it's necessarily true, all.

02:03:38.000 --> 02:03:44.000
So that there are ways in which psychedelics are likely to amplify some of these shared common factors of psychotherapy.

02:03:44.000 --> 02:03:51.000
They produce feelings and psychological insights, they increase mindfulness and acceptance even when they're not being specifically trained.

02:03:51.000 --> 02:03:57.000
They! So they're improving upon some emotional skills.

02:03:57.000 --> 02:04:01.000
And it's also enhances the psychotherapy relationship.

02:04:01.000 --> 02:04:04.000
These are interpersonally intimate experiences. The current trusting environment.

02:04:04.000 --> 02:04:18.000
People generally feel quite bonded with their their facilityitators like it also enhanced suggestibility, which you know that you can say that in a way that sounds very bad.

02:04:18.000 --> 02:04:27.000
That does also make various. Psychotherapeutic interpretations more plausible, that they enhanced the sense of meaning, sense of connection.

02:04:27.000 --> 02:04:34.000
So there are many, many, many ways in which psychedelics may be enhancing some of these common factors of psychotherapy.

02:04:34.000 --> 02:04:44.000
Much is made of the mystical experience thing. But there are other subjective measures which correlate equally and sometimes better mystical experience.

02:04:44.000 --> 02:04:53.000
Psychological insight, for example, is often a stronger predictor of subjective, of a therapeutic benefits.

02:04:53.000 --> 02:04:57.000
I'm I'm gonna just talk about.

02:04:57.000 --> 02:05:08.000
There's no text here. I'm gonna talk about 2 cases where they don't neatly fit with the story of somebody had a mystical experience, and then they're now better.

02:05:08.000 --> 02:05:19.000
These are to individuals in their late thirties, with chronic depression and alcohol, use disorder that we're in a trial for the combination of those both.

02:05:19.000 --> 02:05:41.000
Socially and occupationally pretty functional. So both having pretty chronic depression going on for years, had tried various treatments, including some psychotherapy and various antidepressants, eventually gave up on them.

02:05:41.000 --> 02:05:46.000
But we're like living, you know. They were maintaining their employment.

02:05:46.000 --> 02:05:50.000
They were kind of.

02:05:50.000 --> 02:05:54.000
Achieve, doing what they needed to be doing in their social roles as parents, as husband.

02:05:54.000 --> 02:05:58.000
But with a great deal of difficulty, and we're quite unhappy.

02:05:58.000 --> 02:06:08.000
So one participant had recently started Cbt. Recently, I mean by like, maybe actually like more like 5 months or something.

02:06:08.000 --> 02:06:30.000
And the thing that they had been working on was, you know, reformulating negative health cognition, which the person found incredibly difficult and could sort of understand it intuitively or intellectually, but not really do it very easily and during this person's experience they had so that experience they had they

02:06:30.000 --> 02:06:41.000
witnessed. It was a very visual thing. They witnessed a fun house mirror that was distorting their image of themselves.

02:06:41.000 --> 02:06:43.000
In a way that was negative, and they were able to.

02:06:43.000 --> 02:06:55.000
You know again. It was a very visual kind of visceral experience that's occurring with your eyes closed or able to sort of walk around to the side of the mirror, still feed the mirror.

02:06:55.000 --> 02:07:02.000
Still, see, it's defertionary influence, but also to see that that's not necessarily true representation of reality.

02:07:02.000 --> 02:07:18.000
And in doing so this patient was able to experience themselves the way love ones do without the distortionary impact of the mirror, and they felt great flood of love that you know the way I I'm great.

02:07:18.000 --> 02:07:26.000
And all these qualities that other people around them. No one can identify, but they struggle with.

02:07:26.000 --> 02:07:32.000
But then an integration, you know that was the thing that the person now felt they can do, but they have to do it.

02:07:32.000 --> 02:07:40.000
They have to practice that. So that was one of the gold medals of integration was to practice that, and it became increasingly second nature.

02:07:40.000 --> 02:07:47.000
Another participant. This is somebody who drank much more heavily.

02:07:47.000 --> 02:08:04.000
They experience. There's a lot of pleasant stuff at first, and the details of which don't really matter but then at some point, they found themselves in a room with the door.

02:08:04.000 --> 02:08:12.000
But between them and the door there was a building, black blob, and it kept getting bigger and bigger, and there was something about the blob again very visual.

02:08:12.000 --> 02:08:27.000
Visual experience that was like frightening and disgusting, and they tried to turn away from it, to go back towards the pleasant stuff.

02:08:27.000 --> 02:08:37.000
But found that they were actually done, and the blob kept building and building building until the person literally began to hyperventilate.

02:08:37.000 --> 02:08:40.000
And again we're there making sure blood pressure is fine, vitally fine.

02:08:40.000 --> 02:08:52.000
They're actually safe hyperventilating, starting to feel panicked, and they were not able to turn away from it and we also encourage this person not to.

02:08:52.000 --> 02:09:01.000
In all the prep. Which is something that they would, I think, typically do with that kind of stress and person turned towards it, move towards the blog.

02:09:01.000 --> 02:09:06.000
Blob, kept building until it began to just follow them whole, and in being inside the blob, just begin to experience all of the things that they sort of avoid in their life.

02:09:06.000 --> 02:09:34.000
Difficulties with you know it. Parents. Difficulties with job differenties, with just all, all, the topics of emotional avoidance usually lead to the person to drink, just experience one after the other, after the other, like a good 10 min, and they that was done and then they're able to pass through the door.

02:09:34.000 --> 02:09:43.000
But what the person felt with it. This stuff is incredibly difficult and unpleasant, but I can do it, and it's better that I do.

02:09:43.000 --> 02:09:53.000
And that was another sort of skill that the person was able to then kind of go on and practice in their day to day. Life.

02:09:53.000 --> 02:09:59.000
So again, these experiences have a very odd way of rewarding emotional acceptance and punishing emotional, avoiding.

02:09:59.000 --> 02:10:01.000
They'll invite people to do the thing that they normally do.

02:10:01.000 --> 02:10:04.000
But it won't work, so they have to do something else.

02:10:04.000 --> 02:10:06.000
And these are both examples. The first participant actually did not really have a missile experience.

02:10:06.000 --> 02:10:13.000
The second person did. But it happened later in the session.

02:10:13.000 --> 02:10:23.000
So it's not all about the mystical. I mean, it's hard for me to witness that and not think about it in terms that are translatable to more conventional secret therapy.

02:10:23.000 --> 02:10:32.000
This. This is one of the participants to sort of sent observations after the trial is done, and I got permission to share it.

02:10:32.000 --> 02:10:35.000
I was really hoping the experience would cure my depression.

02:10:35.000 --> 02:10:41.000
It has not. However, it has really changed my perspective about my my own emotional date.

02:10:41.000 --> 02:10:53.000
I much less stuck with the idea that my feelings are permanent, and I, embracing the idea that my emotional state is one of constant change it has allowed me to become a more of a dispassionate observer of my emotions than it may be more curious about what my

02:10:53.000 --> 02:10:59.000
emotions are trying to tell me. For a long time I was stuck on the what now I'm much more interested in the Y.

02:10:59.000 --> 02:11:09.000
This person ended up getting back on antibiotics, and found that to be helpful in combination with this, and was doing quite well.

02:11:09.000 --> 02:11:13.000
I kind of, I guess. Went over time on this section.

02:11:13.000 --> 02:11:18.000
I'm gonna skip this stuff.

02:11:18.000 --> 02:11:25.000
Questions.

02:11:25.000 --> 02:11:32.000
Did I go over time? Yeah, no, I didn't. Sorry.

02:11:32.000 --> 02:11:36.000
We had 30 min for this. So yeah, back to this causal diagram, right?

02:11:36.000 --> 02:11:50.000
So I've been talking about this any secondary connecting subjective effects through sorry enacting therapeutic effects through things that people feel.

02:11:50.000 --> 02:11:56.000
But there is this debate about like, well, maybe the drug itself has having effects, and this is all epiphanominal.

02:11:56.000 --> 02:11:59.000
It's all just extra stuff on top. So what?

02:11:59.000 --> 02:12:09.000
How could that happen? What could this actually be? And one of the things that people talk about is maybe it's enhancing neuroplasticity.

02:12:09.000 --> 02:12:13.000
So first question, there is like, what does that mean?

02:12:13.000 --> 02:12:26.000
What do people mean by neuroplasticity? So, okay, next slide, please.

02:12:26.000 --> 02:12:32.000
I think it's frozen.

02:12:32.000 --> 02:12:36.000
There we go. So first off when you give like it, Alex. Not here.

02:12:36.000 --> 02:12:46.000
I'm talking about silicon. 2 rodents, you see, persistent and rapid growth in dendritic fine and synaps formation.

02:12:46.000 --> 02:12:53.000
Okay. Still. So what I mean that is, I think, a bit unusual.

02:12:53.000 --> 02:12:56.000
And there's an implication there that is doing something that's unique.

02:12:56.000 --> 02:13:00.000
But I personally as a psychiatrist, I don't.

02:13:00.000 --> 02:13:02.000
I don't know what that means or why. That's important.

02:13:02.000 --> 02:13:09.000
Necessarily, but more importantly, there is some evidence. This is from gold. Dolan.

02:13:09.000 --> 02:13:13.000
It's unpublished, which is a neuroscientist from Hopkins.

02:13:13.000 --> 02:13:22.000
But in rodents, so there's evidence that psychedelics may increase functional plasticity in a context-dependent way.

02:13:22.000 --> 02:13:41.000
Let me try to explain that if in rodents there is a developmental window for heightened socially conditioned place preference which means learning to favor a location that was experienced in the context of your peers, so meaning roads will like places that they experience with other rodents more than

02:13:41.000 --> 02:13:47.000
places they experience alone. To this preference is greater in user and then it decreases in adulthood.

02:13:47.000 --> 02:13:51.000
You can kind of analogize that to teenagers actually.

02:13:51.000 --> 02:14:12.000
But this study, I mean, they would give the psychedelic or just the drug or the placebo 2 rodents, and then, a couple of days later, they they would do the conditioning, and then they would see like how much of that sorry I mean back up. The point is though is that this is a phenomenon

02:14:12.000 --> 02:14:16.000
the social preference for the tie when they're young, and then decreases with age.

02:14:16.000 --> 02:14:19.000
So the question was, can we increase that? Their interpretation was, we're reopening this developmental window in aulthood.

02:14:19.000 --> 02:14:27.000
We're reopening a window that's closed.

02:14:27.000 --> 02:14:34.000
But in approximating something it happened in youth or adolescents, and for they would give the drug, and I think, 48 h that they they would do the test.

02:14:34.000 --> 02:14:45.000
The conditioning meaning. Put the road in with their peers or not, and they would test the degree to which that influences their preference.

02:14:45.000 --> 02:14:50.000
And the gist of it here is that Philocybin and Lsd.

02:14:50.000 --> 02:14:55.000
Reopen this window is their interpretation, whereas postcaine does not.

02:14:55.000 --> 02:15:14.000
Failing to not. And so, however, and this only happens if the drug is administered in the social time, if the drug is given in a social context, the drug is given a loan, this doesn't really happen.

02:15:14.000 --> 02:15:23.000
So the point of that is that, like even in rodents, you can show that it is the context plus the drug. That is, that matters.

02:15:23.000 --> 02:15:26.000
It's not necessarily a drug. It's just gonna you just give the drug.

02:15:26.000 --> 02:15:32.000
It's gonna do something. And this effect lasted for weeks.

02:15:32.000 --> 02:15:43.000
Remember, we're talking about roads. It's a week for the long time to road in life, and eventually this window, you know, closes for Silicon remains open for Lsd, so there's a lot here that can potentially shed light.

02:15:43.000 --> 02:15:49.000
On therapeutic use. It's premature to draw any conclusions from this.

02:15:49.000 --> 02:15:52.000
But what's striking about psychedelic therapy is that it is enduring.

02:15:52.000 --> 02:15:53.000
Why should the experience of a single day have any impact later?

02:15:53.000 --> 02:16:07.000
And it is possible that, like it, Alex. Are opening windows of plasticity windows of change, ability that last for a certain amount of time, and then close.

02:16:07.000 --> 02:16:25.000
But the dirt while open. It may be the case that whatever is done during that time has a greater, potentially greater potential to lead to enduring change, and so that's kind of why I say the integration, the follow-up visits are important not only to solidify and make sense of what the experience

02:16:25.000 --> 02:16:33.000
was in a way that can be useful later on, and people will refer back to these experiences years later and find them to be useful.

02:16:33.000 --> 02:16:43.000
But also did ideally change habit. This is much more obvious when it comes to a substance, use disorder, but this is also definitely pertinent to anything for depression.

02:16:43.000 --> 02:16:48.000
For example, changing, making, and maintaining behavioral changes is a very important part.

02:16:48.000 --> 02:16:56.000
This. Okay, that's that section. Let's take a look at the questions. See, we've got here.

02:16:56.000 --> 02:16:59.000
Sounds, like many of these cases, may have some kind of significant trauma.

02:16:59.000 --> 02:17:11.000
History of some kind. Why do you say that I don't think any of the cases I described had that.

02:17:11.000 --> 02:17:14.000
I guess you can't really talk. This is Chandani.

02:17:14.000 --> 02:17:25.000
Shawn me? If you do, wanna answer the question, you can't raise your hand, and I can give you access to the microphone.

02:17:25.000 --> 02:17:31.000
I can just respond to. I mean, not necessarily. Yeah.

02:17:31.000 --> 02:17:38.000
These particular people did not have a substantial trauma history, the one that they cases on.

02:17:38.000 --> 02:17:43.000
There are others that of course, that do, and sometimes that arises in this session.

02:17:43.000 --> 02:17:48.000
Sometimes it doesn't.

02:17:48.000 --> 02:17:53.000
Regarding plasticity would this be utilized for individuals who are diagnosed with autism to deal with social implications?

02:17:53.000 --> 02:18:04.000
I don't know how to answer that nobody is actually discussed.

02:18:04.000 --> 02:18:08.000
I'm not aware of anyone having talked about that.

02:18:08.000 --> 02:18:12.000
But people are doing psychedelic studies for literally everything.

02:18:12.000 --> 02:18:22.000
So it's going to happen at some point. But I don't have a clear. I don't have a clear sense of that sorry.

02:18:22.000 --> 02:18:30.000
Anything else in the chat.

02:18:30.000 --> 02:18:36.000
Really depends on what you mean by trauma. If you're following ladies ace model, I would agree.

02:18:36.000 --> 02:18:43.000
So you can define this in a way that everybody that is in these trials has experienced trauma.

02:18:43.000 --> 02:18:51.000
Nope. The question then becomes like the utility of that, and.

02:18:51.000 --> 02:19:03.000
I think that there is an intuitive way of thinking that these experiences are going to ultimately resolve the root of the trauma.

02:19:03.000 --> 02:19:04.000
The root of the problem and Denver Broth has actually written a lot about this.

02:19:04.000 --> 02:19:30.000
This is somebody who was a psychoanalyst. I think at least, it's like a dynamic therapist to had a particular preconception of how like we were going to work, meaning that in some way or another, they're going to resolve the origin of the problem and they actually

02:19:30.000 --> 02:19:44.000
the birth trauma. Example suggested that that's kind of what he still views of psychedelic therapies route of efficacy which is a bit misleading because actually what he tended to find this is somebody who's done like hundreds and hundreds of

02:19:44.000 --> 02:20:04.000
psychedelic sessions is that people often will come into these sessions with the particular type of story about why they are suffering in a particular motivation to fix the cause of the suffering, and during and after the session they'll end up finding that it's pretty

02:20:04.000 --> 02:20:07.000
unimportant and moving forward, and that their vistas open, they experience all kinds of stuff.

02:20:07.000 --> 02:20:15.000
They turn towards the different set of values and experiences.

02:20:15.000 --> 02:20:23.000
And that I've seen people I've given to people with Ptsd.

02:20:23.000 --> 02:20:37.000
Who for other conditions you have traumas that sometimes they'll get resolved without a ton of specific attention to them, and other times will arise in ways that are very direct and specific.

02:20:37.000 --> 02:20:51.000
I just. I'm talking about this in a confused way, because I'm very hesitant to make any generalizations about this, because again, you go back to that quote about like every psychedelic therapist has their own specific window on to this.

02:20:51.000 --> 02:20:56.000
And they'll find things that confirm them. My general sense of this is that, wow!

02:20:56.000 --> 02:21:02.000
There's a huge range of diversity, and the ways that these experiences happen in the way they're interpreted. Noise.

02:21:02.000 --> 02:21:07.000
They end up being helpful to people. So not sure if that's really answering a question or dodging it.

02:21:07.000 --> 02:21:08.000
But and there has still not been.

02:21:08.000 --> 02:21:16.000
No, there's still. There's still been no trials on a psychedelic.

02:21:16.000 --> 02:21:17.000
4 ptsd obviously excluding Mdma, but for which there's lots of evidence.

02:21:17.000 --> 02:21:27.000
But those are going to start happening. One has opened up at Mount Sinai, and there will be more.

02:21:27.000 --> 02:21:33.000
Other questions, thoughts, concerns.

02:21:33.000 --> 02:21:50.000
On that section.

02:21:50.000 --> 02:21:59.000
I mean, we're seeking a meaningfulness experience that could be integrating once you the oh!

02:21:59.000 --> 02:22:02.000
There's a way of interpreting that question that suggests giving advice to personal use.

02:22:02.000 --> 02:22:14.000
That will not do. However, I will say that in these trials the doses are high.

02:22:14.000 --> 02:22:20.000
How do you protect a traumatized person from being more traumatized by facing their imagination, unconscious?

02:22:20.000 --> 02:22:26.000
Re-traumatization when it comes to figured out that they potentially a big problem.

02:22:26.000 --> 02:22:29.000
And frankly, this is why I feel some fear towards the idea of a silicon trial of Ptsd.

02:22:29.000 --> 02:22:40.000
Mdma, again. This is why I think it's very useful to consider these as different drugs, not collaborative on the being same thing.

02:22:40.000 --> 02:22:45.000
Mdma, which is probably gonna get FDA approved for Ptsd.

02:22:45.000 --> 02:22:53.000
Within the next year is an unusually good drug, or Ptsd, because I mean it.

02:22:53.000 --> 02:23:01.000
Is. It is a rousing, and it brings lots to the surface it's a stimulant, but it produces this sense of safety.

02:23:01.000 --> 02:23:07.000
It allows people to actually process and discuss things that they might normally not.

02:23:07.000 --> 02:23:11.000
And in the appropriate context, I think that they're useful.

02:23:11.000 --> 02:23:26.000
You know what are the implications of you know you're talking about this window of plasticity and lots of changes, and things that are enduring these psychedelic experiences may have the potential to be uniquely beneficial.

02:23:26.000 --> 02:23:34.000
The flip side of that, is it? They may have the potential to be uniquely traumatizing, and so.

02:23:34.000 --> 02:23:44.000
Any study that ventures into this, I think one should have very, very experienced clinicians who know what they're doing involved at all.

02:23:44.000 --> 02:23:52.000
Stages of the study, but also just be very aware of the possibility of re traumatization.

02:23:52.000 --> 02:23:57.000
Part of viewing this through the lens of it's like just Rick.

02:23:57.000 --> 02:23:58.000
Conventional psychotherapy is that these are not problems.

02:23:58.000 --> 02:24:07.000
That are fundamentally different in some ways from those that could occur in more conventional psychotherapy.

02:24:07.000 --> 02:24:19.000
I think that there are more bells and whistles to this, but I think some of that, that the dynamic are similar.

02:24:19.000 --> 02:24:33.000
Okay, perhaps let's move on. So we've got future clinical future clinical considerations here.

02:24:33.000 --> 02:24:42.000
So just a couple of things I'll touch on. So sarahinergic antidepressants, bipolar disorder, future trials.

02:24:42.000 --> 02:24:50.000
So there is some evidence. So basically, generally speaking, people do not combine energy antidepressants.

02:24:50.000 --> 02:24:55.000
By that I mean Ssris and Big One.

02:24:55.000 --> 02:24:58.000
There's this idea that they do still have an effects or other psychedelic aspects.

02:24:58.000 --> 02:25:04.000
But also, maybe there's a least dangerous drug interactions like serotonin syndrome.

02:25:04.000 --> 02:25:19.000
So, and Guy did this study back in the day where he gave an maoai and it's a little complicated, actually, but it it isn't a fairytinergic antidepressant.

02:25:19.000 --> 02:25:28.000
It's very atypical one, and showed that people who we're pre-treated with this we're completely insensitive to the effect of Lsd.

02:25:28.000 --> 02:25:35.000
And this lasted for 14 days.

02:25:35.000 --> 02:25:40.000
And there's a couple of small studies that show similar things with Ssris and Lsd.

02:25:40.000 --> 02:25:49.000
There has only been one published study that dos people with a psychedelic who are on unnecessary.

02:25:49.000 --> 02:25:54.000
And this had retreatment. Sot, telepm, or 14 days.

02:25:54.000 --> 02:26:02.000
I think this is actually this same dosing schedule they use in the Imperial trial.

02:26:02.000 --> 02:26:05.000
This is healthy people. These are not depressed patients.

02:26:05.000 --> 02:26:23.000
There 14 days on, which is not a very long time, and then they got, and the gist of it is that there is minimal decrement in fill 7 effects, and that perhaps most importantly, no adverse events.

02:26:23.000 --> 02:26:24.000
2 days, 2 weeks is probably not long enough to extractapolate.

02:26:24.000 --> 02:26:36.000
To common clinical use of like what is likely to happen with code administration.

02:26:36.000 --> 02:26:40.000
We have the survey. It's not published yet.

02:26:40.000 --> 02:26:47.000
Looking at people who have taken Psilocybin concurrently with an antidepressant, but also had something to compare that to.

02:26:47.000 --> 02:27:01.000
In other words, they took the same dose of that psychedelic silicon prior to starting antidepressant, or they took the same dose for the others, not on ninety-depress, and we've restricted this to people who've only done this once or twice so they were able to

02:27:01.000 --> 02:27:05.000
report on every instance in their life of this. This is a retrospective survey.

02:27:05.000 --> 02:27:09.000
It's not perfect, but what we are seeing is that in 600 people people who took an Ssri or Snri are much more likely to report weaker than expected.

02:27:09.000 --> 02:27:21.000
Still 7 effects compared to the appropriate, which is a non certainergic.

02:27:21.000 --> 02:27:25.000
Thank you, Alex, so!

02:27:25.000 --> 02:27:38.000
So far to me, I think, I mean. And also I should just say, if you Google, you go on Reddit, there's very common sense anecdote that people on Ssris are less likely to feel like italics.

02:27:38.000 --> 02:27:40.000
So not a ton of data from actual dosing studies suggest this.

02:27:40.000 --> 02:27:54.000
But there's not much data at all, but pretty large scale survey suggests that there is something going on in particular with Sarah Tenergic ones as opposed to non-sertrinergic.

02:27:54.000 --> 02:28:00.000
And this effect seems to last, or at least a couple of months.

02:28:00.000 --> 02:28:06.000
We can fill a 7 effects, last at least, up to 3 months.

02:28:06.000 --> 02:28:10.000
So!

02:28:10.000 --> 02:28:17.000
Basic. Take home to me is that chronic dairotenergic antidepressants probably do weaken psychedelic effects.

02:28:17.000 --> 02:28:22.000
This effect may last for weeks to month. Yeah, it's not.

02:28:22.000 --> 02:28:25.000
It's not complete like. It's not like every single person is reporting.

02:28:25.000 --> 02:28:32.000
We can affect, and maybe we shouldn't be excluding people on antidepressants from these trials.

02:28:32.000 --> 02:28:39.000
Talk more about that in a second. I'm actually not gonna really talk too much about this.

02:28:39.000 --> 02:28:42.000
But people always talk about Saratonin Syndrome.

02:28:42.000 --> 02:28:51.000
You give like it, Alex, which are certainergic with dare toergic antidepressant like an Ssri or Snri, and maybe you're gonna cause serotonin syndrome.

02:28:51.000 --> 02:29:00.000
I actually kinda prefer to call the serotonin toxicity because it's a dose dependent phenomenon excess serotonin in the synapse or certain like drugs.

02:29:00.000 --> 02:29:05.000
But it is vanishingly rare even in massive overdoses of Lsd.

02:29:05.000 --> 02:29:09.000
Or Philippine, Lsd. In particular, which is active at the Microgram Dose.

02:29:09.000 --> 02:29:13.000
There have been cases of people mistaking powdered Lsd.

02:29:13.000 --> 02:29:20.000
Which is in, you know, like tens of milligrams.

02:29:20.000 --> 02:29:22.000
It's not hundreds of milligrams of a dose.

02:29:22.000 --> 02:29:27.000
We're talking many, thousands of times higher than an active, just snorting it, mistaking for cocaine.

02:29:27.000 --> 02:29:36.000
And not dying so, and not necessarily even having clear, fair syndrome.

02:29:36.000 --> 02:29:40.000
So I think that it's pretty unlikely that Co.

02:29:40.000 --> 02:29:55.000
Administration of an Ssri, with an with a classic psychedelic, the commonly used ones, at least, is gonna cause serotonin in I'm not entirely sure how familiar people are with what an Mao I is.

02:29:55.000 --> 02:30:04.000
But it's a drug that breaks down various neurotransmitters, including Sarahonin, including most psychedelics.

02:30:04.000 --> 02:30:11.000
And Dmt. Is not orally active. If somebody swallows.

02:30:11.000 --> 02:30:22.000
Dmt. Usually it will do nothing. Whoever, if you administer it with an Maoi which prevents the breakdown of not only serotonin and dopamine, and nor Epinephrine, but also Dmt.

02:30:22.000 --> 02:30:28.000
That's ayahuasca. And that is regularly administered without certain and syndrome.

02:30:28.000 --> 02:30:32.000
So that's a much riskier combination than the Dmt.

02:30:32.000 --> 02:30:37.000
Or Philip, and plus an Ssri. So long story short, I think that there's it's probably pretty safe to Co.

02:30:37.000 --> 02:30:44.000
Administer those, even though it's not really done in studies.

02:30:44.000 --> 02:30:52.000
And there, I think this is a problem, right? I mean, people are on certainergic antidepressants for depression.

02:30:52.000 --> 02:30:57.000
They wanna join a silicon trial for depression, and they can't be on that.

02:30:57.000 --> 02:31:06.000
So there's a bit of a difficulty there.

02:31:06.000 --> 02:31:15.000
That I just say it is worse to mix. I'm saying that.

02:31:15.000 --> 02:31:26.000
This is a bit complicated, so dnt is regularly administered with an Maoi in the form of ayahuasca, which has been used indigenously for at least hundreds of years.

02:31:26.000 --> 02:31:42.000
Mixing, an antidepressant with Msi and mi is incredibly dangerous, incredibly dangerous, and we'll force it has, for sure kill people mixing an Mao with an Ssri is an incredibly dangerous thing to do.

02:31:42.000 --> 02:31:48.000
Mixing, Dmt with an Naa does not appear to be particularly dangerous.

02:31:48.000 --> 02:31:53.000
Does that data on doing that with silicon it's it's not something that I think anyone should do to be clear.

02:31:53.000 --> 02:32:04.000
I don't think there's a good reason to those people on maize, but remember 2, I mean, there's evidence that Lsd.

02:32:04.000 --> 02:32:17.000
Mixed with an Maa, actually has no effect. This is a bit different, because mais will break down will an moi will increase the levels of silicide and increase the levels of Dmt.

02:32:17.000 --> 02:32:34.000
But that's not the case with Lsd. I'm getting probably much more in the than I intended.

02:32:34.000 --> 02:32:35.000
That like, there's probably enough signal of safety that we should research it.

02:32:35.000 --> 02:32:51.000
I'm not saying anything about how this should actually be used, that there should be more research on it.

02:32:51.000 --> 02:32:55.000
Bipolar disorder, so participants with bipolar disorder are generally excluded from psychedelic trials.

02:32:55.000 --> 02:33:03.000
Due to the risk of provoking mania. We even exclude individuals with the first degree. Family history of bipolar disorder.

02:33:03.000 --> 02:33:08.000
One or 2, and this, you know, is plausible.

02:33:08.000 --> 02:33:09.000
Pretty much every effective antidepressant can cause mania.

02:33:09.000 --> 02:33:20.000
Make mistakes for mood cycling so.

02:33:20.000 --> 02:33:32.000
Sure, so if I could cause mania, and I've certainly seen that in clinical practice, not infrequently that people will have manic episodes.

02:33:32.000 --> 02:33:35.000
Either they have bipolar disorder, or they have a family history.

02:33:35.000 --> 02:33:39.000
There's not great data on, like what the actual risk is.

02:33:39.000 --> 02:33:44.000
But I definitely believe that this happens.

02:33:44.000 --> 02:33:53.000
And and yet bipolar disorder the majority of the illness suspended and depressed, episode, bipolar depression is difficult to do.

02:33:53.000 --> 02:34:12.000
People commonly do end up on antidepressants which can improve their depression, but also put them at risk for cycling your media, and so maybe a short term intervention that has the risk of causing mania, but can also potentially improved depression is worth studying there are now some

02:34:12.000 --> 02:34:21.000
bipolar, 2 depression studies that are being done nobody has yet broached the idea, of a bipolar, one study which, frankly, I would like to do.

02:34:21.000 --> 02:34:27.000
But that, I think, should be done in an inpatient setting, because there is a real risk of provoking media.

02:34:27.000 --> 02:34:33.000
But for people that have difficulty, treat depression, risk, benefit.

02:34:33.000 --> 02:34:39.000
One thing I haven't really mentioned is that so?

02:34:39.000 --> 02:34:50.000
There. There's, you know, I've talked about highly contextual effects of psychedelics that are likely to be different, group to group.

02:34:50.000 --> 02:34:59.000
And most of the studies that have been done. It's like upwards of 85% of participants are white.

02:34:59.000 --> 02:35:10.000
Very very few black participants. There's like very limited diversity in patient populations when it comes to psychedelic research.

02:35:10.000 --> 02:35:17.000
And there's also a pretty stark racial difference in who has ever used psychedelic.

02:35:17.000 --> 02:35:29.000
So these are the numbers of in the United States from a nationally representative population, survey people who have ever used a silicon mushrooms or Lsd, and it's about 10%.

02:35:29.000 --> 02:35:32.000
But you compare it by race pretty strict differences.

02:35:32.000 --> 02:35:44.000
Black respondents are way less likely than native, American or white, and.

02:35:44.000 --> 02:35:45.000
Let me just respond to. Are you suggesting that therapist should take it upon themselves to assess those 7 interactions?

02:35:45.000 --> 02:35:55.000
Absolutely not again. I wanna be very clear. This is not the treatment that is available.

02:35:55.000 --> 02:36:02.000
So pretty much everything I'm talking about is in the context of research on a schedule.

02:36:02.000 --> 02:36:08.000
One drug that is not FDA approved for any indication, and is federally illegal across the board.

02:36:08.000 --> 02:36:21.000
So the therapist should not be in a position to be evaluating whether or not somebody should take psilocybin with the drugs that they're on, and should not be in a position of recommending that at all.

02:36:21.000 --> 02:36:37.000
In my opinion, these studies that have been done I'm responding to a question in the that the studies that have been done have largely not included people on antidepressants, even though, or the prime indication of depression.

02:36:37.000 --> 02:36:46.000
Many, many people are, and so I'm simply suggesting that there's actually not an enormous signal of risk.

02:36:46.000 --> 02:36:53.000
And so perhaps we should be studying with populations. But this is nothing at all about any clinical use yet that's way.

02:36:53.000 --> 02:37:03.000
Way way too premature, without having good proper studies, showing that.

02:37:03.000 --> 02:37:15.000
And analogously so, despite all of the great hype and excitement about psychedelics, the vast majority of Americans view the risk of Lsd.

02:37:15.000 --> 02:37:22.000
Trying Lsd. Once or twice to be great, and there are risks. Lsd.

02:37:22.000 --> 02:37:39.000
As I mentioned, physical risk quite low, but the risk of psychological distress and doing something while intoxicated, are there, and we mitigate those in these trials, and clinical settings with a big rapper of psychological support.

02:37:39.000 --> 02:37:48.000
But those risks are are present, more so, and people that are doing it kind of out in the wild.

02:37:48.000 --> 02:37:53.000
But the perception of there being great risk of trying Lsd.

02:37:53.000 --> 02:38:04.000
Once or twice, you know, it's going down over time, but strikingly pretty big racial difference there as well, and.

02:38:04.000 --> 02:38:14.000
Anyway, to say that we need to have representative populations in these studies if we want them to be representative, and that has not really been achieved yet.

02:38:14.000 --> 02:38:17.000
The mdma studies are doing a pretty good job with that, but that's the classic.

02:38:17.000 --> 02:38:23.000
Academic studies are not yet.

02:38:23.000 --> 02:38:31.000
Future studies, I mean, I mentioned bipolar disorder I mean, that's underway with bipolar, 2 nothing with bipolar, one postpartum depression.

02:38:31.000 --> 02:38:39.000
This is a very logical use. Extension of the studies on depression, where you may actually want.

02:38:39.000 --> 02:38:55.000
A more rapid acting treatment, particularly one that doesn't have to be dos daily patients are concerned about effect on, you know, with breastfeeding depressed, inpatient, never been done, to my knowledge, comparative epicacy versus evett has not been done.

02:38:55.000 --> 02:39:06.000
Comorbidity studies. We have one with depression, alcohol use disorder, but if it's being studied for all of these different varied indications, why not combine them and see if it works together shorter acting psychedelics?

02:39:06.000 --> 02:39:11.000
I've mentioned. There is that press release. So there's some work that's being done there.

02:39:11.000 --> 02:39:22.000
Minimal psychotherapy. I've talked a lot about all this great psychological, supportive rapper in which psychedelics are given.

02:39:22.000 --> 02:39:25.000
But we haven't actually shown in an empirical sense.

02:39:25.000 --> 02:39:30.000
That's stuff is necessary. People tend to believe, including myself.

02:39:30.000 --> 02:39:42.000
That is necessary for safety and efficacy. But, strictly speaking, that has not been shown, and if it's not shown, and this is rolled out, people are gonna start doing it without it.

02:39:42.000 --> 02:39:48.000
So we better study it. Group dosing again.

02:39:48.000 --> 02:39:55.000
This is expensive, due to labor costs. If you are able to do group, you know, preparation group dosing group integration.

02:39:55.000 --> 02:40:00.000
Maybe that would work and that would be cheaper. That should be studied.

02:40:00.000 --> 02:40:06.000
Somebody had some question, but I guess it isn't actually your question.

02:40:06.000 --> 02:40:11.000
But there, you know, here's the nice study from 2021 I about 500 patients.

02:40:11.000 --> 02:40:15.000
Who are it? This is a very common clinical scenario.

02:40:15.000 --> 02:40:18.000
They've been maintained on antidepressants for more than 2 years.

02:40:18.000 --> 02:40:23.000
They had a history of.

02:40:23.000 --> 02:40:29.000
Sorry! I don't remember now. If it was 2 depressive episodes or more than 2, I think it's 2 or less to the history of 2 or less.

02:40:29.000 --> 02:40:36.000
Yeah, it's 2 or less depressive. And their intermission, they're feeling well enough to stop.

02:40:36.000 --> 02:40:37.000
And people are randomized to continue the drug or stop meaning take placebo.

02:40:37.000 --> 02:40:46.000
With that a taper. I forget exactly how long the taper was.

02:40:46.000 --> 02:40:53.000
It's arguably not long enough, but but the point is, people who continue their drug, they're antidepressant.

02:40:53.000 --> 02:41:08.000
Majority of them are in remission that year, and people who discontinue majority of them are have every last, and the absolute difference is not it's not like super super stark.

02:41:08.000 --> 02:41:09.000
But that's a very meaningful clinical difference.

02:41:09.000 --> 02:41:29.000
And so is it. Is it the case that you know? Maybe a a psychedelic trial that administers basically for relapse prevention in the context of discontinuation that would need to be a very large study and I'm not really suggesting that people do that now it's not

02:41:29.000 --> 02:41:38.000
really, the probably the best use of resources when we haven't truly shown this treatment works for depression, even though there's a lot of preliminarily suggestive evidence.

02:41:38.000 --> 02:41:50.000
But just ideas for future consideration, and then there's also other psychedelics that work quite differently, that have really yet to be studied.

02:41:50.000 --> 02:42:03.000
I've primarily been talking about research. There are a variety of decriminalization, decriminalization initiatives going on various states.

02:42:03.000 --> 02:42:10.000
There are some, some initialatives, for example, in Oregon that have allowed for legalization, for supported use.

02:42:10.000 --> 02:42:20.000
They're very, very careful in Oregon to not call it psychotherapy or therapeutic use, even though I think that's what most people treat it as so.

02:42:20.000 --> 02:42:26.000
That's supposedly gonna roll out this year.

02:42:26.000 --> 02:42:38.000
I'm a little afraid of it. To be honest, I hope nothing bad happens with it, but it once you're talking about rolling out a and I should be clear.

02:42:38.000 --> 02:42:44.000
I don't support. I don't support these drugs being illegal.

02:42:44.000 --> 02:43:02.000
I I don't think people should be going to jail for them, but that's completely separate from whether or not I think people should be using them, and so unrolling widespread use on the base of exciting clinical trial and other experiences I think there are real rich

02:43:02.000 --> 02:43:07.000
that that as a society we need to be cautious and mindful of there's, of course, religious youth.

02:43:07.000 --> 02:43:25.000
There are certain religious groups, the native American Church which uses Peyote, Brazilian, Iowa, the churches which use iahuasca, which have gone through the courts in order to, and they have religiously sanctioned use that is permitted by the federal government.

02:43:25.000 --> 02:43:31.000
There are very few of those groups, even though many apply it showed you some picture of the Church of Silo with doctrine earlier.

02:43:31.000 --> 02:43:35.000
That's not like an approved, because people are probably gonna get erupted.

02:43:35.000 --> 02:43:43.000
But but that, I suspect, is going to become a more.

02:43:43.000 --> 02:43:44.000
That's gonna grow. I think we're gonna see more and more religious use.

02:43:44.000 --> 02:43:51.000
And that's a topic that's fascinating, that I didn't really get to didn't really get to talk about.

02:43:51.000 --> 02:44:01.000
And that's that's my talk. I wanna you know, thank all the lovely people I work with at the Cpcr.

02:44:01.000 --> 02:44:11.000
And thank you all for the invitation. We have time for questions, and also be mindful of the fact that there's a lot of things that I would have liked to talk about that didn't really have the time for.

02:44:11.000 --> 02:44:26.000
But, you know, happy to touch on truly any aspect of this topic.

02:44:26.000 --> 02:44:32.000
And and let me just pull up the chats. People are saying, Stuff!

02:44:32.000 --> 02:44:39.000
Then you all can use the raise hand feature. I mean, we could be access to speak.

02:44:39.000 --> 02:44:53.000
I'll stop sharing. So I can actually.

02:44:53.000 --> 02:44:59.000
So there's some stuff that I yeah, I think ketamine treatment at its best mimic.

02:44:59.000 --> 02:45:06.000
The supportive monitoring the integrated call that I've been describing.

02:45:06.000 --> 02:45:10.000
I think somebody should study that.

02:45:10.000 --> 02:45:27.000
To show whether it's makes a meaningful difference. I I suspect it will, but right now there's not really any incentive for people to do that, because the people that are administering ketamine as a psychedelic therapy don't have any

02:45:27.000 --> 02:45:32.000
incentive to show that the psychedelic therapy portion of it works.

02:45:32.000 --> 02:45:35.000
They're already doing it.

02:45:35.000 --> 02:45:41.000
So I think it's a worthwhile topic for researchers to take up.

02:45:41.000 --> 02:45:54.000
But there's not. Doesn't seem to be a lot of interest in it, as far as like.

02:45:54.000 --> 02:45:58.000
Can I speak to Thc. In the effects of cannabis, treat, anxiety and depression?

02:45:58.000 --> 02:46:08.000
I'm gonna defer that question. That's I think, such a different topic that brings up its own can of worms.

02:46:08.000 --> 02:46:13.000
Hilight on racial differences. Later researchers hypothesize the limited racial inclusivity.

02:46:13.000 --> 02:46:34.000
Any plans on addressing disparity. So one, I think, is that I mean, if you look at the way that our trials run at Hopkins, they are generally it like not not like written down, but the trials have been done.

02:46:34.000 --> 02:46:44.000
De facto, I think end up requiring people to have flexible supportive job and a strong social network.

02:46:44.000 --> 02:46:51.000
And so basically they end up being de facto targeted to people of hire socioeconomic status.

02:46:51.000 --> 02:47:15.000
In the context of white people are far more likely to do psychedelics and are far more likely to have, you know, positive perception of them, and are also less likely to suffer legal consequences of illegal use of drugs by using them at similar rate of other racial groups so

02:47:15.000 --> 02:47:32.000
it's it's not the case that no studies are being done, that in more diverse populations they didn't get to mention Peter Hendrix at University of Alabama, is doing a study on cocaine addiction in what is largely indigent and

02:47:32.000 --> 02:47:42.000
Black Population there was a lot of work that he had to do to sort of describe like I mean, I think he traveled to a lot of different churches, a lot of different community groups when people come to the studies at Hopkins.

02:47:42.000 --> 02:47:50.000
Many of them, I mean. At this point, I think early on it wasn't like that.

02:47:50.000 --> 02:48:05.000
People were kind of like, what is this like? What very skeptical people are a little too excited now, and if anything, I have to personally spend a lot of time trying to deflate their expectations.

02:48:05.000 --> 02:48:06.000
But but I think Peter's work in Alabama it's like a very different environment.

02:48:06.000 --> 02:48:22.000
People are not pro psychedelics generally they are not they're just incredibly skeptical, but they're willing to try something that might help them, which is different.

02:48:22.000 --> 02:48:31.000
I'm gonna be running a trial. But opioid use disorder that I that I hope is going to be capturing a more representative population of Baltimore.

02:48:31.000 --> 02:48:37.000
And, I should add, people are literally getting on flights and flying across State lines to participate in like trials.

02:48:37.000 --> 02:48:49.000
So we do need to make an effort to make it more accessible and part of that, I think, is just providing more financial resources.

02:48:49.000 --> 02:49:03.000
2 people that are participating in the trial. , we have to just pay people and fund their the transport, and just make it easy for them to actually participate.

02:49:03.000 --> 02:49:05.000
We shouldn't be paying people to participate in the trial.

02:49:05.000 --> 02:49:11.000
But we we should be like providing compensation, for there.

02:49:11.000 --> 02:49:14.000
I think maybe you know what I'm trying to say.

02:49:14.000 --> 02:49:17.000
But bottom line more diversity and research will be a good thing.

02:49:17.000 --> 02:49:27.000
Do I recommendations for how to respond to clients who are taking Ssris or other antidepressants and engaging and recreational psychedelic use?

02:49:27.000 --> 02:49:45.000
So there any additional you have discussed that we, as provider, should be aware of so when it comes to people using psychedelics in the wild, as I say, my kind of prime thing is harm reduction I really do not.

02:49:45.000 --> 02:49:58.000
I mean I have patience to do that. I don't feel comfortable advising them on how to use psychedelics to benefit them. I don't think that's good, but there are a lot of recognizable harms that can come from that if people are going to be using them can be

02:49:58.000 --> 02:50:16.000
reduced one is so. I should have mentioned this, but lithium up here to be very, very bad, to mix with psychedelics it's a low quality evidence, but there's like lots of features that have been reported, hey?

02:50:16.000 --> 02:50:20.000
There are certain drug interaction that may actually just be dangerous.

02:50:20.000 --> 02:50:25.000
I would not advise people on maize to take like it.

02:50:25.000 --> 02:50:38.000
Alex, despite. Maybe it's kind of like I was suggesting that earlier I would not advise that whatsoever beyond those 2 there are not clear.

02:50:38.000 --> 02:50:52.000
Obvious drug interaction people on Athens ride are well, probably less likely to feel the effect of psychedelics, and, let's like you to have cardiovascular effect like it blunt the effect.

02:50:52.000 --> 02:51:11.000
But much of the harm reduction stuff comes from the stuff that we do in the clinical trials, having people being in a safe place where they cannot launder in the traffic, having it done in a setting setting where they have people that are responsible for not only their safety but also helping them, if they're having

02:51:11.000 --> 02:51:20.000
a difficult time. Basically in a psychologically supportive environment.

02:51:20.000 --> 02:51:21.000
Q. And a. You have some additional slides on the default mode network.

02:51:21.000 --> 02:51:37.000
Okay, we will discuss the default mode. So yeah, you will notice that I have not discussed neuroimaging at all.

02:51:37.000 --> 02:51:42.000
And the neuroimaging stuff gets a lot of media attention.

02:51:42.000 --> 02:51:56.000
I'm not a narrow imager, but I spent a lot of time trying to understand it, because I felt like, this is a huge gap in my knowledge.

02:51:56.000 --> 02:51:58.000
You are, yeah, I don't think it's on there.

02:51:58.000 --> 02:52:04.000
Or maybe it's I think you're still. It's the not the presenter mode.

02:52:04.000 --> 02:52:05.000
So I think, yeah.

02:52:05.000 --> 02:52:13.000
And wait. Am I sharing my screen? Yeah. Oh, let's do.

02:52:13.000 --> 02:52:14.000
Yeah, that's right.

02:52:14.000 --> 02:52:19.000
Alright, am I presenter or okay? So.

02:52:19.000 --> 02:52:22.000
I wonder how much detail to get into this. I could talk about this.

02:52:22.000 --> 02:52:26.000
I mean, this is literally a whole talk. Let let me just bring it real quick.

02:52:26.000 --> 02:52:27.000
So this is a very famous image. How many has this tattooed on their body?

02:52:27.000 --> 02:52:31.000
I'm sure, but this is a study of Phil Thibbon versus Placebo, and they used an fmri.

02:52:31.000 --> 02:52:41.000
They put somebody in a scanner scan their brain.

02:52:41.000 --> 02:52:46.000
And you look at how are the different areas of the brain connecting with each other?

02:52:46.000 --> 02:52:56.000
And obviously you can see that there's a lot more activity across regions there's a lot more activity between regions that don't normally talk to each other as much.

02:52:56.000 --> 02:53:04.000
All these different colors represent? No, your network and more connectivity across networks that is typical, but also less obvious.

02:53:04.000 --> 02:53:14.000
You have less connectivity within networks and.

02:53:14.000 --> 02:53:31.000
I just have no idea what that means, and a problem with the resting State study, so, for example, you just put somebody in an Fmri scanner, and you just see what's happening is that you're ultimately just describing Neural activity and if you don't translate

02:53:31.000 --> 02:53:34.000
that into some kind of cognitive process that can explain psychopathology.

02:53:34.000 --> 02:53:37.000
It's not that useful. So we have the default mode network.

02:53:37.000 --> 02:53:43.000
And this is one of the first attempts to do this. So.

02:53:43.000 --> 02:53:59.000
The default mode. Many people have heard of. There's a lot of frankly bad journalism that describes I'll just let you read this stuff like people are talking about like the default mode network is bad.

02:53:59.000 --> 02:54:03.000
It's a signal of.

02:54:03.000 --> 02:54:06.000
Whatever you you can read the headlines. I'll explain this in a second, like.

02:54:06.000 --> 02:54:07.000
So here's like the story of the default mode network.

02:54:07.000 --> 02:54:12.000
And this is now falling apart. So the default.

02:54:12.000 --> 02:54:14.000
These are these things are true. The default mode network is associated with self referential processing.

02:54:14.000 --> 02:54:19.000
And so, including like thinking about the future, thinking about the patch ruminating.

02:54:19.000 --> 02:54:28.000
This is correct. Like italics, reduce default, mode, network activity.

02:54:28.000 --> 02:54:38.000
Also true, like caused ego to solution. I'm putting this in scare quotes, but you can have a well validated questionnaire that will measure that and show.

02:54:38.000 --> 02:54:45.000
So these are 3 facts that are true. And yet people have sort of put that together.

02:54:45.000 --> 02:54:51.000
With they just like linked it all up, and they say the default mode of network is the signal of the ego.

02:54:51.000 --> 02:54:52.000
The default mode network reduction is the mechanism of psychedelic ego.

02:54:52.000 --> 02:55:00.000
Dissolution. Boom! You have a stor of why psychedelics work, and why they're helping.

02:55:00.000 --> 02:55:08.000
But default, mode, network, decoherence, breaking it down is rarely the strongest effect it doesn't actually correlate.

02:55:08.000 --> 02:55:16.000
Very well with the relevant subjective measures. And you see this with other drugs, including alcohol a single dose of an Fsri stimulants.

02:55:16.000 --> 02:55:21.000
Delia, so that this doesn't really explain anything at all.

02:55:21.000 --> 02:55:44.000
I can keep going on and on and on about this, but it's probably best that I don't, because I'll get. But the bottom line is that I think that there's a compelling story there that is not at all specific to psychedelics when you zoom out it doesn't really explain much at all.

02:55:44.000 --> 02:55:48.000
Happy to say more about that if people want, but.

02:55:48.000 --> 02:55:49.000
I think it's one of the perils of neuro imaging research.

02:55:49.000 --> 02:55:56.000
You'd have to know.

02:55:56.000 --> 02:56:01.000
We'll move on. We'll second it out. It's helpful with. I'm gonna be doing a study on this.

02:56:01.000 --> 02:56:05.000
There! Oh, let's!

02:56:05.000 --> 02:56:14.000
So there has been one single study ever on. What is this?

02:56:14.000 --> 02:56:18.000
Oh, there's been one study in the seventies in Baltimore, on Lsd.

02:56:18.000 --> 02:56:25.000
For opioid addiction, and they showed that a year out.

02:56:25.000 --> 02:56:29.000
Yeah, you're looking at a little bit less than 30% abstinence in the treatment group.

02:56:29.000 --> 02:56:42.000
Maybe like 5% upstairs in the control group. So there's one study that showed from what I mean, substantial benefit there's a lot of problems for this trial like they weren't exactly comparing apples to apples.

02:56:42.000 --> 02:56:49.000
But yeah, and I'm gonna be leading a study on opioid use disorder.

02:56:49.000 --> 02:56:55.000
But I mean the only honest answer is, nobody knows yet.

02:56:55.000 --> 02:57:01.000
There's also another unique drug which we don't have time to talk about.

02:57:01.000 --> 02:57:10.000
But if again, there's another drug that has features, of psychedelics, but also have, it's got a completely unique drug.

02:57:10.000 --> 02:57:15.000
And there are some very, very impressive anecdotes about the use of it.

02:57:15.000 --> 02:57:18.000
Again for opioid use disorder, and there's some research going on. Also.

02:57:18.000 --> 02:57:22.000
Not the safest drug I mean there at least 20 people have died.

02:57:22.000 --> 02:57:25.000
Cardiac arrest. But there's something to be researched there, and there are probably safer ways to do it.

02:57:25.000 --> 02:57:34.000
Again. That's not something that I'm involved with at all.

02:57:34.000 --> 02:57:54.000
Other questions.

02:57:54.000 --> 02:57:56.000
Looks like we're coming right up on time, and I don't I'm not seeing any other questions popping up.

02:57:56.000 --> 02:58:03.000
Nayla do you want to jump in and kind of give the closing?

02:58:03.000 --> 02:58:08.000
Info for everyone, with their c certificates and things.

02:58:08.000 --> 02:58:10.000
Absolutely.

02:58:10.000 --> 02:58:11.000
Oh!

02:58:11.000 --> 02:58:13.000
Oh, sorry! Sorry the spotify playlist, so I I can send this.

02:58:13.000 --> 02:58:15.000
What's the best way to do that? Shall I just email review?

02:58:15.000 --> 02:58:16.000
Yeah, email, us, and then we'll send out look in the we'll send it out through the event right?

02:58:16.000 --> 02:58:29.000
Registration, so yeah, just look if it doesn't come through, check your spam.

02:58:29.000 --> 02:58:30.000
Sounds good.

02:58:30.000 --> 02:58:32.000
Sometimes they end up in there, but we'll send it out that way if you want to just email it to us.

02:58:32.000 --> 02:58:38.000
Alright! So we are closing up. Thank you, doctor, for a wonderful training.

02:58:38.000 --> 02:58:54.000
It was really informative. Everyone evaluations will be sent out approximately 3 business days prior to this, after this training our certificates will be provided 3 to 5 business days after completion of the evaluation.

02:58:54.000 --> 02:59:06.000
If you all have any questions, or any information that you want to provide, our email is training@rosscenter.comandyoucanlookonourwebsiterosscensor.com for our upcoming trainings again.

02:59:06.000 --> 02:59:08.000
Thank you, Dr. Dr. Nayak, and everyone for its administration have a great.

02:59:08.000 --> 02:59:14.000
Yeah.