Latest / NO FILTER / Essentials_ Psychedelics _ Neurostimulation for Brain Rewiring _ Dr. Nolan Williams(MP3_160K)

Transcript

Essentials_ Psychedelics _ Neurostimulation for Brain Rewiring _ Dr. Nolan Williams(MP3_160K) · NO FILTER

• 0:06
  Speaker 1: Welcome to Huberman Labissentials, where we revisit past episodes for
• 0:10
  Speaker 1: the most potent and actionable science based tools for mental health,
• 0:14
  Speaker 1: physical health, and performance. I'm Andrew Huberman, and I'm a
• 0:19
  Speaker 1: professor of neurobiology and ophthalmology at Stanford School of Medicine,
• 0:23
  Speaker 1: and now for my discussion with doctor Nolan Williams. Thanks
• 0:27
  Speaker 1: for joining today. I'm really excited to have this conversation.
• 0:30
  Speaker 1: I have a lot of questions about different compounds psychedelics
• 0:34
  Speaker 1: in particular, but before we get into that discussion, I
• 0:38
  Speaker 1: want to ask you about depression broadly speaking. I heard
• 0:42
  Speaker 1: you say in a wonderful talk that you gave that
• 0:45
  Speaker 1: depression is perhaps the most debilitating condition worldwide. Yet in
• 0:50
  Speaker 1: contrast to other medical conditions like cancer, we actually have
• 0:55
  Speaker 1: a fairly limited number of tools to approach depression. And
• 0:58
  Speaker 1: yet number of tools and the potency of those tools
• 1:01
  Speaker 1: is growing.
• 1:02
  Speaker 2: Depression is the most disabling condition worldwide. What's interesting about
• 1:08
  Speaker 2: depression is it's both a risk factor for other illnesses
• 1:12
  Speaker 2: and it makes other medical and psychiatric illnesses worse right. So, recently,
• 1:17
  Speaker 2: the American Heart Association added depression is the fourth major
• 1:22
  Speaker 2: risk factor for coronary artery disease.
• 1:24
  Speaker 3: Right, So alongside the.
• 1:27
  Speaker 2: Risk factors that we know hypertension, high blood pressure, hyperlipidemia,
• 1:31
  Speaker 2: high cholesterol, and diabetes, you know, high blood sugar. Those
• 1:35
  Speaker 2: three have been on the list for a long time,
• 1:37
  Speaker 2: and depression in depth, you know, being added to the
• 1:39
  Speaker 2: list is the fourth one. A lot of what we're
• 1:41
  Speaker 2: doing in the lab actually is measuring kind of brain
• 1:44
  Speaker 2: heart connections and we can actually with transcranial magnetic stimulation
• 1:48
  Speaker 2: a form of brain stimulation, we can actually decelerate the
• 1:51
  Speaker 2: heart rate. We can capture that heart rate acceleration over
• 1:55
  Speaker 2: the mood regulatory regions and so actually a direct probe.
• 1:58
  Speaker 3: Of that connection.
• 2:00
  Speaker 2: Been very interested in a very particular clinical set of
• 2:04
  Speaker 2: problems around the most severe and the most high acuity
• 2:09
  Speaker 2: settings that folks with depression end up being in, and
• 2:13
  Speaker 2: that's in you know, emergency settings where they go into
• 2:16
  Speaker 2: impatient units. The field really hasn't developed a way of
• 2:21
  Speaker 2: you know, consistently being able to treat that problem and
• 2:23
  Speaker 2: folks end up getting the same standard oral antidepressants that
• 2:26
  Speaker 2: they've been getting outpatient.
• 2:29
  Speaker 3: And I came to this.
• 2:30
  Speaker 2: Because you know, dual trained as a neurologists and psychiatrists
• 2:34
  Speaker 2: went back and forth between neurology and psychiatry, saw that
• 2:38
  Speaker 2: in neurology we have all these ways of treating acute
• 2:41
  Speaker 2: brain based problems, and really wanted to emulate that in
• 2:45
  Speaker 2: psychiatry and find ways to develop an engineer new you know,
• 2:49
  Speaker 2: brain based solutions.
• 2:51
  Speaker 1: Many people out there probably think of the relationship between
• 2:53
  Speaker 1: the heart and the mind as kind of woo or
• 2:57
  Speaker 1: kind of a soft biology, but here you're talking about
• 2:59
  Speaker 1: actual physical connection. What area of the brain is it?
• 3:03
  Speaker 2: You know, the first place where the stimulation goes is
• 3:06
  Speaker 2: called the dorsilateral prefrontal cortex. It's kind of the sense
• 3:09
  Speaker 2: of control, kind of governor of the brain. And then
• 3:13
  Speaker 2: what we know is that when you use a magnet
• 3:15
  Speaker 2: kind of what we call Faraday's law, this idea of
• 3:19
  Speaker 2: using a magnetic pulse to induce an electrical current in
• 3:23
  Speaker 2: electrically conducting substances. So in this case brain tissue, but
• 3:27
  Speaker 2: not skull or scalp or any of that, or hair,
• 3:30
  Speaker 2: you avoid all that, just the brain tissue. Then you
• 3:33
  Speaker 2: have a direct depolarization of cortical neurons, you know, the
• 3:37
  Speaker 2: surface of the brain's neurons in this dorsilateral prefrontal and
• 3:42
  Speaker 2: if you do that in the actual scanner, which we
• 3:45
  Speaker 2: can do, you can see that that distributes down into
• 3:48
  Speaker 2: the entracingulate in the insula and the amygdala, and ultimately
• 3:54
  Speaker 2: the tract goes into something called the nucleus, a tract
• 3:56
  Speaker 2: of solitarius, and ultimately into the vagus nerve into the heart,
• 4:00
  Speaker 2: so that the heart very consistently seems to be the
• 4:04
  Speaker 2: end organ of the dorsilateral prefrontal cortex. And if you
• 4:08
  Speaker 2: do that over visual cortex you don't get that, or
• 4:10
  Speaker 2: motor cortex, you don't get any of those findings. It's
• 4:13
  Speaker 2: really specific to this kind of control region of the brain.
• 4:18
  Speaker 2: And so yeah, it seems to you know, it's our work.
• 4:21
  Speaker 2: Other folks work Martin Arns in Europe, the Netherlands work
• 4:26
  Speaker 2: showing the same connections. I think it's been replicated like
• 4:29
  Speaker 2: four or five times, where I think TMS is really interesting. Actually,
• 4:32
  Speaker 2: we had a lot of patients who've told me, like
• 4:34
  Speaker 2: my therapist told me that I wasn't trying hard enough
• 4:37
  Speaker 2: in therapy. These are moderate, pretty severe depressed patients. And
• 4:42
  Speaker 2: as soon as we get them well with the TMS approaches,
• 4:45
  Speaker 2: you know, kind of rapid, you know, five day approach
• 4:48
  Speaker 2: and the next week we come in and see them
• 4:49
  Speaker 2: and they'll say, you know what I did all weekends.
• 4:51
  Speaker 2: I looked at my therapy books and now I can
• 4:53
  Speaker 2: understand it, and so you know, I actually see TMS
• 4:57
  Speaker 2: is a way of having kind of exogenous sorts of
• 5:01
  Speaker 2: cognitive functions that in milder forms of depression we can
• 5:06
  Speaker 2: pull off with psychotherapy.
• 5:08
  Speaker 3: You know, this idea of being able.
• 5:10
  Speaker 2: To kind of turn that prefrontal cortex on and have
• 5:13
  Speaker 2: it govern these deeper regions, and depression the deeper regions
• 5:18
  Speaker 2: govern the prefrontal cortex.
• 5:20
  Speaker 1: In one case, it's like the coach telling the player
• 5:23
  Speaker 1: what to do, and it's like a player telling the
• 5:25
  Speaker 1: coach what to do. And you restore order to the game.
• 5:28
  Speaker 3: You restore order to the game.
• 5:29
  Speaker 2: And what it looks like is depression is a bunch
• 5:32
  Speaker 2: of kind of spontaneous content that's semi volitional, that's being
• 5:37
  Speaker 2: kind of generated out of this conflict detection system, the singulate.
• 5:42
  Speaker 2: In depression, it looks like the left orse lateral does
• 5:45
  Speaker 2: not sufficiently clamp down on it. And what therapy appears
• 5:51
  Speaker 2: to do is to kind of restore that. What we
• 5:54
  Speaker 2: see with TMS over that region is that we just
• 5:56
  Speaker 2: exogenously do the same sort of thing. We restore the
• 6:00
  Speaker 2: governance of the left door selateral over the singulate area,
• 6:05
  Speaker 2: and that is correlated with treatment improvement. So the degree
• 6:09
  Speaker 2: in which you can re time, reregulate in time the
• 6:14
  Speaker 2: left door selateral over the singulate, the more of an
• 6:17
  Speaker 2: antidepressant effect you have. TMS is almost like exercise for
• 6:20
  Speaker 2: the brain. Right You're kind of exercising this region over
• 6:23
  Speaker 2: and over again with a physiologically relevant signal and kind
• 6:27
  Speaker 2: of turning that system on.
• 6:29
  Speaker 3: And what's interesting for this show.
• 6:31
  Speaker 2: Is, you know, we had a couple of folks, you know,
• 6:34
  Speaker 2: probably five or six folks that have actually told me this,
• 6:36
  Speaker 2: where if they remitt early enough in the week, we
• 6:38
  Speaker 2: have this very dense stimulation approach where we can stimulate
• 6:41
  Speaker 2: people really rapidly over a.
• 6:43
  Speaker 3: Five day block.
• 6:44
  Speaker 2: By Wednesday, they're like totally zero down on the depression scales,
• 6:48
  Speaker 2: you know, even better than most people walking around, like
• 6:51
  Speaker 2: really no anxiety, no no depression or anything. By Thursday.
• 6:55
  Speaker 2: The first guy that told me this, he came in
• 6:57
  Speaker 2: and he said, you know, I was driving back to
• 6:59
  Speaker 2: my hotel and I decided to go to the beach
• 7:01
  Speaker 2: and I just sat there and I was totally present
• 7:04
  Speaker 2: in the present moment for an hour, and he's like,
• 7:06
  Speaker 2: I read about this in my mindfulness books, but I
• 7:09
  Speaker 2: experienced it last night and I've never experienced anything like
• 7:12
  Speaker 2: this before. And I was like, hmm, that's interesting, but
• 7:15
  Speaker 2: kind of wasn't sure then. And then I didn't tell
• 7:18
  Speaker 2: any you know, obviously, any more patients about that.
• 7:20
  Speaker 3: And then about five.
• 7:21
  Speaker 2: Over the last couple of years, when they get they
• 7:23
  Speaker 2: remit early in the week. By the end of the week,
• 7:25
  Speaker 2: they're like going to the beach and they're like totally
• 7:28
  Speaker 2: having what people describe as a pretty mindful, present moment
• 7:32
  Speaker 2: sort of experience, which is really interesting. You know what
• 7:35
  Speaker 2: that is. I mean, I don't have full on scientific
• 7:38
  Speaker 2: data to tell you, but it's just it's a it's
• 7:41
  Speaker 2: an interesting anecdote, right that folks, when you push them
• 7:44
  Speaker 2: through this point of feeling kind of clinically well, that
• 7:49
  Speaker 2: some people end up reporting this additional set of features.
• 7:52
  Speaker 1: So I want to make sure that before we dive
• 7:54
  Speaker 1: into ketamine and psilocybin, that we do touch on SSRI
• 7:58
  Speaker 1: selective serotonin reuptaken because we can't really have a discussion
• 8:01
  Speaker 1: about depression without talking about SSRIs. My understanding is that
• 8:05
  Speaker 1: the SSRIs are powerfully effective for certain forms of obsession
• 8:09
  Speaker 1: obsessive compulsive disorder, and may also be effective for treatment
• 8:12
  Speaker 1: of depression. Is that right? And how should we think
• 8:14
  Speaker 1: about SSRIs? Are they useful? Are they not useful?
• 8:17
  Speaker 3: SSRIs clearly work.
• 8:19
  Speaker 2: You know many mini meta analyzes kind of proving that
• 8:23
  Speaker 2: out right, that in a subpopulation of individuals they achieve
• 8:27
  Speaker 2: great benefit for depression or obsessive compulsive disorder, for generalized
• 8:32
  Speaker 2: anxiety sort of panic, you.
• 8:33
  Speaker 3: Know, all these things.
• 8:34
  Speaker 2: You can see an improvement in those symptoms with what
• 8:38
  Speaker 2: we call SSRIs, or selective serotonin reuptake inhibitors. The issue
• 8:42
  Speaker 2: is that they don't work immediately, right, So they don't
• 8:44
  Speaker 2: work like the same day you start taking them, and
• 8:48
  Speaker 2: that suggests that probably it's not exactly the serotonin being
• 8:53
  Speaker 2: in there that's directly driving it. That it's much more
• 8:56
  Speaker 2: likely that it may have some brain plasticity effects.
• 8:59
  Speaker 3: Right.
• 9:00
  Speaker 2: There's not a deficit of serotonin. You're not born with
• 9:05
  Speaker 2: what people call a chemical imbalance. And psychiatry has known this.
• 9:08
  Speaker 2: This is not actually new information anybody, you know, and
• 9:10
  Speaker 2: it's kind of a rehashing of a bunch of information
• 9:13
  Speaker 2: we've known for a while now, but in the lay
• 9:16
  Speaker 2: press it's kind of hit in a way that it
• 9:18
  Speaker 2: didn't seem to grab attention before with previous publications. But
• 9:24
  Speaker 2: this idea that this chemical imbalance idea is wrong. I
• 9:27
  Speaker 2: really think that part's important because I think that what
• 9:30
  Speaker 2: I'll call psychiatry one point h right, this kind of
• 9:32
  Speaker 2: idea of Freud and psychotherapy and its origins, it was
• 9:38
  Speaker 2: a lot around you know, your family and those experiences
• 9:41
  Speaker 2: in psychotherapy kind of going in and correcting or helping
• 9:45
  Speaker 2: you to figure out or you know, showing you being
• 9:49
  Speaker 2: able to see or people hear you so that you
• 9:51
  Speaker 2: can eventually come to the conclusion of certain cognitions that
• 9:56
  Speaker 2: aren't helping you, right, things like the schizophrenagenic mother and
• 9:58
  Speaker 2: all of that. You know, that was a concept at
• 10:00
  Speaker 2: some point, right, And so we've transitioned from that to
• 10:04
  Speaker 2: the you know, for a long time, the chemical imbalance,
• 10:07
  Speaker 2: which I'll call psychiatry two point zero. You know, this
• 10:11
  Speaker 2: idea that there's something chemically missing. The trouble there for
• 10:16
  Speaker 2: a patient, right, is that it's telling it's sending a
• 10:19
  Speaker 2: message of there's something missing with me, whether it be
• 10:22
  Speaker 2: my experiences I had no control of over when I
• 10:25
  Speaker 2: was a child, or a chemical in my brain. What
• 10:28
  Speaker 2: I think is really powerful with with TMS, you know,
• 10:34
  Speaker 2: really powerful TMS and a lovely even powerful with the
• 10:36
  Speaker 2: psychedelic story. Is it saying something different? You know, TMS
• 10:41
  Speaker 2: works and there's no serotonin coming in or out of
• 10:45
  Speaker 2: the brain, right and we're doing a rapid form of
• 10:47
  Speaker 2: TMS that works in one to five days. There's no
• 10:50
  Speaker 2: there's it's very unlikely that there's some long term kind
• 10:54
  Speaker 2: of upregulation of serotonin that's driving that. So our work
• 10:57
  Speaker 2: actually kind of pushes back on this serotonin hypothesis is
• 11:01
  Speaker 2: being kind of the center of depression because it says, look,
• 11:04
  Speaker 2: we're not giving anybody any serotonin. We're simply turning these
• 11:08
  Speaker 2: brain regions on and we're focused on the circuitry. And
• 11:12
  Speaker 2: that's psychiatry three point Oh, it's not just like neuromodulation.
• 11:14
  Speaker 2: Neuromodulations are really nice, you know, use case for psychiatry
• 11:18
  Speaker 2: three point zero because it's so a way to focally
• 11:20
  Speaker 2: and directly perturb brain regions and whatever modality you're using.
• 11:25
  Speaker 2: But you know, there are a lot of a lot
• 11:27
  Speaker 2: of groups that are actually doing neuroimaging before and after,
• 11:29
  Speaker 2: and they're able to see circuit level changes for something
• 11:33
  Speaker 2: like psilocybin or ketamine long after the drug is gone, right,
• 11:38
  Speaker 2: suggesting in those same brain regions converge. So the subgenual
• 11:43
  Speaker 2: default mode network connection that we see is changing with
• 11:46
  Speaker 2: our Stanford neuromodulation therapy technique. It's that same set of
• 11:52
  Speaker 2: brain regions that ketamine and psilocybins seem to act on,
• 11:56
  Speaker 2: act on these connections between brain networks that seem to shift,
• 12:01
  Speaker 2: and so it refocuses the story on something that's highly correctable,
• 12:08
  Speaker 2: and it's it's basically electrophysiology, and it's basically kind of
• 12:13
  Speaker 2: re calibrating a circuit that is recalibratable instead of I
• 12:19
  Speaker 2: have something missing or I have some set of experiences
• 12:22
  Speaker 2: early in life that are that are going to forever
• 12:26
  Speaker 2: trap me in these these psychiatric diagnoses, and so it
• 12:29
  Speaker 2: kind of challenges that idea, and I think that's what's
• 12:31
  Speaker 2: so powerful about psychiatry three point zero, this idea of
• 12:36
  Speaker 2: focusing on the circuit, because it get gets us into
• 12:39
  Speaker 2: thinking about psychiatry and psychiatric illnescies is something that are recoverable.
• 12:44
  Speaker 2: People can get better people. You know, we've seen with
• 12:46
  Speaker 2: our DMS techniques. We've seen it with some of the
• 12:49
  Speaker 2: psychedelic work that we've done, where people are actually in
• 12:52
  Speaker 2: normal levels of mood for sustained periods of time or
• 12:56
  Speaker 2: within five days, within five or less days, and in
• 12:59
  Speaker 2: the case of of the psychedelics, within a few days. Right,
• 13:02
  Speaker 2: so we can get people out of these states they're
• 13:05
  Speaker 2: totally well, there's no drug in their system at that
• 13:08
  Speaker 2: point in the case of psychedelics, it was never a
• 13:10
  Speaker 2: drug in their system in the case of TMS, and
• 13:13
  Speaker 2: it just tells us that that it's fixable. It's just
• 13:16
  Speaker 2: like an a rhythm in the heart. It's like a
• 13:18
  Speaker 2: broken leg. We can go in and do something and
• 13:20
  Speaker 2: we can get somebody better. And I think what's empowering
• 13:24
  Speaker 2: and what a lot of patients have told me is
• 13:26
  Speaker 2: they say, you know, I've gotten to you know, some
• 13:28
  Speaker 2: people will relapse and need more stimulation or need more
• 13:32
  Speaker 2: psychedelics or whatever it is. But they'll tell me, I
• 13:35
  Speaker 2: don't fear that I'm chronically broken. I don't fear that
• 13:38
  Speaker 2: the chemical imbalance is still imbalanced. I don't fear that
• 13:42
  Speaker 2: these things that I couldn't control of my childhood, you know,
• 13:45
  Speaker 2: are going to be there and drive this problem forever.
• 13:48
  Speaker 2: And I think that's that's what's so powerful about this.
• 13:51
  Speaker 1: And that brings me to this question about psychedelics and
• 13:55
  Speaker 1: the frankly, the altered thinking and perception that occurs in
• 14:00
  Speaker 1: high dose psilocybin clinical sessions. Many people do report improvements
• 14:05
  Speaker 1: in trauma related symptomology and depression, as I understand it
• 14:09
  Speaker 1: from my read of the clinical trials after taking psilocybin,
• 14:12
  Speaker 1: because during those sessions something comes to mind spontaneously. They
• 14:17
  Speaker 1: will report, for instance, a new way of seeing the
• 14:19
  Speaker 1: old problem that's the old problem, could be the voice
• 14:22
  Speaker 1: that they're no good, they'll never nothing will ever work out,
• 14:25
  Speaker 1: or could be even more subtle than that. Why do
• 14:27
  Speaker 1: you think the brain would ever hold on to rules
• 14:30
  Speaker 1: that don't serve us?
• 14:33
  Speaker 2: Well, I think an it's an evolutionary neurobiology answer, right.
• 14:39
  Speaker 2: I think that we end up being a result of
• 14:41
  Speaker 2: probably a lot of biology that's not that useful in
• 14:44
  Speaker 2: the modern era.
• 14:45
  Speaker 3: And I think in the brain.
• 14:46
  Speaker 2: For let's say PTSD, right, A lot of a lot
• 14:50
  Speaker 2: of veterans come back and they experience these PTSD symptoms
• 14:52
  Speaker 2: and they're not.
• 14:53
  Speaker 3: At all useful back home.
• 14:55
  Speaker 2: Right, they hear some loud noise and all of a sudden,
• 14:57
  Speaker 2: they're behind a car, or they're behind a you know,
• 15:00
  Speaker 2: I've heard of folks jump and run behind a trash
• 15:02
  Speaker 2: can or whatever in the middle of San Francisco when
• 15:05
  Speaker 2: they hear a loud noise. But if you put them
• 15:08
  Speaker 2: back in the battlefield, yeah, they adaptive.
• 15:11
  Speaker 3: That's highly adaptive. Right.
• 15:12
  Speaker 2: We hold onto those things from I think an evolutionary
• 15:15
  Speaker 2: neurobiology standpoint, But what seems to, for whatever reason, kind
• 15:20
  Speaker 2: of alleviate that are these are these substances, some new
• 15:26
  Speaker 2: like MDMA, some that have been around for thousands of years,
• 15:30
  Speaker 2: like psilocybin, seem to have a therapeutic effect that seems
• 15:34
  Speaker 2: to be pretty long lasting for these phenomenon And so
• 15:37
  Speaker 2: it's just curious, right, It's curious that in the absence
• 15:41
  Speaker 2: of that these things will keep going on and on.
• 15:43
  Speaker 2: But in the presence of that exposure, then all of
• 15:47
  Speaker 2: a sudden, you see a resolution of the problem and
• 15:50
  Speaker 2: we have some work. Now we're treating folks with navy seals.
• 15:53
  Speaker 2: The anecdotes that we're getting, right, or folks are coming
• 15:56
  Speaker 2: back and they're saying, if these set of PTSD symptoms
• 15:58
  Speaker 2: are finally gone. And so this idea that for whatever reason,
• 16:03
  Speaker 2: going into what's probably a highly plastic state and re
• 16:06
  Speaker 2: experienced memories and then as you know, you know, we
• 16:10
  Speaker 2: reconsolidating it in that state for whatever reason may drive
• 16:15
  Speaker 2: drive a therapeutic effect. My business is to find treatments
• 16:19
  Speaker 2: that help people, and so I'm much more like pragmatic
• 16:23
  Speaker 2: about it. You know, if this sort of thing, which
• 16:27
  Speaker 2: has a lot of cultural baggage, but if this sort
• 16:31
  Speaker 2: of thing ultimately ends up being therapeutic, if we can
• 16:33
  Speaker 2: design trials that convince me and others that it is,
• 16:37
  Speaker 2: then we should absolutely use it. And if it doesn't,
• 16:39
  Speaker 2: then we clearly shouldn't use it. Right, the work that's
• 16:41
  Speaker 2: been done so far, the first psilocybin trial, the first
• 16:45
  Speaker 2: MDMA trials published in Nation Medicine recently, and what do.
• 16:49
  Speaker 1: Those generally say, Let's start with psilocybin and MDMA.
• 16:53
  Speaker 2: So MDMA appears too, and you know, one to a
• 16:56
  Speaker 2: few MDMA sessions have an anti PTSD effect that seems
• 17:00
  Speaker 2: to be, you know, outside of the kind of standard
• 17:06
  Speaker 2: assumed levels of PTSD improvement that you can observe in
• 17:09
  Speaker 2: individuals with this level of PTSD, right.
• 17:12
  Speaker 1: So does that mean that for people that have trauma
• 17:16
  Speaker 1: who do a and again we're talking about in a
• 17:18
  Speaker 1: clinical setting, they take one or two doses of MDM.
• 17:22
  Speaker 1: I think the standard MAPS dose is one hundred and
• 17:24
  Speaker 1: fifty to signderd and seventy five milligrams. Again, doing this
• 17:27
  Speaker 1: with a position et cetera control clinical trial, legal exactly,
• 17:31
  Speaker 1: they do it once or twice, And broadly speaking, what
• 17:35
  Speaker 1: percentage of people who had trauma report feeling significant relief
• 17:39
  Speaker 1: from their trauma trauma afterward?
• 17:41
  Speaker 2: It's about two thirds of people had a clinically significant
• 17:46
  Speaker 2: change in their PTSD.
• 17:48
  Speaker 1: That's impressive. And how how long lasting was that?
• 17:50
  Speaker 3: It appears to last for a while.
• 17:51
  Speaker 2: In the earlier trials where they followed people out, it
• 17:53
  Speaker 2: seemed to last for kind of in the year's range
• 17:55
  Speaker 2: for some people. And so it's you know, it's pretty
• 17:58
  Speaker 2: it's pretty compelling. Contrasted with ketamine, which only on average
• 18:02
  Speaker 2: last about a week and a half for a single infusion,
• 18:05
  Speaker 2: so it's a much shorter.
• 18:07
  Speaker 1: So they have to get repeated infusions of kademy in
• 18:09
  Speaker 1: every ten days or so for.
• 18:11
  Speaker 2: Some people, or they end up getting like like like
• 18:14
  Speaker 2: a bunch of doses for a couple of weeks, and
• 18:16
  Speaker 2: then for some people that seems to last a while.
• 18:20
  Speaker 3: You know, that's where I think.
• 18:21
  Speaker 2: I think the psilocybin's story for depression in the in
• 18:24
  Speaker 2: the MDMA story for PTSD seemed more interesting to me.
• 18:27
  Speaker 1: So for psilocybin, what is the rough percentages on and
• 18:31
  Speaker 1: this would be relief not from trauma but from depression.
• 18:34
  Speaker 3: Yeah, exactly.
• 18:35
  Speaker 2: So it's you know, an open label studies, it's closer
• 18:38
  Speaker 2: to like half to two thirds of people end up
• 18:39
  Speaker 2: getting better, depending upon their level of treatment resistance. In
• 18:42
  Speaker 2: the in the blinded trials, it was more like a
• 18:45
  Speaker 2: third or so of people.
• 18:46
  Speaker 1: Since you mentioned psilocybin, let's talk a little bit about
• 18:48
  Speaker 1: the neurochemistry of psilocybin. What's going on when one takes
• 18:50
  Speaker 1: psilocybin and why is it interesting in light of depression?
• 18:55
  Speaker 3: Yeah, definitely so.
• 18:56
  Speaker 2: David Nutt and Robin Carhart Harris's work around or imaging
• 19:00
  Speaker 2: psychedelics are kind of some of the first folks to
• 19:03
  Speaker 2: do that work, and you know, and to their great surprise,
• 19:06
  Speaker 2: they thought there was going to be an increase in
• 19:08
  Speaker 2: activity on psychedelics, and what they found is the opposite, Right,
• 19:11
  Speaker 2: there's kind of an overall decrease in the level of
• 19:13
  Speaker 2: activity in the brain with psychedelics.
• 19:17
  Speaker 3: But they they've also looked.
• 19:18
  Speaker 2: At connectivity and there's this kind of small world, you know,
• 19:22
  Speaker 2: large world connectivity that you think about, and so, you know,
• 19:26
  Speaker 2: small world meaning there's a lot there's kind of a
• 19:28
  Speaker 2: much more kind of focused kind of cortical function or
• 19:31
  Speaker 2: you know, subcortical function or whatever it is. And and
• 19:34
  Speaker 2: what you see is a difference in that in that
• 19:38
  Speaker 2: level of engagement of brain regions, the connectivity, kind of
• 19:42
  Speaker 2: global connectivity kind of increases. And so it's interesting, you know,
• 19:46
  Speaker 2: I think to kind of have a convergent theory on this.
• 19:50
  Speaker 2: It's still you know, to be determined. There's still a
• 19:53
  Speaker 2: lot of work I think that needs to be done,
• 19:56
  Speaker 2: but it's certainly suggestive that there's pretty profound changes in
• 20:03
  Speaker 2: brain activity and brain connectivity after And what we've found
• 20:07
  Speaker 2: to be really interesting is that the anti depressing effects
• 20:11
  Speaker 2: of psilocybin have a particular connectivity change that we also
• 20:17
  Speaker 2: see with our TMS approaches, right, And it's this connectivity
• 20:22
  Speaker 2: between the subgenual antira singulate and the default mode network.
• 20:26
  Speaker 2: And so when we do this effective Stanford neuromodulation therapy stimulation,
• 20:31
  Speaker 2: we see a down regulation the connectivity between the negatively
• 20:35
  Speaker 2: balanced mood state in the case of depressed individuals and
• 20:38
  Speaker 2: the self representation of the brain. And you see that
• 20:41
  Speaker 2: same connectivity change occur posts psilocybin, you know, suggesting there's
• 20:47
  Speaker 2: a convergent mechanism. And it makes sense, right, You've kind
• 20:49
  Speaker 2: of got an over connected, negatively balanced system, conflict system
• 20:55
  Speaker 2: that's kind of you know, kind of attached onto the
• 20:58
  Speaker 2: self representation and people feel stuck. Right, and then when
• 21:02
  Speaker 2: you when you do whatever you do that's effective it
• 21:05
  Speaker 2: and unpairs those two systems.
• 21:07
  Speaker 1: I want to ask you about IBA gain. Is it
• 21:10
  Speaker 1: legal in the US and as a clinical tool, who's
• 21:14
  Speaker 1: using it and for what purposes.
• 21:16
  Speaker 2: Eyebo gain is a is one of the alkaloids that
• 21:21
  Speaker 2: you can extract from an iboga tree root bark that's
• 21:28
  Speaker 2: typically growing in the country of Gabon, Africa. So what
• 21:33
  Speaker 2: individuals taking ibagain will say is it open eyes. They
• 21:37
  Speaker 2: don't see anything but closed eyes. They'll go back through
• 21:40
  Speaker 2: and re experience earlier life memories and they will be
• 21:46
  Speaker 2: able to experience it from a place of empathy. Not
• 21:50
  Speaker 2: only for themselves but from others and kind of detached
• 21:54
  Speaker 2: empathy and being able to see this as almost a
• 21:58
  Speaker 2: third party even though.
• 21:59
  Speaker 3: They were there.
• 22:00
  Speaker 2: I begain is in no way a recreational substance. You're
• 22:03
  Speaker 2: essentially having this what they call a life review. They
• 22:06
  Speaker 2: also call it ten years of psychotherapy in a night.
• 22:09
  Speaker 2: So these are the terminology that people talk about.
• 22:12
  Speaker 1: The issue does it last? Is it truly one night?
• 22:15
  Speaker 2: Depending upon how fast you metabolize it, sometimes twenty four,
• 22:18
  Speaker 2: sometimes thirty six hours.
• 22:19
  Speaker 3: Sometimes it can be shorter, but it is a long time.
• 22:22
  Speaker 3: It's a very long time.
• 22:23
  Speaker 2: So it's definitely the longest acting psychedelic substance I know of.
• 22:28
  Speaker 2: And so you know, we have over the last couple
• 22:31
  Speaker 2: of years, been able to do this first in human
• 22:37
  Speaker 2: kind of full neurobiological, clinical, neurocognitive evaluation of what I
• 22:43
  Speaker 2: Began is doing in this case in special operations, special
• 22:47
  Speaker 2: Forces individuals, former Navy seals, for Army rangers, that kind
• 22:52
  Speaker 2: of crew folks, and look at the PrePost changes that
• 22:56
  Speaker 2: their experience to be able to totally quantitate all of that,
• 22:59
  Speaker 2: and so we've been able to sure all the clinical scales,
• 23:01
  Speaker 2: you know, depression scales, PTSD scales, all that standard stuff,
• 23:05
  Speaker 2: neurocognitive batteries, so how does your executive function work? Specifically,
• 23:08
  Speaker 2: is your verbal memory? All of that and then neuroimaging
• 23:12
  Speaker 2: and eeg. So this will be the first human study
• 23:15
  Speaker 2: of ibogain for those and the reason why is because
• 23:18
  Speaker 2: ibogain is kind of the both seemingly the most potent
• 23:23
  Speaker 2: and most.
• 23:25
  Speaker 3: And most seemingly to me at least.
• 23:27
  Speaker 2: Most powerful psychedelic, but the one that has the most
• 23:32
  Speaker 2: risk too because it has a cardiac effect. It seems
• 23:35
  Speaker 2: to be that you can screen people out that have
• 23:37
  Speaker 2: risk off of their electric cardiogram and reduce the risk
• 23:40
  Speaker 2: quite a bit, and that's what we all did. But
• 23:43
  Speaker 2: but but that's why people haven't really studied it as much,
• 23:46
  Speaker 2: and it's it isn't as In addition, there's no.
• 23:50
  Speaker 3: Right Nobody goes to a rave on ibogain. There's no
• 23:52
  Speaker 3: recreation at all.
• 23:53
  Speaker 1: But it's not fun.
• 23:55
  Speaker 2: People say that it's relieving, but it's hard work, right
• 23:59
  Speaker 2: because yeah, you're re examining things. So then we see
• 24:03
  Speaker 2: these folks after and I'll tell you, you know, we
• 24:05
  Speaker 2: haven't fully analyzed the data yet, but i'll tell you
• 24:07
  Speaker 2: that from what my folks are telling me it's pretty dramatic.
• 24:11
  Speaker 2: You know, people come back and they're doing a lot better.
• 24:13
  Speaker 2: Soldiers experience something called moral injury, right where they maybe
• 24:17
  Speaker 2: they accidentally blew something up and then had a kid
• 24:20
  Speaker 2: in it or something like that, you know, you know,
• 24:22
  Speaker 2: if they're in Afghanistan or Iraq, maybe a child died
• 24:25
  Speaker 2: on accident or maybe maybe you know, a civilian died
• 24:28
  Speaker 2: or whatever it was, right and then and they suffered
• 24:31
  Speaker 2: these moral injuries as part of the job.
• 24:33
  Speaker 3: And it's almost one of the kind of you know,
• 24:35
  Speaker 3: vocational risks.
• 24:36
  Speaker 2: They come back and say that they've they've they've forgiven themselves,
• 24:40
  Speaker 2: you know, which is which is huge, right, and part
• 24:43
  Speaker 2: of that is being able to see themselves in a
• 24:45
  Speaker 2: different light and having empathy finally for themselves and being
• 24:49
  Speaker 2: able to kind of have that experience of forgiving. And
• 24:51
  Speaker 2: so there's this kind of tympathy leary kind of socio
• 24:54
  Speaker 2: cultural construct that ends up being overlaid over psychedelics. And
• 24:59
  Speaker 2: what I think is that if you rid yourself of
• 25:04
  Speaker 2: all of those preconceived notions of what it is and
• 25:08
  Speaker 2: isn't and the counterculture movement, all that stuff that neither
• 25:10
  Speaker 2: of us were ever involved in neither of us are
• 25:13
  Speaker 2: ever partaken. You know, it is kind of straight scientists
• 25:16
  Speaker 2: looking at this, right, if you can kind of rid
• 25:17
  Speaker 2: yourself of all those socio cultural constructions and then re
• 25:21
  Speaker 2: examine this these if we just discovered these today, we
• 25:25
  Speaker 2: would say that these sorts of drugs are a huge
• 25:29
  Speaker 2: breakthrough in psychiatry because they allow for us to do
• 25:32
  Speaker 2: a lot of the sorts of things we've been thinking
• 25:34
  Speaker 2: about with with SSRIs, with psychotherapy, but kind of combined, right,
• 25:40
  Speaker 2: psychotherapy plus plus drugs in a substance that kind of
• 25:45
  Speaker 2: allows you to re examine these things. And so it's
• 25:48
  Speaker 2: it's interesting, it'll you know, there's a lot to do
• 25:50
  Speaker 2: to try to figure out if that's true, you know,
• 25:53
  Speaker 2: and I can say that as it stands right now,
• 25:56
  Speaker 2: we don't know if it's that statement is true, right,
• 25:59
  Speaker 2: There's a lot more work that needs to happen for
• 26:01
  Speaker 2: that statement to be proven to be true. But the
• 26:03
  Speaker 2: hypothesis is if it is true, then it's very likely
• 26:08
  Speaker 2: that this will be seen as a breakthrough because it
• 26:12
  Speaker 2: allows you to do these sorts of things that you
• 26:14
  Speaker 2: can't do with normal waking consciousness. But also why we
• 26:19
  Speaker 2: have to really think about this, and you know, these
• 26:22
  Speaker 2: drugs can't.
• 26:24
  Speaker 3: Be recreational drugs.
• 26:26
  Speaker 2: They really shouldn't be recreational drugs, right, They're really too
• 26:30
  Speaker 2: powerful to be used in the context or recreation because
• 26:35
  Speaker 2: they can put you into these states. And this generation
• 26:39
  Speaker 2: of psychedelic researchers are really clear about that.
• 26:42
  Speaker 3: You know.
• 26:43
  Speaker 2: I think the sixties folks were not clear about that,
• 26:45
  Speaker 2: and they felt like there was this whole kind of
• 26:47
  Speaker 2: cultural thing that was.
• 26:48
  Speaker 3: Going on there.
• 26:50
  Speaker 2: But I think this cohort of individuals really understands that
• 26:55
  Speaker 2: in order to really make this happen, we have to
• 26:57
  Speaker 2: understand that if you need a prescription or an SSRI
• 27:01
  Speaker 2: which doesn't change your consciousness a whole lot, and we
• 27:05
  Speaker 2: were very worried about that, and the doctor has to
• 27:07
  Speaker 2: evaluate you for that every week. That the idea that
• 27:10
  Speaker 2: some of these substances would would go outside of very
• 27:13
  Speaker 2: strict medical supervision is it's kind of preposterous, actually, it's
• 27:18
  Speaker 2: kind of it's kind of a dumb moment. I think
• 27:20
  Speaker 2: for for all of medicine to say, look, we've you know,
• 27:23
  Speaker 2: if we're going to do this right, we've got to
• 27:25
  Speaker 2: do it in such a way that's so protected, that
• 27:28
  Speaker 2: so safe that we make sure people know these things
• 27:31
  Speaker 2: are not recreational and they're really for the pure purposes
• 27:35
  Speaker 2: of really powerfully changing cognition for a while and letting
• 27:39
  Speaker 2: people have these what seemed to be, you know, relatively
• 27:43
  Speaker 2: therapeutic states.
• 27:44
  Speaker 1: Tell me about ayahuasca and as a plant, is it
• 27:49
  Speaker 1: useful for the same sorts of conditions that we've talked
• 27:51
  Speaker 1: about thus far, And if you could perhaps tell me
• 27:55
  Speaker 1: a little bit also about the Brazilian prisoner study.
• 27:58
  Speaker 3: Yeah, yeah, definitely.
• 28:00
  Speaker 2: Yauasca is another psychedelic It's used as a sacrament in Brazil,
• 28:06
  Speaker 2: in Peru and Ecuador and Colombia, so a lot of
• 28:10
  Speaker 2: the South American countries. And what they do is they
• 28:15
  Speaker 2: combine two plants together, where one plant of the two
• 28:20
  Speaker 2: plant combination would effectively do nothing, but the two plant
• 28:24
  Speaker 2: combination together is capable of producing this very profound psychedelic effect.
• 28:29
  Speaker 2: And what's really kind of curious is that they're, as
• 28:35
  Speaker 2: I understand it, ten to twenty thousand plant species in
• 28:39
  Speaker 2: the Amazon, and somehow somebody combined these two plants together
• 28:45
  Speaker 2: in certain proportionality and cooked this for five ten hours
• 28:50
  Speaker 2: to the point where you cook out the dimethyl trip
• 28:53
  Speaker 2: to me and out of one of the plants and
• 28:55
  Speaker 2: cook out the reversible monoamine oxidase inhibitor out of the
• 28:59
  Speaker 2: other plant. It's such a way that the reversible monoamine
• 29:04
  Speaker 2: oxidase inhibitor prevents the GI breakdown of the dimethyl trip
• 29:09
  Speaker 2: tomine in such a way that it's then allowed to
• 29:12
  Speaker 2: cross the blood brain barrier and get into the brain.
• 29:14
  Speaker 2: And if you didn't add the reversible monoamine oxidase inhibitor
• 29:18
  Speaker 2: plant derived into this combination, then it would never cross
• 29:23
  Speaker 2: the brain. If you put people on a standard psychiatry
• 29:28
  Speaker 2: prescribed monoamine oxidase inhibitor that wasn't reversible, you'd throw them
• 29:32
  Speaker 2: into serotonin syndrome.
• 29:33
  Speaker 3: Right.
• 29:33
  Speaker 2: So this kind of like sweet spot that somehow ayahuasca
• 29:39
  Speaker 2: practitioners have found being able to get DMT and the
• 29:42
  Speaker 2: brain from an oral source with this combination of a
• 29:46
  Speaker 2: monoamine oxidase inhibitor.
• 29:48
  Speaker 3: It's curious.
• 29:51
  Speaker 2: And so that substance has been explored as an antidepressant agent,
• 29:55
  Speaker 2: and some studies have looked at that. It also seems
• 29:58
  Speaker 2: to be very safe. There's a psychiatrist down at UCLA
• 30:03
  Speaker 2: Harbor who's done a lot of work with this where
• 30:07
  Speaker 2: he's looked at children even that have been exposed to
• 30:10
  Speaker 2: kind of small doses of ayahuasca is kind of a
• 30:13
  Speaker 2: sacrament within Amazonian tribes, and found no neurocognitive effects, no
• 30:17
  Speaker 2: neurocognitive effects and adults, and so.
• 30:19
  Speaker 3: It appears to be safe.
• 30:21
  Speaker 2: It's kind of part and brought into various religions, including
• 30:25
  Speaker 2: kind of merged with Catholicism in South America, which is
• 30:28
  Speaker 2: kind of very interesting.
• 30:30
  Speaker 3: And so, you know, in some.
• 30:33
  Speaker 2: Sects of Catholicism in Brazil it's used as sacrament during
• 30:39
  Speaker 2: religious ceremonies. And so it became interesting to Brazilian researchers
• 30:45
  Speaker 2: as to whether or not they could affect recidivism rates
• 30:48
  Speaker 2: for prisoners in Brazilian prisons. Right, so they gave half
• 30:53
  Speaker 2: of the prisoners, you know, some sort of inert substance
• 30:57
  Speaker 2: in half of the prisoners a ayahuasca session, and the
• 31:03
  Speaker 2: recidivism rate or the return to prison rate in the
• 31:06
  Speaker 2: ayahuasca exposed individuals with statistically significantly lower than the recidivism
• 31:11
  Speaker 2: rate in the in the control group, suggesting that you know,
• 31:16
  Speaker 2: whatever is going on there seems to have an effect
• 31:19
  Speaker 2: on whatever drives criminal behavior, whatever criminal behavior that happened
• 31:24
  Speaker 2: to be and I don't have the details on the
• 31:26
  Speaker 2: exact nature of the crime.
• 31:28
  Speaker 3: You know.
• 31:29
  Speaker 2: I am also in no way saying that we should
• 31:31
  Speaker 2: just be giving psychedelics to to folks in prison and
• 31:34
  Speaker 2: all of that. I think that that is a very
• 31:38
  Speaker 2: edgy thing to do and probably not something that anybody
• 31:40
  Speaker 2: should try.
• 31:41
  Speaker 3: But but it does.
• 31:42
  Speaker 2: It does kind of bring up this this curious question
• 31:45
  Speaker 2: of of what is it about that that would drive
• 31:48
  Speaker 2: people to to change those behaviors and why why do
• 31:52
  Speaker 2: people make those behavioral decisions.
• 31:54
  Speaker 1: Before we wrap, I do want to give you the
• 31:57
  Speaker 1: opportunity to talk about the Saint Study or what.
• 32:00
  Speaker 2: We're calling at S and T now Stanford Accelerated Intelligent
• 32:04
  Speaker 2: Neuromodulation Therapy or now what we're calling Stanford Neuromodulation therapy.
• 32:08
  Speaker 2: The idea there is that TMS is a device that
• 32:13
  Speaker 2: delivers delivers a treatment, and the treatment is the protocol,
• 32:19
  Speaker 2: and the protocol is the stimulation parameter set in a
• 32:24
  Speaker 2: specific brain region for a specific condition, whether it be
• 32:28
  Speaker 2: transcranial magnetic stimulation or transcranial direct current stimulation or deep
• 32:32
  Speaker 2: brain stimulation like what Casey Haupurn talked about in all
• 32:35
  Speaker 2: of those cases, the device itself is a physical layer
• 32:39
  Speaker 2: conduit of a stimulation protocol that's therapeutic for a given
• 32:44
  Speaker 2: condition in a given brain region. We decided, gosh, you
• 32:47
  Speaker 2: know this problem I talked about at the beginning of
• 32:49
  Speaker 2: the show where you have these you know this problem
• 32:52
  Speaker 2: that we don't have a treatment for people who are
• 32:54
  Speaker 2: in these high acuity psychiatric emergency states.
• 32:58
  Speaker 3: Right, this idea that we're.
• 33:00
  Speaker 2: Going to engineer a treatment where we can reorganize the
• 33:02
  Speaker 2: stimulation approach in time to be much more efficient by
• 33:08
  Speaker 2: utilizing something called space learning theory. And so you probably
• 33:11
  Speaker 2: know about the space learning theories. The idea for the
• 33:13
  Speaker 2: viewers is, if I'm cramming for a test, what I
• 33:17
  Speaker 2: do is I write out sixty note cards and I
• 33:19
  Speaker 2: read each one for a minute until I get to
• 33:21
  Speaker 2: the first note card and again, and that's about an
• 33:23
  Speaker 2: hour later. Right, that space learning theory. It's this idea
• 33:26
  Speaker 2: that you need to see it about every hour to
• 33:28
  Speaker 2: an hour and a half, and that optimizes learning. What
• 33:30
  Speaker 2: we found was is that the old way of doing TMS,
• 33:33
  Speaker 2: this idea of just doing it once a day, every day,
• 33:36
  Speaker 2: five days a week for six weeks, didn't utilize the
• 33:39
  Speaker 2: space learning theory. It's like studying for a month or
• 33:43
  Speaker 2: two just a little bit once a day, like you
• 33:45
  Speaker 2: remember some of that stuff, but it's like not as
• 33:47
  Speaker 2: potent as that week where you're kind of cramming, right.
• 33:50
  Speaker 2: And what we realized is that if we could reorganize
• 33:53
  Speaker 2: the stimulation in times that we took the whole six
• 33:56
  Speaker 2: week course, we actually figured out a way to do
• 33:58
  Speaker 2: it in a day. And then what we also figured
• 34:00
  Speaker 2: out is that people were underdosing TMS because if you
• 34:03
  Speaker 2: just keep going after six weeks out to month three, four, five,
• 34:07
  Speaker 2: more and more people got better. So we figured out
• 34:09
  Speaker 2: it's not just one day we're gonna get five times
• 34:11
  Speaker 2: a normal dose, We're going have seven and a half
• 34:12
  Speaker 2: months worth in five days using space learning theory. So
• 34:17
  Speaker 2: every hour, every hour for ten hours for five days,
• 34:20
  Speaker 2: for five days, so it's a fifty hour block. It's
• 34:22
  Speaker 2: ninety minutes of actual stimulation, but spread out through the
• 34:26
  Speaker 2: day and the same way of learning. What we've found
• 34:28
  Speaker 2: is that folks will will within one to five days,
• 34:33
  Speaker 2: you know, in more cases than not, and depending upon
• 34:36
  Speaker 2: if you're looking at this open label or in trials,
• 34:38
  Speaker 2: somewhere between sixty and ninety percent of the time they
• 34:42
  Speaker 2: will go into full on remission in the sense they're
• 34:45
  Speaker 2: totally normal from a mood standpoint at the end of
• 34:48
  Speaker 2: this and like I said, with variable durability. So that's
• 34:51
  Speaker 2: the part we have to figure out now about dosing
• 34:53
  Speaker 2: and how to keep people well. But for some people,
• 34:55
  Speaker 2: you know, we've had four years of remission, you know,
• 34:57
  Speaker 2: a year of remission, and it's it's really that cramming
• 35:01
  Speaker 2: of the test. It's really that idea that you're laying
• 35:04
  Speaker 2: in that information to the exact right spot, and the
• 35:08
  Speaker 2: signal is a simple signal, but it's a profound one,
• 35:10
  Speaker 2: which is turn on, stay on, remember to stay on.
• 35:16
  Speaker 2: You know that idea that you're sending this memory signal
• 35:19
  Speaker 2: into the brain, and you're doing it in such a
• 35:21
  Speaker 2: way that you're telling the system. You're kind of taking
• 35:24
  Speaker 2: it out of the Hippo campus's hand, your own Hippi
• 35:26
  Speaker 2: campus's hands, and you're sending the same signal the Hippi
• 35:28
  Speaker 2: campus normally signals out. Now you're sending that signal into
• 35:33
  Speaker 2: the prefrontal cortex and kind of utilizing the brain's own
• 35:37
  Speaker 2: communication style.
• 35:39
  Speaker 3: To get it to get out of the state. And
• 35:41
  Speaker 3: what's very.
• 35:42
  Speaker 2: Cool about this is that is that people when they
• 35:46
  Speaker 2: when they kind of exit out of that, they end
• 35:48
  Speaker 2: up they end up saying they don't have any any
• 35:52
  Speaker 2: side effects from it, and they feel back to normal.
• 35:56
  Speaker 1: Thank you so much for taking us on this incredible
• 36:01
  Speaker 1: voyage through the neurocircuitry underlying certain aspects of depression, the
• 36:06
  Speaker 1: coverage of the different types of depression, the various therapeutic compounds,
• 36:10
  Speaker 1: how they work. We've talked about a lot of things
• 36:12
  Speaker 1: that you've shared so much knowledge, and even as I
• 36:15
  Speaker 1: say that, I very much want to have you back
• 36:18
  Speaker 1: to talk about many other things as well that we
• 36:20
  Speaker 1: didn't have time to cover. But to take the time
• 36:22
  Speaker 1: to sit down with us and share all this knowledge
• 36:25
  Speaker 1: that really is in service to mental health and human
• 36:29
  Speaker 1: feeling better and in fact avoiding often suicidal depression. It's
• 36:33
  Speaker 1: just incredible work and an incredible generosity, and just thank
• 36:37
  Speaker 1: you so much.
• 36:37
  Speaker 3: Absolutely thank you