Latest / Wellness, Actually with Emily Oster & Perry Wilson, MD / What's the deal with psychedelics?

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What's the deal with psychedelics? · Wellness, Actually with Emily Oster & Perry Wilson, MD

0:00
Speaker 1: Before we get started. A brief correction from last week
0:03
Speaker 1: when I was talking about the photic sneeze response, I
0:06
Speaker 1: said that there was cross talk between the optic nerve
0:11
Speaker 1: and the ophthalmic nerve. Oh my gosh, you guys, of
0:13
Speaker 1: course it was the optic nerve and the trigeminal nerve.
0:17
Speaker 1: So sorry about that. I'm sure you were all asking,
0:19
Speaker 1: you know who got fired after that episode. But let
0:23
Speaker 1: me come on again.
0:25
Speaker 2: So, Perry, we went to college together, and when we
0:28
Speaker 2: were in college, how frequently did you do psychedelics?
0:32
Speaker 1: I am embarrassed to admit that I have never done
0:37
Speaker 1: a psychedelic. I no mushrooms, no mushrooms, no LSD, no DMT,
0:45
Speaker 1: no ketamine. I know. I was like, no even any
0:49
Speaker 1: not even not even it. I was pure PCP all
0:52
Speaker 1: the time. That's it for me. Angel dust was the
0:55
Speaker 1: drug of choice.
0:57
Speaker 3: Bath seats and nothing, nothing pans.
1:00
Speaker 1: Why my only way of getting in and out of
1:03
Speaker 1: the dorm was by crashing through the window, you remember,
1:07
Speaker 1: I think?
1:08
Speaker 2: And even more embarrassing, so I also perhaps we are
1:11
Speaker 2: not the best people to do an episode in psychedelics.
1:13
Speaker 3: I've also never done any psychedelics.
1:15
Speaker 2: And for me, I think it's even more embarrassing because
1:18
Speaker 2: I once in high school I went to a three
1:22
Speaker 2: day fish content.
1:24
Speaker 3: Oh my god, like and I still have never right.
1:27
Speaker 1: Probably did it. Probably got enough LSD on you that
1:31
Speaker 1: you tripped a little bit, just like by proxy.
1:34
Speaker 2: Yeah, so we can use that and that can be
1:36
Speaker 2: That's our our main experience is proximity to LSD.
1:39
Speaker 3: Use that's as good as it's going to get.
1:42
Speaker 1: I think we're the perfect people for this to give
1:44
Speaker 1: a real unbiased take on what the data says about psychedelics.
1:47
Speaker 1: Let's do it.
1:51
Speaker 2: I'm Emily Astro, I'm an economist and a data expert.
1:54
Speaker 1: And I'm Perry Wilson, I'm a medical doctor.
1:56
Speaker 3: It's Thursday, May fourteenth, twenty twenty six. And this is wellness.
2:01
Speaker 1: Actually, because you're getting a staggering amount of health and
2:04
Speaker 1: wellness information nowadays from every source imaginable, and some of
2:08
Speaker 1: it is awesome and.
2:10
Speaker 3: Some of it is well actually both.
2:14
Speaker 2: Fortunately we are both people who know how to read studies,
2:18
Speaker 2: how to parse the data, and can tell you what's
2:20
Speaker 2: worth thinking about and what you can safely ignore.
2:23
Speaker 1: But before we dig in, a note that this podcast
2:25
Speaker 1: is for educational purposes and should not be construed as
2:28
Speaker 1: medical advice. We don't know your unique situation, so talk
2:31
Speaker 1: to your doctor for personal health decisions.
2:35
Speaker 2: This week we're asking what's the deal with psychedelics? Perry
2:38
Speaker 2: and I will give the official smasher pass and we'll
2:40
Speaker 2: get to your question of the week. But first, let's
2:43
Speaker 2: do the health news roundup after the break. And now
2:58
Speaker 2: for the health news of the week. We covered this
3:01
Speaker 2: last week, but I think we got to go back
3:02
Speaker 2: to haunt of virus. Perry, give us what is happening
3:06
Speaker 2: with the haunt of virus?
3:07
Speaker 3: Now?
3:07
Speaker 1: Yeah, it's a developing situation. So just FYI you're listening
3:11
Speaker 1: to this. The earliest you're listening to this is May fourteenth,
3:14
Speaker 1: but we're recording this on Tuesday, May twelfth. So at
3:18
Speaker 1: this point, the cruise ship is largely evacuated. People have
3:22
Speaker 1: returned home and including about twenty or so to the
3:27
Speaker 1: United States. The current status is that there are seven
3:30
Speaker 1: or eight people on the cruise ship who have tested
3:33
Speaker 1: positive for hauntavirus, with another couple developing symptoms that don't
3:37
Speaker 1: have test results back yet. I think the thing I
3:40
Speaker 1: want to think about now is looking at this particular
3:44
Speaker 1: virus and these virus and the risk for human transmissibility.
3:49
Speaker 1: All of these people are being quarantined for six weeks
3:51
Speaker 1: because there's quite a long latent period of this particular infection,
3:55
Speaker 1: so you might not develop symptoms for that period of time.
3:58
Speaker 1: There's a new England Leernal of Medicine study from twenty
4:01
Speaker 1: eighteen that catalogs a human outbreak of Andy's virus in Argentina,
4:08
Speaker 1: and what had happened was someone got infected, they got
4:12
Speaker 1: their wife infected, the original infected person died at the funeral,
4:17
Speaker 1: like ten people got infected that and then they finally
4:20
Speaker 1: realized what was going on, never got put in quarantine,
4:22
Speaker 1: and the outbreak stopped. So this was the primary epidemiologic
4:27
Speaker 1: evidence for person to person spread. And Emily, we've talked
4:30
Speaker 1: about the basic reproduction number before. This is the average
4:33
Speaker 1: number of people that an infected person spreads the virus
4:38
Speaker 1: two and in that in that outbreak they calculated it
4:42
Speaker 1: to be about two. Any number greater than one means,
4:46
Speaker 1: you know, you can do the math like if one
4:48
Speaker 1: person had spread it to more than one person, it
4:50
Speaker 1: can spread. That's without quarantine. And then once things were
4:53
Speaker 1: put in quarantine, obviously it dropped below one. And everything
4:56
Speaker 1: went back to zero. One bit of positive news. This
5:00
Speaker 1: is likely not spread when people are asymptomatic, in contrast
5:04
Speaker 1: to COVID. By the way, COVID's basic reproduction number prior
5:07
Speaker 1: to vaccination is like ten.
5:08
Speaker 3: So just measles it is twelve. So this is it
5:11
Speaker 3: at very different scale.
5:12
Speaker 1: Even very different scale. People are using the term airborne
5:15
Speaker 1: for this. I don't think that's correct. It looks like
5:17
Speaker 1: this is potentially spread by droplets, which are things like
5:22
Speaker 1: from you know, coughing, spit saliva, which yes, it comes
5:27
Speaker 1: out of your body and goes into the air, but
5:29
Speaker 1: it's heavier than air, so it falls to the ground
5:31
Speaker 1: as opposed to like spreading through air vents and stuff
5:34
Speaker 1: like that, like coronavirus would. The risk remains very low,
5:38
Speaker 1: but we're watching, Yeah.
5:39
Speaker 3: People are watching.
5:40
Speaker 2: I mean I think it is worth like a lot
5:42
Speaker 2: of what I have seen on Twitter as people being like,
5:44
Speaker 2: oh my god, should I be afraid for my children?
5:45
Speaker 2: And like like there'res the pandemic. Epidemiological risk of this
5:50
Speaker 2: remains incredibly low, and so you know, it is something
5:55
Speaker 2: that people are going to watch, but it is not
5:58
Speaker 2: something you should be, you know, thinking too much about
6:02
Speaker 2: it in a terrified way in my view.
6:03
Speaker 1: Yeah, that's correct, But we'll give you updates as they
6:05
Speaker 1: come in.
6:06
Speaker 3: We'll gep you updated.
6:07
Speaker 1: All right. Moving on, the shakeup at Health and Human
6:12
Speaker 1: Services continues potentially now it looks like FDA Director Marty
6:17
Speaker 1: McCarry is in the hot seat. There's been multiple reports
6:21
Speaker 1: last week that Trump had potentially signed off on a
6:26
Speaker 1: measure to fire him, and then that didn't happen. But
6:28
Speaker 1: now new reports are saying, oh, no, he still might
6:30
Speaker 1: be Emily, what's going on at FDA and what are
6:34
Speaker 1: we seeing here? Is this more backlash against the Maha agenda.
6:37
Speaker 2: I don't know that it's more backlash against the MAHA jena.
6:40
Speaker 2: I mean, it's always very hard to tell what's happening
6:41
Speaker 2: inside the administration. The latest thing I saw it again,
6:47
Speaker 2: it's Tuesday the twelfth, was that Marty McCarey has said
6:49
Speaker 2: he is not going to leave or he is not.
6:52
Speaker 2: No one's asked him to leave, and so he's not
6:54
Speaker 2: planning to leave. It seems like some of the reportings
6:58
Speaker 2: suggested that part of the problem is he has been
7:01
Speaker 2: unwilling to follow through on some of the requests of
7:06
Speaker 2: the administration, including a request to approve fruit flavored vapes.
7:11
Speaker 3: He didn't want to approve fruit flavored vapes.
7:14
Speaker 2: Because it seemed like they would be appealing to children,
7:17
Speaker 2: which seems right to me. But the administration wanted fruit
7:21
Speaker 2: flavored vapes, and I think they have now been approved,
7:25
Speaker 2: So I'm not sure. I mean, as generally, people who
7:29
Speaker 2: are threatened to leave the administration are not long for
7:31
Speaker 2: this world of the administration. And so my guess is,
7:35
Speaker 2: you know, by the time we meet again next week,
7:36
Speaker 2: he will be out, but fruit flavors vapes will perhaps
7:39
Speaker 2: be in. Uh.
7:40
Speaker 1: Yeah, that seems like just not a great idea. And
7:44
Speaker 1: also like what a weird thing for the White House
7:46
Speaker 1: to lobby paramount, you know, like you.
7:51
Speaker 3: Know, he was into approving mint, but he didn't want
7:53
Speaker 3: to approve mango. And that's it because you need a
7:57
Speaker 3: mag Also, who wants a mango?
7:59
Speaker 2: I'm sorry we could like get is like, why, dore's
8:01
Speaker 2: your vpe need to be mango flavored?
8:03
Speaker 1: Yeah, I'm not sure. Yeah, it doesn't okay.
8:05
Speaker 2: Last thing, I wanted to ask about a new study
8:08
Speaker 2: that said the GLP one drugs reduce the risk of
8:11
Speaker 2: breast cancer recurrence by like an astronomical amount seventy percent,
8:16
Speaker 2: reducing all cause mortality by ninety one percent. I think
8:19
Speaker 2: the phrasing for this would be amazing if true, So Perry,
8:23
Speaker 2: if true.
8:24
Speaker 1: If true, GLP one drugs like ozepic are the greatest
8:28
Speaker 1: breakthrough in breast cancer treatment in history. Like that's that's
8:33
Speaker 1: the magnitude of this kind of change, and so that
8:36
Speaker 1: should write away clue you in that this is probably
8:39
Speaker 1: not true. This is a study that came out in
8:42
Speaker 1: JAMA Network Open. It's not a randomized trial. It was
8:44
Speaker 1: a study that used administrative data to look at eight
8:47
Speaker 1: hundred thousand women with breast cancer stage one to stage
8:50
Speaker 1: three so no metastatic disease, some of whom got GLP
8:54
Speaker 1: ones through their normal course of care, and some who didn't.
8:57
Speaker 1: And the women who got GLP ones INDI had a
9:01
Speaker 1: ninety one percent reduction and all cause mortality and a
9:03
Speaker 1: substantial reduction in breast cancer recurrence. Now, correlation isn't causation.
9:08
Speaker 1: We say that all the time. People who get GLP
9:11
Speaker 1: one drugs are different in lots of ways than people
9:13
Speaker 1: who don't. They tend to be wealthier, more educated, more
9:17
Speaker 1: access to care, all sorts of things. That are going
9:20
Speaker 1: to also associate with better outcomes after breast cancer. The
9:24
Speaker 1: authors say, no, no, we controlled for this. We used
9:28
Speaker 1: a technique called propensity score matching to sort of take
9:31
Speaker 1: people that are on GLP ones. I know you won't
9:33
Speaker 1: like it, take people on GLP ones and match them
9:35
Speaker 1: to kind of very similar people are not on JLP ones.
9:37
Speaker 1: That's all well and good. It's not perfect. But if
9:40
Speaker 1: you look at this paper, I actually I have to say,
9:43
Speaker 1: like I was, like, I don't understand how this got
9:45
Speaker 1: published at all. I'll give you some examples. If you
9:49
Speaker 1: look at Table one, the description of these women, it
9:51
Speaker 1: says after a diagnosis of stage one to three breast cancer,
9:54
Speaker 1: four percent of them got a mastectomy and two percent
9:58
Speaker 1: of them got a lumpectomy. Six percent got surgery after
10:02
Speaker 1: a diagnosis of breast cancer that's treatable with surgery. Like
10:06
Speaker 1: that is not correct, and this is supposed to be
10:08
Speaker 1: a nationally representative sample. Okay, let's say maybe you believe
10:12
Speaker 1: that that's remotely possible. They report like eight percent of
10:16
Speaker 1: them being estrogen receptor positive and twelve percent or something
10:20
Speaker 1: being eschgen receptor negative, leaving eighty percent to be some
10:25
Speaker 1: third type of like undefined eschen receptor status. What all
10:29
Speaker 1: this is is missing data, and not a small amount
10:31
Speaker 1: of missing data, an enormous amount of missing data. Like
10:34
Speaker 1: most of these women, they couldn't figure out what their
10:36
Speaker 1: essen receptor status was. They didn't even know what kind
10:38
Speaker 1: of surgery they had. So when you say, like, oh,
10:41
Speaker 1: we matched them, you can't match on data you don't have.
10:45
Speaker 1: In my kind of line of work, when we use
10:47
Speaker 1: electronic health record data, we typically draw the line at
10:50
Speaker 1: about ten percent missing data before we start like saying, Okay,
10:54
Speaker 1: we're probably getting out of over our skis and making
10:57
Speaker 1: any inference will sort of tolerate some percent is ridiculous.
11:01
Speaker 1: So I'm sorry. I mean, GP ones might be great,
11:02
Speaker 1: but like this, this society tells us nothing.
11:06
Speaker 2: Yeah, I think it's an interesting It's an interesting example
11:08
Speaker 2: because we often talk about like one of the things
11:10
Speaker 2: you're looking for in a paper to know if it's
11:11
Speaker 2: a good paper or to evaluate is the size of
11:13
Speaker 2: the sample.
11:14
Speaker 3: And this is a case in which the sample size
11:15
Speaker 3: is very very.
11:16
Speaker 2: Large, but the data is quite weak because it isn't
11:20
Speaker 2: electronic medical records, it's billing code data. So you don't
11:25
Speaker 2: actually know that like surprisingly don't know that much about
11:28
Speaker 2: people's about people's health. So it is a good example
11:31
Speaker 2: where I do think reasonably people could ask how could
11:35
Speaker 2: this study get published?
11:36
Speaker 3: And the answer is, actually, this is not a very
11:37
Speaker 3: good journal, honestly.
11:38
Speaker 1: I mean I have published in that journal, but I've
11:42
Speaker 1: published in lots of journals.
11:43
Speaker 2: It's well, I think people get I will just say
11:46
Speaker 2: people get confused because there is a very good journal
11:48
Speaker 2: called JAMA, the Journal of the American Medical Association I published,
11:51
Speaker 2: and there are some very good Yeah, okay, great, now
11:54
Speaker 2: this is gonna be a list of let's read Perry
11:56
Speaker 2: CV and then but and then there is there are
12:01
Speaker 2: some sub journals in JAMMA that are not as strong,
12:03
Speaker 2: of which JAMMA Network Open is one, And this paper
12:07
Speaker 2: is not very good. So GLP ones do not reduce
12:09
Speaker 2: the risk of breast cancer also cause mortality by ninety
12:12
Speaker 2: one percent.
12:13
Speaker 1: Sorry, that's it for the health news of the week.
12:17
Speaker 1: After the break, what's the deal with psychedelics?
12:21
Speaker 3: I've actually also published in JAMA.
12:23
Speaker 1: Oh well, you're not gonna you're not jumping in on
12:25
Speaker 1: that one.
12:25
Speaker 3: Come on, not gonna mention it.
12:33
Speaker 1: And we're back. What's the deal with psychedelics? Emily. Psychedelic
12:38
Speaker 1: medicine is an incredibly new field, boosted on the bats
12:43
Speaker 1: of some really interesting data that we're going to talk about,
12:46
Speaker 1: and then a whole lot of influencers and marketing and
12:51
Speaker 1: amazing anecdotal stories.
12:53
Speaker 2: So I let me just say before we get into this,
12:55
Speaker 2: I think that this has really now stepped into more
13:01
Speaker 2: of the like the mainstream, you know, the Daily The
13:04
Speaker 2: New York Times podcast, which is a very serious podcast
13:07
Speaker 2: frequently about you know, China and stuff, had a whole
13:10
Speaker 2: episode with a reporter who had sort of gone down
13:14
Speaker 2: to Mexico to do us to have a psychedelic experience
13:18
Speaker 2: and to talked about like this being transformative for his
13:22
Speaker 2: relationship with some childhood trauma. So I think this has
13:26
Speaker 2: gotten between that and Michael Poland's book, and so I
13:29
Speaker 2: think this has gotten into the zeitgeist even beyond like
13:33
Speaker 2: influencers on the Internet, who for sure are also talking
13:36
Speaker 2: about it.
13:36
Speaker 3: So good topic.
13:37
Speaker 1: Yeah, absolutely, And the way I want to kind of
13:39
Speaker 1: approach this is first, like let's do some science. Let's
13:42
Speaker 1: talk about how psychedelics work, right, and then we'll kind
13:44
Speaker 1: of go and like if they work for various conditions,
13:48
Speaker 1: we'll hit on a few mental health conditions like PTSD
13:52
Speaker 1: and depression and addiction, which I think a lot of
13:55
Speaker 1: the data is really interesting. But then I think it's
13:58
Speaker 1: worth talking about, like what about people who or otherwise healthy,
14:01
Speaker 1: Like are there potential benefits to you know, supplementing supplementing
14:06
Speaker 1: with psychedelics from time to time.
14:08
Speaker 2: It's not like vitamin D though, don't there's not an
14:11
Speaker 2: unsupervised experience.
14:13
Speaker 1: I want to think about psychedelics starting with neurobiology, and
14:17
Speaker 1: there are three functions that the brain does that psychedelics
14:22
Speaker 1: mess with, and I think if you understand those functions,
14:24
Speaker 1: you get why the psychedelic experience is the psychedelic experience.
14:28
Speaker 1: The first one is called reality testing. So have you
14:30
Speaker 1: ever noticed, Emily that in real life, when like your
14:35
Speaker 1: door burst open and a goblin carrying machetes jumps through,
14:41
Speaker 1: you're like, that's probably not real. But if that happens
14:44
Speaker 1: in a dream, you're like, yeah, that's of course, Like
14:48
Speaker 1: these things happen right right. Your brain is reality testing
14:52
Speaker 1: all the time. When you're conscious and awake. It is
14:54
Speaker 1: getting stimuli from all over the place, not just the
14:57
Speaker 1: you know, it's not just the things you see and
14:59
Speaker 1: feel and smell, tons of stimuli, but also just like
15:01
Speaker 1: random electrical firings in your brain that are happening all
15:04
Speaker 1: the time, and there's a whole system designed to like
15:07
Speaker 1: make sure that the inputs correspond with your knowledge of
15:10
Speaker 1: the world right, like things don't fly up into the
15:13
Speaker 1: air unexpectedly like all of those things. That's what reality
15:16
Speaker 1: testing does. It gets shut down during dreaming, which is
15:19
Speaker 1: why your dreams can be so believable even though bizarre
15:22
Speaker 1: things are happening. It is also shut down by psychedelics,
15:26
Speaker 1: and so all of a sudden, all those inputs that
15:29
Speaker 1: normally your band would filter out. Is like, that's not
15:31
Speaker 1: consistent with reality. It's like, yeah, sure that makes sense.
15:34
Speaker 1: Sure that tree can be melting, Like why not? So
15:37
Speaker 1: that's number one. Yeah.
15:38
Speaker 2: So this is sort of like if I'm in my
15:40
Speaker 2: conscious mind and I out of the corner of my eye,
15:42
Speaker 2: I see something that looks like, you know, buffalo running
15:47
Speaker 2: down the street. My brain is sort of like, well,
15:49
Speaker 2: that's obviously, like is coding, that's obviously.
15:51
Speaker 3: Not a buffalo.
15:52
Speaker 2: And I either look again or I just am like, na,
15:55
Speaker 2: obviously we must have been a dog.
15:57
Speaker 1: It might not even raise to conscious awareness, like you
15:59
Speaker 1: might not even know that you saw a buffalo out
16:02
Speaker 1: of the corner of your eye.
16:03
Speaker 3: Yeah, okay.
16:04
Speaker 1: The second thing, and something I think is really interesting,
16:07
Speaker 1: is technically known as salience, which is that your brain
16:11
Speaker 1: assigns a level of meaning to every experience you have,
16:15
Speaker 1: like is this important. So evolutionarily salience is like you
16:20
Speaker 1: ate some berry and then you get like horribly sick,
16:23
Speaker 1: and your brain will attach a little tag to that
16:25
Speaker 1: memory like this is an important memory, right, Like this
16:28
Speaker 1: is meaningful, and those memories get processed differently, they get
16:33
Speaker 1: stored differently, so it's like, Okay, in the future, you're
16:35
Speaker 1: not gonna eat that berry again. Whereas like walking from
16:39
Speaker 1: your car to your office every day, your brain process
16:42
Speaker 1: is that and it's like this is not important, Like
16:44
Speaker 1: we don't need to remember this, This is nothing important
16:47
Speaker 1: is happening right now, and this is really important because
16:49
Speaker 1: otherwise your brain gets full and you're like that guy
16:51
Speaker 1: in the Far Side cartoon. Psychedelics ramp up the salience
16:58
Speaker 1: metric of everything that is happening, which is why if
17:03
Speaker 1: you're sitting quietly on your couch and nothing in particular
17:07
Speaker 1: is happening, but your brain is saying, like this is
17:09
Speaker 1: really important. Right, you have to like have some explanation
17:14
Speaker 1: for that cognitive dissonance. And one of the ways people
17:17
Speaker 1: explain that is they're like, I'm in the presence of
17:20
Speaker 1: something bigger than me, right, Like God is here, or
17:23
Speaker 1: like an entity is here, because this very banal thing
17:28
Speaker 1: sitting on your couch all of a sudden feels really
17:30
Speaker 1: really important and meaningful. This lack of reality testing and
17:36
Speaker 1: increase in salience is also seen in paranoid schizophrenia, which
17:41
Speaker 1: is why paranoid people have hallucinations. And also, you know,
17:46
Speaker 1: if you're just sitting there, like watching TV and it's
17:48
Speaker 1: just a newscast, but your brain is saying this is
17:51
Speaker 1: incredibly important, you can see how you might jump to
17:53
Speaker 1: the conclusion like, oh, they're talking to me, right, this
17:56
Speaker 1: is about me.
17:57
Speaker 3: Right.
17:58
Speaker 1: So, in fact, the psychedelics when they were originally discovered
18:02
Speaker 1: were called psychoto memetics, like things that give you psychosis.
18:08
Speaker 1: But fortunately with the psychedelics it is temporary, and with
18:13
Speaker 1: schizophrenia obviously it's permanent. So I think this is a
18:17
Speaker 1: good way to start thinking about, like what's actually happening here?
18:22
Speaker 3: That is very cool. So these the compounds. One of
18:27
Speaker 3: the things that's interesting about psychedelics.
18:29
Speaker 2: Is that these compounds have been around and used for
18:34
Speaker 2: I think probably all of human you know, almost all
18:38
Speaker 2: of human history. So you know, we associate in the
18:42
Speaker 2: kind of modern era, we associate this the LSD with
18:46
Speaker 2: I believe it was discovered by Albert Hoffman, but we associate.
18:49
Speaker 1: It with tim Timothy Leary.
18:52
Speaker 3: Timothy Leary, thank you, associated with Timothy Leary.
18:55
Speaker 2: But many of the compounds that are sort of used
18:58
Speaker 2: in some of these psychedelics are from plants or mushrooms
19:02
Speaker 2: or whatever and have been in use, presumably again for millennia.
19:08
Speaker 3: Do we have a sense.
19:09
Speaker 2: Of what people use these for before like using it
19:14
Speaker 2: for PTSD, I assume just for hallucinating because it's fun.
19:18
Speaker 1: I mean, in a lot of indigenous cultures, they're used
19:21
Speaker 1: for spiritual purposes. I think ayahuasca is you know, maybe
19:25
Speaker 1: the one that people will be most familiar with where
19:28
Speaker 1: the idea is commune with something greater than yourself, you know,
19:33
Speaker 1: not just to like have a crazy trip, and you know,
19:36
Speaker 1: there's a whole social fabric around it, and which is
19:40
Speaker 1: which is really interesting and I think even potentially part
19:42
Speaker 1: of the therapeutic benefit that can occur with some of
19:45
Speaker 1: these is like what surrounds the experience. In fact, a
19:48
Speaker 1: lot of the studies and we'll talk about like really
19:50
Speaker 1: need to couple the drug with something, whether it's like
19:55
Speaker 1: psychotherapy or something like that to kind of allow the
19:58
Speaker 1: effects to take route. There's a lot of psychedelics out there.
20:02
Speaker 1: You've alluded to a few, so I think we should
20:04
Speaker 1: just sort of like maybe say a couple of them.
20:08
Speaker 1: I mean we could listen. I don't know, you want
20:09
Speaker 1: to do you want to give us a rundown of
20:11
Speaker 1: like what you see people talking about, Emily in terms
20:13
Speaker 1: of what psychedelics we mean?
20:15
Speaker 2: Yeah, so I think the there I would sort of say,
20:18
Speaker 2: there's a couple of categories that I hear talked about
20:20
Speaker 2: a lot. So one is the kind of psychocybin psilocybin. Yeah,
20:25
Speaker 2: maybe I begin where people talk about usage in a
20:30
Speaker 2: kind of like a true like tripping state we see.
20:34
Speaker 2: I think a lot of discussion of ketamine. I would
20:37
Speaker 2: say ketamine is the one where I hear people both
20:41
Speaker 2: on the Internet and actually in my life talk about
20:45
Speaker 2: using ketamine. So if you hang out in la at all,
20:49
Speaker 2: everyone will talk about how they're doing ketemine in not
20:52
Speaker 2: literally everyone, but all the people that I've encountered recently
20:54
Speaker 2: in LA. You know, we're explaining like this as a
20:57
Speaker 2: sort of standard part of kind of a psychological treatment.
21:01
Speaker 3: And then MDMA, which.
21:03
Speaker 2: Is it's ecstasy, right, I mean yeah again sort of
21:07
Speaker 2: not so much for the therapeutic uses, but almost like
21:10
Speaker 2: for relationship improvement. Interesting, now that we're adults, I feel
21:15
Speaker 2: like everybody who talks to me about psychedelics is talking
21:18
Speaker 2: about it, not for like this is going to make
21:19
Speaker 2: my rave more fun, but like, here's how I'm going
21:21
Speaker 2: to improve my marriage.
21:22
Speaker 3: Ling ecstasy with my partner. Okay, that's what it is
21:26
Speaker 3: to be forty six Perry.
21:27
Speaker 1: I love this. I love this so much, so great.
21:33
Speaker 1: I think it's worth saying that the hallucinogens like psilocybin, LSD,
21:42
Speaker 1: MDMA all work in part on a specific receptor in
21:46
Speaker 1: the brain, the serotonin two A receptor. Ketamine is not
21:49
Speaker 1: quite a hallucinogen. It doesn't work on that receptor. It's
21:52
Speaker 1: a what's called a dissociative anesthetics. So that experience, as
21:55
Speaker 1: I understand it for ketamine is is more just like
21:58
Speaker 1: you're you feel like you're not really in your body,
22:01
Speaker 1: like you're not kind of a participant in reality, So
22:04
Speaker 1: it's definitely an altered state, but it's not quite the
22:06
Speaker 1: same reality testing salience stuff that we talk about with
22:11
Speaker 1: the hallucinogens. So Emily we've gone through kind of a
22:14
Speaker 1: big list of psychedelics. There are others that we won't
22:17
Speaker 1: even get around to mentioning because there's not as many
22:19
Speaker 1: studies on them. But I think one thing that I
22:21
Speaker 1: often hear is like people kind of draw a line
22:25
Speaker 1: between something like mushrooms, which it's like, oh, that's from nature,
22:30
Speaker 1: like an ayahuasca, which is, you know, something that grows
22:35
Speaker 1: versus something like LSD or MDMA, which are synthesized chemicals.
22:40
Speaker 1: Do you think that safety goes along with the fact
22:43
Speaker 1: that something comes from nature versus a synthesized and a
22:46
Speaker 1: lab or like, how do you think about these or
22:48
Speaker 1: do you not divide them at all?
22:49
Speaker 2: I think that most of that division is kind of
22:52
Speaker 2: fake in people's heads. I mean, these are all working
22:56
Speaker 2: on some they're all like sort of chemical processes. They're
22:59
Speaker 2: working on a brain receptor, and often on the same
23:01
Speaker 2: brain receptor as each other. It is true that the
23:04
Speaker 2: synthesized versions tend to be much more potent and a
23:08
Speaker 2: much smaller amount, and so I think there's a sense
23:10
Speaker 2: in which, like it's more difficult to take too many
23:14
Speaker 2: mushrooms than it is to take too much LSD, because
23:17
Speaker 2: you could pretty easily take like quite a lot of
23:20
Speaker 2: LSD without realizing it, and the mushrooms, like you know,
23:23
Speaker 2: there's a little more processing of the experience. But up
23:28
Speaker 2: to that issue, I think these are very like it's
23:31
Speaker 2: just a chemical and so it's not like one of
23:33
Speaker 2: these is natural and one of them is not natural.
23:34
Speaker 2: They're just chemicals that are like produced in different ways.
23:37
Speaker 1: Can I tell you should say?
23:38
Speaker 2: The ketamine is a schedule like most of these drugs
23:42
Speaker 2: are Schedule one, which means they are not they are
23:46
Speaker 2: not legal outside of a research context, I believe, and it's.
23:49
Speaker 1: Even really hard in research to get the approvals.
23:52
Speaker 3: To do it.
23:52
Speaker 2: Yeah, ketemye is Schedule three drug, which means it can
23:55
Speaker 2: be used in certain circumstances.
23:57
Speaker 1: Oh yeah, we use all the time for Oh my god,
23:58
Speaker 1: we use it for kids when they broken bones the
24:01
Speaker 1: first time. I yeah, yeah, the first time I had
24:04
Speaker 1: a kid in the er when I was a med student.
24:06
Speaker 1: I guess, no, yeah, I guess I must have been
24:08
Speaker 1: a med student. Kid had a broken forearm. Little kid,
24:12
Speaker 1: the poor guy, and you know, the orthpedic surgeon was
24:15
Speaker 1: going to come in and like reset it and put
24:16
Speaker 1: it in a cast. And they gave the kid a
24:18
Speaker 1: little bit of kenemine. He like zones out, like not asleep,
24:22
Speaker 1: just like not not there, and they they like you know,
24:27
Speaker 1: do his arm and everything, and he was totally chill.
24:29
Speaker 1: It's really great. It's a great drug.
24:30
Speaker 2: Actually, now that I think about it, they use ketamine
24:32
Speaker 2: all the time on the pit ketamine and rock I
24:35
Speaker 2: believe it is Doctor Robbie is primarily so for those
24:38
Speaker 2: of you who are not yourself set a small child's arm,
24:40
Speaker 2: you can think about doctor Robbie doing awesome.
24:44
Speaker 1: Just a brief tangent on the MDMA for relationship status.
24:48
Speaker 1: There is a totally amazing study of octopuses.
24:54
Speaker 3: Where it's octopi but fine, oh.
24:57
Speaker 1: Okay, I believe it's octopoda.
25:00
Speaker 3: Actually, go ahead, all right.
25:04
Speaker 1: Current Biology, twenty eighteen. They used these octopuses that are okay,
25:12
Speaker 1: the two spot octopus, which are notoriously anti social and
25:16
Speaker 1: like attack each other and stuff like that, and they
25:18
Speaker 1: put them in a tank together. But there was MDMA,
25:21
Speaker 1: like this ecstasy stuff in the tank, and the octopuses
25:27
Speaker 1: like got gentle and were like stroking each other's dctacles
25:30
Speaker 1: and stuff like that. So when you say it's good
25:33
Speaker 1: for like a marriage, I am, I'm on board, okay.
25:39
Speaker 2: So there are many things one could say about the
25:42
Speaker 2: detailed chemical structures of these different of these different drugs,
25:46
Speaker 2: but I think much in some ways much more interesting
25:48
Speaker 2: and practical for people is the question of whether they
25:53
Speaker 2: are effective we used in treatment of various things, and
25:58
Speaker 2: also the question of whether you would like to take
26:00
Speaker 2: them even if you are not looking for a treatment.
26:03
Speaker 2: So I would say we should turn to that. And
26:05
Speaker 2: I actually wanted to start with sort of two sort
26:07
Speaker 2: of big picture pieces of this, maybe three. So one
26:13
Speaker 2: is that by and large these medications are used not
26:18
Speaker 2: like you would use tilinol or even you know, a statin.
26:23
Speaker 2: Like it's not like somebody gives you a bottle of
26:27
Speaker 2: you know, MDMA and every day you take it. And
26:29
Speaker 2: we can talk about micro microdosing, but most of this
26:34
Speaker 2: is like a one time, a couple of times small
26:39
Speaker 2: number of treatments under the supervision of a doctor. Many
26:42
Speaker 2: of these things people are doing in other countries because
26:44
Speaker 2: the drugs are scheduled one, and so this is like
26:47
Speaker 2: a sort of pretty fundamentally different idea behind you know,
26:50
Speaker 2: does this treat the following disease because it's not an
26:54
Speaker 2: ongoing kind of pill form treatment like we often talk about.
26:59
Speaker 2: I think the second thing is we've talked before about
27:02
Speaker 2: placebo effects. This is a place where placebo effects I
27:06
Speaker 2: think are incredibly complicated even to conceptualize, because we are
27:11
Speaker 2: talking about things that are happening in your brain, which
27:14
Speaker 2: is where a placebo effect also happens.
27:16
Speaker 3: And in these cases it's almost impossible to double blind.
27:21
Speaker 2: So you know, these these trips when you talk about this,
27:23
Speaker 2: but people describe these as like the most meaningful experience
27:27
Speaker 2: in my whole life. It's hard to be like, well,
27:30
Speaker 2: do you know if you had like how would they
27:31
Speaker 2: know if they had.
27:32
Speaker 1: It or not?
27:33
Speaker 3: It's like one card.
27:35
Speaker 1: Sugar pill, right, like you know.
27:38
Speaker 2: And and I guess the third piece about placebos here
27:40
Speaker 2: is I'm not even it may not even matter. I guess,
27:44
Speaker 2: like the maybe the whole thing is a police I'm
27:46
Speaker 2: not really sure how to conceptualize it, but it's worth
27:48
Speaker 2: thinking about. Almost none of this can be truly placebo
27:51
Speaker 2: controlled the way we would placebo control, a vaccine or
27:54
Speaker 2: a medication where you give people a sugar pill. You know,
27:57
Speaker 2: you see if they there's cholesterol goes down.
28:00
Speaker 3: And that's just like easy chounders.
28:03
Speaker 1: And when you're talking about mental health as we will
28:05
Speaker 1: be like place he boat like if you who cares?
28:08
Speaker 1: Like if you tell me you're not depressed anymore?
28:10
Speaker 3: Like I guess it worked.
28:11
Speaker 1: Okay, great, you know, like as long as it as
28:14
Speaker 1: long as it works and it lasts. And yeah, so
28:19
Speaker 1: I thought maybe we start with PTSD. And the reason
28:24
Speaker 1: I want to start here is because this has gotten
28:27
Speaker 1: a lot of press recently because of President Trump meeting
28:31
Speaker 1: with Joe Rogan to specifically discuss psychedelics. And I'm going
28:35
Speaker 1: to play you a clip now of President Trump talking
28:39
Speaker 1: about ibogaine.
28:41
Speaker 4: It's called I bogaine treatment, ie bogaine. Remember the name.
28:48
Speaker 4: Is that pronounced relatively properly? When you said, I don't
28:51
Speaker 4: want to get it wrong, I bogang because it's so
28:54
Speaker 4: important and experienced an eighty to ninety percent reduction incmptoms
28:58
Speaker 4: of depression and then niety within one month. Can I
29:02
Speaker 4: have some, please, I'll take you.
29:08
Speaker 1: I'll so, first of all, does anyone else like, whenever
29:12
Speaker 1: you hear eyebogain, are you like I spent the past
29:15
Speaker 1: few years building up an immunity to iebo gain powder.
29:17
Speaker 1: Is that? Does anyone know? Okay, that's the Princess Bride.
29:22
Speaker 1: How are you welcome? It's okay, the Princess Bride. I know,
29:27
Speaker 1: but eyebogain always sounds like that. So Emily, President Trump
29:32
Speaker 1: is referring to a paper in Nature Medicine that had
29:38
Speaker 1: I mean, I have to say, pretty pretty incredible effect
29:42
Speaker 1: sizes here for for eyebogain, for PTSD. Do you want
29:45
Speaker 1: to run us through that one? Yeah?
29:47
Speaker 2: So these guys are talking about a paper in Nature
29:50
Speaker 2: Medicine from twenty twenty four in which they're looking at
29:54
Speaker 2: treatment for traumatic brain injury, which is unfortunately only can
30:00
Speaker 2: be common in veterans and is associated with depression, anxiety,
30:04
Speaker 2: PTSD other kinds of functional disorders. This has proven to
30:08
Speaker 2: be very difficult to very difficult to treat. So they
30:11
Speaker 2: took thirty men with I was a mild mild traumatic
30:17
Speaker 2: brain injury, and they treated them with magnesium IBI game.
30:25
Speaker 2: The paper is not a it's not a clinical trial,
30:28
Speaker 2: so it's not a randomized trial. They took these thirty people,
30:32
Speaker 2: they treated them all, and so again we sort of,
30:35
Speaker 2: you know, it's hard to separate from what might have
30:37
Speaker 2: happened anyway. However, the improvements in functioning were really quite big.
30:45
Speaker 2: They have improvements in depression scales, improvements in PTSD, improvements
30:49
Speaker 2: in anxiety. And these are pretty large, pretty large increases.
30:55
Speaker 2: I'm not sure exactly how we want to like size them,
30:58
Speaker 2: but they are all incredibly significant and a very difficult
31:02
Speaker 2: to treat area.
31:03
Speaker 1: Yeah, I mean, if you look, I'm like just looking
31:06
Speaker 1: at the graph with a paper, and of these thirty
31:08
Speaker 1: people you have, yeah, you have like twenty eight of
31:11
Speaker 1: them with like who went from moderate PTSD to minimal PTSD,
31:16
Speaker 1: which is which is which is amazing after a single
31:19
Speaker 1: dose of this Eyebogain therapy. I think it's worth saying that, Hey,
31:25
Speaker 1: it's just one paper. There was another Ibogain trial. It's
31:29
Speaker 1: not a randomized trial. There was another Ibogain study of
31:33
Speaker 1: PTSD that actually did not show quite a strong effects.
31:36
Speaker 1: Still showed effects, but not like this dramatic and so,
31:39
Speaker 1: and there's no randomized trials whatsoever. Basically, if you look, okay,
31:42
Speaker 1: if you look, you'll find one randomized trial of eyebogain.
31:45
Speaker 1: But it was a safety study, so they're randomizing just
31:47
Speaker 1: to dose, so it's not like there's a control or
31:49
Speaker 1: anything like that. This is clearly a great area for research,
31:53
Speaker 1: and I'm actually enthusiastic that the administration is considering rescheduling
31:58
Speaker 1: some of these drugs so that they can be easier
31:59
Speaker 1: to REA search. But you know what we want in
32:02
Speaker 1: these types of trials is, yes, we want placebo controls,
32:05
Speaker 1: even though it's incredibly hard to control, but we also
32:08
Speaker 1: want longer turn them outcomes. Right, Like a month is great,
32:12
Speaker 1: but you know six months, a year, two years, what's
32:15
Speaker 1: the mental health of the people who got treated?
32:18
Speaker 2: Yeah, and I think that there's a there's a I
32:20
Speaker 2: mean people have experimented with treatment with MDMA, with stilocybin,
32:24
Speaker 2: with I began, like all three of these have come
32:27
Speaker 2: up in this treatment. Relaxing the rules about this would
32:32
Speaker 2: let researchers figure out things about randomizing, but also dosing
32:36
Speaker 2: and what is the best approach to dosing and how
32:39
Speaker 2: many times you need to do this and does it
32:40
Speaker 2: need to re up you know, every six months or
32:43
Speaker 2: like what is the sort of treatment protocol. The other
32:46
Speaker 2: issue is, of course, like when you only have three
32:49
Speaker 2: studies of something and they are all significant. One worries
32:53
Speaker 2: a little bit about like our you know, did someone
32:55
Speaker 2: did actually twenty five different studies of this get run
32:58
Speaker 2: and only three of them and publish. That's where you
33:02
Speaker 2: need like pre registered, large randomized controlled trials, which are
33:06
Speaker 2: only going to happen if.
33:08
Speaker 3: These drugs are easier to use in a trial setting.
33:12
Speaker 2: Yeah.
33:13
Speaker 1: Yeah, absolutely, so we'll close the book on PTSD. I
33:16
Speaker 1: begain kind of interesting, some good data for MDMA, and
33:20
Speaker 1: very preliminary data on psilocybin. Just to run through the
33:24
Speaker 1: psychedelics that are being used here. Let's move on to depression.
33:28
Speaker 1: That depression, Yeah, I mean this is obviously incredibly common
33:33
Speaker 1: and a place where there are current therapies. Obviously there
33:37
Speaker 1: are multiple therapies for depression, both pharmacologic and non pharmacologic,
33:41
Speaker 1: and so but I think the public understands that, you know,
33:45
Speaker 1: the standard of care right now for major depression disorder,
33:48
Speaker 1: which are the SSRIs, are moderately effective and come with
33:54
Speaker 1: some side effects that people find not great. And so
33:58
Speaker 1: if you did something else, you might be open to
34:02
Speaker 1: something else. Is that fair to say?
34:04
Speaker 3: Yeah, I think that's fair to say.
34:05
Speaker 2: I mean I think the administration has recently been quite negative.
34:08
Speaker 2: RFKJ has been quite negative on SSRIs, and I think
34:11
Speaker 2: that you know, that's probably some of his statements are overstated,
34:15
Speaker 2: but I think it is it is true that these
34:18
Speaker 2: have not proven to be a magic bullet for many
34:20
Speaker 2: people with depressions. They have been very helpful for a
34:23
Speaker 2: large number of people, but not so amazing that we
34:26
Speaker 2: should not be looking for other approaches.
34:28
Speaker 3: Is how I would is how I would put it.
34:31
Speaker 3: And this is a place I don't know if you
34:33
Speaker 3: want to talk about.
34:34
Speaker 2: My favorite thing here is the twenty twenty three JAMA paper,
34:37
Speaker 2: because Jama is such a great journal.
34:38
Speaker 3: Do you know that one time Perry published in that.
34:41
Speaker 1: I understand that you've also published in Jamma.
34:44
Speaker 2: Emily, I do it dous about the large clinical trial
34:48
Speaker 2: in Jamma of silas ivan, on which matter of us
34:51
Speaker 2: as an author, but we still like it.
34:54
Speaker 1: Yeah. So this is a study in twenty twenty three
34:58
Speaker 1: which took one hundred and four or adults with major
35:02
Speaker 1: depressive disorder and randomize them to a single dose twenty
35:05
Speaker 1: five milligrams of psilocybin. And also, and as I said,
35:09
Speaker 1: this was important, eleven hours of psychological support, which included
35:13
Speaker 1: like preparation for the psilocybin dose, support on the dosing day,
35:17
Speaker 1: and then after that what they call integration, which is
35:20
Speaker 1: like processing the experience that you had. They did do
35:23
Speaker 1: a placebo control one hundred milligrams of nyasin, which is
35:28
Speaker 1: a vitamin. But at that dose it's going to cause
35:31
Speaker 1: some flushing. Now I don't think flushing is quite the
35:34
Speaker 1: same as a psilocybin trip, but it's not nothing at least,
35:38
Speaker 1: so they you know, if you if they didn't know
35:40
Speaker 1: what psilocybin was like to begin with, maybe they thought
35:42
Speaker 1: they were getting I thought.
35:43
Speaker 3: I just made them hot. Okay, yeah, I don't know.
35:46
Speaker 1: But they also got that psychological supportive protocol. The primary
35:50
Speaker 1: outcome was a score, a depression score, and I won't
35:55
Speaker 1: go through the score, but I'll tell you it went
35:57
Speaker 1: down by twelve points, which was a highly significant difference,
36:02
Speaker 1: Like that is a clinically meaningful difference, a twelve point
36:05
Speaker 1: reduction in depression scores, and that was out at day
36:09
Speaker 1: forty three. The sustained response rate, which meant like you
36:14
Speaker 1: had sustained improvement in symptoms out that far at day
36:17
Speaker 1: forty three, was forty two percent in the psilocybin group
36:20
Speaker 1: versus eleven percent in the niosin group. So this was,
36:25
Speaker 1: you know, a trial that said, okay, we've got something here.
36:31
Speaker 1: Yes you're integrating it. But remember it's only one it's
36:33
Speaker 1: a single dose at one time. There's a bit of
36:36
Speaker 1: biology here. These drugs that stimulate the serotonin to eight
36:40
Speaker 1: receptor might increase neural plasticity, which means you can form
36:44
Speaker 1: new neural connections. So psychiatrists are psychologists are wondering if
36:49
Speaker 1: like that initial dose kind of like shakes up your
36:52
Speaker 1: brain a little bit, and then it's actually that integration
36:55
Speaker 1: phase where you know, now the patient is sort of
36:59
Speaker 1: ready to make those cognitive changes that's going to improve
37:03
Speaker 1: their underlying status. So it's both the drug and then
37:06
Speaker 1: like which kind of shakes things up and then you
37:08
Speaker 1: kind of put things back together in a better way
37:10
Speaker 1: moving forward. That's all hypothetical obviously, but pretty pretty exciting results.
37:14
Speaker 3: Yeah, I thought that was exciting.
37:15
Speaker 2: I mean not everything in this space is as exciting,
37:19
Speaker 2: and in particular, there's a Nangeum paper from around the
37:24
Speaker 2: same time which did a trial of stilocybin versus a
37:28
Speaker 2: standard antidepressant.
37:31
Speaker 1: Yeah. Oh yes, an SSRI I this is a better control,
37:34
Speaker 1: like act.
37:35
Speaker 2: A better control, not just flushing, but something is actually
37:38
Speaker 2: think so the primary outcome in the paper does not
37:44
Speaker 2: show differences in efficacy. There are some secondary outcomes which do,
37:49
Speaker 2: although they test many of those.
37:51
Speaker 3: So I would say the results in this one were
37:53
Speaker 3: decidedly more mixed.
37:55
Speaker 2: But both of these together tell me, Okay, you know,
37:57
Speaker 2: we're doing these trials with sixty you know, sixty year
38:00
Speaker 2: one hundred people. We need to do these trials with
38:04
Speaker 2: a thousand people. And for depression unlike you know PTSD,
38:09
Speaker 2: there certainly are a thousand people you could find with
38:11
Speaker 2: depression who one could experiment on.
38:14
Speaker 1: Absolutely absolutely. The issue versus SSRI is like you want
38:19
Speaker 1: to be a little skeptical when you hear people saying,
38:22
Speaker 1: you know, oh, these things blow SSRIs out of the water,
38:25
Speaker 1: like SSRIs don't work and psilocybin does. You know, the
38:27
Speaker 1: actual trial here says like they're close. But again there
38:31
Speaker 1: are other reasons that you might you know, a single
38:33
Speaker 1: dose of psilocybin might feel a lot better to people
38:36
Speaker 1: than a daily dose of an SSRI going on forever
38:40
Speaker 1: with you know, the attendant side effects that one might
38:42
Speaker 1: have with those the sort of flip side, not the
38:45
Speaker 1: flip side. I always think of depression and anxiety together
38:49
Speaker 1: the two most common psychologic disorders affecting people in the
38:52
Speaker 1: United States. Anxiety when it comes to psychedelics always made
38:56
Speaker 1: me a little nervous, just in principle, I think, because
39:01
Speaker 1: like the psychedelic experience, as I understand, it can be
39:04
Speaker 1: anxiety inducing. In fact, some of the adverse events that
39:08
Speaker 1: were reported in some of those depression trials were like anxiety.
39:12
Speaker 1: And you can sort of imagine that if you're an
39:14
Speaker 1: anxious person already and then all of a sudden the
39:16
Speaker 1: walls are melting and you feel like you're like melting
39:18
Speaker 1: into the floor or whatever, Like maybe that's not great
39:21
Speaker 1: for you. But even here, and I should say, like,
39:26
Speaker 1: we don't have nearly as much data in anxiety yet
39:29
Speaker 1: as there is for major depression disorder. But I was
39:32
Speaker 1: looking at this twenty sixteen study from the Journal of Psychopharmacology.
39:36
Speaker 1: Did you see this one, Emily that seemed like there
39:39
Speaker 1: might be some use here.
39:41
Speaker 3: This was Yeah, I mean they're treating.
39:43
Speaker 1: High dose of psilocybin.
39:45
Speaker 2: Yeah, they're treating people with cancer related anxiety and depression.
39:50
Speaker 2: So it's a kind of combo group and they're giving
39:54
Speaker 2: them a really highly dosi slocybin, but it does seem
39:59
Speaker 2: to have improved anxiety depression and they're kind of decreasing
40:02
Speaker 2: cancer related demoralization.
40:04
Speaker 3: That's from the paper, So you know, positive, there.
40:09
Speaker 1: Not enough data to be sure, and I think, if.
40:11
Speaker 2: Not enough data to be sure, which is the tagline
40:14
Speaker 2: for this episode, if.
40:15
Speaker 1: You're an anxious person, this is maybe not the thing
40:18
Speaker 1: to jump right into quite yet. The other big category
40:23
Speaker 1: before we get to just the you know, healthy people
40:25
Speaker 1: who are curious alcohol addiction. So what Joe Rogan was
40:33
Speaker 1: talking about in when he was meeting with Trump actually
40:36
Speaker 1: was was not Ibogain's effect on PTSD, but Ibogain's effect
40:40
Speaker 1: on addiction. And like all things Joe Rogan, he has
40:43
Speaker 1: some story like it's always an anecdote with him, which
40:45
Speaker 1: is like he had this guy was addicted to heroin
40:48
Speaker 1: and everything was horrible and then you know, single dose
40:51
Speaker 1: of IBA gain and cleaned himself up and were off
40:55
Speaker 1: to the races again. There is no randomized trial for
40:59
Speaker 1: eyebo gain whatsoever. There's some open labeled data though I
41:04
Speaker 1: found there's a study of one hundred and ninety one
41:08
Speaker 1: people who were using opioids or cocaine, and they did
41:13
Speaker 1: show that a single dose of ibogain diminished withdrawal symptoms
41:17
Speaker 1: and drug cravings at one month follow up. This comes
41:21
Speaker 1: from Frontiers in Pharmacology in twenty eighteen. You know, this
41:25
Speaker 1: is open label, there's no control here. It's a little
41:28
Speaker 1: hard to say any thoughts on ibogain for addiction.
41:34
Speaker 2: I mean, again, I think this is a space where
41:36
Speaker 2: people are is very treatment resistant, and so having something
41:43
Speaker 2: to try is interesting. We also worry that when people
41:47
Speaker 2: get to the point, at least in this case, I worry.
41:50
Speaker 2: So you get to the point where you're like I'll
41:51
Speaker 2: try anything, I'm going to go to ibgain, maybe you are.
41:54
Speaker 2: That actually is a signal of sort of motivation to
41:57
Speaker 2: fix things. And so if you thought of this as
41:59
Speaker 2: like we're just going to sign this random, like we're
42:00
Speaker 2: going to sign this to people, it might it might
42:02
Speaker 2: show up differently.
42:03
Speaker 3: There's actually a bit better data for silocybin in alcohol
42:07
Speaker 3: use disorder.
42:08
Speaker 2: I was trying to think this is from randomized trial data,
42:12
Speaker 2: and we see you know, a production uh sort of
42:15
Speaker 2: a larger reduction in heavy drinking days with silocybin versus
42:21
Speaker 2: the in this case in versus.
42:23
Speaker 1: The control used to benadryl as a control in this
42:26
Speaker 1: in this study, which is another It's like, I kind
42:29
Speaker 1: of it's sort of like it's fun to imagine these
42:31
Speaker 1: scientists being like, what the hell are we going to
42:33
Speaker 1: use as a control, Like, let's give someone.
42:36
Speaker 3: Your cabinet? Should we try pepsid?
42:39
Speaker 1: No? Like that makes you feel weird but not too weird?
42:47
Speaker 2: And then I mean I wondered here about how large
42:49
Speaker 2: this effect is relative to g lp ones, which we're
42:51
Speaker 2: constantly talking about, like you know, like for the alcohol stuff.
42:56
Speaker 2: It seems like we're increasingly having some other other options. Okay,
43:00
Speaker 2: can we talk about healthy forty somethings like us and
43:04
Speaker 2: whether we should have this experience?
43:07
Speaker 1: I have to say I wrote about a new article
43:11
Speaker 1: that just came out recently was looking at the effect
43:15
Speaker 1: of a single dose of twenty five milligrams of psilocybin
43:20
Speaker 1: in healthy forty somethings who were psychedelic naive. So like
43:25
Speaker 1: I yes, I was like Spiderman meme like that that's me, Like,
43:31
Speaker 1: you know, who are these people? Because all these prioritizes,
43:33
Speaker 1: even the studies in healthy people in the past, like
43:36
Speaker 1: many of them are are people who have had experiences
43:39
Speaker 1: with psychedelics, and so it's like, maybe it affects your brain,
43:42
Speaker 1: but it already did affect your brain anyway, Right, this
43:45
Speaker 1: is a super cool study, So psychedelic benive otherwise healthy
43:48
Speaker 1: forty somethings. They got twenty five milligrams of psilocybin or
43:52
Speaker 1: one milligram of psilocybin, which is sort of a sub
43:54
Speaker 1: therapeutic dose, which they gave them first, and then they
43:58
Speaker 1: did egs of their brain and a functional MRI a
44:02
Speaker 1: month later. So the question was like, we're there are
44:04
Speaker 1: acute changes in your brain waves and then where they're
44:06
Speaker 1: lasting changes one month down, small studies. Still twenty eight
44:11
Speaker 1: volunteers for this, to your point, twenty seven of the
44:15
Speaker 1: twenty eight rated it as the single most unusual conscious
44:18
Speaker 1: state of their entire lives. YEA, one guy didn't, who's
44:23
Speaker 1: like awesome, obviously.
44:25
Speaker 3: Guys having a lot of grain.
44:27
Speaker 1: I said it was in the top five. I'm like,
44:29
Speaker 1: in the top.
44:30
Speaker 3: I would be curious about what number two was.
44:33
Speaker 1: Yeah, So to break this down, the EG finding is
44:37
Speaker 1: really interesting. What they showed acutely was a reduction in
44:40
Speaker 1: alpha power, which is alpha is are the waves that
44:43
Speaker 1: are sort of like they're like the lid on your brain.
44:47
Speaker 1: They're the they're like our self control almost, like they sort
44:50
Speaker 1: of tamp down all the crazy stuff that's going on
44:54
Speaker 1: under the surface. So it's like calm, RESTful consciousness is
44:58
Speaker 1: alpha waves. That power goes down, which sort of means
45:00
Speaker 1: like the lid is off, and then the EEG complexity
45:04
Speaker 1: went way up, so you know, all of a sudden,
45:09
Speaker 1: just like the stuff that was coming out of the
45:11
Speaker 1: brain was much crazier than what had come out of
45:13
Speaker 1: the brain with a one miligram dose.
45:16
Speaker 2: Sounds right, it's so it makes me so curious.
45:22
Speaker 1: That's exactly I was, like, that sounds that sounds kind
45:24
Speaker 1: of amazing. Now, one month later, they did some stuff
45:31
Speaker 1: they didn't fMRI, and honestly, it didn't show very much,
45:34
Speaker 1: Like it didn't show like dramatic structural or functional changes
45:37
Speaker 1: in the brain, Okay, which is different than what has
45:41
Speaker 1: been shown in some like depression related studies of psilocybin.
45:46
Speaker 1: Maybe because maybe if your brain is kind of like
45:48
Speaker 1: functioning normally to begin with, like I don't know what's
45:51
Speaker 1: going to change as much or something like that, But
45:52
Speaker 1: they didn't show that. But psychological well being was significantly
45:58
Speaker 1: higher one month after the twenty five million dose versus
46:01
Speaker 1: the one milligram dose, and they measured the day after
46:05
Speaker 1: you took the thing. They gave people a survey of insight,
46:09
Speaker 1: so they ask questions like do you feel this experience
46:12
Speaker 1: led you to think about yourself differently? Like there's you know,
46:17
Speaker 1: have you learned important new ways of thinking about yourself
46:20
Speaker 1: and your problems. That's a measure of insight. And the
46:23
Speaker 1: people who had hire insight had hire well being at
46:27
Speaker 1: the one month mark. So there's this little bit of
46:29
Speaker 1: like a mechanistic like you take the drug, you kind
46:33
Speaker 1: of think about it, you think, you work through some stuff,
46:36
Speaker 1: you kind of shake up your brain, and then a
46:37
Speaker 1: month later you're doing better. What I can't tell you
46:40
Speaker 1: is because there's no like, yes, it's different than the
46:44
Speaker 1: one milligram dose, but like obviously that's not It's a
46:47
Speaker 1: totally different experience, right, Like twenty five milligrams is the
46:50
Speaker 1: most unusual conscious state of your entire life. One milligram
46:53
Speaker 1: they had like no sensations whatsoever. You're feeling better a
46:56
Speaker 1: month later, is that because something fundamentally about you has changed?
47:00
Speaker 1: Or like do you feel good a month after a
47:03
Speaker 1: nice vacation, right, Like, is it just the memory of
47:05
Speaker 1: this very cool, unusual experience just kind of like breaks
47:08
Speaker 1: up the monotony of your life for a little bit
47:10
Speaker 1: and does it even matter?
47:12
Speaker 3: I don't know, Yeah, I don't know. I mean I
47:14
Speaker 3: think that.
47:15
Speaker 2: What's so what I find so compelling about this is
47:17
Speaker 2: like I could not tell you right now.
47:20
Speaker 3: Now that's not true.
47:21
Speaker 2: I could tell you, but like if I think about,
47:23
Speaker 2: like what is the single most like unusual and meaningful
47:27
Speaker 2: experience of my life, it is heavy. It is birth
47:30
Speaker 2: of my children. Yeah, the experience of like producing a
47:32
Speaker 2: new person. It was not comfortable, It wasn't like a
47:36
Speaker 2: you know, which I think is also true, but like
47:37
Speaker 2: it was a very unusual experience that I still could
47:41
Speaker 2: I could tell you almost to the minute in both
47:44
Speaker 2: of the.
47:44
Speaker 3: Births, like exactly what happened.
47:47
Speaker 1: Because your salience system was rev so high, and.
47:50
Speaker 2: Like I could I usually like could tell you who
47:52
Speaker 2: you know, who was in the room at each of
47:53
Speaker 2: these moments exactly exactly what happened.
47:56
Speaker 3: And so I'm I'm so curious about I find this.
48:00
Speaker 2: Whole thing very curious, like totally interested to have an
48:03
Speaker 2: experience like that where you didn't also have to push
48:05
Speaker 2: an person out of your vagina, which has some negatives
48:08
Speaker 2: in the long run, and you know, I mean positives.
48:11
Speaker 1: Also, you wouldn't be worried that like it would push
48:15
Speaker 1: the meaningfulness of those experiences down right. You'd be like, yes,
48:18
Speaker 1: the birth of my children was the second most important
48:21
Speaker 1: thing that ever happened to me.
48:22
Speaker 2: Sitting on a couch like staring at the re here and.
48:30
Speaker 1: Sorry, you're not that replaceable, Sorry, kiddos.
48:34
Speaker 2: All right, two other things before we end, I think
48:36
Speaker 2: we should touch on. So one is I hear a
48:38
Speaker 2: fair amount about microdosing. But my read, which is like
48:42
Speaker 2: maybe I take a little bit of my mushrooms every
48:45
Speaker 2: single day to improve some aspect of well being, my
48:48
Speaker 2: read is actually, people have tried a little.
48:51
Speaker 3: Bit of this and it doesn't work.
48:54
Speaker 1: Yeah, the studies of micro and microdoses, you know, first
48:58
Speaker 1: of all, there's no great definition of this, Like in theory,
49:01
Speaker 1: a microdose should be a dose low enough that you
49:04
Speaker 1: don't experience the psychedelic effects, like you're not supposed to
49:09
Speaker 1: feel much if you're really microdosing. And I'm not sure
49:11
Speaker 1: that's how people are doing it, right, yeah, you know,
49:15
Speaker 1: it's like it's like I'm microdosing wine by only drinking
49:18
Speaker 1: a glass, Like, well, that's not really so, but yeah,
49:22
Speaker 1: the studies that have looked at microdosing, my read is
49:26
Speaker 1: that it does show some improvement in well being on
49:30
Speaker 1: the day people microdose, but it doesn't persist to the
49:34
Speaker 1: next day, and it certainly doesn't persist in the long term,
49:37
Speaker 1: which also feels like drinking a glass of wine to me.
49:40
Speaker 1: So maybe that's what it is.
49:42
Speaker 2: Yeah, maybe, or maybe it's just a placebo effect of.
49:46
Speaker 1: It could definitely be a placibo effect, which is also
49:49
Speaker 1: what a glass of wine. To some extent.
49:53
Speaker 3: There are some safety concerns we should run through.
49:56
Speaker 2: People who are schizophrenic should not use these medications.
50:00
Speaker 3: They're also illegal. They're illegal.
50:04
Speaker 1: Oh yeah, so that's I have to say. As I
50:06
Speaker 1: was reading all this stuff, and especially about the healthy
50:08
Speaker 1: forty somethings and it being this incredibly meaningful experience, it's like,
50:11
Speaker 1: you know, I'm curious, like I would probably want to try,
50:14
Speaker 1: and then I'm like, oh, I have literally no idea,
50:18
Speaker 1: like how to obtain a psychedelic Like short, have you
50:21
Speaker 1: been to a fish concert?
50:24
Speaker 3: Have you been to a fish concert do they still exist?
50:28
Speaker 5: That's the But I think that that relates to the
50:31
Speaker 5: second point, which is, of course, like these drugs are illegal,
50:34
Speaker 5: and so if you decided you're just going to go
50:36
Speaker 5: out and get yourself some you know, silos ibin on
50:39
Speaker 5: the on the street corner, and like do it, do
50:41
Speaker 5: it yourself.
50:42
Speaker 3: You don't know that that's what it is, and so
50:45
Speaker 3: you know, please do not do not do that.
50:47
Speaker 1: Yes, adulterated stuff particularly, I mean, I guess mushrooms kind
50:52
Speaker 1: of look like mushrooms. But first of all, mushrooms are
50:54
Speaker 1: very scary because some mushrooms look like other mushrooms and
50:57
Speaker 1: some are toxic. So there's just mushrooms, donty mushrooms. And
51:00
Speaker 1: then LSD is so potent, Like an amount of LSD
51:06
Speaker 1: the size of a grain of table salt is a
51:11
Speaker 1: real dose of LSD. It is a thousand times more
51:14
Speaker 1: potent than psilocybin at the serotonin two A receptor. So
51:17
Speaker 1: that's that's fine if it's being like synthesized and careful
51:20
Speaker 1: and everything is proper, but like it does mean that
51:23
Speaker 1: you can't inspect it, like you're trusting that whatever's not
51:26
Speaker 1: like dissolved on this piece of paper you're putting on
51:28
Speaker 1: your tongue is what people tell you it is. And yes,
51:31
Speaker 1: things absolutely get adulterated, so be careful out there. The
51:34
Speaker 1: psychedelics increased blood pressure a little bit. We should say that,
51:37
Speaker 1: you know whatever, if you have blood pressure problems, be
51:39
Speaker 1: aware of that. And then yeah, you want to be
51:41
Speaker 1: in a you know, safe place. You're not going to
51:44
Speaker 1: be operating vehicles, folks, you got to be got to
51:47
Speaker 1: be careful.
51:48
Speaker 3: Gotta be careful, all right, Perry, smash your pass on
51:52
Speaker 3: the psychedelics.
51:54
Speaker 1: I'm smashing psychedelics. I mean as someone as again as
51:59
Speaker 1: someone who's ever done them. I think that the data
52:02
Speaker 1: for mental health is highly compelling. Obviously I want to
52:04
Speaker 1: see more research here, but I'm so excited that that
52:08
Speaker 1: is potentially opening up that that that a new door
52:11
Speaker 1: is opening for people who suffer from these conditions. Super exciting,
52:14
Speaker 1: you know. In terms of general wellness, I'm mostly curious,
52:18
Speaker 1: Like I don't I don't certainly think it would ever
52:20
Speaker 1: become part of my you know, wellness routine. But like
52:25
Speaker 1: I am, I going to die never having experienced the
52:29
Speaker 1: single most unusual conscious state of my life. That doesn't
52:31
Speaker 1: seem like a good idea.
52:33
Speaker 6: And.
52:35
Speaker 3: I am also a smash on this.
52:38
Speaker 2: I think I like to wait until we get a
52:41
Speaker 2: little it gets a little more like you know, regularized.
52:45
Speaker 1: Or regulated, like so you know that you're getting a
52:48
Speaker 1: safe amount or something.
52:49
Speaker 2: Yeah, yes, but I think definitely, you know when I
52:51
Speaker 2: feel like when I was in we were in.
52:53
Speaker 3: College, like pot was illegal, but now.
52:56
Speaker 2: Like there's a drive through like dispensary exactly like on
53:00
Speaker 2: the highway, And I feel that when there is a
53:04
Speaker 2: drive through silocybin treatment option, I'm going to do it.
53:11
Speaker 1: And when that happens, should we do an entire wellness
53:14
Speaker 1: actually episode.
53:17
Speaker 3: About what happened in the different.
53:19
Speaker 1: Gobles I'm saying during.
53:22
Speaker 3: During Okay, I think these things are like ten hours long.
53:25
Speaker 2: I'm not sure that people's case for us live stre
53:28
Speaker 2: but we can edit it.
53:30
Speaker 3: We can edit it down.
53:34
Speaker 1: Sounds great. Your question of the week after the break.
53:43
Speaker 3: I am Eily and Perry.
53:44
Speaker 6: This is Meredith in Phoenix, and I have kind of
53:47
Speaker 6: a love hate relationship with tracking, you know, calories and
53:51
Speaker 6: steps and sleep. I think I'll love it and then
53:56
Speaker 6: I get kind of obsessed with it, and then I
53:57
Speaker 6: hate it. So I have a question for you, what
54:01
Speaker 6: is your relationship with tracking? What do you guys each track?
54:06
Speaker 3: Thanks?
54:07
Speaker 2: All right, Perry, I would I would venture this is
54:09
Speaker 2: a place in which we are almost polar opposites for
54:12
Speaker 2: people who otherwise share like a pretty similar like demographic lifestyle.
54:19
Speaker 3: Like you don't do any self tracking, do you?
54:21
Speaker 6: Uh?
54:22
Speaker 1: I'm really trying to think here, what do I track
54:26
Speaker 1: on like a daily basis? Like, yes, I've been tracking
54:30
Speaker 1: our podcast rankings, so hey, everyone leave weave a review
54:34
Speaker 1: and give us a five stars on Apple podcasts selt
54:39
Speaker 1: my daily tracking. No, I don't weigh myself daily. I
54:42
Speaker 1: think my phone tracks my steps, but like I don't
54:44
Speaker 1: know what they are. I don't track calories. Yeah, I
54:48
Speaker 1: am not a tracker. But Emily, how many different spreadsheets
54:55
Speaker 1: do you use to track zero?
54:58
Speaker 3: I'm just going to say it's not zero.
55:01
Speaker 2: I track a lot of things, and I want to
55:05
Speaker 2: explain why because I generally don't think it's a good idea.
55:09
Speaker 2: I feel like this is a like don't do like
55:11
Speaker 2: do as I say that as I do. I think
55:13
Speaker 2: for almost no one is it a good idea to
55:16
Speaker 2: obsessively track a huge number of the things that you're doing.
55:19
Speaker 3: Because I think for a lot of people. It makes
55:21
Speaker 3: it very anxious.
55:21
Speaker 1: Yeah, yeah, yeah.
55:22
Speaker 2: People always tell me like, Okay, I'm tracking my sleep,
55:24
Speaker 2: but like I woke up this morning and my sleep
55:26
Speaker 2: tracker said I didn't sleep good, but I felt like
55:28
Speaker 2: slept good.
55:28
Speaker 3: And now I'm like, worry.
55:29
Speaker 2: Now I'm laying up and I worrying my sleep tracker
55:31
Speaker 2: is going to judge me for my lack of sleep,
55:34
Speaker 2: and that's really bad for your for your sleep.
55:36
Speaker 3: So I think for most people.
55:39
Speaker 2: This there is like no, people don't like it. It
55:44
Speaker 2: makes them anxious and there's not a lot of value.
55:47
Speaker 2: Like if you just said, like I'm interested in like
55:49
Speaker 2: improving my health, yeah for the most part, Like you
55:52
Speaker 2: don't need to do any tracking for that.
55:55
Speaker 3: Why do I do this?
55:56
Speaker 1: Then?
55:56
Speaker 3: Given, I wonder what you do?
55:59
Speaker 1: Give me, Like what thing is that you track?
56:02
Speaker 2: So I have a whoop which tracks my sleep and
56:05
Speaker 2: my recovery. I track the miles that I run and
56:07
Speaker 2: the workouts that I do. I track how much proptein
56:10
Speaker 2: I get. Sometimes I track other macro nutrients. Right now
56:14
Speaker 2: I'm doing that because I wasn't eating enough and now
56:19
Speaker 2: I need to eat more for so I'm tracking my
56:22
Speaker 2: macro nutrients and that's probably it.
56:27
Speaker 1: Okay, right, Yeah, that's not bad.
56:29
Speaker 2: So it's it's a lot of different things. But I yeah,
56:34
Speaker 2: but I will say the two reasons I do this
56:37
Speaker 2: other than being crazy, which is I guess. The third
56:39
Speaker 2: reason is that I really like it. It's like a
56:41
Speaker 2: thing that like it's like a like it's like a
56:43
Speaker 2: thing I enjoy. Like it's to say, but it's like
56:47
Speaker 2: I like it.
56:47
Speaker 3: It's hum. I'm a numbers person. I like data. I
56:51
Speaker 3: liked I track.
56:52
Speaker 2: When my kids were babies, we would like track, you know,
56:54
Speaker 2: the diapers and then now amount of time they slept
56:56
Speaker 2: and all kinds of other stuff because like, even though
56:59
Speaker 2: I realized it was you so this, I just like
57:00
Speaker 2: thought it was fun. Yeah, And I care, as I
57:04
Speaker 2: have previously mentioned four hundred times on every episode of
57:07
Speaker 2: this podcast, I care tremendously about my athletic performance, and
57:12
Speaker 2: a fair amount of the tracking I do is in
57:14
Speaker 2: the service of like trying to link like behaviors to
57:18
Speaker 2: performance out christ Right, So that's it. But I don't
57:22
Speaker 2: think other I'm not. Maybe I'm just saying other people
57:25
Speaker 2: shouldn't do this so.
57:25
Speaker 3: I can run faster than them. Perhaps that's this is
57:28
Speaker 3: a competitive advantage.
57:30
Speaker 1: I would not put it past you. All Right. That's
57:34
Speaker 1: it for us today. Stick with us next week when
57:36
Speaker 1: we'll ask what's the deal with methylene blue?
57:43
Speaker 2: Wellness Actually is produced in association with iHeartMedia. Our senior
57:48
Speaker 2: producer is Tamar Avisheik. Our executive producer at iHeart is
57:51
Speaker 2: Jennifer Bassett. Our theme music is by Eric Deutsch, and
57:55
Speaker 2: our content is for educational purposes only.
57:58
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58:00
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Speaker 1: the show. You can follow us on Instagram at Wellness
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Speaker 1: a future show.
58:19
Speaker 3: We'll let the influencers have the last word. We found
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Speaker 3: this one swimming naked in the fermentarium. I am eligit,
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Speaker 3: Queen