WEBVTT
1
00:00:00.120 --> 00:00:04.000
Hey there, Ashley here. I'm currently off gallivanting in Denver
2
00:00:04.120 --> 00:00:07.799
at podcast Movement, so I'm re releasing this very popular
3
00:00:07.839 --> 00:00:11.119
episode that dropped back in twenty twenty one. Chances are
4
00:00:11.160 --> 00:00:13.199
you've never heard it before, but even if you have,
5
00:00:13.439 --> 00:00:16.480
it's worth hearing again, not just because the stuff that
6
00:00:16.480 --> 00:00:19.480
doctor Santa Kora has to say is only getting more important,
7
00:00:19.839 --> 00:00:24.120
but also because it's fully remastered with fancy AI audio
8
00:00:24.120 --> 00:00:28.640
tools thanks to script, so it's a much better listen. Seriously,
9
00:00:28.800 --> 00:00:31.039
if you're curious, check out the original in the feed
10
00:00:31.120 --> 00:00:33.920
and then listen to this one. The difference is pretty dramatic.
11
00:00:34.640 --> 00:00:38.320
And if you're watching on YouTube, hi, I didn't record
12
00:00:38.399 --> 00:00:40.439
video for this back in the day, so you're going
13
00:00:40.479 --> 00:00:42.960
to get an audiogram. I made it as fancy as
14
00:00:43.000 --> 00:00:46.359
I could for you. Hope you'll like it. I'll be
15
00:00:46.479 --> 00:00:48.840
back at the end to see you off for now
16
00:00:49.119 --> 00:00:56.039
on with the show. I used to think that depression
17
00:00:56.600 --> 00:01:00.479
was easy to spot. I mean, I knew that people
18
00:01:00.479 --> 00:01:04.120
with depression were sad, and they'd start to skip their
19
00:01:04.120 --> 00:01:08.200
favorite activities to stay in bed all day. They'd basically
20
00:01:08.280 --> 00:01:12.120
just shut off from the world. But it turns out
21
00:01:12.200 --> 00:01:18.159
that depression is so much more complicated than that. Like,
22
00:01:18.439 --> 00:01:21.920
depression can make it hard to concentrate. You can be
23
00:01:21.959 --> 00:01:25.040
going to work every day like you always do, but
24
00:01:25.079 --> 00:01:27.799
you just start to forget things and make silly mistakes.
25
00:01:28.640 --> 00:01:32.680
Some people, particularly older people, they might even fall more
26
00:01:32.719 --> 00:01:38.840
frequently because they're not paying attention. Depression can make you angry.
27
00:01:38.920 --> 00:01:42.280
If you feel hopeless on the inside, you might lay
28
00:01:42.280 --> 00:01:44.920
the blame with others, and that can make you lash
29
00:01:44.959 --> 00:01:51.920
out at friends and family. And depression can hurt. Studies
30
00:01:51.920 --> 00:01:55.120
have shown that people with depression have a decreased tolerance
31
00:01:55.159 --> 00:01:59.640
for pain. Your head, your joints, your whole body might
32
00:01:59.719 --> 00:02:04.239
just feel worse overall. And just like there are a
33
00:02:04.319 --> 00:02:07.719
lot of different symptoms of depression, there are also a
34
00:02:07.760 --> 00:02:12.919
lot of different causes, causes that scientists haven't fully untangled.
35
00:02:14.159 --> 00:02:18.520
In fact, depression is still a pretty big mystery. We
36
00:02:18.599 --> 00:02:22.439
can't fully explain why it happens, what's going on in
37
00:02:22.479 --> 00:02:26.159
the brain when it does happen, or how exactly therapies
38
00:02:26.159 --> 00:02:30.960
and medications help. But one thing we do know is
39
00:02:31.000 --> 00:02:35.199
that they do help, and that our treatments for depression
40
00:02:35.240 --> 00:02:39.280
are getting better all the time, despite the fact that
41
00:02:39.319 --> 00:02:45.240
those treatments can come from some pretty strange places. Today,
42
00:02:45.280 --> 00:02:47.360
we're going to talk about what we do and don't
43
00:02:47.400 --> 00:02:52.280
know about depression, why not knowing is actually okay, and
44
00:02:52.479 --> 00:02:57.560
why hallucinogens are making their way into the clinic. I'm
45
00:02:57.599 --> 00:03:01.240
Ashley Hamer, and this is Taboo Science, the podcast that
46
00:03:01.280 --> 00:04:08.479
answers the questions you're not allowed to ask. Depression is
47
00:04:08.840 --> 00:04:14.439
incredibly common, scarily common, Like more than two hundred and
48
00:04:14.439 --> 00:04:20.279
sixty million people worldwide are affected by depression. So you'd
49
00:04:20.319 --> 00:04:23.600
think this would be an easy thing to answer. What
50
00:04:24.040 --> 00:04:24.800
is depression?
51
00:04:25.920 --> 00:04:27.600
That is actually a very good question.
52
00:04:28.759 --> 00:04:32.279
That's doctor Gerard Santa Kora. He's the director of the
53
00:04:32.360 --> 00:04:35.399
Yale Depression Research Program and co director of the Yale
54
00:04:35.439 --> 00:04:39.720
Interventional Psychiatry Service, And to him, the question isn't so
55
00:04:39.879 --> 00:04:42.680
much what depression is as what it isn't.
56
00:04:44.759 --> 00:04:47.920
Depression is an interesting thing. That is actually what we
57
00:04:48.000 --> 00:04:52.279
call a diagnosis of exclusion. So in medicine, that means
58
00:04:52.319 --> 00:04:55.800
that you have a set of symptoms signs and we
59
00:04:55.879 --> 00:05:00.879
can't find an explanation, so for depression, and it's typically
60
00:05:00.920 --> 00:05:07.120
a set of nine core symptoms related to sleet, appetite, mood, concentration,
61
00:05:08.000 --> 00:05:12.759
zest for life, willingness, to live relating to those general
62
00:05:12.800 --> 00:05:17.720
categories that affect your cognition, perception, emotions, and we can't
63
00:05:17.720 --> 00:05:20.360
find another explanation for it. So, in other words, we
64
00:05:20.439 --> 00:05:26.319
can't find an endochronological problem such as hypothyroidism, or we
65
00:05:26.399 --> 00:05:30.759
don't find another neurologic disorders such as parkinson as that.
66
00:05:30.720 --> 00:05:31.560
Could be related.
67
00:05:32.199 --> 00:05:35.680
According to the latest edition of the Diagnostic and Statistical
68
00:05:35.720 --> 00:05:39.720
Manual of Mental Disorders, or the DSM five, these are
69
00:05:39.720 --> 00:05:42.639
the things the symptoms can't be caused by in order
70
00:05:42.680 --> 00:05:45.680
for it to be categorized as depression. They can't be
71
00:05:45.720 --> 00:05:48.959
caused by a medication or drug abuse. They can't be
72
00:05:49.000 --> 00:05:52.720
caused by another medical condition, and they can't be linked
73
00:05:52.720 --> 00:05:56.920
with manic episodes or better explained by other psychotic disorders
74
00:05:56.959 --> 00:06:02.639
like schizophrenia. Until twenty thirteen, they also couldn't be explained
75
00:06:02.680 --> 00:06:05.839
by bereavement after the loss of a loved one, but
76
00:06:05.879 --> 00:06:09.399
the DSM five removed that as an exclusion. That's because
77
00:06:09.519 --> 00:06:12.879
grief doesn't exactly protect you from depression, and it can
78
00:06:12.920 --> 00:06:17.160
sometimes lead to it. Do we know what does cause it?
79
00:06:17.199 --> 00:06:18.800
Then? I think the.
80
00:06:18.920 --> 00:06:22.560
Big question is is it an it? Which you said,
81
00:06:22.600 --> 00:06:26.399
do what causes it? It's probably many different path of
82
00:06:26.439 --> 00:06:30.000
physiological pathways to get to what we call depression. And
83
00:06:30.040 --> 00:06:34.399
there's probably many different paths of physiologies actually chysical changes
84
00:06:34.879 --> 00:06:39.000
and bringing structured function that we call depression.
85
00:06:39.079 --> 00:06:39.720
So it's very.
86
00:06:39.680 --> 00:06:42.959
Unlikely that it's a single illness or a single disease.
87
00:06:43.279 --> 00:06:46.319
It's a disorder that probably is what we call heterogeneous,
88
00:06:46.399 --> 00:06:50.720
meaning there's many different ways you can get that diagnosis.
89
00:06:51.399 --> 00:06:54.759
Yeah, that strikes me as strange because you did just
90
00:06:54.839 --> 00:06:58.040
say that if it's something that we know isn't endocrine
91
00:06:58.040 --> 00:07:00.759
and it isn't like it isn't these things, but it
92
00:07:00.800 --> 00:07:04.680
sounds like it could be a lot of different things exactly.
93
00:07:04.759 --> 00:07:07.279
So we can tell you. That's why the diagnosis of
94
00:07:07.319 --> 00:07:09.199
exclusion is. We can tell you what it isn't, but
95
00:07:09.240 --> 00:07:10.480
we can't tell you what it is.
96
00:07:11.680 --> 00:07:14.439
There are a few risk factors we know can lead
97
00:07:14.480 --> 00:07:17.920
to depression, though stress at home or at work, a
98
00:07:17.959 --> 00:07:23.040
traumatic event, isolation, and other stressors can all have an effect.
99
00:07:23.480 --> 00:07:27.199
Chronic pain and other ongoing medical symptoms can lead to depression.
100
00:07:27.879 --> 00:07:31.959
And then, of course there are the biological factors. Your brain, chemistry,
101
00:07:32.120 --> 00:07:35.519
your genetics, and even your personality can all influence your
102
00:07:35.600 --> 00:07:40.439
risk of depression. So if depression can be caused by
103
00:07:40.480 --> 00:07:43.199
lots of different things, both in your life and in
104
00:07:43.240 --> 00:07:45.279
your brain, how do we fix it.
105
00:07:46.240 --> 00:07:50.560
For the past five or six decades, the primary types
106
00:07:50.600 --> 00:07:56.199
of treatment has been either talk therapy or antidepressant therapies
107
00:07:56.240 --> 00:07:59.959
for the most part. There are neuromodulatory therapies and other
108
00:08:00.079 --> 00:08:02.759
types of therapy that's used there too, but those are
109
00:08:02.839 --> 00:08:06.279
the predominant, especially as a first step in the treatment
110
00:08:06.319 --> 00:08:06.959
of depression.
111
00:08:07.839 --> 00:08:11.839
Right, And there are a lot of different types of antidepressants,
112
00:08:11.879 --> 00:08:13.040
I understand.
113
00:08:13.120 --> 00:08:16.079
So yes and no, there are a lot of different
114
00:08:16.160 --> 00:08:21.319
antidepressants or when we're talking about oral antidepressant medications, so
115
00:08:21.399 --> 00:08:23.839
there are a lot of individual, different ones that are
116
00:08:23.839 --> 00:08:27.920
well over two dozen approved antidepressants, but they do generally
117
00:08:27.959 --> 00:08:31.639
tend to fall in one of a few small categories.
118
00:08:32.200 --> 00:08:36.320
The monoaminergic medicine, So the ones that go back the
119
00:08:36.360 --> 00:08:40.120
furthest of the ones that we currently use, the monoamine
120
00:08:40.159 --> 00:08:45.919
oxidation inhibiting drugs or the tricyclic antidepressant drugs, those really
121
00:08:46.000 --> 00:08:49.720
target primarily neuropinephrine serotonin.
122
00:08:52.080 --> 00:08:54.440
That was a lot of big words, so let's back up.
123
00:08:55.679 --> 00:09:00.879
Monoaminergic medicines target monoamines, which is just an umbrella term
124
00:09:00.960 --> 00:09:05.679
for dopamine, serotonin, and norepinephrine. Those are the brain chemicals
125
00:09:05.679 --> 00:09:08.840
that are thought to be involved in depression, specifically when
126
00:09:08.879 --> 00:09:12.039
you've got low levels of them. It's the job of
127
00:09:12.080 --> 00:09:15.200
these chemicals to help brain cells communicate with one another,
128
00:09:15.639 --> 00:09:18.519
and when there isn't enough of them, those signals can't
129
00:09:18.519 --> 00:09:24.000
get through. So then monoamine oxidase inhibitor drugs block an
130
00:09:24.120 --> 00:09:28.639
enzyme called monoamine oxidase, which is responsible for coming in
131
00:09:28.720 --> 00:09:32.000
and cleaning up any leftover monoamines. Once they've done their
132
00:09:32.080 --> 00:09:36.000
job by blocking the enzyme, the drug is believed to
133
00:09:36.120 --> 00:09:41.679
keep levels of those feel good chemicals high. Tricyclic antidepressants
134
00:09:41.679 --> 00:09:45.120
to do something similar, just in a different way. They
135
00:09:45.240 --> 00:09:49.399
keep some of these chemicals, mostly norepinephrine, from being reabsorbed
136
00:09:49.440 --> 00:09:53.600
into nerve cells. Like doctor Santacorus said, these are the
137
00:09:53.679 --> 00:09:57.039
drugs that go back the farthest. They've also got a
138
00:09:57.080 --> 00:09:59.799
lot of side effects, so these days they're not the
139
00:10:00.320 --> 00:10:03.799
choice for someone who's new to antidepressants. We've got more
140
00:10:03.840 --> 00:10:04.879
options these days.
141
00:10:05.879 --> 00:10:09.159
And then the SSRIs that many people heard of that
142
00:10:09.200 --> 00:10:12.519
we developed later, the prozacs and others in that class
143
00:10:13.120 --> 00:10:15.480
are the selective serotonin reuptake and hignism.
144
00:10:16.519 --> 00:10:23.080
Selective serotonin reuptake inhibitors, or SSRIs inhibit the reuptake of serotonin,
145
00:10:23.440 --> 00:10:26.320
or to put it another way, they keep nerve cells
146
00:10:26.360 --> 00:10:30.320
from reabsorbing serotonin in order to maintain high levels in
147
00:10:30.360 --> 00:10:35.000
the brain. This sounds a little bit like those tricyclic antidepressants,
148
00:10:35.039 --> 00:10:38.720
but these are different. For one thing, tricyclics mostly work
149
00:10:38.799 --> 00:10:44.440
on norepinephrin and SSRIs mostly work on serotonin. And SSRIs
150
00:10:44.519 --> 00:10:48.639
are a lot more precise than tricyclic antidepressants. They're better
151
00:10:48.679 --> 00:10:51.960
at targeting the receptors that are important, rather than just
152
00:10:52.159 --> 00:10:55.720
hitting receptors all over the body and causing unpleasant side effects.
153
00:10:56.279 --> 00:10:58.519
Prozac is one kind of ssri.
154
00:11:00.039 --> 00:11:03.639
Most of those drugs, and even many of the versions
155
00:11:03.639 --> 00:11:07.320
that are followed after that, really are drugs that either
156
00:11:07.399 --> 00:11:11.240
target ner epinephrinurse or at one and that is the
157
00:11:11.480 --> 00:11:15.039
large majority of the medications out there. There are a
158
00:11:15.120 --> 00:11:18.919
few other smaller classes that are beginning to develop that
159
00:11:19.080 --> 00:11:23.759
actually are targeting different neurotransmitter systems and different mechanisms of action.
160
00:11:25.000 --> 00:11:26.879
So do these drugs work?
161
00:11:27.600 --> 00:11:29.919
This is a little bit of a loaded question, because
162
00:11:30.120 --> 00:11:34.399
in fact they are quite effective. The medicines do tend
163
00:11:34.480 --> 00:11:40.840
to work very well. The struggle is that placebo also
164
00:11:40.919 --> 00:11:44.480
works fairly well too, in the treatment of depression, and
165
00:11:44.480 --> 00:11:45.919
it works fairly well in the treatment of a lot
166
00:11:45.960 --> 00:11:50.639
of different disorders, even outside of psychiatry. So I personally
167
00:11:50.759 --> 00:11:53.559
don't like the term placebo because I think at this
168
00:11:53.639 --> 00:11:57.679
point it is laden with a connotation of sort of
169
00:11:58.240 --> 00:12:00.559
shouldn't have an effect. It's sort of a trick or
170
00:12:00.639 --> 00:12:04.440
something where you know, giving that shouldn't have benefit. I
171
00:12:04.480 --> 00:12:07.200
think the term that is more appropriately used as a
172
00:12:07.279 --> 00:12:12.159
non specific effect. So we know that, for example, a diet,
173
00:12:12.480 --> 00:12:16.000
if you sawt somebody on a diet, besides the diet,
174
00:12:16.159 --> 00:12:18.000
they start to pay a lot more attention to what
175
00:12:18.039 --> 00:12:23.000
they're eating, they start to increase exercise, they start.
176
00:12:22.840 --> 00:12:25.080
To do a lot of other things.
177
00:12:25.720 --> 00:12:28.759
That is, in addition, it's non specific to the type
178
00:12:28.759 --> 00:12:31.840
of diet that you give. And it's very much like
179
00:12:31.879 --> 00:12:35.919
that with medications or any treatment. Once you start to
180
00:12:35.960 --> 00:12:38.679
get involved in the treatment, it's not just the pill
181
00:12:38.720 --> 00:12:42.639
you're taking, and even the pill itself has years of conditioning.
182
00:12:42.720 --> 00:12:45.039
So we learned that if we take a pill or
183
00:12:45.120 --> 00:12:48.720
headache goes away. So the next time we have a headache,
184
00:12:48.840 --> 00:12:52.279
even this the simple act of taking anything, we're conditioned
185
00:12:52.279 --> 00:12:54.000
to have that belief that our headache is going to work.
186
00:12:54.039 --> 00:12:56.440
So you become conditioned to certain things are going to work.
187
00:12:56.840 --> 00:12:59.200
So that's part of a placebole response, But there are
188
00:12:59.480 --> 00:13:02.799
many other parts of that placebo response that have big effects,
189
00:13:02.879 --> 00:13:05.279
like you start to pay more attention to your emotions,
190
00:13:05.360 --> 00:13:08.440
you start to think about things differently, and you start
191
00:13:08.480 --> 00:13:11.720
to see a therapist or a doctor, so somebody else
192
00:13:11.919 --> 00:13:14.440
that is now you can share your concerns and thoughts
193
00:13:14.440 --> 00:13:17.879
to it. So it's a lot more involved in taking
194
00:13:18.159 --> 00:13:21.759
a medicine or any fulm medical treatment than the simple
195
00:13:21.960 --> 00:13:25.200
specific effect of the drug or the surgery or whatever
196
00:13:25.200 --> 00:13:27.639
you're getting it. So it's all those non specific effects
197
00:13:27.879 --> 00:13:31.639
and they are incredibly palatful. The medicines work quite well
198
00:13:31.679 --> 00:13:33.799
if you would just look at people that took medicine
199
00:13:33.840 --> 00:13:36.519
and people that didn't take medicine. But it's called a
200
00:13:36.559 --> 00:13:38.919
wait less type approach where you look at people that
201
00:13:39.039 --> 00:13:42.639
started on treatment people that don't. Where it becomes more
202
00:13:42.679 --> 00:13:46.120
difficult to reliably show a difference is when you have
203
00:13:46.200 --> 00:13:49.279
a treatment used against the placebo because the non specific
204
00:13:49.360 --> 00:13:53.559
attacks are so large, you need large sample sizes to
205
00:13:53.720 --> 00:13:56.960
really show how much benefit the drug has over the
206
00:13:57.039 --> 00:14:00.679
non specific effects. The danger is that I really do
207
00:14:00.759 --> 00:14:03.679
try to make clear, is that you don't get the
208
00:14:03.759 --> 00:14:06.519
nonspecific effects unless you take the drug in many care,
209
00:14:06.600 --> 00:14:08.440
or unless you take the treatment, whether it's a drug,
210
00:14:08.440 --> 00:14:11.799
whether it's a talk therapy, whether it's whatever. You can't
211
00:14:11.919 --> 00:14:15.240
really extract one from the other so clearly, And that's
212
00:14:15.279 --> 00:14:16.960
where things get very complicated.
213
00:14:17.440 --> 00:14:20.080
Got it. So when someone just sees the headline that
214
00:14:20.799 --> 00:14:24.480
antide presents work about the same as placebo, there's a
215
00:14:24.519 --> 00:14:27.960
lot more going on there. It's much more complicated than
216
00:14:28.360 --> 00:14:30.639
you just think, like, oh, that just means it doesn't work.
217
00:14:30.679 --> 00:14:32.000
Like that's not what it means.
218
00:14:32.080 --> 00:14:36.519
Exactly, And that's where the there's a miscommunication or it
219
00:14:36.559 --> 00:14:40.399
could be misleading. And it's very important. And I don't
220
00:14:40.440 --> 00:14:43.320
think too many people spend nearly as much time as
221
00:14:43.360 --> 00:14:45.720
I do and others looking at this issue. So if
222
00:14:45.759 --> 00:14:48.720
you just hear that, I think it's a natural response
223
00:14:48.720 --> 00:14:51.360
to say, oh, well, if it doesn't work much better placebo,
224
00:14:51.399 --> 00:14:52.600
then it doesn't work very well.
225
00:14:52.639 --> 00:14:54.639
But that's not really what it.
226
00:14:54.639 --> 00:14:58.200
Means, but it does seem like with some drugs, I
227
00:14:58.200 --> 00:15:01.399
don't know, for heart conditions, it's like you give the
228
00:15:01.480 --> 00:15:04.919
drug and most people have about the same reaction. Maybe
229
00:15:04.919 --> 00:15:06.879
I'm oversimplifying, but I.
230
00:15:06.799 --> 00:15:09.200
Think you're oversimplifying much more than you think you are.
231
00:15:09.600 --> 00:15:14.279
Really well, yeah, I mean, I guess that's like the perception, right, yeah.
232
00:15:14.080 --> 00:15:18.039
And I think that's a misperception. There are relatively high
233
00:15:18.039 --> 00:15:23.120
placebo response rates for anti hypertensors. They're relatively high sham
234
00:15:23.159 --> 00:15:29.399
response rates to surgeries like orthopedic surgeries. The non specific
235
00:15:29.399 --> 00:15:34.399
effects go well beyond what we typically think of in depression.
236
00:15:35.240 --> 00:15:38.559
Even things like Parkinson's disease, which you wouldn't imagine would
237
00:15:38.600 --> 00:15:44.519
have big nonspecific effects as notorious or very large placebo effects.
238
00:15:45.360 --> 00:15:48.559
Doctor Santa Korus says that even the experience some people
239
00:15:48.639 --> 00:15:51.519
have with antidepressants where they need to try many different
240
00:15:51.600 --> 00:15:54.360
kinds before they find one that works for them, that's
241
00:15:54.440 --> 00:15:58.720
pretty similar to hypertension medications. People usually start on, say
242
00:15:58.799 --> 00:16:01.799
a diuretic that doesn't work, They'll try a beta blocker,
243
00:16:02.000 --> 00:16:02.759
and on and on.
244
00:16:03.399 --> 00:16:06.639
It's very common, especially in the treatment of hyperrotections. It
245
00:16:06.720 --> 00:16:09.000
is a good example of that. So the trumant of
246
00:16:09.039 --> 00:16:11.200
depression isn't so unique in that way.
247
00:16:11.919 --> 00:16:16.399
But antidepressants like these aren't the only options out there. Recently,
248
00:16:16.559 --> 00:16:20.080
research has demonstrated real promise for some drugs that I,
249
00:16:20.279 --> 00:16:23.759
for one, was told to stay away from in their class.
250
00:16:27.080 --> 00:16:30.759
You study a bunch of different therapies for depression, and
251
00:16:30.759 --> 00:16:33.519
one of those is ketamine. Like when I first heard
252
00:16:33.600 --> 00:16:35.960
that people were using ketamine to treat depression, I was like,
253
00:16:36.679 --> 00:16:39.840
how could that possibly work? Like that's like a street drug, right,
254
00:16:39.960 --> 00:16:40.799
how does that work?
255
00:16:41.360 --> 00:16:45.000
So ketamine was originally an anesthetic agent. It was a
256
00:16:45.039 --> 00:16:48.200
major breakthrough in the field of anesthesia, and you have
257
00:16:48.279 --> 00:16:49.879
to approve in nineteen.
258
00:16:49.679 --> 00:16:53.200
Seven, as you said, it's an anesthetic. It really gained
259
00:16:53.200 --> 00:16:54.639
a lot of prominence because it's.
260
00:16:54.480 --> 00:16:58.679
A relatively safe aesthetic that could be used in situations
261
00:16:58.679 --> 00:17:01.159
where you weren't able to monitor patients as closely, so
262
00:17:01.240 --> 00:17:04.359
in chill pass orles. It became very popu in third
263
00:17:04.359 --> 00:17:07.680
world countries. It's still a critical drug as the use
264
00:17:07.720 --> 00:17:10.599
of an anesthetic, and it's even in the US. It's
265
00:17:10.680 --> 00:17:14.119
use commonly in pediatric anesthesia or emergency rooms where you
266
00:17:14.160 --> 00:17:16.519
need a quick use of an anesthetic.
267
00:17:17.200 --> 00:17:21.279
If you're wondering why someone would use an anesthetic illegally, well,
268
00:17:21.400 --> 00:17:24.759
it's because ketamine works by putting people in a dissociative
269
00:17:24.799 --> 00:17:28.039
state that detaches them from any pain. You can see
270
00:17:28.079 --> 00:17:31.559
how that might be desirable outside of the operating room.
271
00:17:32.240 --> 00:17:35.279
And that's before you get to its hallucinogenic effects.
272
00:17:35.759 --> 00:17:37.680
Again, the lay person may look at this as kind
273
00:17:37.680 --> 00:17:40.359
of a street drug, but it has a fifteen year
274
00:17:40.519 --> 00:17:43.960
history of being considered a critical drug to the world
275
00:17:44.000 --> 00:17:47.039
by the World Health Organization. So this is a long
276
00:17:47.200 --> 00:17:50.119
medical history, but it still is a pretty unique story
277
00:17:50.160 --> 00:17:54.039
that this anesthetic drug would have antidepressing effects.
278
00:17:54.240 --> 00:17:58.000
Yeah, and so how why does it have antidepress and effects?
279
00:17:58.440 --> 00:18:01.119
So I would I could to do exactly why.
280
00:18:01.160 --> 00:18:03.720
I can tell you why we think it does, and
281
00:18:03.759 --> 00:18:06.240
I can tell you why it was initially testing.
282
00:18:06.759 --> 00:18:11.000
There was increasing evidence, really towards.
283
00:18:10.640 --> 00:18:12.839
The end of the last millennium, in the nineteen nineties
284
00:18:12.960 --> 00:18:18.160
or so, that the neurobiology of depression was much more
285
00:18:18.200 --> 00:18:21.440
involved than that idea of the chemical imbalance or that
286
00:18:21.519 --> 00:18:24.839
there was low serotonin, low Europe and effort levels, which
287
00:18:24.880 --> 00:18:28.400
is really where the thinking was in the nineteen eighties
288
00:18:28.400 --> 00:18:31.680
and nineties, and we started to realize that the brain
289
00:18:31.799 --> 00:18:35.039
was much more complex and there was many other neurotransmitter
290
00:18:35.079 --> 00:18:38.559
systems that were involved, and also that the plasticity of
291
00:18:38.559 --> 00:18:40.880
the brain, the way the brain can actually change and
292
00:18:40.960 --> 00:18:43.480
adapt to different environments and.
293
00:18:43.599 --> 00:18:47.319
Different evensfe was very important.
294
00:18:48.119 --> 00:18:51.319
And they became increasing evidence that parts of the brain
295
00:18:51.359 --> 00:18:55.799
that were predominantly using glutamate, which is the major neurotransmitter
296
00:18:55.839 --> 00:18:59.000
in the brain. So about eighty percent of all your neurons,
297
00:18:59.039 --> 00:19:02.680
the cells in your brain use glutamate as its primary communication.
298
00:19:02.920 --> 00:19:05.599
You know, it's primary or a transmitter. So it began
299
00:19:05.680 --> 00:19:08.960
increasing that glutimate and gabba, which is a major in emiture.
300
00:19:09.640 --> 00:19:12.359
That those two charatrisms probably have pots to do with
301
00:19:12.400 --> 00:19:15.400
the path of the physiology of depression. As we said,
302
00:19:15.480 --> 00:19:18.839
whatever depression is that broader sense of and the ability
303
00:19:18.880 --> 00:19:20.240
to modulate plasticity.
304
00:19:21.440 --> 00:19:24.480
One thing we've learned is that stress and trauma can
305
00:19:24.519 --> 00:19:28.440
actually change the structure of the brain. Animal studies have
306
00:19:28.519 --> 00:19:31.960
found that chronic stress can degrade neurons and parts of
307
00:19:32.000 --> 00:19:36.519
the brain responsible for learning, memory, and executive function. Those
308
00:19:36.519 --> 00:19:40.400
areas are also smaller with fewer connections in patients with depression.
309
00:19:41.160 --> 00:19:43.519
Some of that is probably because of problems with the
310
00:19:43.559 --> 00:19:46.119
neurons that deal with glutamate and GABBA.
311
00:19:47.240 --> 00:19:52.319
So is at that time some of my colleagues had, Yeah,
312
00:19:52.400 --> 00:19:57.599
John Crystal Brobern and others had the idea that ketamine
313
00:19:57.720 --> 00:20:01.960
being a drug that specifically targets the glutamate system what's
314
00:20:02.039 --> 00:20:05.200
called the NMBA receptor which binds to glutamate.
315
00:20:05.559 --> 00:20:07.000
The fact that they knew that there was this.
316
00:20:07.079 --> 00:20:11.039
Drug out there that had been used safely for decades
317
00:20:12.000 --> 00:20:16.480
had a dramatic effect on this neurotransmitter system. They really
318
00:20:16.680 --> 00:20:19.039
followed a pretty simple apothesis that just may have an
319
00:20:19.039 --> 00:20:22.759
effect on people with depression, and that was the original
320
00:20:22.799 --> 00:20:25.240
study done in the late nineteen nineties published in two
321
00:20:25.279 --> 00:20:28.240
thousand that shows this very rapid on set of effect,
322
00:20:28.720 --> 00:20:32.000
which really was a surprise to everybody. I mean, everybody
323
00:20:32.200 --> 00:20:35.599
was interested in it, but I don't think anybody in
324
00:20:35.640 --> 00:20:39.559
New tact I'm sure none of those primary office, because
325
00:20:39.599 --> 00:20:42.359
they make it very clear thought that they would see
326
00:20:42.359 --> 00:20:45.799
this rapid improvement within hours that would be sustained for
327
00:20:45.880 --> 00:20:48.279
at least days following a treatment.
328
00:20:48.839 --> 00:20:49.279
Wow.
329
00:20:50.400 --> 00:20:53.160
But because it's an anesthetic, does it I mean, does
330
00:20:53.200 --> 00:20:55.240
it make it so you have you can't do everyday
331
00:20:55.240 --> 00:20:56.519
activities when you're using it.
332
00:20:57.480 --> 00:21:00.960
So that's the other extremely interest in resting an important
333
00:21:00.960 --> 00:21:04.599
point to make with ketemine, especially the early studies with ketymine.
334
00:21:04.839 --> 00:21:08.200
So it's not giving at the level that you would
335
00:21:08.440 --> 00:21:11.480
use for anesthesia, but it is still given at a
336
00:21:11.519 --> 00:21:15.839
level that would dramatically impair your cognition. So you at
337
00:21:15.880 --> 00:21:20.920
the dose that is being used original studies, yes, you
338
00:21:21.000 --> 00:21:24.039
do need to be monitored closely and you're not going
339
00:21:24.119 --> 00:21:27.559
to be going about your normal daily activities. But unlike
340
00:21:27.640 --> 00:21:29.799
most other antidepressants where you have to take it all
341
00:21:29.839 --> 00:21:33.200
the time, this was something that you take and typically
342
00:21:33.200 --> 00:21:35.960
an infusion originally was lasting for about forty minutes and
343
00:21:35.960 --> 00:21:38.480
then you stop it. Ketymine is metabolized very quick thing
344
00:21:38.519 --> 00:21:41.160
about it, so it disappears out of your system pretty rapidly.
345
00:21:42.240 --> 00:21:45.920
But then the antidepressant effect actually build over time after
346
00:21:46.000 --> 00:21:49.359
you stop it, so the majority of the large majority
347
00:21:49.400 --> 00:21:51.599
of that time you're not on the drought that you
348
00:21:51.680 --> 00:21:56.599
actually get to benefit, which is again a novel approach
349
00:21:56.799 --> 00:22:00.000
and really a completely new finding within the field.
350
00:22:01.279 --> 00:22:04.640
So is this becoming more widespread? Are more people using
351
00:22:04.680 --> 00:22:07.039
this in just like therapy settings.
352
00:22:07.319 --> 00:22:14.359
So it is growing dramatically in twenty nineteen, the FDA
353
00:22:14.599 --> 00:22:18.400
has approved a version of kenemine, which is actually esketemine,
354
00:22:18.400 --> 00:22:22.400
which is really just half of the natural substance that
355
00:22:22.599 --> 00:22:25.920
carves in what we were seen a ketemine. It's just
356
00:22:26.200 --> 00:22:29.599
half of what we would normally find in regular academy.
357
00:22:30.079 --> 00:22:33.720
It was approved for the treatment of patients with treatment
358
00:22:33.759 --> 00:22:37.720
resistant depression, and then more recently in twenty twenty, was
359
00:22:37.720 --> 00:22:44.119
actually approved for patients with depression who also have suicidal ideations.
360
00:22:46.599 --> 00:22:50.400
Even though it wasn't FDA approved until twenty nineteen, clinics
361
00:22:50.400 --> 00:22:53.839
had been using ketamine to treat depression since twenty twelve,
362
00:22:54.279 --> 00:22:57.880
and that wasn't illegal. Instead, it was just yet another
363
00:22:57.920 --> 00:23:00.279
benefit of a drug that had been used for something
364
00:23:00.319 --> 00:23:05.720
else for decades. See these clinics just used ketamine off label,
365
00:23:06.079 --> 00:23:09.440
the way doctors commonly prescribe an anti seizure medication for
366
00:23:09.599 --> 00:23:13.799
bipolar disorder, or how some musicians I know get beta blockers,
367
00:23:13.880 --> 00:23:17.799
a type of blood pressure medication for stage fright. It's
368
00:23:17.839 --> 00:23:22.240
a thing. Using drugs off label is legal. It just
369
00:23:22.279 --> 00:23:25.359
carries some extra risks since the FDA hasn't determined that
370
00:23:25.400 --> 00:23:28.519
the drug is safe and effective for that off label use.
371
00:23:29.240 --> 00:23:32.440
But that was then, so it is now n FDA
372
00:23:32.480 --> 00:23:37.680
approved indicated medicine for depression, but it's not a medicine
373
00:23:37.680 --> 00:23:40.799
for everybody, definitely, and it is still a medicine that
374
00:23:40.960 --> 00:23:46.160
requires relative and close monitoring, especially in the way that
375
00:23:46.200 --> 00:23:49.319
it is being given as of today and according to
376
00:23:49.359 --> 00:23:50.200
the SDA.
377
00:23:50.160 --> 00:23:51.480
Regulations and guidance.
378
00:23:51.960 --> 00:23:54.559
We talked a lot about kidamine as a game changer,
379
00:23:54.599 --> 00:23:57.160
which I really think it was because we were locked
380
00:23:57.160 --> 00:24:02.759
into about fifteen years of thinking very specifically about how
381
00:24:02.799 --> 00:24:05.839
to treat depression and either would talk therapies or with
382
00:24:06.400 --> 00:24:11.079
oral antipress medications that primarily targeted serotomin Europe and efferent.
383
00:24:11.359 --> 00:24:12.960
I mean, there was always the treatments like.
384
00:24:12.960 --> 00:24:17.839
ECT that actually predate electro convulsive therapy, that predate even
385
00:24:17.680 --> 00:24:22.880
the oral medications. But since that time of ketamine, there's
386
00:24:22.960 --> 00:24:28.079
really been an explosion of alternatives treatments. Besides the regular
387
00:24:28.440 --> 00:24:35.119
oral antidepressants and talk therapies, there's neurostimulatory therapies like transcrinomagnetic
388
00:24:35.160 --> 00:24:41.640
stimulation that has really become quite popular. There's nerve simulation,
389
00:24:42.200 --> 00:24:45.839
there's even studies with deep brain stimulation that are going on.
390
00:24:46.319 --> 00:24:49.640
But then in terms of other pharmacologic treatments. There are
391
00:24:49.680 --> 00:24:53.279
several new lines of interest, but the one that I
392
00:24:53.319 --> 00:24:55.799
think recently has gained a lot of attention and it
393
00:24:55.880 --> 00:24:58.839
is extremely interesting to many people, is the idea of
394
00:24:58.920 --> 00:25:02.759
using drugs such as psilocybin, drugs that fall into this
395
00:25:02.920 --> 00:25:05.839
general psychedelic category of drugs.
396
00:25:06.200 --> 00:25:09.680
Yep Ketamine isn't the only dark horse in this race.
397
00:25:10.240 --> 00:25:14.160
There's also psilocybin, the active ingredient in what some call
398
00:25:15.279 --> 00:25:21.400
magic mushrooms. Yeah, how does psilocybin help with depression? Do
399
00:25:21.480 --> 00:25:21.920
we know that?
400
00:25:23.000 --> 00:25:23.079
So?
401
00:25:23.440 --> 00:25:25.559
First of all, I don't think we can say we
402
00:25:25.640 --> 00:25:27.000
know that it does help with depression.
403
00:25:27.079 --> 00:25:29.960
It we're still doing those studies. So there are early
404
00:25:30.079 --> 00:25:31.240
reports that.
405
00:25:31.240 --> 00:25:35.000
Look very promising, but I always do emphasize these are
406
00:25:35.000 --> 00:25:39.680
early reports and we really still have to demonstrate that
407
00:25:39.759 --> 00:25:43.480
this isn't effective treatment and depression, and that really is
408
00:25:43.519 --> 00:25:45.960
the first step, and that I think many of us
409
00:25:45.960 --> 00:25:52.200
are working very hard to determine what the actual efficacy
410
00:25:52.319 --> 00:25:55.400
and obviously the safety of this treatment would be true depression.
411
00:25:56.240 --> 00:25:58.680
In terms of if it does work, how it works,
412
00:25:58.880 --> 00:26:03.559
there are many different hypotheses. I think sort of the
413
00:26:03.640 --> 00:26:06.440
mainstreamline of thinking about it is that it may work
414
00:26:06.559 --> 00:26:09.200
very similar to ketamine. So we think what ketamine, we do,
415
00:26:09.400 --> 00:26:14.319
and quite possibly these psychedelic medications I mentioned before, this
416
00:26:14.400 --> 00:26:18.680
idea of neuroplasticity actually altering the way the brain cells
417
00:26:18.720 --> 00:26:22.279
communicate with each other, and actually even structurally altering the
418
00:26:22.279 --> 00:26:24.880
way the brain cells communicate with each other and how
419
00:26:24.880 --> 00:26:29.039
they adapt to novel environments and novel events. And it
420
00:26:29.079 --> 00:26:32.640
looks like just as ketamine can have these rapid effects
421
00:26:32.720 --> 00:26:35.640
on the neuron's ability to communicate with each other, it
422
00:26:35.640 --> 00:26:38.839
looks like some of these psychedelic type methicines like psilocybin,
423
00:26:38.960 --> 00:26:43.039
may have very similar effects. Now, obviously these are still
424
00:26:43.119 --> 00:26:46.519
hypotheses that need to be tested, and there are other hypotheses.
425
00:26:46.920 --> 00:26:47.839
These may have.
426
00:26:48.000 --> 00:26:51.720
More more effects that go well beyond the simple brain
427
00:26:51.799 --> 00:26:55.759
chemistry or even the neuroplasticity, in terms of some of
428
00:26:55.759 --> 00:27:00.440
the spiritual side of these drugs and the other they
429
00:27:00.440 --> 00:27:05.039
may have in social relatedness. So there are many different hypotheses,
430
00:27:05.079 --> 00:27:07.960
so we really don't know how any of them work
431
00:27:08.039 --> 00:27:09.839
for sure, but we are starting to learn.
432
00:27:09.839 --> 00:27:10.319
Quite a bit.
433
00:27:10.759 --> 00:27:14.039
Yeah, one thing I've heard is that an idea might
434
00:27:14.079 --> 00:27:17.720
be that it gives you more of a sense of
435
00:27:17.880 --> 00:27:20.160
oneness with the world and takes you out of your
436
00:27:20.200 --> 00:27:23.200
own like focusing in on your own self. And because
437
00:27:23.240 --> 00:27:26.680
depression is there's a lot of like looking inward that
438
00:27:26.799 --> 00:27:27.759
it helps that way.
439
00:27:28.720 --> 00:27:31.359
So that is definitely one of the hypotheses that have
440
00:27:31.480 --> 00:27:35.599
been proposed, and there's a fair amount of research looking
441
00:27:35.640 --> 00:27:38.640
into that. I don't think any of these mechanisms are
442
00:27:38.799 --> 00:27:42.079
necessarily exclusive. I think the likelihood is that there's some
443
00:27:42.279 --> 00:27:46.160
component of all of these in generating the bashits that
444
00:27:46.240 --> 00:27:46.759
are seen.
445
00:27:47.319 --> 00:27:48.799
But I do say, yeah, the first.
446
00:27:48.599 --> 00:27:51.880
Part is we'd have to demonstrate to a high degree
447
00:27:51.880 --> 00:27:54.519
of certainty that these are effective and safe treatments.
448
00:27:54.519 --> 00:27:55.799
We're still at that stage.
449
00:27:55.839 --> 00:28:01.519
So here's what I didn't realize about depression. Just because
450
00:28:01.519 --> 00:28:04.480
we don't fully understand how it works in the brain
451
00:28:05.079 --> 00:28:08.519
doesn't mean we can't find better ways to give people relief.
452
00:28:09.160 --> 00:28:11.400
You don't have to know how something works to know
453
00:28:11.519 --> 00:28:15.640
that it does work. Millions of people suffer from depression,
454
00:28:16.200 --> 00:28:19.920
and researchers like doctor Santa Kora are constantly making progress
455
00:28:19.960 --> 00:28:25.079
toward more effective treatments and maybe someday we'll know how
456
00:28:25.119 --> 00:28:35.839
they work. So well, thanks for listening. I'm back in
457
00:28:35.880 --> 00:28:39.119
twenty twenty three to read the credits. Thanks a ton
458
00:28:39.200 --> 00:28:41.400
to Girard Santa Kora for talking to me back in
459
00:28:41.400 --> 00:28:44.400
twenty twenty one. He's since done a lot more work
460
00:28:44.440 --> 00:28:47.319
on ketamine's role in treating depression, and all include links
461
00:28:47.359 --> 00:28:49.640
to some of that work in the citations on the website.
462
00:28:49.880 --> 00:28:52.279
And if you'd like to hear a really excellent podcast
463
00:28:52.279 --> 00:28:56.039
episode all about ketamine which also features doctor Santa Kora,
464
00:28:56.240 --> 00:28:59.240
definitely check out the Science Versus episode about it from
465
00:28:59.279 --> 00:29:01.480
April of this year. All include a link in the
466
00:29:01.519 --> 00:29:04.759
show notes. Taboo Science is written and produced by me
467
00:29:04.920 --> 00:29:08.519
Ashley Hamer. The theme was by Danny Lapotka of DLC Music.
468
00:29:08.839 --> 00:29:12.160
Episode music is from Epidemic Sound. If you need music
469
00:29:12.160 --> 00:29:14.400
for a project, just use my referral link in the
470
00:29:14.400 --> 00:29:17.480
show notes and it'll help out the show. We've got
471
00:29:17.519 --> 00:29:20.640
some really fascinating new topics coming in the next couple months.
472
00:29:20.759 --> 00:29:24.000
I for one am really excited, so hit that subscribe
473
00:29:24.039 --> 00:29:26.359
button to make sure you don't miss an episode and
474
00:29:26.519 --> 00:29:32.559
tune in next time. I won't tell anyone
1
00:00:00.120 --> 00:00:04.000
Hey there, Ashley here. I'm currently off gallivanting in Denver
2
00:00:04.120 --> 00:00:07.799
at podcast Movement, so I'm re releasing this very popular
3
00:00:07.839 --> 00:00:11.119
episode that dropped back in twenty twenty one. Chances are
4
00:00:11.160 --> 00:00:13.199
you've never heard it before, but even if you have,
5
00:00:13.439 --> 00:00:16.480
it's worth hearing again, not just because the stuff that
6
00:00:16.480 --> 00:00:19.480
doctor Santa Kora has to say is only getting more important,
7
00:00:19.839 --> 00:00:24.120
but also because it's fully remastered with fancy AI audio
8
00:00:24.120 --> 00:00:28.640
tools thanks to script, so it's a much better listen. Seriously,
9
00:00:28.800 --> 00:00:31.039
if you're curious, check out the original in the feed
10
00:00:31.120 --> 00:00:33.920
and then listen to this one. The difference is pretty dramatic.
11
00:00:34.640 --> 00:00:38.320
And if you're watching on YouTube, hi, I didn't record
12
00:00:38.399 --> 00:00:40.439
video for this back in the day, so you're going
13
00:00:40.479 --> 00:00:42.960
to get an audiogram. I made it as fancy as
14
00:00:43.000 --> 00:00:46.359
I could for you. Hope you'll like it. I'll be
15
00:00:46.479 --> 00:00:48.840
back at the end to see you off for now
16
00:00:49.119 --> 00:00:56.039
on with the show. I used to think that depression
17
00:00:56.600 --> 00:01:00.479
was easy to spot. I mean, I knew that people
18
00:01:00.479 --> 00:01:04.120
with depression were sad, and they'd start to skip their
19
00:01:04.120 --> 00:01:08.200
favorite activities to stay in bed all day. They'd basically
20
00:01:08.280 --> 00:01:12.120
just shut off from the world. But it turns out
21
00:01:12.200 --> 00:01:18.159
that depression is so much more complicated than that. Like,
22
00:01:18.439 --> 00:01:21.920
depression can make it hard to concentrate. You can be
23
00:01:21.959 --> 00:01:25.040
going to work every day like you always do, but
24
00:01:25.079 --> 00:01:27.799
you just start to forget things and make silly mistakes.
25
00:01:28.640 --> 00:01:32.680
Some people, particularly older people, they might even fall more
26
00:01:32.719 --> 00:01:38.840
frequently because they're not paying attention. Depression can make you angry.
27
00:01:38.920 --> 00:01:42.280
If you feel hopeless on the inside, you might lay
28
00:01:42.280 --> 00:01:44.920
the blame with others, and that can make you lash
29
00:01:44.959 --> 00:01:51.920
out at friends and family. And depression can hurt. Studies
30
00:01:51.920 --> 00:01:55.120
have shown that people with depression have a decreased tolerance
31
00:01:55.159 --> 00:01:59.640
for pain. Your head, your joints, your whole body might
32
00:01:59.719 --> 00:02:04.239
just feel worse overall. And just like there are a
33
00:02:04.319 --> 00:02:07.719
lot of different symptoms of depression, there are also a
34
00:02:07.760 --> 00:02:12.919
lot of different causes, causes that scientists haven't fully untangled.
35
00:02:14.159 --> 00:02:18.520
In fact, depression is still a pretty big mystery. We
36
00:02:18.599 --> 00:02:22.439
can't fully explain why it happens, what's going on in
37
00:02:22.479 --> 00:02:26.159
the brain when it does happen, or how exactly therapies
38
00:02:26.159 --> 00:02:30.960
and medications help. But one thing we do know is
39
00:02:31.000 --> 00:02:35.199
that they do help, and that our treatments for depression
40
00:02:35.240 --> 00:02:39.280
are getting better all the time, despite the fact that
41
00:02:39.319 --> 00:02:45.240
those treatments can come from some pretty strange places. Today,
42
00:02:45.280 --> 00:02:47.360
we're going to talk about what we do and don't
43
00:02:47.400 --> 00:02:52.280
know about depression, why not knowing is actually okay, and
44
00:02:52.479 --> 00:02:57.560
why hallucinogens are making their way into the clinic. I'm
45
00:02:57.599 --> 00:03:01.240
Ashley Hamer, and this is Taboo Science, the podcast that
46
00:03:01.280 --> 00:04:08.479
answers the questions you're not allowed to ask. Depression is
47
00:04:08.840 --> 00:04:14.439
incredibly common, scarily common, Like more than two hundred and
48
00:04:14.439 --> 00:04:20.279
sixty million people worldwide are affected by depression. So you'd
49
00:04:20.319 --> 00:04:23.600
think this would be an easy thing to answer. What
50
00:04:24.040 --> 00:04:24.800
is depression?
51
00:04:25.920 --> 00:04:27.600
That is actually a very good question.
52
00:04:28.759 --> 00:04:32.279
That's doctor Gerard Santa Kora. He's the director of the
53
00:04:32.360 --> 00:04:35.399
Yale Depression Research Program and co director of the Yale
54
00:04:35.439 --> 00:04:39.720
Interventional Psychiatry Service, And to him, the question isn't so
55
00:04:39.879 --> 00:04:42.680
much what depression is as what it isn't.
56
00:04:44.759 --> 00:04:47.920
Depression is an interesting thing. That is actually what we
57
00:04:48.000 --> 00:04:52.279
call a diagnosis of exclusion. So in medicine, that means
58
00:04:52.319 --> 00:04:55.800
that you have a set of symptoms signs and we
59
00:04:55.879 --> 00:05:00.879
can't find an explanation, so for depression, and it's typically
60
00:05:00.920 --> 00:05:07.120
a set of nine core symptoms related to sleet, appetite, mood, concentration,
61
00:05:08.000 --> 00:05:12.759
zest for life, willingness, to live relating to those general
62
00:05:12.800 --> 00:05:17.720
categories that affect your cognition, perception, emotions, and we can't
63
00:05:17.720 --> 00:05:20.360
find another explanation for it. So, in other words, we
64
00:05:20.439 --> 00:05:26.319
can't find an endochronological problem such as hypothyroidism, or we
65
00:05:26.399 --> 00:05:30.759
don't find another neurologic disorders such as parkinson as that.
66
00:05:30.720 --> 00:05:31.560
Could be related.
67
00:05:32.199 --> 00:05:35.680
According to the latest edition of the Diagnostic and Statistical
68
00:05:35.720 --> 00:05:39.720
Manual of Mental Disorders, or the DSM five, these are
69
00:05:39.720 --> 00:05:42.639
the things the symptoms can't be caused by in order
70
00:05:42.680 --> 00:05:45.680
for it to be categorized as depression. They can't be
71
00:05:45.720 --> 00:05:48.959
caused by a medication or drug abuse. They can't be
72
00:05:49.000 --> 00:05:52.720
caused by another medical condition, and they can't be linked
73
00:05:52.720 --> 00:05:56.920
with manic episodes or better explained by other psychotic disorders
74
00:05:56.959 --> 00:06:02.639
like schizophrenia. Until twenty thirteen, they also couldn't be explained
75
00:06:02.680 --> 00:06:05.839
by bereavement after the loss of a loved one, but
76
00:06:05.879 --> 00:06:09.399
the DSM five removed that as an exclusion. That's because
77
00:06:09.519 --> 00:06:12.879
grief doesn't exactly protect you from depression, and it can
78
00:06:12.920 --> 00:06:17.160
sometimes lead to it. Do we know what does cause it?
79
00:06:17.199 --> 00:06:18.800
Then? I think the.
80
00:06:18.920 --> 00:06:22.560
Big question is is it an it? Which you said,
81
00:06:22.600 --> 00:06:26.399
do what causes it? It's probably many different path of
82
00:06:26.439 --> 00:06:30.000
physiological pathways to get to what we call depression. And
83
00:06:30.040 --> 00:06:34.399
there's probably many different paths of physiologies actually chysical changes
84
00:06:34.879 --> 00:06:39.000
and bringing structured function that we call depression.
85
00:06:39.079 --> 00:06:39.720
So it's very.
86
00:06:39.680 --> 00:06:42.959
Unlikely that it's a single illness or a single disease.
87
00:06:43.279 --> 00:06:46.319
It's a disorder that probably is what we call heterogeneous,
88
00:06:46.399 --> 00:06:50.720
meaning there's many different ways you can get that diagnosis.
89
00:06:51.399 --> 00:06:54.759
Yeah, that strikes me as strange because you did just
90
00:06:54.839 --> 00:06:58.040
say that if it's something that we know isn't endocrine
91
00:06:58.040 --> 00:07:00.759
and it isn't like it isn't these things, but it
92
00:07:00.800 --> 00:07:04.680
sounds like it could be a lot of different things exactly.
93
00:07:04.759 --> 00:07:07.279
So we can tell you. That's why the diagnosis of
94
00:07:07.319 --> 00:07:09.199
exclusion is. We can tell you what it isn't, but
95
00:07:09.240 --> 00:07:10.480
we can't tell you what it is.
96
00:07:11.680 --> 00:07:14.439
There are a few risk factors we know can lead
97
00:07:14.480 --> 00:07:17.920
to depression, though stress at home or at work, a
98
00:07:17.959 --> 00:07:23.040
traumatic event, isolation, and other stressors can all have an effect.
99
00:07:23.480 --> 00:07:27.199
Chronic pain and other ongoing medical symptoms can lead to depression.
100
00:07:27.879 --> 00:07:31.959
And then, of course there are the biological factors. Your brain, chemistry,
101
00:07:32.120 --> 00:07:35.519
your genetics, and even your personality can all influence your
102
00:07:35.600 --> 00:07:40.439
risk of depression. So if depression can be caused by
103
00:07:40.480 --> 00:07:43.199
lots of different things, both in your life and in
104
00:07:43.240 --> 00:07:45.279
your brain, how do we fix it.
105
00:07:46.240 --> 00:07:50.560
For the past five or six decades, the primary types
106
00:07:50.600 --> 00:07:56.199
of treatment has been either talk therapy or antidepressant therapies
107
00:07:56.240 --> 00:07:59.959
for the most part. There are neuromodulatory therapies and other
108
00:08:00.079 --> 00:08:02.759
types of therapy that's used there too, but those are
109
00:08:02.839 --> 00:08:06.279
the predominant, especially as a first step in the treatment
110
00:08:06.319 --> 00:08:06.959
of depression.
111
00:08:07.839 --> 00:08:11.839
Right, And there are a lot of different types of antidepressants,
112
00:08:11.879 --> 00:08:13.040
I understand.
113
00:08:13.120 --> 00:08:16.079
So yes and no, there are a lot of different
114
00:08:16.160 --> 00:08:21.319
antidepressants or when we're talking about oral antidepressant medications, so
115
00:08:21.399 --> 00:08:23.839
there are a lot of individual, different ones that are
116
00:08:23.839 --> 00:08:27.920
well over two dozen approved antidepressants, but they do generally
117
00:08:27.959 --> 00:08:31.639
tend to fall in one of a few small categories.
118
00:08:32.200 --> 00:08:36.320
The monoaminergic medicine, So the ones that go back the
119
00:08:36.360 --> 00:08:40.120
furthest of the ones that we currently use, the monoamine
120
00:08:40.159 --> 00:08:45.919
oxidation inhibiting drugs or the tricyclic antidepressant drugs, those really
121
00:08:46.000 --> 00:08:49.720
target primarily neuropinephrine serotonin.
122
00:08:52.080 --> 00:08:54.440
That was a lot of big words, so let's back up.
123
00:08:55.679 --> 00:09:00.879
Monoaminergic medicines target monoamines, which is just an umbrella term
124
00:09:00.960 --> 00:09:05.679
for dopamine, serotonin, and norepinephrine. Those are the brain chemicals
125
00:09:05.679 --> 00:09:08.840
that are thought to be involved in depression, specifically when
126
00:09:08.879 --> 00:09:12.039
you've got low levels of them. It's the job of
127
00:09:12.080 --> 00:09:15.200
these chemicals to help brain cells communicate with one another,
128
00:09:15.639 --> 00:09:18.519
and when there isn't enough of them, those signals can't
129
00:09:18.519 --> 00:09:24.000
get through. So then monoamine oxidase inhibitor drugs block an
130
00:09:24.120 --> 00:09:28.639
enzyme called monoamine oxidase, which is responsible for coming in
131
00:09:28.720 --> 00:09:32.000
and cleaning up any leftover monoamines. Once they've done their
132
00:09:32.080 --> 00:09:36.000
job by blocking the enzyme, the drug is believed to
133
00:09:36.120 --> 00:09:41.679
keep levels of those feel good chemicals high. Tricyclic antidepressants
134
00:09:41.679 --> 00:09:45.120
to do something similar, just in a different way. They
135
00:09:45.240 --> 00:09:49.399
keep some of these chemicals, mostly norepinephrine, from being reabsorbed
136
00:09:49.440 --> 00:09:53.600
into nerve cells. Like doctor Santacorus said, these are the
137
00:09:53.679 --> 00:09:57.039
drugs that go back the farthest. They've also got a
138
00:09:57.080 --> 00:09:59.799
lot of side effects, so these days they're not the
139
00:10:00.320 --> 00:10:03.799
choice for someone who's new to antidepressants. We've got more
140
00:10:03.840 --> 00:10:04.879
options these days.
141
00:10:05.879 --> 00:10:09.159
And then the SSRIs that many people heard of that
142
00:10:09.200 --> 00:10:12.519
we developed later, the prozacs and others in that class
143
00:10:13.120 --> 00:10:15.480
are the selective serotonin reuptake and hignism.
144
00:10:16.519 --> 00:10:23.080
Selective serotonin reuptake inhibitors, or SSRIs inhibit the reuptake of serotonin,
145
00:10:23.440 --> 00:10:26.320
or to put it another way, they keep nerve cells
146
00:10:26.360 --> 00:10:30.320
from reabsorbing serotonin in order to maintain high levels in
147
00:10:30.360 --> 00:10:35.000
the brain. This sounds a little bit like those tricyclic antidepressants,
148
00:10:35.039 --> 00:10:38.720
but these are different. For one thing, tricyclics mostly work
149
00:10:38.799 --> 00:10:44.440
on norepinephrin and SSRIs mostly work on serotonin. And SSRIs
150
00:10:44.519 --> 00:10:48.639
are a lot more precise than tricyclic antidepressants. They're better
151
00:10:48.679 --> 00:10:51.960
at targeting the receptors that are important, rather than just
152
00:10:52.159 --> 00:10:55.720
hitting receptors all over the body and causing unpleasant side effects.
153
00:10:56.279 --> 00:10:58.519
Prozac is one kind of ssri.
154
00:11:00.039 --> 00:11:03.639
Most of those drugs, and even many of the versions
155
00:11:03.639 --> 00:11:07.320
that are followed after that, really are drugs that either
156
00:11:07.399 --> 00:11:11.240
target ner epinephrinurse or at one and that is the
157
00:11:11.480 --> 00:11:15.039
large majority of the medications out there. There are a
158
00:11:15.120 --> 00:11:18.919
few other smaller classes that are beginning to develop that
159
00:11:19.080 --> 00:11:23.759
actually are targeting different neurotransmitter systems and different mechanisms of action.
160
00:11:25.000 --> 00:11:26.879
So do these drugs work?
161
00:11:27.600 --> 00:11:29.919
This is a little bit of a loaded question, because
162
00:11:30.120 --> 00:11:34.399
in fact they are quite effective. The medicines do tend
163
00:11:34.480 --> 00:11:40.840
to work very well. The struggle is that placebo also
164
00:11:40.919 --> 00:11:44.480
works fairly well too, in the treatment of depression, and
165
00:11:44.480 --> 00:11:45.919
it works fairly well in the treatment of a lot
166
00:11:45.960 --> 00:11:50.639
of different disorders, even outside of psychiatry. So I personally
167
00:11:50.759 --> 00:11:53.559
don't like the term placebo because I think at this
168
00:11:53.639 --> 00:11:57.679
point it is laden with a connotation of sort of
169
00:11:58.240 --> 00:12:00.559
shouldn't have an effect. It's sort of a trick or
170
00:12:00.639 --> 00:12:04.440
something where you know, giving that shouldn't have benefit. I
171
00:12:04.480 --> 00:12:07.200
think the term that is more appropriately used as a
172
00:12:07.279 --> 00:12:12.159
non specific effect. So we know that, for example, a diet,
173
00:12:12.480 --> 00:12:16.000
if you sawt somebody on a diet, besides the diet,
174
00:12:16.159 --> 00:12:18.000
they start to pay a lot more attention to what
175
00:12:18.039 --> 00:12:23.000
they're eating, they start to increase exercise, they start.
176
00:12:22.840 --> 00:12:25.080
To do a lot of other things.
177
00:12:25.720 --> 00:12:28.759
That is, in addition, it's non specific to the type
178
00:12:28.759 --> 00:12:31.840
of diet that you give. And it's very much like
179
00:12:31.879 --> 00:12:35.919
that with medications or any treatment. Once you start to
180
00:12:35.960 --> 00:12:38.679
get involved in the treatment, it's not just the pill
181
00:12:38.720 --> 00:12:42.639
you're taking, and even the pill itself has years of conditioning.
182
00:12:42.720 --> 00:12:45.039
So we learned that if we take a pill or
183
00:12:45.120 --> 00:12:48.720
headache goes away. So the next time we have a headache,
184
00:12:48.840 --> 00:12:52.279
even this the simple act of taking anything, we're conditioned
185
00:12:52.279 --> 00:12:54.000
to have that belief that our headache is going to work.
186
00:12:54.039 --> 00:12:56.440
So you become conditioned to certain things are going to work.
187
00:12:56.840 --> 00:12:59.200
So that's part of a placebole response, But there are
188
00:12:59.480 --> 00:13:02.799
many other parts of that placebo response that have big effects,
189
00:13:02.879 --> 00:13:05.279
like you start to pay more attention to your emotions,
190
00:13:05.360 --> 00:13:08.440
you start to think about things differently, and you start
191
00:13:08.480 --> 00:13:11.720
to see a therapist or a doctor, so somebody else
192
00:13:11.919 --> 00:13:14.440
that is now you can share your concerns and thoughts
193
00:13:14.440 --> 00:13:17.879
to it. So it's a lot more involved in taking
194
00:13:18.159 --> 00:13:21.759
a medicine or any fulm medical treatment than the simple
195
00:13:21.960 --> 00:13:25.200
specific effect of the drug or the surgery or whatever
196
00:13:25.200 --> 00:13:27.639
you're getting it. So it's all those non specific effects
197
00:13:27.879 --> 00:13:31.639
and they are incredibly palatful. The medicines work quite well
198
00:13:31.679 --> 00:13:33.799
if you would just look at people that took medicine
199
00:13:33.840 --> 00:13:36.519
and people that didn't take medicine. But it's called a
200
00:13:36.559 --> 00:13:38.919
wait less type approach where you look at people that
201
00:13:39.039 --> 00:13:42.639
started on treatment people that don't. Where it becomes more
202
00:13:42.679 --> 00:13:46.120
difficult to reliably show a difference is when you have
203
00:13:46.200 --> 00:13:49.279
a treatment used against the placebo because the non specific
204
00:13:49.360 --> 00:13:53.559
attacks are so large, you need large sample sizes to
205
00:13:53.720 --> 00:13:56.960
really show how much benefit the drug has over the
206
00:13:57.039 --> 00:14:00.679
non specific effects. The danger is that I really do
207
00:14:00.759 --> 00:14:03.679
try to make clear, is that you don't get the
208
00:14:03.759 --> 00:14:06.519
nonspecific effects unless you take the drug in many care,
209
00:14:06.600 --> 00:14:08.440
or unless you take the treatment, whether it's a drug,
210
00:14:08.440 --> 00:14:11.799
whether it's a talk therapy, whether it's whatever. You can't
211
00:14:11.919 --> 00:14:15.240
really extract one from the other so clearly, And that's
212
00:14:15.279 --> 00:14:16.960
where things get very complicated.
213
00:14:17.440 --> 00:14:20.080
Got it. So when someone just sees the headline that
214
00:14:20.799 --> 00:14:24.480
antide presents work about the same as placebo, there's a
215
00:14:24.519 --> 00:14:27.960
lot more going on there. It's much more complicated than
216
00:14:28.360 --> 00:14:30.639
you just think, like, oh, that just means it doesn't work.
217
00:14:30.679 --> 00:14:32.000
Like that's not what it means.
218
00:14:32.080 --> 00:14:36.519
Exactly, And that's where the there's a miscommunication or it
219
00:14:36.559 --> 00:14:40.399
could be misleading. And it's very important. And I don't
220
00:14:40.440 --> 00:14:43.320
think too many people spend nearly as much time as
221
00:14:43.360 --> 00:14:45.720
I do and others looking at this issue. So if
222
00:14:45.759 --> 00:14:48.720
you just hear that, I think it's a natural response
223
00:14:48.720 --> 00:14:51.360
to say, oh, well, if it doesn't work much better placebo,
224
00:14:51.399 --> 00:14:52.600
then it doesn't work very well.
225
00:14:52.639 --> 00:14:54.639
But that's not really what it.
226
00:14:54.639 --> 00:14:58.200
Means, but it does seem like with some drugs, I
227
00:14:58.200 --> 00:15:01.399
don't know, for heart conditions, it's like you give the
228
00:15:01.480 --> 00:15:04.919
drug and most people have about the same reaction. Maybe
229
00:15:04.919 --> 00:15:06.879
I'm oversimplifying, but I.
230
00:15:06.799 --> 00:15:09.200
Think you're oversimplifying much more than you think you are.
231
00:15:09.600 --> 00:15:14.279
Really well, yeah, I mean, I guess that's like the perception, right, yeah.
232
00:15:14.080 --> 00:15:18.039
And I think that's a misperception. There are relatively high
233
00:15:18.039 --> 00:15:23.120
placebo response rates for anti hypertensors. They're relatively high sham
234
00:15:23.159 --> 00:15:29.399
response rates to surgeries like orthopedic surgeries. The non specific
235
00:15:29.399 --> 00:15:34.399
effects go well beyond what we typically think of in depression.
236
00:15:35.240 --> 00:15:38.559
Even things like Parkinson's disease, which you wouldn't imagine would
237
00:15:38.600 --> 00:15:44.519
have big nonspecific effects as notorious or very large placebo effects.
238
00:15:45.360 --> 00:15:48.559
Doctor Santa Korus says that even the experience some people
239
00:15:48.639 --> 00:15:51.519
have with antidepressants where they need to try many different
240
00:15:51.600 --> 00:15:54.360
kinds before they find one that works for them, that's
241
00:15:54.440 --> 00:15:58.720
pretty similar to hypertension medications. People usually start on, say
242
00:15:58.799 --> 00:16:01.799
a diuretic that doesn't work, They'll try a beta blocker,
243
00:16:02.000 --> 00:16:02.759
and on and on.
244
00:16:03.399 --> 00:16:06.639
It's very common, especially in the treatment of hyperrotections. It
245
00:16:06.720 --> 00:16:09.000
is a good example of that. So the trumant of
246
00:16:09.039 --> 00:16:11.200
depression isn't so unique in that way.
247
00:16:11.919 --> 00:16:16.399
But antidepressants like these aren't the only options out there. Recently,
248
00:16:16.559 --> 00:16:20.080
research has demonstrated real promise for some drugs that I,
249
00:16:20.279 --> 00:16:23.759
for one, was told to stay away from in their class.
250
00:16:27.080 --> 00:16:30.759
You study a bunch of different therapies for depression, and
251
00:16:30.759 --> 00:16:33.519
one of those is ketamine. Like when I first heard
252
00:16:33.600 --> 00:16:35.960
that people were using ketamine to treat depression, I was like,
253
00:16:36.679 --> 00:16:39.840
how could that possibly work? Like that's like a street drug, right,
254
00:16:39.960 --> 00:16:40.799
how does that work?
255
00:16:41.360 --> 00:16:45.000
So ketamine was originally an anesthetic agent. It was a
256
00:16:45.039 --> 00:16:48.200
major breakthrough in the field of anesthesia, and you have
257
00:16:48.279 --> 00:16:49.879
to approve in nineteen.
258
00:16:49.679 --> 00:16:53.200
Seven, as you said, it's an anesthetic. It really gained
259
00:16:53.200 --> 00:16:54.639
a lot of prominence because it's.
260
00:16:54.480 --> 00:16:58.679
A relatively safe aesthetic that could be used in situations
261
00:16:58.679 --> 00:17:01.159
where you weren't able to monitor patients as closely, so
262
00:17:01.240 --> 00:17:04.359
in chill pass orles. It became very popu in third
263
00:17:04.359 --> 00:17:07.680
world countries. It's still a critical drug as the use
264
00:17:07.720 --> 00:17:10.599
of an anesthetic, and it's even in the US. It's
265
00:17:10.680 --> 00:17:14.119
use commonly in pediatric anesthesia or emergency rooms where you
266
00:17:14.160 --> 00:17:16.519
need a quick use of an anesthetic.
267
00:17:17.200 --> 00:17:21.279
If you're wondering why someone would use an anesthetic illegally, well,
268
00:17:21.400 --> 00:17:24.759
it's because ketamine works by putting people in a dissociative
269
00:17:24.799 --> 00:17:28.039
state that detaches them from any pain. You can see
270
00:17:28.079 --> 00:17:31.559
how that might be desirable outside of the operating room.
271
00:17:32.240 --> 00:17:35.279
And that's before you get to its hallucinogenic effects.
272
00:17:35.759 --> 00:17:37.680
Again, the lay person may look at this as kind
273
00:17:37.680 --> 00:17:40.359
of a street drug, but it has a fifteen year
274
00:17:40.519 --> 00:17:43.960
history of being considered a critical drug to the world
275
00:17:44.000 --> 00:17:47.039
by the World Health Organization. So this is a long
276
00:17:47.200 --> 00:17:50.119
medical history, but it still is a pretty unique story
277
00:17:50.160 --> 00:17:54.039
that this anesthetic drug would have antidepressing effects.
278
00:17:54.240 --> 00:17:58.000
Yeah, and so how why does it have antidepress and effects?
279
00:17:58.440 --> 00:18:01.119
So I would I could to do exactly why.
280
00:18:01.160 --> 00:18:03.720
I can tell you why we think it does, and
281
00:18:03.759 --> 00:18:06.240
I can tell you why it was initially testing.
282
00:18:06.759 --> 00:18:11.000
There was increasing evidence, really towards.
283
00:18:10.640 --> 00:18:12.839
The end of the last millennium, in the nineteen nineties
284
00:18:12.960 --> 00:18:18.160
or so, that the neurobiology of depression was much more
285
00:18:18.200 --> 00:18:21.440
involved than that idea of the chemical imbalance or that
286
00:18:21.519 --> 00:18:24.839
there was low serotonin, low Europe and effort levels, which
287
00:18:24.880 --> 00:18:28.400
is really where the thinking was in the nineteen eighties
288
00:18:28.400 --> 00:18:31.680
and nineties, and we started to realize that the brain
289
00:18:31.799 --> 00:18:35.039
was much more complex and there was many other neurotransmitter
290
00:18:35.079 --> 00:18:38.559
systems that were involved, and also that the plasticity of
291
00:18:38.559 --> 00:18:40.880
the brain, the way the brain can actually change and
292
00:18:40.960 --> 00:18:43.480
adapt to different environments and.
293
00:18:43.599 --> 00:18:47.319
Different evensfe was very important.
294
00:18:48.119 --> 00:18:51.319
And they became increasing evidence that parts of the brain
295
00:18:51.359 --> 00:18:55.799
that were predominantly using glutamate, which is the major neurotransmitter
296
00:18:55.839 --> 00:18:59.000
in the brain. So about eighty percent of all your neurons,
297
00:18:59.039 --> 00:19:02.680
the cells in your brain use glutamate as its primary communication.
298
00:19:02.920 --> 00:19:05.599
You know, it's primary or a transmitter. So it began
299
00:19:05.680 --> 00:19:08.960
increasing that glutimate and gabba, which is a major in emiture.
300
00:19:09.640 --> 00:19:12.359
That those two charatrisms probably have pots to do with
301
00:19:12.400 --> 00:19:15.400
the path of the physiology of depression. As we said,
302
00:19:15.480 --> 00:19:18.839
whatever depression is that broader sense of and the ability
303
00:19:18.880 --> 00:19:20.240
to modulate plasticity.
304
00:19:21.440 --> 00:19:24.480
One thing we've learned is that stress and trauma can
305
00:19:24.519 --> 00:19:28.440
actually change the structure of the brain. Animal studies have
306
00:19:28.519 --> 00:19:31.960
found that chronic stress can degrade neurons and parts of
307
00:19:32.000 --> 00:19:36.519
the brain responsible for learning, memory, and executive function. Those
308
00:19:36.519 --> 00:19:40.400
areas are also smaller with fewer connections in patients with depression.
309
00:19:41.160 --> 00:19:43.519
Some of that is probably because of problems with the
310
00:19:43.559 --> 00:19:46.119
neurons that deal with glutamate and GABBA.
311
00:19:47.240 --> 00:19:52.319
So is at that time some of my colleagues had, Yeah,
312
00:19:52.400 --> 00:19:57.599
John Crystal Brobern and others had the idea that ketamine
313
00:19:57.720 --> 00:20:01.960
being a drug that specifically targets the glutamate system what's
314
00:20:02.039 --> 00:20:05.200
called the NMBA receptor which binds to glutamate.
315
00:20:05.559 --> 00:20:07.000
The fact that they knew that there was this.
316
00:20:07.079 --> 00:20:11.039
Drug out there that had been used safely for decades
317
00:20:12.000 --> 00:20:16.480
had a dramatic effect on this neurotransmitter system. They really
318
00:20:16.680 --> 00:20:19.039
followed a pretty simple apothesis that just may have an
319
00:20:19.039 --> 00:20:22.759
effect on people with depression, and that was the original
320
00:20:22.799 --> 00:20:25.240
study done in the late nineteen nineties published in two
321
00:20:25.279 --> 00:20:28.240
thousand that shows this very rapid on set of effect,
322
00:20:28.720 --> 00:20:32.000
which really was a surprise to everybody. I mean, everybody
323
00:20:32.200 --> 00:20:35.599
was interested in it, but I don't think anybody in
324
00:20:35.640 --> 00:20:39.559
New tact I'm sure none of those primary office, because
325
00:20:39.599 --> 00:20:42.359
they make it very clear thought that they would see
326
00:20:42.359 --> 00:20:45.799
this rapid improvement within hours that would be sustained for
327
00:20:45.880 --> 00:20:48.279
at least days following a treatment.
328
00:20:48.839 --> 00:20:49.279
Wow.
329
00:20:50.400 --> 00:20:53.160
But because it's an anesthetic, does it I mean, does
330
00:20:53.200 --> 00:20:55.240
it make it so you have you can't do everyday
331
00:20:55.240 --> 00:20:56.519
activities when you're using it.
332
00:20:57.480 --> 00:21:00.960
So that's the other extremely interest in resting an important
333
00:21:00.960 --> 00:21:04.599
point to make with ketemine, especially the early studies with ketymine.
334
00:21:04.839 --> 00:21:08.200
So it's not giving at the level that you would
335
00:21:08.440 --> 00:21:11.480
use for anesthesia, but it is still given at a
336
00:21:11.519 --> 00:21:15.839
level that would dramatically impair your cognition. So you at
337
00:21:15.880 --> 00:21:20.920
the dose that is being used original studies, yes, you
338
00:21:21.000 --> 00:21:24.039
do need to be monitored closely and you're not going
339
00:21:24.119 --> 00:21:27.559
to be going about your normal daily activities. But unlike
340
00:21:27.640 --> 00:21:29.799
most other antidepressants where you have to take it all
341
00:21:29.839 --> 00:21:33.200
the time, this was something that you take and typically
342
00:21:33.200 --> 00:21:35.960
an infusion originally was lasting for about forty minutes and
343
00:21:35.960 --> 00:21:38.480
then you stop it. Ketymine is metabolized very quick thing
344
00:21:38.519 --> 00:21:41.160
about it, so it disappears out of your system pretty rapidly.
345
00:21:42.240 --> 00:21:45.920
But then the antidepressant effect actually build over time after
346
00:21:46.000 --> 00:21:49.359
you stop it, so the majority of the large majority
347
00:21:49.400 --> 00:21:51.599
of that time you're not on the drought that you
348
00:21:51.680 --> 00:21:56.599
actually get to benefit, which is again a novel approach
349
00:21:56.799 --> 00:22:00.000
and really a completely new finding within the field.
350
00:22:01.279 --> 00:22:04.640
So is this becoming more widespread? Are more people using
351
00:22:04.680 --> 00:22:07.039
this in just like therapy settings.
352
00:22:07.319 --> 00:22:14.359
So it is growing dramatically in twenty nineteen, the FDA
353
00:22:14.599 --> 00:22:18.400
has approved a version of kenemine, which is actually esketemine,
354
00:22:18.400 --> 00:22:22.400
which is really just half of the natural substance that
355
00:22:22.599 --> 00:22:25.920
carves in what we were seen a ketemine. It's just
356
00:22:26.200 --> 00:22:29.599
half of what we would normally find in regular academy.
357
00:22:30.079 --> 00:22:33.720
It was approved for the treatment of patients with treatment
358
00:22:33.759 --> 00:22:37.720
resistant depression, and then more recently in twenty twenty, was
359
00:22:37.720 --> 00:22:44.119
actually approved for patients with depression who also have suicidal ideations.
360
00:22:46.599 --> 00:22:50.400
Even though it wasn't FDA approved until twenty nineteen, clinics
361
00:22:50.400 --> 00:22:53.839
had been using ketamine to treat depression since twenty twelve,
362
00:22:54.279 --> 00:22:57.880
and that wasn't illegal. Instead, it was just yet another
363
00:22:57.920 --> 00:23:00.279
benefit of a drug that had been used for something
364
00:23:00.319 --> 00:23:05.720
else for decades. See these clinics just used ketamine off label,
365
00:23:06.079 --> 00:23:09.440
the way doctors commonly prescribe an anti seizure medication for
366
00:23:09.599 --> 00:23:13.799
bipolar disorder, or how some musicians I know get beta blockers,
367
00:23:13.880 --> 00:23:17.799
a type of blood pressure medication for stage fright. It's
368
00:23:17.839 --> 00:23:22.240
a thing. Using drugs off label is legal. It just
369
00:23:22.279 --> 00:23:25.359
carries some extra risks since the FDA hasn't determined that
370
00:23:25.400 --> 00:23:28.519
the drug is safe and effective for that off label use.
371
00:23:29.240 --> 00:23:32.440
But that was then, so it is now n FDA
372
00:23:32.480 --> 00:23:37.680
approved indicated medicine for depression, but it's not a medicine
373
00:23:37.680 --> 00:23:40.799
for everybody, definitely, and it is still a medicine that
374
00:23:40.960 --> 00:23:46.160
requires relative and close monitoring, especially in the way that
375
00:23:46.200 --> 00:23:49.319
it is being given as of today and according to
376
00:23:49.359 --> 00:23:50.200
the SDA.
377
00:23:50.160 --> 00:23:51.480
Regulations and guidance.
378
00:23:51.960 --> 00:23:54.559
We talked a lot about kidamine as a game changer,
379
00:23:54.599 --> 00:23:57.160
which I really think it was because we were locked
380
00:23:57.160 --> 00:24:02.759
into about fifteen years of thinking very specifically about how
381
00:24:02.799 --> 00:24:05.839
to treat depression and either would talk therapies or with
382
00:24:06.400 --> 00:24:11.079
oral antipress medications that primarily targeted serotomin Europe and efferent.
383
00:24:11.359 --> 00:24:12.960
I mean, there was always the treatments like.
384
00:24:12.960 --> 00:24:17.839
ECT that actually predate electro convulsive therapy, that predate even
385
00:24:17.680 --> 00:24:22.880
the oral medications. But since that time of ketamine, there's
386
00:24:22.960 --> 00:24:28.079
really been an explosion of alternatives treatments. Besides the regular
387
00:24:28.440 --> 00:24:35.119
oral antidepressants and talk therapies, there's neurostimulatory therapies like transcrinomagnetic
388
00:24:35.160 --> 00:24:41.640
stimulation that has really become quite popular. There's nerve simulation,
389
00:24:42.200 --> 00:24:45.839
there's even studies with deep brain stimulation that are going on.
390
00:24:46.319 --> 00:24:49.640
But then in terms of other pharmacologic treatments. There are
391
00:24:49.680 --> 00:24:53.279
several new lines of interest, but the one that I
392
00:24:53.319 --> 00:24:55.799
think recently has gained a lot of attention and it
393
00:24:55.880 --> 00:24:58.839
is extremely interesting to many people, is the idea of
394
00:24:58.920 --> 00:25:02.759
using drugs such as psilocybin, drugs that fall into this
395
00:25:02.920 --> 00:25:05.839
general psychedelic category of drugs.
396
00:25:06.200 --> 00:25:09.680
Yep Ketamine isn't the only dark horse in this race.
397
00:25:10.240 --> 00:25:14.160
There's also psilocybin, the active ingredient in what some call
398
00:25:15.279 --> 00:25:21.400
magic mushrooms. Yeah, how does psilocybin help with depression? Do
399
00:25:21.480 --> 00:25:21.920
we know that?
400
00:25:23.000 --> 00:25:23.079
So?
401
00:25:23.440 --> 00:25:25.559
First of all, I don't think we can say we
402
00:25:25.640 --> 00:25:27.000
know that it does help with depression.
403
00:25:27.079 --> 00:25:29.960
It we're still doing those studies. So there are early
404
00:25:30.079 --> 00:25:31.240
reports that.
405
00:25:31.240 --> 00:25:35.000
Look very promising, but I always do emphasize these are
406
00:25:35.000 --> 00:25:39.680
early reports and we really still have to demonstrate that
407
00:25:39.759 --> 00:25:43.480
this isn't effective treatment and depression, and that really is
408
00:25:43.519 --> 00:25:45.960
the first step, and that I think many of us
409
00:25:45.960 --> 00:25:52.200
are working very hard to determine what the actual efficacy
410
00:25:52.319 --> 00:25:55.400
and obviously the safety of this treatment would be true depression.
411
00:25:56.240 --> 00:25:58.680
In terms of if it does work, how it works,
412
00:25:58.880 --> 00:26:03.559
there are many different hypotheses. I think sort of the
413
00:26:03.640 --> 00:26:06.440
mainstreamline of thinking about it is that it may work
414
00:26:06.559 --> 00:26:09.200
very similar to ketamine. So we think what ketamine, we do,
415
00:26:09.400 --> 00:26:14.319
and quite possibly these psychedelic medications I mentioned before, this
416
00:26:14.400 --> 00:26:18.680
idea of neuroplasticity actually altering the way the brain cells
417
00:26:18.720 --> 00:26:22.279
communicate with each other, and actually even structurally altering the
418
00:26:22.279 --> 00:26:24.880
way the brain cells communicate with each other and how
419
00:26:24.880 --> 00:26:29.039
they adapt to novel environments and novel events. And it
420
00:26:29.079 --> 00:26:32.640
looks like just as ketamine can have these rapid effects
421
00:26:32.720 --> 00:26:35.640
on the neuron's ability to communicate with each other, it
422
00:26:35.640 --> 00:26:38.839
looks like some of these psychedelic type methicines like psilocybin,
423
00:26:38.960 --> 00:26:43.039
may have very similar effects. Now, obviously these are still
424
00:26:43.119 --> 00:26:46.519
hypotheses that need to be tested, and there are other hypotheses.
425
00:26:46.920 --> 00:26:47.839
These may have.
426
00:26:48.000 --> 00:26:51.720
More more effects that go well beyond the simple brain
427
00:26:51.799 --> 00:26:55.759
chemistry or even the neuroplasticity, in terms of some of
428
00:26:55.759 --> 00:27:00.440
the spiritual side of these drugs and the other they
429
00:27:00.440 --> 00:27:05.039
may have in social relatedness. So there are many different hypotheses,
430
00:27:05.079 --> 00:27:07.960
so we really don't know how any of them work
431
00:27:08.039 --> 00:27:09.839
for sure, but we are starting to learn.
432
00:27:09.839 --> 00:27:10.319
Quite a bit.
433
00:27:10.759 --> 00:27:14.039
Yeah, one thing I've heard is that an idea might
434
00:27:14.079 --> 00:27:17.720
be that it gives you more of a sense of
435
00:27:17.880 --> 00:27:20.160
oneness with the world and takes you out of your
436
00:27:20.200 --> 00:27:23.200
own like focusing in on your own self. And because
437
00:27:23.240 --> 00:27:26.680
depression is there's a lot of like looking inward that
438
00:27:26.799 --> 00:27:27.759
it helps that way.
439
00:27:28.720 --> 00:27:31.359
So that is definitely one of the hypotheses that have
440
00:27:31.480 --> 00:27:35.599
been proposed, and there's a fair amount of research looking
441
00:27:35.640 --> 00:27:38.640
into that. I don't think any of these mechanisms are
442
00:27:38.799 --> 00:27:42.079
necessarily exclusive. I think the likelihood is that there's some
443
00:27:42.279 --> 00:27:46.160
component of all of these in generating the bashits that
444
00:27:46.240 --> 00:27:46.759
are seen.
445
00:27:47.319 --> 00:27:48.799
But I do say, yeah, the first.
446
00:27:48.599 --> 00:27:51.880
Part is we'd have to demonstrate to a high degree
447
00:27:51.880 --> 00:27:54.519
of certainty that these are effective and safe treatments.
448
00:27:54.519 --> 00:27:55.799
We're still at that stage.
449
00:27:55.839 --> 00:28:01.519
So here's what I didn't realize about depression. Just because
450
00:28:01.519 --> 00:28:04.480
we don't fully understand how it works in the brain
451
00:28:05.079 --> 00:28:08.519
doesn't mean we can't find better ways to give people relief.
452
00:28:09.160 --> 00:28:11.400
You don't have to know how something works to know
453
00:28:11.519 --> 00:28:15.640
that it does work. Millions of people suffer from depression,
454
00:28:16.200 --> 00:28:19.920
and researchers like doctor Santa Kora are constantly making progress
455
00:28:19.960 --> 00:28:25.079
toward more effective treatments and maybe someday we'll know how
456
00:28:25.119 --> 00:28:35.839
they work. So well, thanks for listening. I'm back in
457
00:28:35.880 --> 00:28:39.119
twenty twenty three to read the credits. Thanks a ton
458
00:28:39.200 --> 00:28:41.400
to Girard Santa Kora for talking to me back in
459
00:28:41.400 --> 00:28:44.400
twenty twenty one. He's since done a lot more work
460
00:28:44.440 --> 00:28:47.319
on ketamine's role in treating depression, and all include links
461
00:28:47.359 --> 00:28:49.640
to some of that work in the citations on the website.
462
00:28:49.880 --> 00:28:52.279
And if you'd like to hear a really excellent podcast
463
00:28:52.279 --> 00:28:56.039
episode all about ketamine which also features doctor Santa Kora,
464
00:28:56.240 --> 00:28:59.240
definitely check out the Science Versus episode about it from
465
00:28:59.279 --> 00:29:01.480
April of this year. All include a link in the
466
00:29:01.519 --> 00:29:04.759
show notes. Taboo Science is written and produced by me
467
00:29:04.920 --> 00:29:08.519
Ashley Hamer. The theme was by Danny Lapotka of DLC Music.
468
00:29:08.839 --> 00:29:12.160
Episode music is from Epidemic Sound. If you need music
469
00:29:12.160 --> 00:29:14.400
for a project, just use my referral link in the
470
00:29:14.400 --> 00:29:17.480
show notes and it'll help out the show. We've got
471
00:29:17.519 --> 00:29:20.640
some really fascinating new topics coming in the next couple months.
472
00:29:20.759 --> 00:29:24.000
I for one am really excited, so hit that subscribe
473
00:29:24.039 --> 00:29:26.359
button to make sure you don't miss an episode and
474
00:29:26.519 --> 00:29:32.559
tune in next time. I won't tell anyone
