Essentials: Psychedelics & Neurostimulation for Brain Rewiring | Dr. Nolan Williams

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Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable [music] science-based tools for mental health, physical health, and performance. I’m Andrew Huberman and I’m a professor of neurobiology and opthalmology at Stanford School of Medicine. And now for my discussion with Dr. Nolan Williams. Thanks for joining today.

I’m really excited to have this conversation. I have a lot of questions about different compounds, psychedelics in particular. >> Yeah. >> But before we get into that discussion, I want to ask you about depression, broadly speaking. >> Sure.

I heard you say in a wonderful talk that you gave that depression perhaps the most debilitating condition worldwide. Yet in contrast to other medical conditions like cancer, we actually have a fairly limited number of tools to approach depression. And yet the number of tools and the potency of those tools is growing. >> Depression is u the most disabling condition worldwide. Um what’s interesting about depression is it’s both a risk factor um for other illnesses and it makes other medical and psychiatric illnesses worse.

Right? So recently the American Heart Association added depression as the fourth uh major risk factor for coronary artery disease. Right? So alongside the the risk factors that we know hypertension, high blood pressure, hyper lipidmia, high cholesterol and diabetes, you know, high blood sugar, those three have been on the list for a long time and depression end up, you know, being added to the list as the fourth one. A lot of what we’re doing in the lab actually is um is measuring kind of brain heart connections and we can actually with transcranial magnetic stimulation a form of brain stimulation we can actually decelerate the heart rate we can capture that heart rate deceleration um over the mood regulatory regions and so actually a direct probe of that connection.

We’ve been very interested in a very particular um clinical set of problems around the the most severe and the most high acuity settings that folks with depression end up being in and that’s in you know emergency settings where they go into inpatient units. the field really hasn’t developed a way of um you know consistently being able to treat that problem and folks end up getting the same standard oral anti-depressants that they’ve been getting outpatient and and I came to this because I’ve you know dual trained as a neurologist and psychiatrist went back and forth between neurology and psychiatry saw that in neurology we have all of these ways of treating acute brainbased problems and really wanted to emulate that in psychiatry and find ways to develop and engineer new, you know, brainbased solutions. >> Many people out there probably think of the relationship between the the heart and the mind as kind of woo or kind of a a soft biology. But here you’re talking about an actual physical connection. >> Y what area of the brain is it?

You know, the first place where the stimulation goes is called the dorsalateral prefrontal cortex. It’s kind of the sense of control kind of governor of the brain. And then it’ll and then what we know is that when you use a magnet kind of what we call Faraday’s law this idea of um using a magnetic pulse to induce uh an electrical current in electrically conducting substances. So in this case brain tissue but not skull or sk sc scalp or any of that or hair you avoid all that just the brain tissue. Then you have a direct depolarization of cortical neurons, you know, the surface of the brain’s neurons in this dorsal prefrontal.

And if you do that in the actual scanner, which we can do, you can see that that distributes down into the anterior singulate in the insula and the amydala and ultimately the tract goes into something called the nucleus tract of solitarius and ultimately into the vagus nerve into the heart. So the the heart uh very consistently seems to be the end organ of the uh dorsal prefrontal cortex and if you do that over visual cortex you don’t get that or motor cortex you don’t get any of those findings it’s really specific to this kind of control region of the brain and so yeah it seems to you know it’s our work other other folks work Martin ARS in um in in Europe uh the Netherlands work showing the same connections I think it’s been replicated like four or five times where I think TMS is really interesting. Actually, we had a lot of patients who’ve told me like my my therapist told me that I wasn’t trying hard enough in therapy. [snorts] These are, you know, moderate to pretty severe depressed patients. And as soon as we get them well with with the TMS approaches, you know, kind of rapid, you know, 5day approach, and the next week we come in and see them and they’ll say, you know what I did all weekend is I looked at my therapy books and now I can understand it.

And so, you know, I actually see TMS as a way of having kind of exogenous sorts of cognitive functions that in milder forms of depression, we can pull off with psychotherapy. You know, this idea of being able to kind of turn that prefrontal cortex on and have it govern these deeper regions. In depression, the deeper regions govern the prefrontal cortex. In one case, it’s like the coach telling the player what to do and in the other case it’s like a player telling the coach what to do and you you restore order to the game. >> You restore order to the game and what it looks like is depression is a bunch of kind of spontaneous content that’s semi valitional that’s being kind of generated out of this conflict um detection system.

the singulate. In depression, it looks like the left dorsal lateral does not sufficiently clamp down on it. And what therapy appears to do is to kind of restore that. What we see with TMS over that region is that we just exogenously do the same sort of thing. We restore the governance of the left dorsal lateral over the singulate area and that is correlated with treatment improvement.

So the degree in which you can re- time or reeregulate in time the left dorsal lateral over the singulate, the more of an anti-depressant effect you have. TMS is almost like exercise for the brain, right? You’re kind of exercising this region over and over again with a physiologically relevant signal and kind of turning that system on. And what’s interesting for this show is, you know, we had a couple of folks um you know, probably five or six folks that have actually told me this where if they remit early enough in the week, we have this very dense stimulation approach where we can stimulate people really rapidly over a 5day block. By Wednesday, they’re like totally zero down on the depression scales, you know, even better than most people walking around, like really no anxiety, no no depression or anything.

By Thursday, the first guy that that told me this, he came in and he said, “You know, I was driving back to my hotel and I decided to go to the beach and I just sat there and I was totally present in the present moment for an hour. ” And he’s like, “I read about this in my mindfulness books, but I experienced it last night and I’ve never experienced anything like this before. ” And I was like, “hm, that’s interesting, but kind of wasn’t sure. ” And then and then I didn’t tell any, you know, obviously any more patients about that. And then about five over the last couple of years when they get they were mid early in the week by the end of the week they’re like going to the beach and they’re like totally having a what people describe as a pretty mindful present moment sort of experience which is really interesting you know what that is.

I mean, I don’t have full-on scientific data to tell you, but it it’s just it’s a it’s an interesting anecdote, right, that that folks when you push them through thi