Huberman Lab
Essentials: Psychedelics & Neurostimulation for Brain Rewiring | Dr. Nolan Williams
04 Jun 2026
Transcript generated automatically by AI and may contain errors.
Chapter 1: What are the latest treatments for depression and PTSD?
Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
Chapter 2: How does transcranial magnetic stimulation (TMS) work for depression?
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. But before we get into that discussion, I want to ask you about depression, broadly speaking.
I heard you say in a wonderful talk that you gave that depression is 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.
Chapter 3: What role do SSRIs play in treating depression?
Depression is the most disabling condition worldwide. What's interesting about depression is it's both a risk factor for other illnesses and it makes other medical and psychiatric illnesses worse, right? So recently, the American Heart Association added depression as the fourth major risk factor for coronary artery disease, right? So alongside depression,
The risk factors that we know, hypertension, high blood pressure, hyperlipidemia, high cholesterol and diabetes, high blood sugar, those three have been on the list for a long time and depression end up being added to the list as the fourth one. A lot of what we're doing in the lab actually is measuring kind of brain heart connections and we can actually with
Chapter 4: How do psychedelics like psilocybin and MDMA impact mental health?
transcranial magnetic stimulation, a form of brain stimulation, we can actually decelerate the heart rate. We can capture that heart rate deceleration over the mood regulatory regions. And so actually a direct probe of that connection.
Chapter 5: What insights do clinical trials provide about MDMA and PTSD?
We've been very interested in a very particular clinical set of problems around the most severe and the most high acuity settings that folks with depression end up being in. And that's in emergency situations. settings where they go into inpatient units. The field really hasn't developed a way of, you know, consistently being able to treat that problem.
And folks end up getting the same standard oral antidepressants that they've been getting outpatient.
Chapter 6: How does ibogaine facilitate empathy and behavior change?
And I came to this because, 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 brain-based problems and really wanted to emulate that in psychiatry and find ways to develop and engineer new brain-based solutions.
Many people out there probably think of the relationship between the heart and the mind as kind of woo or kind of a soft biology, but here you're talking about an actual physical connection. What area of the brain is it?
The first place where the stimulation goes is called the dorsolateral prefrontal cortex. It's kind of the sense of control, kind of governor of the brain.
Chapter 7: What are the therapeutic potentials of ayahuasca?
And then what we know is that when you use a magnet, kind of what we call Faraday's Law, this idea of using a magnetic pulse to induce an electrical current in electrically conducting substances, so in this case, brain tissue, but not skull or 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 dorsolateral prefrontal. And if you do that in the actual scanner, which we can do, you can see that that distributes down into the anterior cingulate, in the insula, in the amygdala, and ultimately the tract goes into something called the nucleus tractus solitarius, and ultimately into the vagus nerve, into the heart. So the heart...
very consistently seems to be the end organ of the dorsolateral prefrontal cortex. If you do that over visual cortex, you don't get that, or motor cortex, you don't get any of those findings.
Chapter 8: What is the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)?
It's really specific to this kind of control region of the brain. Yeah, it seems to, you know, it's our work, other folks work, Martin Arns in Europe, 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 therapist told me that I wasn't trying hard enough in therapy. These are, you know, moderate to pretty severe depressed patients.
And as soon as we get them well with the TMS approaches, kind of rapid five-day approach, then 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 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. 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 the player telling the coach what to do. And 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-volitional, that's being kind of generated out of this conflict detection system, the cingulate. In depression, it looks like the left dorsolateral 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 dorsolateral over the cingulate area, and that is correlated with treatment improvement. So the degree in which you can re-time, re-regulate in time the left dorsolateral over the cingulate, the more of an antidepressant 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 we had a couple of folks, 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 five-day block. By Wednesday, they're like totally zeroed out on the depression scales, you know, even
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