Andrew Huberman
June 4, 2026
Psychedelics, TMS, and Brain Rewiring for Depression Treatment
TL;DR
Dr. Nolan Williams discusses emerging neurostimulation and psychedelic therapies that can rapidly treat severe depression and PTSD by rewiring specific brain circuits rather than correcting chemical imbalances.
Key Takeaways
- 1Depression is the most disabling condition worldwide and acts as a major risk factor for coronary artery disease, yet current treatments are limited in efficacy and speed
- 2Transcranial magnetic stimulation (TMS) works by activating the dorsolateral prefrontal cortex, which regulates deeper emotional regions—essentially restoring 'governance' in the brain similar to how therapy works but exogenously
- 3Stanford accelerated neurostimulation therapy (SANT) compresses 6 weeks of TMS into 5 intense days using spacing learning theory, achieving 60–90% remission rates within 1–5 days with minimal side effects
- 4Psychedelics like psilocybin and MDMA produce lasting therapeutic effects (weeks to years) by altering connectivity between the default mode network and self-referential brain regions, allowing people to reprocess trauma with detachment and empathy
- 5MDMA-assisted therapy resolves PTSD in approximately two-thirds of patients in just one to two clinical sessions, substantially outperforming conventional treatments like ketamine which requires repeated infusions
- 6Ibogaine, a long-acting psychedelic (24–36 hours), shows promise for treating moral injury in military personnel by enabling self-forgiveness through life review experiences
- 7'Psychiatry 3.0' shifts the paradigm from chemical imbalance theory to circuit-level correction, fundamentally changing how patients understand their condition from 'chronically broken' to 'fixable'
Notable Quotes
“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.”
— Dr. Nolan Williams
“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 restore order to the game.”
— Dr. Nolan Williams
“These drugs can't be recreational drugs. They really shouldn't be recreational drugs because they're really too powerful to be used in the context of recreation.”
— Dr. Nolan Williams
“Psychiatry 3.0 is saying something different. TMS works and there's no serotonin coming in or out of the brain. We're simply turning these brain regions on and we're focused on the circuitry.”
— Dr. Nolan Williams
Chapters
1. Depression as a Global Health Crisis
Dr. Williams establishes depression as the world's most disabling condition and the fourth major risk factor for coronary artery disease, alongside hypertension, high cholesterol, and diabetes. He emphasizes the gap between the severity of depression and the limited therapeutic tools available.
2. Brain-Heart Connections and Transcranial Magnetic Stimulation (TMS)
TMS uses magnetic pulses to induce electrical currents in the dorsolateral prefrontal cortex (the 'governor' of mood), which then regulates deeper emotional regions including the anterior cingulate, insula, and amygdala, ultimately affecting heart rate deceleration—demonstrating a direct physical mind-body connection.
3. Stanford Accelerated Neurostimulation Therapy (SANT)
A revolutionary protocol condensing 6 weeks of standard TMS into 5 intensive days using spacing learning theory (stimulation every hour). Achieves 60–90% full remission rates in 1–5 days, with some patients maintaining remission for years without side effects.
4. SSRIs and the Evolution of Psychiatric Theory
SSRIs work for depression and OCD but take weeks due to brain plasticity effects, not immediate serotonin elevation. The 'chemical imbalance' theory is incorrect; psychiatry is shifting from 'missing chemical' (2.0) to circuit-level understanding (3.0), emphasizing that psychiatric conditions are recoverable.
5. Psilocybin for Depression and Trauma
Psilocybin shows 50–67% improvement rates in open-label depression studies and 33% in blinded trials. Brain imaging reveals decreased overall activity but increased global connectivity. It causes the same subgenial anterior cingulate–default mode network disconnection as effective TMS, suggesting convergent mechanisms.
6. MDMA-Assisted Therapy for PTSD
MDMA in clinical sessions (150–175 mg) administered one to two times results in clinically significant PTSD relief for approximately two-thirds of patients, with effects lasting for years—substantially exceeding outcomes from ketamine (lasting ~1.5 weeks) or standard psychotherapy.
7. Ibogaine: Life Review and Moral Injury Recovery
Ibogaine, a 24–36 hour psychedelic from the iboga tree root bark, induces a life-review experience enabling emotional reprocessing with detached empathy. Early research with Navy SEALs shows promise for treating moral injury (guilt over inadvertent civilian harm), with patients reporting self-forgiveness.
8. Ayahuasca: Plant Medicine and Behavioral Change
Ayahuasca, a two-plant Amazonian combination containing DMT and a reversible MAOI, is used as a sacrament in South American religions. A Brazilian prison study found it reduced recidivism rates significantly, raising questions about its potential role in addressing criminal behavior and moral decision-making.
9. Neuroimaging Convergence and the Psychedelic Hypothesis
Psilocybin, ketamine, and TMS all produce changes in the same brain circuits (subgenial anterior cingulate–default mode network connectivity), suggesting a converging therapeutic mechanism. This supports the hypothesis that psychedelics could be psychiatric breakthroughs if administered under strict medical supervision.
10. Medical Framework and Ethical Deployment
Dr. Williams emphasizes that psychedelics are too powerful for recreational use and require strict medical supervision comparable to SSRIs. He advocates for pragmatic, evidence-based deployment while rejecting 1960s counterculture frameworks, positioning modern psychedelic research as rigorous clinical science.
Key People & Entities
- Dr. Nolan Williams
- Psychiatrist and neuroscientist at Stanford; developer of Stanford Accelerated Neurostimulation Therapy; researcher on TMS, psychedelics, and novel treatments for treatment-resistant depression and PTSD
- Andrew Huberman
- Host of Huberman Lab; professor of neurobiology and ophthalmology at Stanford School of Medicine
- David Nutting
- Neuroscientist; pioneering researcher on neuroimaging of psychedelic effects
- Robin Carhart-Harris
- Neuroscientist; leading researcher on brain imaging and mechanisms of psilocybin and other psychedelics
- Martin Angermeyer
- Researcher in the Netherlands; contributed work on brain-heart connections and TMS effects
- Casey Halpern
- Researcher; developer of deep brain stimulation techniques for psychiatric conditions
- MAPS (Multidisciplinary Association for Psychedelic Studies)
- Organization conducting FDA-tracked clinical trials of MDMA-assisted therapy for PTSD
Glossary
- Dorsolateral prefrontal cortex (DLPFC)
- The 'governor' region of the brain responsible for executive control, decision-making, and mood regulation; overrides activity in deeper emotional regions like the amygdala and anterior cingulate.
- Transcranial magnetic stimulation (TMS)
- A non-invasive brain stimulation technique using magnetic pulses to induce electrical currents in cortical neurons, activating specific brain regions to treat psychiatric conditions.
- Spacing learning theory
- A cognitive principle that optimal learning occurs when information is reviewed at spaced intervals (approximately every 1–1.5 hours), maximizing retention and consolidation.
- Default mode network (DMN)
- A large-scale brain network involved in self-referential thinking, mind-wandering, and negative rumination; overconnected in depression and dysregulated by psychedelics and TMS.
- Anterior cingulate cortex (ACC)
- A brain region involved in conflict detection, emotional processing, and error monitoring; hyperactive in depression and a target of therapeutic interventions.
- Selective serotonin reuptake inhibitors (SSRIs)
- A class of antidepressant medications that increase available serotonin in the brain; effective for depression, OCD, and anxiety but require weeks to work and don't correct a serotonin deficiency.
- Psilocybin
- A naturally occurring psychedelic compound from psilocybe mushrooms; rapidly produces antidepressant and anti-trauma effects by altering brain connectivity.
- MDMA (3,4-methylenedioxymethamphetamine)
- A psychoactive compound used in clinical PTSD trials at doses of 150–175 mg; increases empathy and emotional openness, facilitating trauma reprocessing in therapeutic settings.
- Ibogaine
- A naturally occurring alkaloid from the iboga tree root bark; induces a 24–36 hour life-review experience enabling emotional reprocessing with detached empathy.
- Ayahuasca
- A two-plant Amazonian brew combining DMT (from one plant) with a reversible monoamine oxidase inhibitor (from another); used ceremonially and explored for depression and behavioral change.