October 10, 2022 • 2hr 44min

Dr. Nolan Williams: Psychedelics & Neurostimulation for Brain Rewiring

Huberman Lab

In this episode, Dr. Andrew Huberman interviews Dr. Nolan Williams, a psychiatrist and professor at Stanford School of Medicine who specializes in using brain stimulation and psychedelic therapies to treat depression and other psychiatric disorders. They discuss the neurocircuitry underlying depression, various treatment approaches including transcranial magnetic stimulation (TMS) and psychedelics, and Dr. Williams' work developing rapid TMS protocols for depression.

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Key Takeaways

Depression is the most disabling condition worldwide and is both a risk factor for other illnesses and makes other medical/psychiatric illnesses worse
The left dorsolateral prefrontal cortex (DLPFC) is connected to heart rate regulation and mood. Stimulating this area with TMS can decelerate heart rate and improve depressive symptoms
Depression involves dysregulation of brain circuits, not just chemical imbalances. Treatments like TMS and psychedelics may work by recalibrating these circuits
Psychedelics like psilocybin, MDMA, and ibogaine show promise for treating depression, PTSD, and other disorders when used in controlled clinical settings
Cannabis has both potential benefits and risks. High-THC cannabis may increase psychosis risk, while CBD shows anti-psychotic and anti-epileptic effects
Sleep deprivation can temporarily improve depression symptoms, likely by resetting circadian rhythms. Maintaining good sleep hygiene is important for mood regulation
Stanford Neuromodulation Therapy (SNT) is a new accelerated form of TMS that can rapidly treat depression in 5 days by utilizing spaced learning principles

Introduction

In this episode, Dr. Andrew Huberman interviews Dr. Nolan Williams, a psychiatrist and professor at Stanford School of Medicine who specializes in using brain stimulation and psychedelic therapies to treat depression and other psychiatric disorders. They discuss the neurocircuitry underlying depression, various treatment approaches including transcranial magnetic stimulation (TMS) and psychedelics, and Dr. Williams' work developing rapid TMS protocols for depression.

Topics Discussed

Depression and Brain-Heart Connections (00:09:16)

Dr. Williams explains that depression is the most disabling condition worldwide and a major risk factor for other illnesses. He discusses how the brain and heart are connected, with the left dorsolateral prefrontal cortex (DLPFC) linked to heart rate regulation and mood control.

The left DLPFC can decelerate heart rate when stimulated with TMS
This connection may explain links between depression and cardiovascular health
Depression involves dysregulation of brain circuits, not just chemical imbalances

Transcranial Magnetic Stimulation (TMS) for Depression (00:22:34)

Dr. Williams describes how TMS works to treat depression by stimulating the DLPFC:

TMS can activate or quiet specific brain circuits to regulate mood
It may work by restoring top-down control from the DLPFC over emotional centers like the anterior cingulate
TMS allows for targeted stimulation without affecting the rest of the brain/body

Psychedelics for Treating Depression and PTSD (00:54:27)

The discussion covers various psychedelics being studied for psychiatric treatments:

Ketamine - Rapid antidepressant effects, may work through opioid system
Psilocybin - Promising for depression, changes brain connectivity
MDMA - Effective for PTSD in clinical trials
Ibogaine - Potential for addiction and PTSD treatment

Dr. Williams emphasizes these should only be used in controlled clinical settings, not recreationally.

Cannabis: Potential Benefits and Risks (02:06:55)

The conversation covers the complex effects of cannabis:

THC may increase psychosis risk, especially with early/heavy use
CBD shows anti-psychotic and anti-epileptic effects
Medical uses for pain, chemotherapy side effects, etc. are promising
Overall safety profile better than alcohol for adults

Sleep, Circadian Rhythms and Depression (02:20:42)

Dr. Williams discusses links between sleep and depression:

Sleep deprivation can temporarily improve depression symptoms
This may work by resetting disrupted circadian rhythms
Maintaining good sleep hygiene is important for mood regulation
Light exposure timing is crucial for circadian entrainment

Stanford Neuromodulation Therapy (SNT) (02:28:43)

Dr. Williams describes his lab's accelerated TMS protocol for depression:

Delivers 7.5 months worth of standard TMS in just 5 days
Uses spaced learning principles to optimize brain plasticity
Targets individualized brain circuits using fMRI guidance
60-90% remission rates in trials so far

Conclusion

This wide-ranging discussion covered cutting-edge research on treating depression and other psychiatric disorders using brain stimulation and psychedelic therapies. Dr. Williams emphasized the importance of understanding depression as a circuit-level brain disorder, not just a chemical imbalance. New rapid TMS protocols and carefully controlled psychedelic therapies show great promise for providing faster, more effective treatments with fewer side effects than traditional medications. However, more research is still needed to optimize these approaches and understand their long-term effects. Overall, this emerging work offers hope for better treatments for the millions suffering from depression and related disorders worldwide.