Revolutionizing Psychiatry: Dr. Nolan Williams on Rapid Neurostimulation

Added: Jan 6, 2024

In this podcast episode, Tim Ferriss interviews Dr. Nolan Williams, a psychiatrist who specializes in rapid-acting neurostimulation approaches for treating mood disorders.

Key takeaways


Rapid-acting neurostimulation can treat severe depression in hours.


Personalized TMS offers a new paradigm in treating mood disorders.


Ibogaine shows promise in treating TBI and addiction.


Delayed remission in TMS may be linked to neuroplasticity.


Psychiatry is moving towards personalized, circuit-based treatments.

The Remarkable Effects of Rapid-Acting Neurostimulation

He shares a personal story about a patient named Deardra, who suffered from severe depression and bipolar disorder. Deardra was in a very bad shape, exhibiting symptoms of severe depression and suicidal tendencies. Her psychiatrist reached out to Dr. Williams for treatment, and he decided to treat her with a rapid-acting neurostimulation approach.

Deardra's condition was so severe that Dr. Williams initially thought she needed to be hospitalized. However, he and his team were able to treat her as an outpatient. They used a rapid-acting neurostimulation approach, which involved reorganizing conventional transcranial magnetic stimulation (TMS) in time and space. This approach allowed them to deliver a whole six-week course of treatment in a single day, equivalent to 30 sessions of conventional TMS.

The results were remarkable. Deardra went from being in a severe depressive state to completely normal in just 24 hours. She showed no signs of suicidality or depression, and her husband and daughter were amazed at the rapid transformation. This experience led to further research and trials, ultimately leading to FDA clearance for the rapid-acting neurostimulation approach.

Using Electrical Stimulation to Modulate Brain Circuits

Dr. Williams explains that the approach is part of the broader field of electroceuticals, which involves using electrical stimulation to modulate brain circuits. The goal is to address the underlying circuit problems in the brain rather than relying solely on pharmaceutical interventions. This new paradigm in psychiatry, which Dr. Williams refers to as "Psychiatry 3.0," focuses on circuit-based treatments for mood disorders.

The rapid-acting neurostimulation approach involves delivering high-intensity TMS pulses to specific brain regions, personalized to each patient's brain. The treatment has been shown to be effective in rapidly alleviating symptoms of depression and bipolar disorder. It also offers a level of empowerment to patients, as it provides a tangible solution for managing their condition.

Dr. Williams also discusses the sequencing of brain activation and how it relates to treatment response. Using resting state functional connectivity MRI, his team identified a biomarker that predicts treatment response to rapid-acting neurostimulation. This biomarker is associated with the timing of blood flow in different brain regions, indicating a potential causal relationship in mood disorders.

Promising Results

Dr. Williams discusses the results of his research on accelerated TMS for depression, highlighting the high remission rates observed in clinical trials, with over 400-500 patients undergoing the treatment. He explains that in their original pilot study, 90% of patients experienced remission, and in the randomized control trial, 79% of patients transitioned through remission at some point in the four-week follow-up. He compares these results to conventional treatments, such as SSRIs and conventional TMS, and notes that accelerated TMS has shown higher efficacy in severe treatment-resistant cases.

The approach has been well-tolerated, with no serious adverse events reported. While some patients experience temporary side effects such as headaches and fatigue, the overall benefits of the treatment outweigh these minor discomforts.

Delayed Remission and Neuroplasticity

Dr. Williams addresses the phenomenon of delayed remission observed in some patients undergoing accelerated TMS. He speculates that this may be related to neuroplasticity, particularly in older adults, as the brain's plasticity decreases with age. He suggests that the stimulation pattern used in accelerated TMS may take time to lay its tracks into the brain, leading to delayed remission in some individuals. He also discusses the confluence of neurotransmitter systems affected by accelerated TMS and its potential role in producing rapid and durable antidepressant effects.

Other Treatment Modalities

In addition to accelerated TMS, Dr. Williams explores other treatment modalities for psychiatric conditions, including the use of ibogaine for military traumatic brain injury (TBI) and associated psychiatric symptoms. He describes a study involving veterans with TBI, depression, PTSD, and alcohol use disorder, where ibogaine was administered as a monotherapy. The results of the study showed significant improvements in the participants, leading to a publication in a prestigious journal. Dr. Williams emphasizes the importance of exploring alternative treatments for specific patient populations, such as veterans, and the potential impact of these therapies on mental health outcomes.

Challenges and Ethical Considerations

Dr. Williams acknowledges the challenges and ethical considerations associated with conducting research on novel treatments, such as ibogaine. He discusses the rigorous process of obtaining approval from the institutional review board and the need to address safety concerns, particularly regarding the potential cardiac risks associated with ibogaine. He also highlights the importance of advocating for research funding and support for alternative therapies, especially for underserved populations, such as veterans with TBI and psychiatric conditions.

Psychedelic Therapy and Patient Perception

Dr. Williams touches on the topic of psychedelic therapy and the challenges of assessing patient perception and self-reporting in clinical trials. He mentions the phenomenon of alexithymia, where individuals have difficulty describing their emotions, and how this can impact their self-assessment of treatment outcomes. He shares insights from his experience with patients undergoing psychedelic therapy and the need for clinician-rated assessments to complement patient self-reports.

Future Directions in Psychiatry

Dr. Williams emphasizes the need for personalized approaches in psychiatry, where treatments are tailored to individual neuroanatomy and symptomatology. He envisions a future where psychiatric conditions are categorized into specific biotypes or endophenotypes, allowing for targeted interventions based on personalized brain imaging and neurobiology.

Ibogaine's Mechanism of Action

Dr. Williams explains that ibogaine's mechanism of action is different from other psychedelics like psilocybin and ayahuasca. While these drugs primarily affect the 5-HT2A receptors, ibogaine interacts with a broad range of receptor systems, including serotonin, kappa, and NMDA receptors. Additionally, ibogaine upregulates brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, which are important for brain plasticity. Dr. Williams describes ibogaine as a "symphony" of effects, suggesting that its unique combination of actions may contribute to its therapeutic potential.

Safety Profile and Therapeutic Effects

Dr. Williams addresses concerns about ibogaine's safety profile, particularly its potential cardiac risks. He discusses the use of IV magnesium to mitigate the risk of torsades de pointes, a type of abnormal heart rhythm associated with ibogaine use. Dr. Williams also highlights the potential of ibogaine in treating traumatic brain injury, citing a study that showed significant improvement in TBI disability after ibogaine treatment. He emphasizes the need for further research to understand the specific mechanisms underlying these therapeutic effects.

Ibogaine and Addiction

The podcast delves into the potential of ibogaine in treating addiction, particularly opioid use disorder. Dr. Williams discusses reports of ibogaine's ability to attenuate physical withdrawal symptoms in opioid addicts, suggesting that ibogaine may interrupt the reward circuitry associated with addiction. He compares ibogaine's unique effects to traditional opioid replacement therapies like Suboxone and methadone, highlighting the need for novel approaches to address treatment-resistant addiction.

Challenges and Future Research

The podcast addresses the challenges of studying ibogaine and the need for further research to elucidate its mechanisms of action. Dr. Williams highlights the importance of exploring ibogaine's effects in pure TBI populations, as well as its potential in interrupting addictive behaviors. He also discusses the societal and cultural attitudes towards novel therapies like ibogaine, emphasizing the need to shift perspectives and prioritize innovative treatments for complex conditions.

Ibogaine and Public Policy

The podcast touches on the public policy implications of using ibogaine as a therapeutic intervention. Dr. Williams discusses his involvement in testifying before the opiate abatement commission in Kentucky, where discussions centered on the use of state funds for novel therapeutics. He emphasizes the importance of exploring innovative treatments for treatment-resistant conditions and challenges the traditional approach to evaluating and adopting new therapies.

Ethical Considerations and Sustainability

Dr. Williams addresses ethical considerations and sustainability in the use of psychedelic drugs. He discusses the ethical implications of using these substances, particularly in terms of sourcing them from natural supplies and the potential impact on indigenous cultures. He also talks about the sustainability of using psychedelic drugs and the need to consider the environmental and ethical implications of their production and use.

Performance Enhancement in Sports

Dr. Williams touches on the potential for using neuromodulation to enhance performance in sports. He discusses anecdotal reports of increased visual acuity and color contrast in individuals undergoing neuromodulation, as well as the potential for athletes to use these methods for performance enhancement. He also mentions the ethical considerations and potential implications of using neuromodulation for performance enhancement in sports.


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