714 A Glimpse of the Future: Electroceuticals for 70%–90% Remission of Depression, Brain Stimulation for Sports Performance, and De-risking Ibogaine for TBI/PTSD
This is a OPEN AI summary of the Tim Ferriss Podcast #714- visit www.TinyTim.blog for more AI summaries, or www.Tim.blog for the official Tim Ferriss Podcasts
Tim Ferriss and Dr. Nolan Williams discuss a patient named Deirdre Lehman who suffers from bipolar disorder. Her psychiatrist reached out to Dr. Williams for help when she fell into a severe depressive episode. They had to wait until Monday for treatment, and on that day, their first stimulator broke, causing a lot of stress. They were able to use a second machine to treat Deirdre successfully.
Dr. Nolan Williams discusses a patient who experienced a rapid recovery from severe depression after receiving accelerated TMS treatment. The patient's husband became an advocate for the therapy and helped fund trials and gain clearance for its use. Dr. Williams also explains the abnormal sequencing of brain activity in depression and the potential for TMS to provide quick and long-lasting relief.
Anish Mitra, a former research track resident postdoc at Stanford, had an interest in using resting-state functional connectivity MRI to study brain imaging. This technique measures the time-locked blood flow between brain regions, which is a surrogate for electrical activity. Mitra's research showed that the timing of this blood flow can infer causality and may play a role in mood disorders. The results also showed that individuals who responded to a rapid-acting TMS approach had a specific biomarker for this timing, while those who did not respond did not have the biomarker.
The conversation discusses the use of tests in medicine, specifically in psychiatry, and the different eras of psychiatry. The current focus is on finding a test that can accurately diagnose and treat disorders instead of relying on trial and error with medications. This new paradigm could potentially revolutionize treatment for mental health disorders.
Psychiatry 2.0 emerged with the serendipitous discovery of antipsychotics and antidepressants, leading to the deinstitutionalization of schizophrenia patients. However, recent research has shifted towards understanding mental health issues as circuit problems rather than chemical imbalances, empowering patients to take control of their own treatment through focal neuromodulation. This approach has shown promising results in improving symptoms and reducing suicidal ideation in patients.
TMS (transcranial magnetic stimulation) is a neuromodulation technique used for therapeutic purposes. It was originally developed in the mid-80s as a motor probe to map the motor system of the brain. However, with advancements in technology, TMS has been reorganized in time and space to target specific areas of the brain for therapeutic purposes. This new approach, known as SAINT (Stanford Accelerated Intelligent Neuromodulation Therapy), has shown promising results in alleviating feelings of hopelessness and empowerment in individuals struggling with mental health issues. TMS works by pulsing a magnet on the head, inducing current in electrically conducting substances in the brain. While it may cause some discomfort due to scalp nerves, it does not affect the brain itself. SAINT is a part of the broader term of electroceuticals, which refers to medical treatments that use electrical stimulation for therapeutic purposes.
The mapping exercise initially started as a way to non-invasively study the brain and its consistency among individuals. Researchers discovered that they could send a signal into the brain to change its excitability, and this led to the idea of using this technique to treat depression by increasing activity in the prefrontal cortex. The original trials used average coordinates and a low-dose approach once a day for several weeks, which was less efficient but considered safer. This is different from electroconvulsive therapy, which aims to produce seizures, while this technique aims to increase brain activity.
TMS is a non-invasive treatment for depression that uses magnetic stimulation to activate specific areas of the brain. It is different from ECT, which induces seizures, and is more convenient for patients as it can be done in an outpatient setting. The new method of TMS, called iTBS, allows for a full course of treatment to be completed in just one day, making it more accessible and effective for those in high acuity situations. This personalized and efficient approach has shown promising results in treating major depressive disorder.
People in certain professions, such as airline pilots, firefighters, and police officers, may not report mental health issues due to fear of being suspended or relieved of duty. A compressed protocol for treatment has been developed in order to quickly get these individuals well and back to their lives with minimal impact. The safety and ethics of this treatment have been approved by the IRB and FDA. The treatment involves testing the motor threshold and delivering a sub-motor threshold dose of transcranial magnetic stimulation, which has been deemed safe and effective.
Dr. Nolan Williams discusses the use of accelerated TMS for migraine treatment and the evidence that supports its effectiveness. He explains that the intensity of the pulse, rather than the frequency or density, is what affects risk. The treatment has been deemed non-significant risk by FDA and has shown positive results in reducing migraine headaches and pain. However, some patients may experience headaches and fatigue as side effects. Studies have shown that the treatment can release endogenous opioids, providing an anti-pain effect. Tim Ferriss shares his personal experience with the treatment, noting that while he did experience some headaches and fatigue, it was not the same as the fatigue associated with depression.
Dr. Nolan Williams and Tim Ferriss discuss the results of the SAINT treatment for depression, which is targeted towards patients who have had multiple failed interventions. The study found that patients with more severe depression and impaired attention tend to respond better to the treatment, while those with obsessive/depressive symptoms may benefit more from a different type of stimulation. The team is also working on using brain imaging to personalize the treatment for each patient. There are currently open trials for those interested in enrolling in the study.
The Stanford Brain Stimulation Lab is conducting ongoing clinical trials for various mental health conditions such as depression, obsessive compulsive disorder, and addiction. In a pilot study, 90% of participants experienced remission after treatment with SAINT. However, there is a subpopulation of patients who have a slower time to remission and may have a different neuroanatomy. This is similar to how Parkinsonism used to be categorized before being split into different diagnoses.
Dr. Nolan Williams discusses the UK Brain Bank, where individuals can donate their brains after death for research on neurological diseases. This allows for a deeper understanding of symptoms and can lead to more personalized treatments. The goal is to identify different biotypes or endophenotypes of disorders like depression and anxiety, and match them with specific brain physiology for more effective treatment. This approach can save time, reduce risk, and lower costs. Currently, it takes an average of seven years to diagnose someone with bipolar disorder, highlighting the need for more efficient methods.
In this conversation, Dr. Nolan Williams and Tim Ferriss discuss the challenges of finding a solution for depression, which can take years and multiple treatments. They compare the remission rates of conventional antidepressants to those of TMS therapy, which has shown to have higher efficacy rates. The efficacy of TMS decreases with more severe cases, but it still surpasses other treatments such as electroconvulsive therapy.
Neuromodulation treatments, such as ketamine and accelerated TMS, have shown promising results for conditions like borderline personality disorder and bipolar disorder. These treatments may be more accessible to patients who would not qualify for other therapies, such as psychedelic-assisted psychotherapy. Some patients experience delayed remission with these treatments, which may be due to a cascade of neuroplasticity triggered by the treatment. However, the exact mechanism is still unknown and further research is needed.
Brain plasticity decreases in older adults, making it harder for them to form new memories. This is because the brain takes longer to adapt to new information. Research is being done using fMRI scans to understand this process, and it is believed that a combination of different neurotransmitter systems may be necessary for effective treatments for depression. One potential treatment being studied is ibogaine for military traumatic brain injury.
A group of senior professors, uninvolved in the research, review and approve the safety and ethical standards of a proposed study involving accelerated TMS and the use of an illegal root bark extract for treating addiction. The lead researcher, Dr. Nolan Williams, was known for his open-mindedness and pragmatism in exploring new treatments for patients. He was chosen to lead the study despite the stigma and bias surrounding the drug. The idea for the study came from a book Dr. Williams read while stuck in an airport on his way to Peru.
Dr. Nolan Williams discusses his personal experience and research on using psychedelic treatment for veterans with traumatic brain injury, depression, and PTSD. Despite initial doubts, the study showed significant and consistent improvements in patients' conditions. The results were published in a prestigious biomedical journal, indicating the effectiveness of this treatment approach. The issue of placebo effect is also addressed, with the use of a blind guess control group.
Dr. Nolan Williams discusses the results of a study where patients were asked to guess whether they received an active or sham treatment, and found that they were only correct about 50% of the time. He also mentions the phenomenon of alexithymia, where people have difficulty accurately describing their mood, and how this can affect self-reported results in psychiatric conditions. Tim Ferriss adds that this is a common issue with self-reporting in general.
In a study involving military personnel with traumatic brain injuries, it was found that the use of ibogaine alone produced a stereotyped trip characterized by a replay of emotionally salient memories. This effect was observed in a closed-eye setting and was associated with cathartic re-evaluation of these memories. The study has received attention from the government and may lead to further funding and research on the potential therapeutic benefits of psychedelics, particularly for veterans.
The conversation discusses reasons for feeling and behaving a certain way, and how people are able to gain insight into their past experiences. The analogy of Scrooge in A Christmas Carol is used to explain how individuals become observers of their own past. The drug ibogaine is discussed as a tool for accessing traumatic memories and resolving them through understanding and empathy. The conversation also touches on the overlap between childhood trauma and high performance in stressful situations. The difference between ibogaine and other psychedelics, particularly in relation to glial cells, is explored.
Dr. Nolan Williams and Tim Ferriss discuss the unique properties of glial-derived neurotrophic factor (GDNF) compared to other molecules like psilocybin. GDNF affects a broad range of receptor systems and has been shown to improve alcohol addiction in mice. However, its complex mechanism of action makes it difficult for scientists to fully understand its effects. Tim Ferriss compares it to a symphony, with multiple components working together to produce its therapeutic effects.
The speaker discusses the complexity of the drug ibogaine and its unique effects on neurotransmitter systems. They also touch on the potential risks and challenges in studying and reproducing its effects, including potential cardiac complications. The conversation also delves into potential uses for ibogaine in treating addiction and the need for further research and development.
The primary metabolite of ibogaine that targets 2D6 receptors has a similar cardiac risk profile. Some researchers are trying to modify this molecule to reduce the risk, but others believe in preserving the original molecule and managing the risk, such as using IV magnesium. There have been no reported cases of torsades (a potentially fatal heart rhythm) in the thousands of people who have received ibogaine treatment in Mexico. However, it is important to consider the risks and have proper monitoring and medical support in place when using ibogaine.
Tim Ferriss and Dr. Nolan Williams discuss the use of Ibogaine as a potential treatment for addiction. They mention the social proof in the community and how high-performing special operators have found success with this treatment. They also discuss the potential overlap with other drugs, such as those used for type two diabetes, and the unexpected side effects, such as decreased coffee consumption. Overall, they believe that there is strong evidence to suggest that Ibogaine could be a promising treatment for addiction.
The article discusses the use of ibogaine, a drug that has shown promise in helping people with addiction and mental health issues. It works by creating a pause between stimulus and response, allowing individuals to make unbiased choices. The drug can also help individuals reevaluate their habits and establish new patterns. It is different from other drugs, such as Ozempic, which suppress cravings, as it introduces a level of choice. There is also potential for combining ibogaine with other drugs for more effective treatment. The article also touches on the importance of post-treatment care and rehab for successful recovery.
Ibogaine has shown potential in treating TBI, addiction, and PTSD. There are reports of opiate addicts experiencing a reduction in withdrawal symptoms after treatment with ibogaine. However, more research is needed to understand its effectiveness in a pure TBI population. The mechanism of action is not fully understood, but it may involve interactions with multiple neurotransmitter systems. Ibogaine is a promising treatment but further research is needed to fully understand its effects.
Ibogaine is a unique drug that has shown promising results in treating opioid addiction and various psychiatric disorders. Its mechanism of action is still unknown, but it is believed to interact with opioid receptors and the glutamate system. Ibogaine has been gaining attention in the scientific community and there are ongoing efforts to understand how it works. In Kentucky, there are efforts to use funds from opiate overprescription lawsuits to support research on novel therapeutics, including ibogaine. Traditional treatments for opiate addiction have high failure rates, leading some patients to consider brain surgery as an alternative.
Deep brain stimulation (DBS) is a surgical form of neuromodulation where an implanted device is used to stimulate the reward system. This method is being explored as a potential treatment for opioid addiction and weight loss. However, there is a one-in-100 risk of a head bleed associated with DBS. In comparison, ibogaine, another potential treatment for addiction, has a one-in-300 risk of a torsades risk. There are debates about whether state funds should be used for these treatments, but some argue that they could help a subpopulation of people who do not respond to traditional treatments. Both DBS and ibogaine aim to interrupt the addictive circuit in the brain and reorganize it in order to change behavior.
The discussion is about the hubris of humans and their desire to create and innovate, even when a solution already exists. This is seen in the historical example of scurvy and the current debate over using ibogaine as a treatment for addiction in Kentucky. The guest, Dr. Nolan Williams, argues that the focus should be on scientific complexity and not just creating the latest and greatest treatment. There are various factors to consider, including insurance reimbursement, availability of therapists, and scaling for widespread use. However, it is clear that further research is necessary due to the severity and prevalence of the addiction problem.
The speaker is interested in studying rate-limiting steps and unintended consequences of using natural compounds. They also discuss the difficulty of obtaining ethical approval for studies on extended fasting in humans. However, they suggest that if the potential benefits outweigh the risks, such studies can be justified. The speaker also mentions the potential benefits of studying extended fasting in relation to psychiatric conditions, drawing parallels to research on ketogenic diets and psychedelics. They reference a journalist's work on MDMA-assisted psychotherapy and iboga in Gabon.
The article discusses the global demand for ibogaine and iboga, two psychedelic substances, and the ethical implications of their use. It also explores alternative options for obtaining these substances, such as extracting them from other plants or synthesizing them chemically. The sustainability and ethical concerns of using 5-MeO-DMT are also mentioned.
The article discusses the use of the Bufo alvarius, also known as the Sonoran Desert Toad, in a therapeutic and commercial context. While it can be synthesized, there is interest in using the natural form for its short but intense effects. The use of 5-MeO-DMT in conjunction with ibogaine during therapy is also mentioned, with some evidence that it may alleviate negative side effects. However, further research is needed to determine its effectiveness.
Ferriss and Dr. Nolan Williams discuss the use of 5-MeO-DMT as a potential treatment for PTSD and depression. The doctor explains that it can cause significant improvements in people's scores on assessments, but it is not without risks. Ferriss questions the use of 5-MeO-DMT and its potential as a distraction from FDA-approved treatments. Dr. Nolan Williams acknowledges the risks but believes there may be justification for its use in certain cases. He also mentions ongoing trials for ibogaine and fibromyalgia, suggesting that more research is needed before making conclusions about the effectiveness of 5-MeO-DMT.
The discussion revolves around the potential use of population-based drugs for PTSD and the current limitations in understanding their effects. There is speculation about future developments in psychiatry, such as using neurostimulation to manipulate specific content in the brain. Anecdotal evidence is shared about a patient whose musical taste changed after receiving deep brain stimulation for OCD.
Dr. Nolan Williams discusses the potential of using specific brain interventions, such as content manipulation and targeted drug delivery, to treat mental illnesses. He believes that as technology advances, we will be able to intervene earlier in the illness process and achieve more specific and effective results. He also discusses a current study involving ketamine and ultrasound technology, and suggests that behavior mapping may be more important than simply modifying molecules in understanding the effectiveness of certain treatments.
The speaker discusses the potential for using anesthetics or neuromodulation to temporarily shut down certain areas of the brain, such as the amygdala, in order to treat conditions like psychosis and schizophrenia. They also mention the possibility of using these methods to change handedness in childhood or aid in neuro-rehabilitation. These ideas are still speculative but could have promising implications for future treatments.
The discussion is about using psychedelic drugs to treat neurological deficits, which is an area that is not widely studied. The use of psychedelics has been reported to enhance visual perception and may be used as a means of performance enhancement in sports. Patients who have undergone treatment with psychedelics have reported increased mindfulness and ability to be present in the moment.
Dr. Nolan Williams discusses the potential benefits of using neurostimulation and psychedelics to improve performance and treat various conditions. He also mentions an experiment where participants were given motor tasks after being primed with neurostimulation, resulting in improved performance. While these treatments are still in early stages, they offer exciting possibilities for better understanding and controlling brain function.
The speaker expresses gratitude for the help and support they have received while exploring a new field of experimentation. They were inspired by a friend's family who experienced a dramatic transformation through this field. The results have been durable and there is excitement for its future potential. The speaker thanks the person being interviewed and encourages kindness towards others and oneself.
https://tim.blog/2024/01/05/nolan-williams/
