Published September 2021 on YouTube

Dr. Matthew Johnson: Psychedelics for Treating Mental Disorders | Huberman Lab Podcast #38

1. Introducing Dr. Matthew Johnson

Dr. Matthew discusses the use of psychedelics for the treatment of mental disorders, including micro and macro dosing. He also walks us through an experiment of a patient taking psychedelics for the treatment of depression in his laboratory.+

2. Supporting Sponsors

Nutritional Health:Andrew emphasizes the importance of maintaining a healthy gut microbiome and covers his foundational nutritional needs by taking Athletic Greens. Listeners can try Athletic Greens and get five free travel packs and a year supply of vitamin D Three and K Two by going to The podcast is also sponsored by Inside Tracker, a personalized nutrition platform that analyzes data from blood and DNA to help individuals reach their health goals.+
Health Insights:Andrew shares his insights on the importance of getting regular blood work and DNA tests to understand one's health better. He also talks about the benefits of regenerative agriculture and how it impacts our health and the environment.+

3. ‘Psychedelics’ Defined

Understanding Psychedelics:Matthew Johnson explains the challenges of defining psychedelics based on pharmacology and how they all have the ability to alter one's sense of reality. He also discusses the different classes of psychedelics, including classic psychedelics, and their structural classes based on chemistry.+
Understanding Psychedelics:Matthew and Andrew discuss the different types of psychedelic compounds, including tryptamine and phenethylamine based compounds, as well as NMDA antagonists. They also delve into the receptor effects of these compounds, specifically their agonist or partial agonist effects on the serotonin two A receptor. Additionally, they touch on MDMA's unique mechanism of action, which involves flooding the synapse with serotonin.+

4. Psychedelics and Perception

Psychedelics and Perception:Andrew discusses the impact of psychedelics on perception, including hallucinations and altered senses of reality. He explores the relationship between psychedelics and the brain's analysis of space and time, and compares their effects to those of alcohol and benzodiazepines.+
Psychedelics and Predictions:Matthew and Andrew discuss how psychedelics can alter our predictions and models of the world, leading to surprising experiences. They use the example of a child learning about gravity to illustrate how our brains create predictions and how psychedelics can dissolve those models. They also touch on the rare cases of people believing they can fly while under the influence of psychedelics.+

5. Serotonin & Dopamine

Andrew and Matthew discuss the differences between the serotonin and dopamine systems in the brain and how they are affected by psychedelics and other drugs. They explore the biology and chemistry behind these systems and the distinct experiences they create.+

6. Ketamine & Glutamate

Ketamine Hallucinations:Matthew and Andrew discuss the dissociative effects of ketamine, including the potential for hallucinations and the infamous "K hole." They also touch on the therapeutic use of ketamine in the form of Spravado nasal spray.+
Ketamine Therapy:Matthew discusses the potential benefits of using Ketamine as a form of psychedelic therapy for addiction treatment and depression. While the FDA-approved spray form of Ketamine has mild psychedelic effects, higher doses have been successful in treating addiction. Matthew suggests that treating Ketamine like psychedelic therapy could potentially yield better results.+

7. An Example Psychedelic Experiment

Psychedelic Clinical Trials:Matthew and Andrew discuss the process of preparing for a psychedelic clinical trial, including screening for disorders and developing a therapeutic rapport with the guides. They also mention the potential benefits of psychedelics for a variety of issues, including smoking cessation.+
Psychedelic Effects:Matthew and Andrew discuss the effects of psychedelics and the importance of understanding the potential outcomes before taking them. They also talk about the different ways to consume psilocybin and the importance of dosage.+
Psychedelic Chemistry:Andrew and Matthew discuss the chemical structure of serotonin and psilocybin, and how they can have vastly different effects on the brain despite their similarities. They caution against self-experimentation and highlight the importance of proper dosing and therapeutic environments for psychedelic experiences.+

8. ‘Letting Go’ with Psychedelics

Letting Go:Andrew discusses the importance of letting go of control during a psychedelic experience and how it can expand one's perceptual bubble. He also talks about the trust built between the patient and the analyst in psychotherapy and how it can become a template for trust more generally and trust in oneself.+
Perceptual Bubbles:Matthew and Andrew discuss how psychedelics can expand one's perceptual bubble and how safety protocols are in place to ensure a safe experience. They also touch on the brain's default to jump around with the visual and auditory systems, and how wearing eye shades can help people go further into these bubbles.+

9. Our Mind’s Eye

Andrew and Matthew discuss the value of going into a restricted perceptual bubble during a psychedelic experience and how it can lead to therapeutic effects in the realm of depression. They explore how vastly different experiences can lead to similar exports of feeling a better relationship to the world and oneself.+

10. Redefining Your Sense of Self

Self Representation:Matthew discusses the persisting changes in self representation caused by certain experiences, such as falling in love with a pen. He suggests that these experiences can alter the models we hold of reality, including our sense of self, and may lead to a transformed understanding of the self.+
The Power of "I Am":Andrew and his friend discuss the power of the phrase "I am" and how it can shape one's perception of self. They explore the idea that defining oneself internally can have a significant impact on one's emotional state and discuss the potential for neuroplasticity in reshaping the perception of self.+
Psychedelics and Identity:Matthew discusses the idea that psychedelic experiences can lead to changes in self-representation and identity. He shares examples from their work with cancer patients and smokers, where participants experienced a shift in how they viewed themselves and their habits. These "Duh experiences" can be explained from a naturalist point of view, without the need for supernatural or religious explanations.+
Reshaping Neural Circuitry:Matthew and Andrew discuss the power of somatic and perceptual experiences, particularly with the use of psychedelics, in reshaping neural circuitry and treating trauma. They also challenge the idea that language alone can change neural networks, emphasizing the importance of experience and neuromodulators like serotonin and dopamine in the process.+

11. Psychedelic Integration

Psychedelic Therapy Transition:Andrew discusses the transition out of the psychedelic state and the importance of guiding individuals through the tunnel as they exit. He emphasizes the need for more experimentation in the clinical model to determine the most effective methods for integration during the latter half of the session.+
Psychedelic Experiences:Matthew discusses the importance of taking psychedelic experiences seriously and not dismissing them as just a drug effect. He emphasizes the need for integration sessions and follow-up discussions to process the experience and its potential impact on one's life. The integration process involves supportive therapy and reflective listening, with encouragement to follow up on insights gained during the experience.+

12. Flashbacks

Flashbacks and Perceptual Disorders:Andrew and Matthew discuss the phenomenon of flashbacks, specifically hallucinogen persisting perceptual disorder (HPPD), which is a rare and mysterious condition that causes persisting perceptual disorders. They explore the possible causes of HPPD, including neurological susceptibility and illicit drug use, and how it can be exacerbated by other substances like alcohol and cannabis.+
Psychedelic Misconceptions:Matthew discusses the misconceptions surrounding hallucinogens and how they are often attributed to rare neurological susceptibilities due to xenophobia. He also clarifies the common misconception of flashbacks and explains that they can be a result of state-dependent learning or perceptual anomalies, rather than HPPD.+

13. ASMR and Reordering the Self

Andrew and Matthew discuss the phenomenon of ASMR and its connection to psychedelics. They also touch on the idea of reordering the self and how certain drugs can help individuals tune into a deeper sense of somatic self.+


MDMA and Neural Networks:Andrew discusses the unusual situation of MDMA leading to robust increases in both dopamine and serotonin simultaneously, which are almost mutually exclusive neurochemical states. He speculates on the potential benefits of this combination and how it differs from experiences on psilocybin or more serotonergic agents. MDMA is being used clinically for trauma and may be better for a broader number of people because the chances of having an extremely challenging experience are much lower.+
Psychedelic Surrender:Matthew discusses the concept of surrendering to the psychedelic experience and how it can lead to positive outcomes such as transcendental mystical experiences and a sense of unity with all things. He explains that trying to hold on to reality during the experience can lead to a bad trip. He also mentions the need for further experimentation and brain imaging to understand the operant behavior of surrendering to the experience.+
DMT and Terrence McKenna:Andrew and Matthew discuss DMT and the effects it has on the self, with Terrence McKenna being known as the bard of DMT. They also touch upon McKenna's background and his role as an advocate for psychedelics.+

15. Psychedelic Risks

Psychedelic Dangers:Andrew Huberman discusses the potential dangers of using psychedelics, particularly for individuals with predispositions to certain mental health conditions. He questions whether certain drugs should be used more carefully than others and highlights the importance of understanding the risks before experimenting with these substances.+
Risks and Psychedelics:Matthew and Andrew discuss the potential risks of using psychedelics for people with severe psychiatric illnesses such as schizophrenia and bipolar disorder. While there are anecdotes of psychedelics helping those with schizophrenia, the risks are too high to consider it a therapeutic option at this time.+
Psychedelic Risks:Matthew discusses the risks associated with psychedelic experiences, including the potential for those with psychotic disorders to have negative reactions and the likelihood of bad trips even for psychologically healthy individuals. He also emphasizes the importance of proper screening and preparation to minimize these risks.+
Psychedelic Dangers:Matthew and Andrew discuss the dangers of taking psychedelics and the importance of conducting clinical trials to understand their effects and create a safe transition to legality. They share examples of extreme cases and emphasize the importance of context and dosage in psychedelic experiences.+

16. Micro-Dosing

Microdosing Misconceptions:Andrew and Matthew discuss the misconceptions surrounding microdosing and the confusion caused by the term "micro." They clarify what constitutes a microdose and the difference between micro and macro dosing, using LSD as an example. They also touch on the challenges of measuring doses outside of a medical setting.+
Psychedelic Dosages:Matthew discusses the varying methods of measuring and distributing psychedelic dosages, from volumetric measurement to cutting up blotter paper. He highlights the importance of proper dosage and distribution for safe and effective use of psychedelics.+
Microdosing Psilocybin:Andrew Huberman and Matthew Johnson discuss the concept of microdosing psilocybin, its aim, and the clinical evidence behind it. They also emphasize that plasticity is a process, not the goal, and that it should be goal-directed.+
Psychedelic Supplements:Andrew and Matthew discuss the claims and lack of evidence behind taking psilocybin as a daily supplement for ADHD and depression. While some believe it can act as a better version of traditional drugs, no peer-reviewed studies have shown a benefit. However, there may be potential for improving focus and mood.+
Microdosing Reality Check:Matthew discusses the lack of evidence supporting the benefits of microdosing and the importance of placebo control in studies. He also mentions the impairment of time estimation and the potential for abuse liability. No studies have shown sustained improvement in mood or cognition.+
Placebo Effects:Andrew and Matthew discuss the power of placebo effects in medicine and how belief can have a significant impact on the effectiveness of treatments. They mention studies that show the power of belief in weight loss and the use of placebos in treating conditions like irritable bowel syndrome.+
Microdosing Risks:Matthew Johnson warns about the potential risks of microdosing, specifically the possible negative effects on heart valves due to the serotonin 5H2B receptor. While he believes there may be some reality to the antidepressant effects of microdosing, he emphasizes the importance of considering the cumulative effects of long-term microdosing.+

17. Psychedelics and Young People

Psychedelics and Young People:Andrew and Matthew discuss the potential risks and benefits of young people taking psychedelics, as well as the lack of formal research on the topic. They also touch on the FDA's concerns about age specificity in drug approval and the potential for future studies on psychedelics and young people.+
Biological Variables:Andrew Huberman discusses the importance of considering biological variables such as gender, sex, and age in scientific studies. He explains that federally funded grants now require studies on both males and females, and that age is also becoming a crucial factor. Huberman also touches on the potential benefits of prescribing psychedelics for therapeutic purposes, especially for high-pressure academic environments where suicide rates are high.+

18. Psychedelic Legalization Insights

Psychedelic Legal Status:Andrew discusses the current legal status of psychedelic compounds in the US, including the transition to legality for prescription purposes, possession and criminal charges, and the potential for psilocybin to become a taxable item. Despite some forms of decriminalization, possession and sale of these compounds is still illegal and can result in jail time.+
Legalization Ambiguity:Matthew discusses the potential for selective enforcement and the ambiguity surrounding the legalization of psilocybin therapy in Oregon, as it remains illegal at the federal level. He compares it to the history of cannabis legalization and the potential for local and state level authorities to charge individuals with federal crimes.+
Psychedelic Therapy Culture:Andrew and Matthew discuss the culture of psychedelic therapy in Oregon and the West Coast, where experimentation with plant compounds is common. They also touch on the contrast between the West Coast's innovation and the East Coast's tradition.+
Future Drug Regulation:Matthew and Andrew discuss the future of drug regulation and criminalization in the United States. While psychiatry departments tend to be conservative, Andrew believes that in the future, there will be a shift towards regulating drugs at the right level instead of criminalizing them. He predicts that in the future, psilocybin may be regulated similarly to how cannabis is currently regulated.+
Psychedelic Legalization:Matthew and Andrew discuss the potential for legalizing psychedelics and the importance of medical research in their development. They also touch on the nuance of legalization and regulation, and how the legal status has not hindered the psychedelic community's exploration of these substances.+

19. Psychedelics for Brain Repair

Psychedelics and Neurological Injuries:Andrew and Matthew discuss the potential of psychedelics, particularly psilocybin, for the treatment and possible reversal of neurological injuries such as traumatic brain injury (TBI). While it is still exploratory, anecdotal evidence and rodent research suggest that psychedelics may help with cognitive function and neuroplasticity.+
Brain Repair Potential:Matthew and Andrew discuss the potential for repairing the brain from injuries underlying neurological issues and repetitive head impact. They explore the idea of using drugs that increase certain neuromodulators like serotonin or dopamine in a controlled way and coupling that with learning to lead to reordering of circuitry.+
UFC's Commitment:Andrew and Matthew discuss the UFC's commitment to athlete health and their exploration of treatments for traumatic brain injury. The UFC is interested in bringing in academics to improve human performance in sports and the general public.+

20. Psychedelic Philanthropy

Pioneering Psychedelic Research:Andrew discusses how pioneering research on psychedelics has largely been funded by philanthropy, rather than taxpayer dollars through the National Institutes of Health. While NIH funding has been available for some work on understanding these substances as drugs of abuse, the most interesting work has been funded by private philanthropy.+
Ethnobotany and Psychedelics:Andrew and Matthew discuss the intersection of anthropology and psychoactive plant compounds, specifically ethnobotany, and how it has played a role in the study of psychedelics. They also mention organizations that have provided funding for their research, including the Hefter Research Institute and the Beckley Institute.+
Philanthropy and Progress:Matthew Johnson discusses the impact of philanthropy on clinical trials and the recent $17 million gift that has transformed their work. Andrew Huberman shares a powerful statement made by someone who underwent a clinical exploration involving Dmt.+
Funding and Exploratory Research:Matthew and Andrew discuss how funding works in academia and how it allows for researchers to focus on exploratory realms like psychedelic research without jeopardizing their careers. They also touch on the NCCIH's initiative and how it's engaging scientists and the general public in a dialogue about problems like depression, PTSD, and ADHD.+
Psychedelics and Neuroscience:Andrew discusses the use of psychedelics in neuroscience with a guest who has made real progress in the field. They acknowledge the importance of psychedelics in changing the brain's circuitry and the level of rigor required to make progress in this area.+
Academic Grants:Andrew and Matthew discuss the importance of grants in academia, how they affect job security, and the impact of academic research on the real world. They share personal experiences and insights on the challenges faced by researchers in securing grants and the pressure to produce impactful work.+
Psychedelic Breakthroughs:Matthew discusses the recent breakthrough designations by the FDA for psilocybin and MDMA in treating disorders like PTSD and depression. He emphasizes the potential for these treatments to have a larger effect size than traditional medications and the emerging psychedelic startup industry.+

21. Psychedelic Trials and Research

Clinical Trials Information:Andrew and Matthew discuss how people can find information about clinical trials for psychedelic treatments. They provide a website for those interested in participating and advise against emailing directly.+
Psychedelic Research:Matthew Johnson discusses the current state of psychedelic research and the importance of participating in clinical trials for legal and safe treatment. He also mentions upcoming studies on opioid addiction and LSD for chronic pain, and provides links to survey studies on therapeutic use of psychedelics and breath work.+

22. Support the Podcast

Andrew and Dr. Matthew Johnson discuss ways to support the podcast, including partnering with Thorn for high-quality supplements and joining their Patreon community.+