Summary of Huberman Lab Podcast Episode: The Brain-Rewiring Power of Psilocybin: Therapeutic Benefits & Risks
Podcast: Huberman Lab
8 min. read
— Description —
Discover the transformative power of psilocybin as it rewires the brain, leading to new ideas and insights Clinical trials show its superiority in treating depression, while a combination of psilocybin and talk therapy yields long-lasting results Learn the best practices for a guided psilocybin journey and explore its potential in treating various conditions.
The Brain-Rewiring Power of Psilocybin: Therapeutic Benefits & Risks
Table of contents
Key Takeaways
- Psilocybin’s main effect is to mimic serotonin in a very specific way, leading to neuroplasticity
- The goal of psilocybin is the adaptive rewiring of the brain, not just rewiring of the brain – you want to rewire that leads to new and interesting ideas
-
Clinical trials using psilocybin for the treatment of depression are outperforming standard therapy and SSRIs (and other antidepressants)
- A combination of psilocybin + talk therapy shows evidence of the strongest long-lasting results
- Psilocybin increases communication across the brain and reduces the hierarchical organization of the brain, broadening the flow of information (including interoception and exteroception)
- “During the psilocybin journey, people have the opportunity to learn new relationships between different sensory and emotional states. Those new relationships seem to persist long after the psychedelic journey is finished.” – Dr. Andrew Huberman
-
Best practices for an effective guided psilocybin journey:
- Sit or lie down comfortably with eyes closed or an eye mask
- Music is critical to the experience
- 1 or more people present should not be on psilocybin
- No food at least 4 hours prior to the journey
- Key features of the trip from those who experience positive results: a sense of unity, sense of spirituality, sense of bliss at some point during the experience, insight, and learning about one’s life
-
Current clinical studies and areas of promise for psilocybin use: treatment resistance depression, cancer-related depression, and anxiety
- Newer studies are exploring use for alcohol abuse, tobacco addiction, OCD, and more
Introduction
- Dr. Andrew Huberman, Ph.D. is a Professor of Neurobiology and Ophthalmology at Stanford University School of Medicine. His lab focuses on neural regeneration, neuroplasticity, and brain states such as stress, focus, fear, and optimal performance.
- Andrew Huberman breaks down everything you’ve been curious to know about psilocybin: what it is, how it works at the cellular level, emerging clinical trial evidence of use for mental health, and much more.
- Host: Andrew Huberman (@hubermanlab)
What Is Psilocybin?
- Psilocybin is a tryptamine, closely resembling serotonin (naturally made in the brain and body)
- The active derivative of psilocybin is psilocin
-
Serotonin is a neuromodulator (changes the activity of other neurons) to produce a net effect of satiety, mood regulation, sense of pleasure, and many more functions that impact daily life
- There are a lot of serotonin receptors and can change expressions to produce hundreds and maybe thousands of functions
-
Psilocybin mainly binds to the serotonin 2A receptor which allows for specific types of neural circuitry to take place and last even after exposure
- Serotonin 2A receptors have a lot of expression in the neocortex, responsible for understanding context, behavior, thoughts, speech patterns, perception, sensation
- There’s also a very high amount of serotonin 2A receptors in the visual cortex (which is why psilocybin triggers hallucinations)
- When using psilocybin, there’s a shift from the brain being more segmented to more extensive communication and integration
Psilocybin Dosing
- Psilocybin in a study setting is administered orally or in its synthetic form – not just eating mushrooms which is too hard to dose
- Clinical study dose options: (1) 1mg-3mg per day repeatedly over time; (2) 10mg dose given once or twice in two separate sessions; (3) 5-30mg dose given once or twice in two separate sessions
- Mushrooms are often measured in grams or ounces – 1,000mg = 1g; there’s about 1% psilocybin present in mushrooms(about 10mg psilocybin)
- Heroic doses: approximately 5g dose of mushrooms (translates into about 50mg psilocybin)
- Remember, sourcing is key – not all mushrooms are created equal
Understanding The Elements Of An Effective Psilocybin Journey
- Conditions of participation: 25 years of age or older, no previous psychotic episodes, no first relatives with schizophrenia, not on antidepressants
- Set (mindset of person) and setting (environment and people present) need to be crafted in just the right manner to bias the experience towards a beneficial journey instead of a ‘bad trip’
-
Best practices for psilocybin use in the clinical setting:
- Use an eye mask or keep your eyes closed for the majority of sessions because too much time will be spent on the altered perception of the environment (visual hallucinations) if your eyes are open
- 1 or more people not on psilocybin should be present to make sure the person experiencing the trip doesn’t do anything harmful to oneself or others
- The person should be seated or lying down comfortably
- Music is a huge element of positive experience because it drives cognitive and emotional experience – usually starts calm then moves into something with more percussion at the peak of a journey then gets softer again until it completes with nature or soothing sounds
- The journey is usually 4-6 hours
- No food at least 4 hours prior to the journey
- There is usually a lot of perceptual and emotional blending throughout the course of the journey
- Psilocybin journeys are contraindicated for women who are pregnant or breastfeeding
- There is an anxiety component around the peak of experience that will taper off after 2-3 hours as you move toward the end of the journey
Lasting Effects Of Psilocybin On Brain Networks
- Psilocybin expands functional connectivity of the brain while on and persists after psilocybin has worn off
- The goal of psilocybin is the adaptive rewiring of the brain, not just rewiring of the brain – you want rewiring that leads to new and interesting ideas that are accessible after the journey and allow for improved function
- Positive effects on creativity have only been studied in a narrow context but proper use does seem to enhance creativity
-
Psilocybin changes one’s experience and emotional response to music during the journey and after, allowing people to feel more joy with music
- Psilocybin enhances positive feelings about music and dulls feelings of sadness when listening to sad music
- Some of the thinking and emotional states of depression are habitual: they relate to an implicit feeling of being let down that A didn’t lead to B didn’t lead to C the way you thought – all negative outcomes
- Psilocybin can lead to new learning and thinking patterns and rewiring of the brain that allow you to consider other possibilities – the journey initiates the neuroplasticity process but isn’t the entire process
- The brain does not really change from neurogenesis (creating new neurons) in the adult human brain
Benefits & Risks Of Psilocybin
- A key feature of a positive experience is a feeling of boundlessness, not aligned with any single feeling, process, or direction
-
During the ‘peak’ of the experience when ego dissolution is highest, it is the guide’s role to allow them to experience the peak and provide security to get through the discomfort
- Anxiety itself is an important feature of positive therapeutic benefit but it can’t be so high that it leads to pervasive elevated mood
- Letting go is important to the process
- A physiologic sigh can be used during peak to bring down anxiety: 5-minutes of two deep inhales through the nose, one long exhale through the mouth
-
Responders who report positive clinical outcomes experience: a sense of unity, sense of spirituality, the experience of bliss at some point, insight, and learning about one’s life
- Non-responders experience: less unity, less bliss, less insight into life, etc.
- Just seeing hallucinations doesn’t lead to a positive therapeutic outcome
Clinical Applications Of Psilocybin
- The most evidence is for cancer-related depression, cancer-related anxiety, and treatment-resistant depression
- There is moderate evidence for alcohol use and abuse and tobacco addiction
- There is low evidence for OCD, demoralization from AIDS diagnosis, and cluster headaches and migraines
-
The most effective dose in a clinical context for therapeutic benefit in treatment-resistant depression is 25-30mg dose
- Note, there is greater relief at higher doses but also greater adverse events ranging from mild headaches to suicidal ideation
-
Promising results: in sessions where 25mg psilocybin is taken twice across two sessions about one week apart, 60-75% of people report a good, lasting experience with minimal adverse effect
- Intervention was supported with psychotherapy for maximal results
Articles & Other Resources
-
Articles
- The neural basis of psychedelic action (Nature Neuroscience)
- The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers (Frontiers in Human Neuroscience)
- Increased low-frequency brain responses to music after psilocybin therapy for depression (Journal of Affective Disorders)
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression (Frontiers in Pharmacology)
- Brief structured respiration practices enhance mood and reduce physiological arousal (Cell Reports Medicine)
- Therapeutic use of psilocybin: Practical considerations for dosing and administration (Frontiers in Psychiatry)
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo (Neuron)
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics (Frontiers in Psychiatry)
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression (The New England Journal of Medicine)
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder (JAMA Psychiatry)
- The costs and benefits of psychedelics on cognition and mood (Neuron)
-
Other Resources
- The Physiological Sigh
- Dr. Matthew Johnson: Psychedelic Medicine