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How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks

Episode 123 May 8, 2023 2h 5m 25 insights
In this episode, I discuss what psilocybin is (chemically) and how it works at the cellular and neural circuit level to trigger neuroplasticity, which is our brain’s ability to rewire itself in ways that lead to long-lasting shifts in our emotional, cognitive and behavioral patterns and abilities. I discuss the emerging clinical trial evidence for the use of psilocybin in the treatment of depression, addictions and other psychiatric challenges. I explain the typical duration and phases of a psilocybin journey, the different categories of dosages often used and I explain the importance of set, setting and support when using psychedelics. I explain which groups of people place themselves at great risk by taking psilocybin as well as groups that could benefit, and I highlight the rapidly changing legal and medical landscape around psilocybin. This episode is a thorough exploration of psilocybin from the scientific and clinical literature perspective and ought to be of interest to anyone curious about psilocybin, mental health, neuroplasticity and/or psychedelics more generally. For the full show notes, visit hubermanlab.com.
Actionable Insights

1. Avoid Psilocybin with Psychosis Risk

Do not use psilocybin if you have an existing predisposition to psychotic or bipolar episodes, or if a first-degree relative has bipolar, schizophrenic, or schizotypal issues, as it can trigger such episodes.

2. Avoid Psilocybin Under 25

Individuals 25 years old or younger should avoid psilocybin because their brains are still undergoing significant developmental neuroplasticity, and most clinical studies focus on adults 25 and older.

Be aware that psilocybin is a Schedule I drug and generally illegal in the United States, with rare exceptions in clinical studies or decriminalized areas, making possession or sale unlawful. This is critical for personal safety and legal protection.

4. Consult Doctor on Antidepressants

If currently taking antidepressants, do not cease them to use psilocybin without consulting your physician or psychiatrist, as stopping medication abruptly can be very dangerous. Clinical studies typically require abstinence from antidepressants prior to psilocybin use.

5. Ensure Safe Physical Environment

The physical setting for a psilocybin journey must be absolutely safe, free from hazards like open windows, moving traffic, or bodies of water, to prevent harm to the individual.

6. Have Sober Guides Present

Always have at least one, and ideally two or more, sober individuals present during a psilocybin journey to ensure the safety of the person under the influence and prevent self-harm or harm to others.

7. Prioritize Set and Setting

For a therapeutically beneficial psilocybin journey and to avoid a ‘bad trip,’ it is crucial to prioritize ‘set’ (mindset) and ‘setting’ (environment and people present), as these bias the probability of a positive outcome.

8. Combine Psilocybin with Psychotherapy

For major depressive disorder, combining psilocybin therapy with supportive psychotherapy (talk therapy) is significantly more efficacious than either intervention alone, producing large, rapid, and sustained antidepressant effects.

9. Consider Therapeutic Psilocybin Dosage

For pronounced therapeutic outcomes in clinical studies, a dosage of 25 to 30 milligrams of psilocybin, taken once or twice, has been shown most effective, compared to microdosing (1-3mg daily) or lower single doses (10mg).

10. Optimize Psilocybin Journey Conditions

To ensure a psilocybin journey is therapeutically adaptive and leads to long-term positive changes, pay close attention to conditions such as eyes closed vs. open, the presence and type of music, dosage, and who is present or not.

11. Utilize Eye Mask for Inward Focus

Wear an eye mask or keep eyes covered for most, if not all, of the psilocybin session to limit focus on external visual hallucinations and encourage an inward journey of thoughts, memories, and emotions for therapeutic benefit.

12. Incorporate Music Strategically

Music is a critical driver of the cognitive and emotional experience during a psilocybin journey, profoundly influencing whether it is perceived as beneficial and one of life’s most important positive experiences.

13. Tailor Music to Journey Phases

Select music that matches the journey’s contour: start with low-volume, non-vocal classical music, transition to intense, percussive music during the peak (45-90 minutes), and conclude with softer, melodic music or nature sounds.

14. Fast Before Psilocybin Journey

Do not eat for at least four hours prior to a psilocybin journey, especially if consuming mushrooms, as food in the gut can impact the conversion of psilocybin to psilocin and affect the journey’s duration and intensity.

15. Allow Ego Dissolution and Anxiety

During the peak of a psilocybin journey, embrace the anxiety and ’ego dissolution’ by letting go and moving through the experience, understanding that this intense phase is temporary and crucial for therapeutic benefit, with guides providing support.

16. Use Physiological Sigh for Anxiety

If anxiety becomes too high during a psilocybin session, use the physiological sigh (two inhales through the nose, followed by a long exhale through the mouth) as a real-time tool to rapidly and significantly reduce stress and regain calm.

17. Engage in Post-Journey Integration

Understand that much of the therapeutic benefit and neuroplasticity from psilocybin occurs after the session; actively use your conscious brain to guide this plasticity in adaptive ways, clearing paths through old, ineffective thought patterns.

18. Consider Psilocybin for Depression/Anxiety

Psilocybin shows the strongest evidence for positive therapeutic outcomes in treating cancer-related depression, cancer-related anxiety, and treatment-resistant depression when administered with appropriate dosage, set, and setting.

19. Consider Psilocybin for Addiction

There is some evidence supporting the use of psilocybin journeys for improving outcomes in alcohol use disorder and tobacco addiction, typically involving one or two sessions with proper support.

20. Consider Psilocybin for OCD/Headaches

Minimal clinical trial support exists for psilocybin providing relief or partial relief for obsessive-compulsive disorder, cluster headaches, migraines, and demoralization due to an AIDS diagnosis.

21. Convert Mushroom Weight to Psilocybin

To estimate psilocybin content from mushrooms, remember that one gram of mushrooms (1000mg) typically contains approximately 10 milligrams of psilocybin, based on an average 1% psilocybin concentration.

22. Be Aware of Psilocybin Variability

The actual concentration of psilocybin in mushrooms can vary significantly (0.5% to 2%) depending on strain, age, and storage, meaning a gram of mushrooms might contain anywhere from 5 to 20 milligrams of psilocybin.

23. Ensure Daily Electrolyte Hydration

To maintain optimal brain and body function and prevent diminished cognitive/physical performance, ensure adequate hydration and electrolyte intake (sodium, magnesium, potassium) by drinking an electrolyte mix like Element, especially upon waking and during exercise.

24. Practice Meditation or Yoga Nidra

Engage in meditation, mindfulness training, or yoga nidra/non-sleep deep rest (NSDR) sessions, even for just 10 minutes, to restore cognitive and physical energy and explore different states of consciousness.

25. Cover Foundational Nutrition with AG1

Take a vitamin, mineral, and probiotic drink like AG1 daily to support gut health with probiotics, which are vital for microbiota communication with the brain and immune system, and to meet foundational nutritional needs with adaptogens, vitamins, and minerals.