May 8, 2023 • 2hr 5min
How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks
Huberman Lab
Key Takeaways
- Psilocybin is a psychedelic compound that closely resembles serotonin and primarily activates the serotonin 2A receptor in the brain
- Psilocybin induces neuroplasticity by increasing connectivity between brain regions and promoting growth of new neural connections
- Clinical trials show psilocybin can provide significant relief from treatment-resistant depression, with effects 2.5-4x greater than typical antidepressants
- Proper "set and setting" are critical for safe and therapeutic psilocybin experiences, including having trained guides present
- Typical therapeutic doses are 25-30mg, given in 1-2 sessions spaced about a week apart
- Psilocybin is still illegal in most places and should only be used in approved clinical/research settings
- Psilocybin is contraindicated for those with or predisposed to psychosis, under 25 years old, or currently on antidepressants
- More research is still needed to fully understand psilocybin's mechanisms and optimize its therapeutic potential
Introduction
In this episode, Dr. Andrew Huberman provides a comprehensive overview of psilocybin - the psychedelic compound found in "magic mushrooms". He discusses what psilocybin is chemically, how it works in the brain, its effects on neuroplasticity, the latest clinical research on its therapeutic potential, proper protocols for its use, and important safety considerations.
Huberman emphasizes that while the research on psilocybin is very promising, especially for treatment-resistant depression, it is still a powerful compound that carries risks. He stresses it should only be used in approved clinical/research settings under proper medical supervision. The goal of the episode is to explain the science behind psilocybin and its potential, not to encourage recreational use.
Topics Discussed
What is Psilocybin? (0:12:00)
- Psilocybin is a tryptamine compound that closely resembles serotonin chemically
- It is converted to psilocin in the gut, which is the active form that enters the brain
- Psilocybin/psilocin primarily activate the serotonin 2A receptor in the brain
- "Psilocybin basically is serotonin. Now, for those of you that are familiar with psilocybin and serotonin, you might think, wait, that's not true. But in fact, psilocybin's main effect is to mimic serotonin, but it does it in a very specific way."
How Psilocybin Affects the Brain (0:48:58)
- Increases connectivity between brain regions that don't normally communicate as much
- Reduces the brain's normal hierarchical organization and increases lateral communication
- Leads to perceptual blending/synesthesia (e.g. "seeing" music)
- Activates visual cortex even with eyes closed, leading to hallucinations
- Promotes neuroplasticity by inducing growth of new dendritic spines on neurons
The Psilocybin Journey Experience (0:36:21)
- Typically lasts 4-6 hours, with effects starting 30-45 minutes after ingestion
- Peak effects occur around 2-3 hours in, often accompanied by anxiety
- Common experiences include:
- Visual hallucinations (even with eyes closed)
- Perceptual distortions and synesthesia
- Emotional intensity
- Ego dissolution
- "Oceanic boundlessness" - feeling of unity/connectedness
- "The ability to move through that stressful period to somewhat guide oneself or to be encouraged to guide oneself through that peak and that anxiety and the fear of losing oneself and the so called ego dissolution that occurs, is an important feature for an effective therapeutic session."
Proper "Set and Setting" (0:36:21)
- Set refers to mindset/intention of the person taking psilocybin
- Setting refers to the physical environment and people present
- Key elements for therapeutic sessions:
- Safe, controlled environment
- Trained guides/therapists present
- Lying down with eye mask on
- Carefully selected music playlist
- Proper set/setting is critical for safety and positive outcomes
Dosing and Administration (0:30:28)
- Typical therapeutic doses are 25-30mg of synthetic psilocybin
- This is roughly equivalent to 2.5-3g of dried mushrooms
- Clinical trials often use two sessions spaced about a week apart
- Microdosing (1-3mg daily) has less evidence for therapeutic effects
- Higher doses tend to have greater therapeutic effects but also more adverse events
Clinical Research on Therapeutic Effects (1:48:08)
- Most promising evidence is for treatment of:
- Major depressive disorder
- Treatment-resistant depression
- Cancer-related anxiety/depression
- Some evidence also for:
- Alcohol use disorder
- Tobacco addiction
- OCD
- Recent clinical trials show:
- 60-75% of participants experience significant depression relief
- Effects 2.5x greater than psychotherapy alone
- Effects 4x greater than typical antidepressants
- "The present trial showed that psilocybin administered in the context of supportive psychotherapy...produced large, rapid, and sustained antidepressant effects. The effect sizes reported in this study were approximately 2.5 times greater than the effects sizes found in psychotherapy and more than four times greater than the effect sizes found in psychopharmacologic depression treatment studies."
Proposed Mechanisms of Action (1:36:11)
- Promotes growth of new dendritic spines on neurons
- Increases connectivity between brain networks
- Reduces activity in the default mode network
- Allows formation of new cognitive/emotional associations
- May help "reset" dysfunctional thought/behavior patterns
Safety Considerations and Contraindications (0:27:21)
- Psilocybin is still illegal in most places and should only be used in approved clinical/research settings
- Contraindicated for:
- Those with or predisposed to psychosis/bipolar disorder
- People under 25 years old
- Pregnant/breastfeeding women
- Can have dangerous interactions with antidepressants and other medications
- Potential adverse events include:
- Anxiety/panic attacks
- Temporary psychotic-like symptoms
- Cardiovascular issues (increased heart rate/blood pressure)
- "Psilocybin is a powerful, powerful drug, not just to be under the influence of, but also in terms of its long standing changes after the effects of psilocybin have worn off."
Future Research Directions (1:48:08)
- Optimizing dosing protocols and number of sessions
- Combining psilocybin with psychotherapy
- Exploring effects on other conditions beyond depression
- Better understanding neuroplasticity mechanisms
- Developing new compounds inspired by psilocybin
Conclusion
Huberman concludes that psilocybin is an extremely promising compound for treating depression and potentially other mental health conditions. Its ability to rapidly induce neuroplasticity and provide long-lasting relief from a single or few doses is unprecedented. However, he emphasizes that much more research is still needed to fully understand its mechanisms and optimize its use.
He reiterates that psilocybin is still illegal in most places and carries significant risks if used improperly. It should only be used in approved clinical/research settings under proper medical supervision. Huberman is excited about psilocybin's potential but urges caution, stating:
"So I consider the science and use of psilocybin to be an exciting but still preliminary area that I certainly am paying a lot of attention to, and I know there's a lot of excitement about. [...] They are sharp blades, as we say. And with sharp blades you can do incredible things, but you can also cut yourself very badly."
Overall, this episode provides a comprehensive scientific overview of psilocybin, explaining what we currently know about how it works in the brain, its therapeutic potential, and important considerations around its use. Huberman's goal is to educate about the science, not encourage recreational use, and he emphasizes the need for continued rigorous research in this promising but still early field.
