Dr. Andrew Huberman about Psilocybin

1) Andrew Huberman discusses various aspects related to psilocybin, including its chemical composition, how it works on neural networks and neuroplasticity, clinical studies, dosages, and conditions. He points out that psilocybin is still illegal in the United States except for rare clinical studies and some decriminalized areas, such as Oregon and Oakland, California. He also covers safety considerations, including whether young people, those under 25 years old, should consider psilocybin, and if it is safe for people with a history of psychosis or related psychiatric conditions.

2) Psilocybin is a tryptamine, which is a class of compounds that includes psilocybin, DMT, and 5mao DMT. These compounds are structurally and chemically similar to serotonin, a neuromodulator that is naturally produced by the body and brain. Serotonin is involved in many functions, such as regulating mood, pleasure, motivation, and satiety. Psilocybin is similar to serotonin in that it also changes the activity of other neurons, which is why it can have therapeutic benefits.

3) Andrew explains the role of serotonin and its receptors in the brain, and how psilocybin, a hallucinogenic compound found in certain mushrooms, works. Psilocybin closely resembles serotonin and mainly binds to and activates the serotonin 2A receptor, leading to significant relief from depression and other compulsive disorders. The clinical trials for psilocybin are outperforming standard therapy and other antidepressants inproviding relief, leading to excitement within the psychiatric community.However, the narrator also notes the controversy and growing concerns over drugs like SSRIs and emphasizes the importance of understanding how psilocybin works to make it work optimally for a given condition or goal.

4) Andrew discusses the differences between selective serotonin reuptake inhibitors (SSRIs) and psilocybin in terms of their effects on serotonin transmission in the brain. SSRIs increase the amount of serotonin around, making it available for binding to various receptors non-specifically, while psilocybin selectively and strongly binds to and activates the serotonin 2A receptor. This receptor has a high expression in the neocortex, which includes the prefrontal cortex responsible for appropriate behavior, speech, and thought patterns. Psilocybin triggers visual hallucinations by having a very high expression of serotonin 2A receptors in the visual cortex.

5) The typical dosage used in clinical studies ranges from one milligram to 3 milligrams given repeatedly from day to day, referred to as microdosing. On the other hand, a single 10 milligram dose is given once, or a 25 to 30 milligram dosage given once or twice is referred to as macro or quote-unquote heroic dosing. The concentration of psilocybin in most so-called magic mushrooms is about 1%, meaning one gram of mushrooms contains approximately 10 milligrams of psilocybin, and the so-called heroic dose, which refers to the ingestion of 5 grams of mushrooms, translates to 50 milligrams of psilocybin.

6) Under the influence of the psychedelic and who can provide safety and support throughout the journey. The setting should also be comfortable and calming, with minimal distractions and access to water and other necessities. On the other hand, the mindset or set of the person undergoing the journey is also crucial, as it can heavily influence the outcome of the experience. It is recommended that individuals approach the experience with a positive attitude, a willingness to let go of control, and a sense of curiosity and openness. Overall, while the dosing and sourcing of psilocybin are important factors to consider, the set and setting of the psilocybin journey can have a significant impact on its safety and efficacy.

7) The importance of set and setting when taking psychedelics, particularly psilocybin, is emphasized. Set refers to the mindset and intention of the person taking the psychedelic while setting refers to the physical and social environment. It is emphasized that responsible individuals who are not using the psychedelic should be present to ensure the safety of the person taking psilocybin. The ideal setting is a quiet, closed, and dimly lit environment where the person can lie down and have their eyes covered or at least wear an eye mask. Music is also a critical component of the setting, as it is one of the major drivers of the cognitive and emotional experience that someone has on psilocybin.

8) Andrew centers on perceptual blending and emotional control that can occur through the use of psilocybin. The overall effect is synesthesia and an unordinary sense of control over emotions and perceptions. The discussion explores the cell biology and chemistry behind this phenomenon, including the activation of serotonin 2A receptors and pyramidal neurons. There's a shift from the brain being more modular to there being an increase in integration of communication across different brain regions.

9) Andrew explains that when psilocybin is present in the system and serotonin 2A receptors are activated, there is a broadening of the flow of sensory information from the bottom up, resulting in less hierarchical activation of brain circuitry. This broadening of the flow of information includes the blending of different senses, such as the sense of interception of the body and what's happening inside. It partially explains why psilocybin can cause someone to link their breathing to a sound or to link a particular motif or voice in a song to a particular emotional state.

10) Andrew explores the impact of psilocybin on creativity and experience of life, aside from its well-documented positive effects on treating depression and addiction. The positive effects of psilocybin on creativity and life experiences have only been explored in a limited set of dimensions, but where explored, the findings are interesting. For instance, studies have shown that psilocybin changes one's emotional response to music, not only during the journey but also thereafter.

11) Andrew discusses how psilocybin can rewire the connections between the emotion centers in the brain and the networks that control auditory perception of music. While it is not specifically focused on during a psilocybin session, music that one likes can tone down or reduce the depressiveness and sadness it may cause even after the drug has worn off. The study he highlights shows that psilocybin can bring about both subjective and structural and functional changes in the brain, which can expand connectivity between different brain areas, leading to an increase in creativity and a new learning approach that generates alternative perspectives.

12) Andrew delves into the subjective experiences and changes in perception that people often have during a psilocybin journey. These experiences may include the dissolution of the ego, feelings of connectedness, and profound insights. He talks about how scientific studies on psilocybin use subjective measures to put numbers and statistics to these experiences, allowing for comparisons between different groups and studies, and thus providing insights into what psilocybin may be doing when it's effective or not.

13) Andrew discusses a study on the effects of psilocybin and how it showed that a positive psychedelic experience is characterized by a feeling of oceanic boundlessness. This feeling is described as an unusual, mystical experience that is beyond this world and not linked to any specific outcome. The intensity of this experience seems to be positively correlated with therapeutic outcomes such as relief from major depression. The study also found that during the peak of the psychedelic journey, when people often experience ego dissolution, anxiety, and fear, the guides' role is to keep the person safe while encouraging them to let go and move through the experience. The experience of unity, spirituality, insights, and bliss during the psilocybin journey correlates with positive clinical outcomes.

14) Andrew discusses the differences between responders and non-responders in a psilocybin treatment study. Those who benefited from the treatment tended to report more spiritual experiences, unity, insightfulness, and complex imagery, while non-responders reported less of these experiences. The importance of ego dissolution, or letting go, as a component of the psychedelic journey is emphasized by researchers in the field, especially during the peak phase of the experience. However, extreme levels of anxiety are negatively correlated with positive therapeutic outcomes and can hinder neuronal rewiring that leads to a more pervasive elevated mood.

15) Andrew discusses the importance of having a real-time tool to adjust anxiety while under the influence of psychedelics like psilocybin. He explains that Dr. Matthew Johnson's laboratory and at least one other laboratory have incorporated real-time breathing tools like the physiological side to reduce levels of autonomic arousal, anxiety, and stress during psychedelic sessions. This self-directing calm reduces anxiety levels so people can move through the peak and other phases of the psychedelic journey with ease.

16) Andrew discusses how psilocybin and other psychedelic drugs can induce neuroplasticity by adding or strengthening new neural connections in the human brain. While neurogenesis has been suggested as a possible mode of plasticity, it does not explain most of the plasticity that occurs in the adult human brain. The predominant theory is that psilocybin induces neuroplasticity through the growth of dendrites and dendritic spines on pyramidal neurons in different parts of the brain, which appear like little mushroom-shaped protrusions.

17) Andrew discusses the therapeutic benefits of psilocybin, which induces both structural and functional changes in brain circuitry in both animal and human brains. Though animal studies tend to use higher doses than therapeutic human doses, psilocybin has been shown to have minimal to strong evidence of therapeutic benefits in treating disorders such as major depression and addictive disorders. However, it wasn't until recently, when psilocybin received "breakthrough status" at the FDA about five years ago, that significant research was conducted to explore its potential in treating various disorders.

18) Andrew discusses the exciting results of recent clinical studies exploring the use of psilocybin journeys as a way to treat depression. The studies involve one or two psilocybin sessions, with dosages ranging from zero milligrams of placebo to 30 milligrams. The studies found that the most effective dosage for treatment-resistant depression is 25-30 milligrams, and that higher dosages tend to lead to a greater chance of adverse events, including feelings of suicidal ideation. However, overall, the studies show that psilocybin can provide significant relief from depressive symptoms and that it has the potential to be a powerful therapeutic tool.

19) Huberman discusses various studies and clinical trials regarding the therapeutic benefits of psilocybin. A single dose of 25 milligrams of psilocybin was found to provide significant relief from treatment-resistant depression, although the degree of relief varied depending on the individual. However, the majority of patients in the trials experienced long-lasting relief from depression with two sessions spaced a week apart. It was found that anywhere from 60 to 75 percent of people who have major depressive disorder report a good experience with the psilocybin sessions, with minimal adverse events, and substantial positive relief from depression in the weeks following the sessions.