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Understanding Psychedelics and Their Potential Clinical Applications

• Dr. Robin Carhart Harris is a distinguished professor of Neurology and Psychiatry at the University of California San Francisco and a leading researcher in the field of psychedelics.

• His laboratory studies how psychedelics change neural circuitry in the brain, leading to new ideas and forms of learning.

• Clinical trials have shown that appropriate dosages of psilocybin, found in magic mushrooms, can alleviate major depression in more than 67% of people.

• In this podcast, Dr. Carhart Harris discusses the clinical trials, the history of the study of psychedelics, and how psychedelics are being applied to expand different aspects of the human mind.

• Psychedelics are a class of compounds that work on a particular receptor in the brain, the serotonin 2A receptor.

• The term "psychedelic" comes from two ancient Greek words meaning "to make visible" or "to make clear" and "the human mind or soul," referring to the compounds' ability to reveal aspects of the psyche that are ordinarily not visible.

• The action of classic psychedelics reveals material that may have been repressed, catalyzing the therapeutic process with strong emotional release and insights.

• The action of classic psychedelics is what makes them different from other compounds like ketamine and cannabis.

• The pharmacology of psychedelics is useful, but the phenomenology and subjective experience cannot be neglected.

• The legislation surrounding psychedelics is evolving in the United States and elsewhere for the use of psychedelics to treat psychiatric challenges.

• The podcast is part of the effort to bring science-based tools for everyday life to the general public.

• The sponsors of the podcast include Eight Sleep, Levels, and HVMN Ketone IQ.Psilocybin Clinical Trials and the Importance of the Psychedelic Experience

• Psilocybin is the principal hallucinatory psychedelic agent in magic mushrooms.

• Clinical trials typically use dosages of 25 milligrams of psilocybin.

• A gram of magic mushrooms contains roughly 10 milligrams of psilocybin.

• Microdosing is a sub-perceptible dose of a classic psychedelic like LSD or psilocybin.

• Microdosing is believed to improve well-being and aspects of cognition, but the evidence is still thin.

• A clinical trial comparing 25 milligrams of psilocybin to 10 milligrams and a placebo found that the placebo performed just as well as the microdose in terms of therapeutic outcomes.

• The psychedelic experience is important for therapeutic outcomes, and studies show that certain types of experiences are predictive of positive outcomes.

• Psychedelic therapy involves two mental health professionals and an individual ingesting the drug with music playing throughout the session.

• The music starts off spacious and builds into more emotional music as the drug effects become stronger.

• The combination of psychedelics and therapy is believed to have a positive interaction and synergy.

• The psychedelic experience in therapy involves shutting one's eyes and experiencing organic, dynamic, and fascinating patterns and colors.

• Psychedelic therapy is being studied for the treatment of otherwise intractable depression with promising results.Psychedelics and the Importance of Letting Go: A Discussion with Dr. Robin Carhart-Harris

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• Psychedelics can induce visual and auditory hallucinations, synesthesia, and somatic sensations.

• Music is a key variable in psychedelic clinical trials.

• The patient's willingness to let go and allow the experience to take them mentally is critical in psychedelic therapy.

• Trust, letting go, and being open are the three components of successful psychedelic therapy.

• The initial struggle in psychedelic therapy is against the general drug effects.

• The initial struggle is not specific to any prior event but is related to the breaking down of the sense of assuredness about oneself and the environment.

• Psychedelics increase global functional connectivity in the brain, transcending modular communication and crossing different modalities.

• Computational modeling shows that the activation of serotonin 2A receptors leads to increased connectivity.

• The causality between the increased connectivity and the subjective experience is circular.

• Laboratories are modifying psychedelics to treat depression without producing hallucinations.

• The modified psychedelics would be more acceptable to the medical system and patients who are not inclined toward psychedelic experiences.Psychedelic Therapy, Modularity, and Microdosing: A Discussion

• There is a desire for a therapeutic drug that treats depression without psychedelic effects.

• Microdosing, while sub-perceptible, may not have the same therapeutic effects as macro doses.

• There are currently no selective serotonin 2A receptor agonists that are non-psychedelic and used in psychiatry.

• Psychedelic therapy has been shown to increase communication between brain areas (global connectivity) and decrease modularity.

• This increase in connectivity has been observed both during and after the psychedelic experience for depression patients.

• The decrease in modularity correlates with a positive therapeutic outcome for depression patients.

• The increase in global connectivity has also been observed in healthy individuals and correlates with an improvement in well-being.

• Microdosing is not as compelling as macro doses in a controlled, safe setting for psychedelic therapy.

• Anorexia nervosa patients have seen positive results with psilocybin therapy, with a decrease in obsessive thoughts about food and an improvement in willingness to consume healthier amounts of food.

• Anorexia nervosa is the most deadly of all psychiatric illnesses.

• Suicide is also a leading cause of premature death in those with depression.

• There is a need for further research and development of non-psychedelic selective serotonin 2A receptor agonists for therapeutic use in psychiatry.