Psilocybin is emerging as a promising "therapeutic psychedelic" across various different conditions and diseases. What is the buzz about, and how does psilocybin work?
In this video, we dive into psilocybin's rich history, chemical structure and biochemical mechanism of action. This includes striking effects like dendritogenesis and synaptic rewiring in mice. We will review a large scale synthesis of psilocybin, delivering an impressive 1.2 kg of cGMP material for clinical supply this works using quite standard chemical reactions that most of you will understand. We then turn to the clinical evidence where it is strong and where less so in particular, treatmentresistant depression. This data in published late 2022, has drawn a lot of public attention to psilocybin but is just one of many interesting reports. Finally, we try to understand psilocybin's effect on brain network modularity/ connectivity which makes it different from traditional antidepressants.

NOTE:
This video does not lay out the practical synthesis of psychedelics or drugs
This video does not suggest that psilocybin is a "wonder drug" for everyone there are important safety precautions and supervision through qualified medical staff is key

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00:00 Psilocybin a therapeutic psychedelic?
01:09 Disclaimer and Andrew Huberman psilocybin podcast
01:40 Psilocybin's history might date back 10'000 years
04:20 Albert Hofmann's investigations, including selfexperiment
07:23 Hofmann's synthesis and "war on drugs"
08:19 Psilocybin becomes pislocin which can pass the bloodbrain barrier
11:22 Psilocybin literally changes the brain of mice
12:36 Organic chemistry and 1.2 kg synthesis by the Usona Institute
16:16 What is the evidence? What is the entourage effect?
17:48 Psilocybin's efficacy in alcohol use disorder
18:28 Psilocybin efficacy in treatmentresistant depression
21:42 How brain networks are "changed and reshuffled"
25:36 Why do different people experience trips differently?


Disclaimer This channel does not provide medical advice!
No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on Youtube.

Key references:
SingleDose Psilocybin for a TreatmentResistant Episode of Major Depression | NEJM 2022, 387, 1637
Therapeutic use of psilocybin: Practical considerations for dosing and administration | Front. Psychiatry, 2022, 13, 1040217
Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics | Front. Psychiatry, 2021, 12, 724606
Increased global integration in the brain after psilocybin therapy for depression | Nature Medicine 2022, 28, 844
Percentage of Heavy Drinking Days Following PsilocybinAssisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder | JAMA Psychiatry 2022, 79, 953
DARK Classics in Chemical Neuroscience: Psilocybin; ACS Chem. Neuroscience 2018, 9, 2438
Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention | NeuroImage 2020, 218, 116980
Die psychotropen Wirkstoffe der mexikanischen Zauberpilze (Albert Hofmann) | Verhandlungen der Naturforschenden Gesellschaft in Basel 1960, 71, 239
Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice; Toxins 2015, 7, 1018


Some recommended books on organic synthesis:
Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
Nicolaou; Classics in Total Synthesis 13 (the ultimate total synthesis trilogy)
Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)