Psilocybin Synthesis in 4 Steps & How Magic Mushrooms Rewire Brain Networks (Psychedelic Science)

Поділитися
Вставка
  • Опубліковано 6 тра 2024
  • 🍄 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, treatment-resistant 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 anti-depressants.
    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
    / totalsynthesis
    🚀 Thanks to all channel supporters!!!
    / totalsynthesis_official
    👉 Follow me on Instagram to follow updates on other random chemistry research and interesting news!
    total-synthesis.com
    total-synthesis.com/psilocybi...
    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 self-experiment
    07:23 Hofmann's synthesis and "war on drugs"
    08:19 Psilocybin becomes pislocin which can pass the blood-brain 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 treatment-resistant depression
    21:42 How brain networks are "changed and re-shuffled"
    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 UA-cam.
    Key references:
    - Single-Dose Psilocybin for a Treatment-Resistant 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 Psilocybin-Assisted 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 1-3 (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)
  • Наука та технологія

КОМЕНТАРІ • 226

  • @totalsynthesis
    @totalsynthesis  11 місяців тому +33

    Thanks for watching!
    Massive thank you to all channel supporters!
    www.patreon.com/totalsynthesis; instagram.com/totalsynthesis_official/
    Note: I'm reviewing comments on this video to manage spam from shady IG drug dealers!

  • @sarlol00
    @sarlol00 11 місяців тому +685

    It is anecdotal but, after 6 years of heavy drinking, it took exactly one trip to get completely sober. This was almost 2 years ago, psilocybin completely changed my life for the better.

    • @totalsynthesis
      @totalsynthesis  11 місяців тому +44

      Awesome, Im happy you are doing well

  • @patriaciasmith3499
    @patriaciasmith3499 8 місяців тому +105

    Psilocybin saved my life. I was addicted to heroin for 15 years and after Psilocybin treatment I will be 3 years clean in September. I have zero cravings.
    This is something that truly needs to be more broadly used in addiction treatment.

  • @goosecf
    @goosecf 10 місяців тому +73

    IDK about all the specific details, but I've noticed that mushrooms seem to help a lot with my ADHD. I find it so much easier to just relax and enjoy things now, whereas previously I could barely do anything without getting distracted by some meaningless crap I'd end up wasting all my time on. As a whole I think I just appreciate life more now and it's lovely.

  • @donaldaustin7007
    @donaldaustin7007 9 місяців тому +57

    Psilocybin containing mushrooms save my life. The drastically reduced my benzodiazepine withdrawal allowing me to quite illicit pill addiction after three years of heavy daily use before it would had became medically dangerous to quit

  • @jerryflecther17
    @jerryflecther17 9 місяців тому +69

    Psychedelic is the answer to most severe anxiety and depression. The use of magic mushrooms completely helps one get over depression and makes you feel like yourself.

  • @Eraserhedd
    @Eraserhedd 7 місяців тому +74

    I’ve been on Prozac and Wellbutrin for decades. it kept my depression at bay, but I felt numb. I switched to shrooms twice a month and I no longer take those meds. And actually feel things again…being able to feel chills from amazing music even came back.

  • @Joe-bh7pf
    @Joe-bh7pf 9 місяців тому +33

    I can honestly say psychedelics experience was probably one of the most profound and beautiful collection of moments I have ever had.

  • @jaspernewcomb5656
    @jaspernewcomb5656 9 місяців тому +25

    I was 14 the first time i took psychedelics. Up until that point i had smoked pot a few times with my older brother and his buddy. They'd ask, are you getting a buzz yet? I finally told them I didn't know what a buzz was do you hear it or what? They laughed at that, no you'll know when you get one. A couple weeks later they said give us two dollars and we can get you a hit of acid. Ok i didn't know what acid was but I was willing to find out. The next day they had it. Come on we have some too we can all take it together. It was 9:30 or 10pm when we took it and then they told me come on we're supposed to meet some girls uptown you can hang out with us till they come pick us up. They were supposed to be on their way but close to an hour had went by and they hadn't showed up. Then a cop drove by and they decided to head for the house because of curfew. So we took off running for home full blast and as we came up the back alley the acid kicked in and we all stopped and fell down laughing our ass off. That was just the beginning. Mom must have heard us and started yelling for us to come in. So they told me come on and try not to act like you're high. I hid behind the newspaper reading the comics while mom was watching my brother and his friend like a hawk asking what they were up too. Meanwhile I was cracking up over the cartoons and couldn't stop laughing which made my brother and his buddy start laughing. Then mom grabbed the paper and asked me what was so funny. I said the cartoons but my mom knew better she looked at me and said my God whats wrong with your eyes? That's when she noticed all three of us had dialated pupils so big our eyes looked black. She was pissed and ordered us to go to bed and told my brothers friend, GO HOME. I shot up the stairs to my bedroom and watched out the window as Tommy ran for home. He tried to jump through this swing we had but his foot caught the seat and shot his leg up and laid him out on his back in the yard. Damn i saw tracers coming off of him. It only took him a couple minutes to show back up and I could hear him telling mom his parents had already went to bed and the door was locked. Please he begged her let me stay the night. She was furious now, you get up those stairs and you better not make a noise. I was getting higher by the second our house was on main street and the street light had my curtains lit up and they were billowing out like the wind was moving them but my windows were shut. I tried closing my eyes and i could see a Kaleidescope of vivid intense colors moving in geometric patterns that was beautiful but my eyes seemed spring loaded and I couldnt keep them shut. Everything in my room was moving now i watched tracers coming off my hand when i moved it. Whew, i felt like just a head on my pillow. Then i looked at the clock so many things were happening how long has it been. What only a minute, shit this is crazy i started wondering how long it lasts. Turns out it lasts a really long time. That acid was called Love Saves pure as the driven snow and potent big ol doses. Supposedly Owsley had made it, the best on the planet. I wish i still had some myself i love tripping. I did a quarter ounce of mushrooms once and when they kicked in it was full blast instant. Not only visual but audible as well. There's that buzz you can hear. To me i felt like a big python had me that kept squeezing me. Mushrooms dont last near as long as acid but i only did them that one time. For awhile we were getting what was called purple mesc, supposedly synthetic mescaline. From what I know now i think it was actually a form of speed the king of lsd was making. Whatever it was it was good. Colors were brighter lots of energy feeling good and laughing soaking it all in. Tripping isn't for everybody. When i did it the first time i had no idea what to expect so i had no fear. I loved it. Im 64 now and over the last 50 years i took hundreds and hundreds of hits of acid. The last time i did some has been several years ago and it was good but personally I think the chemistry isnt the same as what it once was. I don't actively seek it now and I'm gonna stop talking and thinking about it because I don't want to call it to me. It does work that way...

  • @chanelleblack3816
    @chanelleblack3816 9 місяців тому +31

    Last year, I took shrooms thinking it was going to hit like an edible or something. Shit was scary at first but amazing once you start getting deeper into your thoughts

  • @MrND7
    @MrND7 11 місяців тому +54

    Was on Sertraline, Fluoxetine, Amitriptyline around 3/4 years ago and I wanted to end my life. Constant chronic pain and depression until I tried DMT. Was the polar opposite of all them horrible meds those Dr’s “trialed” me on, so positive and gave me hope to get out of the mess I was in. I then did Paul Stamets stack on micro dosing and have done that twice this year. So grateful I opened my mind with psychedelics. Love from Liverpool UK

  • @mixskillter4785
    @mixskillter4785 11 місяців тому +148

    This is incredibly insightful, instead of repeating how good psilocybin is and it's basic concepts, you digged deep into complex mechanisms of its action, statistics and study based evidence. This is what people interested in psychedelic treatments should know, it brings and makes the knowledge easily accessible. Your research and work is really appreciated

    • @totalsynthesis
      @totalsynthesis  11 місяців тому +11

      Thank you mate!! Appreciate your comment

  • @andueskitzoidneversolo2823
    @andueskitzoidneversolo2823 11 місяців тому +49

    hey um, so like i have schizophrenia and a history of psychosis. i been micro dosing and it actually helps me stay calm and not be depressed. i been stable for almost 10 years now. i do believe that with more research we might find the best medication for schizophrenia this way. i have found that using hallucinogens actually stop my hallucinations for a while. this is how my friends would test out of they had good stuff or not. they would give me some for free as long as i reported back if my hallucinations went away or not. i found that it is the same with adderal. if you give somone who is already hyper active and you give them adderal it will slow them down. but if you are not hyper active it will speed you up. i found most hallucinates work that way for me. i cannot speak for all people with sz. but hallucinates have the opposite effect on this schizophrenic supposedly because i hallucinate naturally anyways. .

  • @harkyo
    @harkyo 11 місяців тому +14

    I quit smoking after 30 years while being on a particularly high dosage of mushrooms one time two years ago. I had stepped down from vaping. Never went back. Had no desire or craving.

  • @Basidium_King
    @Basidium_King 11 місяців тому +15

    Psilocybin is the greatest medicine of our time

  • @science_and_anonymous
    @science_and_anonymous 11 місяців тому +56

    One of my absolute favorite videos thus far as a tryptamine chemist. This video didn't get to touch on some of the really fascinating heterocyclic building reactions involved in tryptamine synthesis. Fascinating stuff there. Fungi have a tremendously large area of pharmacological interest, and any medicinal chemist will tell you that. Great video, and excited to see more.

  • @kimcamiliamingang1813
    @kimcamiliamingang1813 11 місяців тому +42

    Psychedelic are just an amazing discovery. Is quite fascinating how effective they are for depression and stress disorder. Really saved my life.

  • @emilianopereda7643
    @emilianopereda7643 11 місяців тому +36

    What about a honorable mention to Maria Sabina? the Mexican healer that introduced psilocybin to Albert Hoffman? And Wesson. I mean she is in the pictures! Both with Wasson and Hoffman. As always native indigenous people get snubbed out of history when history is told.
    Maria Sabina was the original
    Curandera as she conducted “Veladas” a ritual in which the participant and their family took a heavy dose of psilocybin mushrooms while Maria sang and hummed native songs in her indigenous language. She was doing family therapy before it was a “thing” and helped thousands of people with the help of psylocibin and “folk” knowledge of nature.
    Source: hallucinogenic fungi etnomicology studies by Italian author Giorgio Samorini.

  • @mr.ch4rli3_
    @mr.ch4rli3_ 11 місяців тому +44

    Fun fact, the brain is always developing, just at slower rates, but changes in the amygdala have been observed in patients over 40.

  • @michaeld4861
    @michaeld4861 11 місяців тому +9

    32 medium sized mushrooms for his first trip! Holy crap, dude had no fear.

  • @MichaelWilliamz
    @MichaelWilliamz 11 місяців тому +18

    I never understood why governments would make this specific substance illegal

  • @pucky8231
    @pucky8231 11 місяців тому +34

    The funny thing is, as a psychedelic ,the acetate works just as well as the phosphate

  • @SetTheCurve
    @SetTheCurve 11 місяців тому +23

    Would have loved to hear more about the various synthetic and non synthetic routes to this molecule. It’s not only fascinating but also the amount of misinformation about it out there is incredible.

  • @matteroftim3
    @matteroftim3 10 місяців тому +16

    Yeah. More people should try psychedelics. Not only in a medical environment because in some countries they are illegal. But with the right set and setting they can do wonders.

  • @gamaxgbg
    @gamaxgbg 11 місяців тому +47

    Actually the most potent mushrooms aren't from the Psilocybe genus, but from Panaelous, some of which contain more than 4% of tryptamines in their dry weight.

  • @TheRusschannel
    @TheRusschannel 11 місяців тому +20

    Its a CRIME to keep these drugs from the people!

  • @smileygladhands
    @smileygladhands 11 місяців тому +12

    I wish I could try this to get over my issues, but i wouldn't even know where to start. I've googled it and haven't found a place that looks legit to me. It's illegal where I am, so I can't just go out and buy it or get a doctor to give it to me. I'm not asking for leads btw. I'm just stating that it's hard to acquire if it's illegal and you don't really know many people, which is unfortunate. Thanks for the video, brother. Maybe one day I'll save up enough to travel somewhere where it's legal and/or simple to acquire.

  • @PexiTheBuilder
    @PexiTheBuilder 11 місяців тому +19

    Definetly work on cluster headaches! Even small, barely mind altering dose keep it away few months, when before would be weekly or even multiple times a day. Also helps with depression, go deep inside head to solve problems there. Helped way more than any legal meds, which gave bad side effects, or changed whole personality to mindless zombie.

  • @owenleynes7086
    @owenleynes7086 8 місяців тому +3

    This is one of the best explanations I've seen online that isn't like 50% mis or dis information. You presented everything very eloquently and still remained sceptical, what more could anyone ask for?

  • @koukouzee2923
    @koukouzee2923 11 місяців тому +15

    Iam from algeria
    Even tho the paintings showed mushrooms
    Mushrooms use is very unknown here
    Only small comunities that apreciate it

  • @raymondready7496
    @raymondready7496 11 місяців тому +22

    Always liked mushrooms. But also lsd, mescaline and nndmt. It works to reboot my brain and thought process. About once a year or so. Your videos are awesome. Thanks

  • @samcollins8291
    @samcollins8291 11 місяців тому +10

    Suffered from encephalitis the difference of my well being was night and day, and the pain relief substantial.

  • @Neuropharmacist
    @Neuropharmacist 10 місяців тому +7

    Great video and interesting info on the synthesis! Here are some points from a neuropharmacologist working on plasticity. There is no solid evidence of psychedelic induced plasticity in the human brain. Studies have shown plasticity promoting effects mostly in rodents. While effects on dendritic spines have been reported in multiple studies, it remains somewhat unclear what these spine changes indicate. Changes in spine dynamics are influenced by many factors, including the simple housing of rodents in enriched environments. For example, in most mouse studies the mice are housed in cages with relatively little to do, but if they are placed in a cage that has "enrichment", e.g. toys, running wheels, opportunities for various activities, increases in dendritic spines are observed. Moreover, circadian rhythms and sleep are likely also important for changes in spinogenesis. My point is, that there are many variables that we still don't completely understand to really say what the changes in spine dynamics reflect, and thus I remain still cautious about saying that psychedelics unequivocally increase plasticity.
    Also, no scientific evidence to support an entourage effect with psilocybin at this stage.

  • @sneaks9150
    @sneaks9150 3 місяці тому +2

    Hoffman was crazy. He felt funny from LSD exposure to skin or something, and just consumed like a gallon of LSD, and in the middle of testing shrooms on mice, he gets inpatient and consumes over 30 mushrooms.... he could have had anywhere between 20g-50g of mushrooms and thats enough to see God and buy a waterfront property next door.

  • @Mr.Cucumba
    @Mr.Cucumba 11 місяців тому +13

    Finally! Thanks for uploading yet another video about the synthesis of psychoactive molecules.
    It is important to normalize these topics so people recognize that compounds are not inherently malignant. It is how we deal with drugs, legal or illegal, that determines the fate of people using them. I pledge for reassessing drug policy, legalization, education, harm reduction and destigmatization.

  • @ihavenoideawhatimdoinghere6285
    @ihavenoideawhatimdoinghere6285 11 місяців тому +5

    I went back to school to study this❤

  • @GOREilla.
    @GOREilla. 6 місяців тому +3

    "You gotta love 20th century chemistry"
    Oh, hell yeah, bruh!

  • @randomtimessomehow
    @randomtimessomehow 9 місяців тому +5

    This is the best video about Psilocybin here on UA-cam. Very well explained and visualized

    • @totalsynthesis
      @totalsynthesis  9 місяців тому +2

      Thank you! It's definitely quite loaded with info so I'm glad people still manage to watch it, haha

  • @austinball9068
    @austinball9068 9 місяців тому +3

    Man, I would love to see someone cover how it is that 4-ACO-DMT is isolated and how it also naturally metabolizes in vivo into psilocin. Fantastic, deeply informative video!

  • @nowknow
    @nowknow 10 місяців тому +6

    Thanks for the informative video. I'm really interested in the pharmacology of psilocin. Your video brought up a lot of insights and topics that I'm excited to dive deeper into.

  • @sobussin
    @sobussin 2 місяці тому +2

    @3:57 I know you will not believe it, but that stuff is still consumed in America. Chef Boyardee and Spaghetti’Os with hot dog slices was a delicacy for kids in the 80’s 😋

  • @anon2234
    @anon2234 11 місяців тому +10

    "Before getting your hopes up, piloerection is a fancy word for your hair standing up"
    My man who do you think is watching these videos? 😂😂😂
    Really great information though. I knew a bit of Albert Hoffman's work, but I didn't realize that he had worked heavily with psilocybin as well.

  • @austindanielek4437
    @austindanielek4437 6 місяців тому +2

    this video is so wonderfully dense with valueable information. The best I've found so far explaining the currently understood mechanisms of action. Thankyou so much for your work!

  • @wernerustettler9731
    @wernerustettler9731 10 місяців тому +3

    Canadian bioscience company Core One Labs Inc. developed and patented the process to produce synthetic Psilocybine. They today can produce pharma grade psilocybine in large volumes.

  • @ebonies7472
    @ebonies7472 2 місяці тому +1

    Wow, thank you for taking the time to create this insightful video!

  • @MrM0saic
    @MrM0saic 11 місяців тому +2

    It’s like THE COUNT, explaining the third form of life/ consciousness to me…..
    Love you brother

  • @seleneoana
    @seleneoana 7 місяців тому +5

    Few days ago I wanted to have my fist at ever psychedelic experience and took 2g of dried mushrooms. I didn’t feel anything at all. Did anyone have a similar experience and most of all does anyone know why it didn’t have any effect on me?

  • @coruscatio9
    @coruscatio9 8 місяців тому +3

    Great review.

  • @Andrew-rc3vh
    @Andrew-rc3vh 11 місяців тому +4

    Thank you for a very interesting video and well researched.

  • @KittyCatSpartan117
    @KittyCatSpartan117 11 місяців тому +3

    This reminds me of Acid Test by Tom Shroder, great book about the therapeutic effects with the administration of psychedelics on those who suffered from trauma induced PTSD. MAPS(Multidisciplinary Association for Psychedelic Studies)is also mentioned in connection to Rick Doblin. A great read 🍄✨ can’t wait to try the mushrooms I just bought to help with my healing process(physically and mentally) and must admit I’m confused on dosage. Excited nonetheless to try the mushy ❤

  • @malcolmcarter1726
    @malcolmcarter1726 11 місяців тому +10

    Fascinating. Psilocyibin definetly has a place in medicine, as does LSD 25 ALD 52 ,and 5 Meo DMT.
    I suffer with manic depression and also migraines which are very debilatating. However during the years that I was fairly regularly using LSD and Magic Mushrooms, these conditions virtualy vanished. Especially the Migraines which completely stopped!
    Then I got married and had work responsibilities so tripping was slowly left behind.
    Now Im 58 divored and had a long.period of homelessness. (thankfully that is over now) And the Migraines have returned with a vengeance, as has depression - Peaks and Troughs- along with alcoholism and opioid addiction. The availability of 'Good' LSD in the UK is practically nil, so its online mail order for me.
    I did pick some Wavy cap mushrooms last year which were interesting and helped. But for myself my favourite psychedelic is ALD 52 because of its low to no body loading, and 'smooth ride!' Also I found the visual aspect to be better than LSD 25 though 1P LSD trips can be be super visual and auditory.
    I love your videos, they make me wish I had stuck with inorganic chemistry instead of switching to human biology at school and later college.
    Very good work. Ive just subscribed and look forward to seeing more of these enlightening videos. Thank you.

  • @Kanal-ns4sq
    @Kanal-ns4sq 11 місяців тому +8

    I'm getting a tattoo of the psilocybin molecule tomorrow and today you upload that video lmao, coincidence?

  • @santiagonottoli
    @santiagonottoli 11 місяців тому +3

    Excellent presentation!

  • @thecsslife
    @thecsslife 11 місяців тому +5

    Psilocybin "2 mg" pills from the 20th centuary? Looks like microdosing has been around much longer than we thought

  • @insanitycubed8832
    @insanitycubed8832 11 місяців тому +29

    Thank god Hoffman didn't have a bad trip that turned him off of his work. Otherwise we would be set back decades in psychedelics

  • @JennTN411
    @JennTN411 8 місяців тому +4

    I'm just a few months into any non-prescription drug, but only thc edibles and/or microdosing amanita myscaria gummies. It's been pretty amazing since, I'll spare the details because they make me sound crazy😆

  • @julian_david4556
    @julian_david4556 11 місяців тому +3

    I took Zoloft for IBS or Gerd and have found a mini dose a day keeps those tummy aches away. I also have no urge to binge drink or do heavy drugs like coke or benzos

  • @mmmhorsesteaks
    @mmmhorsesteaks 11 місяців тому +11

    You know, P(III) usually works more easily than P(V) in synthesis. Wonder if you could use PCl3 and workup with peroxide, in stead of the oxychloride (pocl3 is sterically encumbered so substitutions can be difficult)
    might not work because the ring and amine could be quite sensitive to oxidation...

  • @stevengill1736
    @stevengill1736 9 місяців тому +3

    Man, that Speeter-Anthony synthesis is old school, but it still works. ;*[}There's another lesser known method that reacts indolylmagnesium bromide with 1-chloro-2-dimethylaminoethane that works fine at about 50% yield for N,N-DMT - I wonder if this would work for the 4-acetoxy?
    A lot of companies are messing with prodrugs, mostly phenolic derivatives of psilocin which purportedly have improved properties.
    4-acetoxyDMT itself was legal and available online for a few years, I found it quite enjoyable.
    Fascinating video, takes me back to my pot boiling days. Cheers...

  • @qcard76
    @qcard76 9 місяців тому +2

    3:29 what a title: "Investigational mushroom connoisseur"

  • @wk8219
    @wk8219 8 місяців тому +2

    Thank you for a great video

  • @MyNameisAI-dh6kh
    @MyNameisAI-dh6kh 3 місяці тому +1

    amazing stuff, thank you for the time you've put into this material.

  • @zizu1911
    @zizu1911 11 місяців тому +5

    Hahah amazing video ! Even after writing a paper on the topic I still learned a bunch, keep up the great work !

  • @midi510
    @midi510 11 місяців тому +2

    Really good content and some great graphics. Thanks.

  • @aldobayliss1271
    @aldobayliss1271 11 місяців тому +3

    Hello, thanks for the video, it is very valuable information, but I have a question, how is it that psilocybin is not recommended for bipolar disorder and some mental health diseases, but if tests are done with users with major depression? and I would like to know if you have a video about ibogaine

  • @CLAROSCURO-uu7vs
    @CLAROSCURO-uu7vs 2 місяці тому +2

    I am interested

  • @Michael-ie7iv
    @Michael-ie7iv 8 місяців тому +1

    Psilocybin is an ancient and powerful medicine. Its amusing that modern medicine is only now trying to understand what indigenous people have known for a millennial.

  • @dxublexxsplicitxxsplicit4943
    @dxublexxsplicitxxsplicit4943 5 місяців тому +2

    Would love to hear about ibotenic acid and muscimol

  • @knivesnico8775
    @knivesnico8775 11 місяців тому +4

    Top tier video as always
    I cant wait to get my hands on delicious gourmet mushrooms which may or may not be related to the contents of this video

  • @jedi36mindtricks
    @jedi36mindtricks 11 місяців тому +2

    Great video. The 6:15 was very interesting. I've noticed when I take 1.5g - 2g, I begin to twitch if I'm lying down trying to sleep or watching a movie. It only happens during this dosage weight. Thoughts? Anything 4g or higher, I do not have twitches. I believe it's because I'm at the actual trip/hallucination/visual dosage.

  • @kallah4999
    @kallah4999 11 місяців тому +2

    Good video bro. There so much videos only out for clout so keep up the good work bro.

  • @mona9857
    @mona9857 11 місяців тому +3

    Interessante video ,heb net een kweekset besteld 😊

  • @vratysanu
    @vratysanu 10 місяців тому

    Please make a video on Psilocybin synthesis from L-Tryptophan or 5 htp

  • @Marksonfixedmatches
    @Marksonfixedmatches 11 місяців тому +3

    I've heard so many wonderful things about magic mushrooms but I can't easily get some, Is there any realiable source I can purchase from??

  • @bludeat7398
    @bludeat7398 11 місяців тому +13

    these videos are great for preparing on test

    • @totalsynthesis
      @totalsynthesis  11 місяців тому +3

      Hey man, thanks a lot! Doesnt need LA, slight excess of oxalyl chloride though (1.2 eq). Can be rationalized with 1) high nucleophilicity of the indole, really electron rich; and 2) doesnt lose aromaticity fully during the substitution

  • @ryeweskey
    @ryeweskey 6 місяців тому +1

    As someone who has the luck of being the son of a schizophrenic man who also has tinges of this debilitating brain gnawing. Eating mushrooms and playing video games once a week... on a weekend... after the Mrs goes to bed. Has helped tremendously. It's like a giant reset button. I say this as there's no mention of such a disorder in the list you shown in your video

  • @rocknrollmanic
    @rocknrollmanic 11 місяців тому +2

    Thank you for meantioning Cigatoxin. Cigatoxin is found in extremely high amount in specific species of fish that can be mislabeled or confused for white fish. Be careful out there

  • @deathragh1
    @deathragh1 11 місяців тому +5

    I'm slightly confused on the major warnings for people with BPD, since there are currently studies being conducted into psilocybin on BPD with depression, where are the warnings coming from, huberman didn't state it just that you shouldn't if you have BPD, and same here?

    • @totalsynthesis
      @totalsynthesis  11 місяців тому +2

      There is a general high level of caution but yes there is (much needed) research going on. However that is very controlled research vs. recreational psychedelic use of potential high risk individuals.
      This review gives some info on this topic: www.sciencedirect.com/science/article/pii/S2666915321001669
      "This case review revealed a low number of cases of persistent manic symptoms that appeared to be brought on by use of a psychedelic substance, which may suggest that the rate of psychedelic-induced mania is low. However, not knowing the actual number of people who have bipolar disorder who have taken a psychedelic substance tempers this conclusion. Nonetheless, given the existing clinical and basic research, epidemiological studies, and published case histories, and importantly the lack of treatment options for depressive symptoms in bipolar disorder, we believe that a cautious approach to conducting trials in bipolar depression with psilocybin therapy, to examine the effects and safety is warranted. In such a prospective trial, it is crucial that attention be given to a carefully regulated environment where researchers can screen participants, emphasize set and setting, and follow patients for an extended period."
      E.g.

  • @codemiesterbeats
    @codemiesterbeats 11 місяців тому +2

    Describing different pathology as "constricted or narrowed" thinking is about as accurate as I think we humans can surmise.
    Likewise I would describe the effects as a "broadening or expansion" of your thoughts...(perception more broadly) and not in an anxiety inducing way but more like seeing things topographically from a "birds eye view"
    You can almost feel your brain being interconnected in ways you would have otherwise neglected.
    I think it could be extremely useful therapeutically in a vast swath of mental issues.
    As far as prohibition I think it is absolutely ridiculous to ban things that occur naturally... perhaps in extracted forms and such.
    I think the thing that chaps me about any prohibition is that there are things that you can buy over the counter from different plants that can unalive you but god forbid you experience anything that could be construed as enjoyable lol

  • @blackswan1983
    @blackswan1983 9 місяців тому +1

    I've tried several times, even microdosing for a short while, and had no effects worth keeping it up for.
    It seems to work for most others, so I was disappointed.

  • @weisland2807
    @weisland2807 11 місяців тому +4

    Well done sir!

  • @henryrroland
    @henryrroland 11 місяців тому +2

    Nice video

  • @enterbalak
    @enterbalak 11 місяців тому +5

    Saver then the poisons of antidepressants.

  • @oberstvilla1271
    @oberstvilla1271 11 місяців тому +5

    I think the biotechnological production of psilocybin in yeast is the much better way. The chemicals used in the synthesis are not exactly environmentally friendly.

  • @henryschwaiger6568
    @henryschwaiger6568 3 місяці тому +1

    Great video. Thank you!

  • @aug.jam.1
    @aug.jam.1 3 місяці тому +1

    What a great video!

  • @chrisbrent7487
    @chrisbrent7487 11 місяців тому +2

    Wasson definitely wasn't the first white fella to trip on mushrooms. There are a number of accidental poisonings in the record. We have quite a few on the record in Australia from accidental poisonings in the early 20th century.

  • @cacogenicist
    @cacogenicist 11 місяців тому +1

    sih-LAH-sih-bee :-)
    The genus _Panaeolus_ contains some _very_ potent species as well -- a few of which (at least) are at least 2x the potency of _Psilocybe cubensis_

  • @HiyaEverybody.
    @HiyaEverybody. 11 місяців тому +1

    Would a synthesized psilocybin pill prescription help to either slow down or reverse the effects of Alzheimer's and Dementia? I'm going to now do some online research on this subject but would really appreciate any positive response or answers thanks.

    • @totalsynthesis
      @totalsynthesis  11 місяців тому +3

      We have really low understanding of Alzheimers disease in terms of underlying mechanisms and therapeutic levers. You might have heard about anti-amyloid antibodies (finally) getting some traction clinically but even there, the benefit is questioned by some. For psilocybin, I think there is only pre-clinical (animal) or human anecdotal evidence; here is a paper you can look at:
      www.frontiersin.org/articles/10.3389/fnsyn.2020.00034/full
      "Animal models testing the neurobiological effects of psychedelic compounds have demonstrated hippocampal neurogenesis at lower doses and suppression at higher doses and potent neuroprotective properties. Studies in people suffering from depression and anxiety disorders have demonstrated lasting neuroplastic changes following just one or two large doses. This suggests a potential role for both sub-perceptual “micro”- and psychedelic-doses as a strategy for neuroprotection and cognitive enhancement in prodromal AD. For cognitive enhancement, the ideal dose and frequency have yet to be determined however the rapid desensitization of 5HT2A receptors by both psilocybin and LSD suggests that daily dosing is unlikely to be the optimal strategy."

  • @chrisdowny7763
    @chrisdowny7763 Місяць тому +2

    Currently in Ochem 2 lecture not paying attention because I am trying to figure out how to do a synthesis of psilocybin 😅😂

  • @The_errant_society
    @The_errant_society 8 місяців тому +1

    yeth i knew thith years ago thnx captian obvious.

  • @forex_shark6042
    @forex_shark6042 11 місяців тому +1

    I hard a copy of the book Total Synthesis 2 :)

  • @ytv3910
    @ytv3910 11 місяців тому +15

    🍄

  • @dfgdfg_
    @dfgdfg_ 11 місяців тому +2

    I don't really like the psychedelic effects, it's fine but I can't do my work - but I'll do anything to keep my cluster headaches manageable.

  • @bluegodofspeed
    @bluegodofspeed 11 місяців тому +3

    What a fucking amazing video.

  • @mikro7976
    @mikro7976 8 місяців тому +1

    Yea Agar cloning i pondered purity of potency that Agar is something

  • @Darko.Damjanovic
    @Darko.Damjanovic 2 місяці тому +1

    Does anyone know can it help with gambling addiction?

  • @veybiee
    @veybiee 11 місяців тому +3

    Wrong, in Switzerland there are psychadelic Therapies since years...
    L Australia xd

  • @kim_2060
    @kim_2060 4 місяці тому

    Research has shown psilocybin to have potent to treat a range of psychedelic and behavioral disorder.

  • @marcosdenizatrailhiker2037
    @marcosdenizatrailhiker2037 11 місяців тому +3

    “Heroic dose my ass, Terence” Albert Hoffman