> "It's unfeasible and way too expensive to extract psilocybin from magic mushrooms and the best chemical synthesis methods require expensive and difficult to source starting substrates...”
This is one of those situations where I feel like we (humans) are approaching it all wrong. Why over complicate it by trying to “extract” the psilocybin instead of treating it like marijuana and growing the mushrooms in highly controlled settings and then testing for potency?!
As someone who’s recently had very positive experiences with both large/small doses of magic mushrooms, it’s disheartening to see us remake the mistakes of the past by trying to over-engineer something from nature. IMO, the optimum approach would be to have humility and simply be stewards of this wonderful gift. There is no reason That psilocybin shouldn’t be administered in its most common form, as it has been for thousands of years, other than it would be harder to profit off of.
Hey, drug on wars still exists in the world. You can get excessive jail time just for having some (regardless of quantity) marijuana on you - and that is in "western" country. It was not so long ago that "marijuana had no possible medical application" and was scheduled as a class A drug in UK (and I think, still is). There is a lot of stigma, and decades of bad science, propaganda, and manufactured hatred run deep. Research is difficult, if at all possible because excessively harsh legislation. And who benefits?.. criminal cartels and enforcement agencies. This is also why scientists go such extreme lengths to create psychoactive mimics ("legal highs") - so they can research the stuff that is at least similar without going to jail. It's a fucked up world, my friend.
It's not the scientists' approach that is wrong, it's the legislators...
As far as I understand it's too inconsistent, i.e. very unevenly distributed within one fruiting body. Not sure if that's the reason, but: if you ever bought mushrooms/truffles in the Netherlands, there is no psylocibin content on the box. And if you try googling, the estimates vary pretty wildly (although it's possible that it's just a lack or proper research)
Also not everyone enjoys the taste of mushrooms or truffles. And psychedelic entities don't care whether they are coming from naturally occurring or synthesized psylocibin ;)
Also, humility and appreciation come in different shapes: for example I recall that Shulgin never consumed his pure psychedelics with juice because he could distinguish 'chemical' tastes and had appreciation for that
Growing it in yeast would be great if you are trying to get a consistent quantity of the drug. You could do vats at a time all genetically identical and producing the same yield batch over batch, and can scale up and down your operation for as much as you have vats and yeast food.
This is something you want if you are going to press this into pills at a certain dose and give to people for psychiatric disorders, not for people looking to go on spiritual journeys or see a phish concert.
How about we don't do that either . Psilocybin doesn't have any effect on the human body afaik before breaking down to psilocin . 4-aco-dmt is easy to make and readily breaks down to psilocin .
Why are trials and research concentrating on this prodrug like it's necessary is beyond my understanding . It's a waste of money and time
Someone more knowledgeable please step in to correct me but: I think what can be desirable from this process is the lack of variability in the product when you produce it at scale.
Standardized total extracts of natural sources are pretty standard in the pharmacopeia, so what you're saying makes total sense. Making sure that the dosage is standardized is a solved problem.
Unfortunately this type of drug preparation is not that fashionable. One example of this is the total extract of St. John's Wort, which is superior to synthetic antidepressants in many cases, but doctors often prefer to prescribe the latter (presumably because a plant based medicine doesn't sound as powerful?).
It can and is being done. It requires a lot of worker safety because toxic molds can grow in the environment as well. Cannabis now has the same worker safety so I'm confident higher standards can be brought to psilocybin production.
To those of you complaining about dosage you can take a representative sample of a batch, grind it up, and test it for potency via GC/MS. Same way it's done in cannabis. For cannabis edibles we have an allowable range of 4.9-5.1mg/dose on a serving labeled 5mg. I'm pretty sure we can nail 1000mg doses of psilocybin pretty accurately.
I like how mushrooms taste, but my sister doesn't. Her husband even insisted that we don't serve any mushrooms at their wedding.
(Granted, it's been years since I last ate magic mushrooms. I loved the way they tasted, but I don't think it's fair for someone who doesn't like they way they taste to have to gag them down just for a trip. I can still remember how they tasted, and the wonderful visions I had.)
Mushrooms also don't store well.
Extracting psilocybin so it can be served in a more palatable and easily stored form is a good thing.
I remember reading about growing these mushrooms online at some point. The article strongly cautionend against it unless you know very well what you are doing. Growing any kind of mushroom has the potential to also grow nasty and very unhealthy molds and bacteria. You can easily kill yourself by ingesting those, if you are not very careful to avoid contamination. This is absolutely not taken to be lightly and proper lab procedures would for example require you to perform the inoculation in a glove box.
Nature didn't give psilocybin to us as a "gift" in order to help us figure out the world. Just like everything else that can be used and consumed by humans, we co-opted this organism for our own purposes. Psilocybin was evolved by these mushrooms as a defense mechanism against animals trying to eat it, just like every other psychoactive drug. It's a poison, not a medicine. We just so happened to be big enough and our brains wired in a certain way wherein it doesn't kill us or make us feel awful, instead it has the opposite effect.
Yes, we absolutely SHOULD be extracting and studying psilocybin and all of the ways it interacts with our brain. With any luck, we can pinpoint the extremely beneficial parts of the drug and create new synthetic compounds that aren't rife with the normal side effects of a psychedelic experience. Perhaps we'll be able to give this new compound to people with mental disabilities or conditions which would prevent them from taking a psychedelic of kind. Or if it was safe enough, it might make an entire class of SSRIs obsolete as mushrooms have a beneficial effect on those of us with anxiety and depression. I have anxiety, and while micro-dosing every day would probably solve that problem, a whole host of side effects comes along for the ride that wouldn't really be great for things like my job, so the SSRI works for now. But if you told me I could take 1 pill of $SOME_SYNTHETIC_DERIVED_FROM_PSILOCYBIN every 2 weeks instead of 1 pill of lexapro every day, I'd sign up for that in a heartbeat, and I'm sure everyone else would too.
That doesn't mean 'shrooms would go away, far from it. In fact, I think the more research Big Pharma does on psychedelics, the easier it will be to obtain them. It's already pretty easy (and legal) if you know where to look for spores, and at that point it's just buying some equipment and waiting. I pine for the day that mushroom growing kits are sold that make it totally painless for people to grow their own.
Yes, I'd rather just eat the mushrooms. We used to grow them on autoclaved rice, in mason jars. Also, it's not at all obvious that psilocybin is the only active compound. And conversely, I wouldn't want to experiment with analogs that don't predominate in mushrooms.
I think you could make the same argument about.... everything? Farming and selective breeding vs. hunting and gathering? Inventing modern materials rather than using wood and stone and animal parts? Pretty much everything. "Mistakes from the past?" Which specific ones are you speaking of? I don't doubt there have been many, but if you are talking about choosing not to simply take things as nature gives them to us, well, I guess you want to return to the stone age or something, but the world doesn't support 7 billion people doing things that way.
I do wonder what is lost, too. Some folks talk about "mushroom pills" (simply powdered, full spectrum mushrooms) and some talk about "psilocybin extract". It's my understanding that different psilocybe mushrooms species have different effects due to varying levels of not just psilocybin, but psilocin (psilocybin metabolizes to psilocin, but it is also in many species), baeocystin (mexicanas tend to be higher in this) and norbaeocystin.
It does a little bit cut into the organic/spiritual nature of the experience. If I am going to get high I have recently gone back to just smoking weed instead of eating a 'watermelon burst' gummy or something. Smoking with a pipe is timeless and the ritual, smell, taste are all a part of it for me.
Same thing with mushrooms, preparing the tea for me is a part of the experience.
> There is no reason That psilocybin shouldn’t be administered in its most common form, as it has been for thousands of years
They’re using very large doses in therapy, and there are a lot of unpleasant things that are going to happen already even at the minimum effective dose.
What is the going price for 1 mg of psilocybin? I am seeing a site sell magic mushrooms (Psilocybe Aztecorum) with a psilocybin quantity of ~1g for $15. 7 g for $72. Is this the publicly available norm or does it seem cheap.
It’s not hard or expensive to turn brown rice flour and vermiculite into mushrooms. The bit about expensive to create a pharmaceutical compound growing from a mushroom is just silly. Extraction can’t be that expensive.
They were doing it in Amsterdam for years for the recreational market, and still do with truffles. Is it just profit making motive that is coming into play here?
I think a lot of this discussion is missing the forest for the trees. Here we have people arguing whether it’s better to make powder out of these psychoactive mushrooms and use that as a drug vs extract pure psilocybin and use that as a drug.
I know little of pharmacology but I can see one use of pure compounds: further research. Analyzing how psilocybin affects serotonin receptors could potentially help design other drugs that act on those receptors without psychedelic side effects. It could also help with creating other psilocybin analogs with different effects. And of course having the ability to study in detail the effects that other substances in the psychoactive mushrooms have might help identify other areas of study.
As a software analogy, this is like the debate whether it’s better to have Google Maps vs mapping software and all the underlying data. Of course it’s better to have the latter even if some romanticize the former.
When "researching cannabis", using just pure thc may not be optimal because cbd, cbn, and other chemicals produce a different kind of high and, if I recall correctly, especially cbd counters some of the most negative effects of thc, etc.
Similarily, people might be worrying about oversimplifying mushrooms to just psilocybin because mushrooms have more than one chemical in them and they might work in a synergistic way as well.
> the best chemical synthesis methods require expensive and difficult to source starting substrates
This type of thing always amazes me about nature -- obviously all the ingredients necessary exist in the soil the mushroom is grown in!
Yet the best we can do to mimic nature is get some hard-to-acquire substrates. It's so interesting how, given enough time, the universe can produce a self-replicating organism that can do something with basic building blocks that we can't do with current technology...
(okay, maybe this is a bit romantic, but it's still fun to think about)
> all the ingredients necessary exist in the soil the mushroom is grown in
I can't speak for mushrooms, but for plants, the vast majority of the mass actually comes from carbon in the air (breathes in CO2, takes the carbon, breathes out O2) and obviously water.
The mail innovation to come out of 4 billion years of natural selection are essentially just really really really good catalysists: enzymes. They've got an admirable specificity and efficiency. We dont have 4 billion years to figure out how to do it as well, but we've gotten not that terrible in just a few thousand!
Psilocybin may be an underrated chemical precursor. 4-substituted indoles are notoriously difficult to synthesize. Psilocin is a rare example of a natural one. (LSD is another.) For example, a milliliter of 4-bromoindole costs a whopping $75:
Be careful thinking about potential cost of bringing a synthesis to market based on Sigma Aldrich catalog prices. SA is a supply house for research chemicals, prioritizing quantity of compounds offered and consistent, specified quality over price. The range of products they offer is insane, even considering the reactivity and instability of some of them.
If your commercialize a compound, you source these starting materials (eg. Bromoindole) directly through manufacturers. You will be able to buy in bulk at 10-1000x lower prices, sometimes. Of course you need to do judicious quality controls yourself, but you likely have the scaling benefits to do.
Are you sure that these precursors aren't just expensive because so many of the compounds that go into them, or which come from them, are controlled substances?
There are a lot of bulk reactants that I'd like to buy for chemistry experiments, but can't (because they're controlled, because they can be used to make illegal things), so I have to make them myself from even earlier precursor chemicals; this adds (via labor costs) to the cost of making the final product. Presumably, even big producers like Sigma are in the same situation.
There's a long history of pairing entheogenic substances with yeast and its bi-products.
For around 1900 years a biannual event took place near Athens known as The Eleusinian Mysteries.[1] This was a real occurrence of which Plato, Socrates, Cicero, Marcus Aurelius and many others wrote about or attended in person.
The event culminated in a secret ceremony in which participants invariably reported losing their fear of death [2]
Much has been written on the topic, with growing speculation through the 20th century that the initiates took an entheogenic substance, such as psilocybin or ergotamine, from mushrooms, beer or barley. [3]
Psylocibin is already synthetically available as I understand - its a pill they get in Johns Hopkins trails for smoking cessation. Anyone know how that is produced?
Another point they make is about psylocin. As I understand, as soon as psylocibin hits your stomach acid it gets converted to psylocin anyway. People use lemon to do the process before ingesting in order for it to hit them faster.
Generally, most genetic modifications like these are harmful to the competitiveness of the microorganism in the wild. It's possible that producing psilocybin could help it be more competitive, but this would be the exception rather than the rule. Generally, the organism expends so much energy and material producing the engineered substance that it's worse at doing other things.
I've never once heard a bit of insight from a psychonaut that was particularly game-changing. We're all connected, consciousness is an illusion, societal structures are somewhat arbitrarily defined, etc. These are the existential thoughts of teenagers. Life is just energy, energy is just vibrations, everything is a fractal, etc, these are just the existential speculations of people making baseless claims.
Consciousness as a useful frontier, in my opinion, will only have utility as it intersects with neuroscience and artificial intelligence. Producing consciousness with AI will be game-changing. Altering or affecting consciousness with neuroscience, or allowing consciousness to interact with neuroscience in such a way that interfaces with other technologies will be game-changing, sure.
But giving people psychedelics and having them explore their own consciousnesses is not going to catalyze our society forward by leaps and bounds, that has been done since at least the 60s. I obviously don't care if people do whatever they'd like, I just don't see the point in romanticizing them.
- psilocybin is pretty easy to synthesize with the exception of the phosphorylation (can be hard to purify without degrading it)
- this is a research publication, so of course they put their findings in the best possible light (“finally the synthesis everyone has been waiting for”)
[+] [-] mikeg8|6 years ago|reply
This is one of those situations where I feel like we (humans) are approaching it all wrong. Why over complicate it by trying to “extract” the psilocybin instead of treating it like marijuana and growing the mushrooms in highly controlled settings and then testing for potency?!
As someone who’s recently had very positive experiences with both large/small doses of magic mushrooms, it’s disheartening to see us remake the mistakes of the past by trying to over-engineer something from nature. IMO, the optimum approach would be to have humility and simply be stewards of this wonderful gift. There is no reason That psilocybin shouldn’t be administered in its most common form, as it has been for thousands of years, other than it would be harder to profit off of.
[+] [-] colechristensen|6 years ago|reply
Dosage is important. There isn't a way to test for potency which would ensure a reliable dose.
Argument fallacies:
* your anecdotal positive experiences
* suggesting superiority because something is "from nature"
* referring to "mistakes from the past" without naming any
* suggesting superiority that "has been (done) for thousands of years"
Think about why these kinds of arguments are made on different topics which you disagree with and then rethink why you are making them here.
[+] [-] arpa|6 years ago|reply
It's not the scientists' approach that is wrong, it's the legislators...
[+] [-] karlicoss|6 years ago|reply
Also not everyone enjoys the taste of mushrooms or truffles. And psychedelic entities don't care whether they are coming from naturally occurring or synthesized psylocibin ;)
Also, humility and appreciation come in different shapes: for example I recall that Shulgin never consumed his pure psychedelics with juice because he could distinguish 'chemical' tastes and had appreciation for that
[+] [-] asdff|6 years ago|reply
This is something you want if you are going to press this into pills at a certain dose and give to people for psychiatric disorders, not for people looking to go on spiritual journeys or see a phish concert.
[+] [-] jokowueu|6 years ago|reply
Why are trials and research concentrating on this prodrug like it's necessary is beyond my understanding . It's a waste of money and time
[+] [-] ninetax|6 years ago|reply
[+] [-] svara|6 years ago|reply
Unfortunately this type of drug preparation is not that fashionable. One example of this is the total extract of St. John's Wort, which is superior to synthetic antidepressants in many cases, but doctors often prefer to prescribe the latter (presumably because a plant based medicine doesn't sound as powerful?).
[+] [-] cannaceo|6 years ago|reply
To those of you complaining about dosage you can take a representative sample of a batch, grind it up, and test it for potency via GC/MS. Same way it's done in cannabis. For cannabis edibles we have an allowable range of 4.9-5.1mg/dose on a serving labeled 5mg. I'm pretty sure we can nail 1000mg doses of psilocybin pretty accurately.
[+] [-] gwbas1c|6 years ago|reply
(Granted, it's been years since I last ate magic mushrooms. I loved the way they tasted, but I don't think it's fair for someone who doesn't like they way they taste to have to gag them down just for a trip. I can still remember how they tasted, and the wonderful visions I had.)
Mushrooms also don't store well.
Extracting psilocybin so it can be served in a more palatable and easily stored form is a good thing.
[+] [-] orbifold|6 years ago|reply
[+] [-] tomphoolery|6 years ago|reply
Yes, we absolutely SHOULD be extracting and studying psilocybin and all of the ways it interacts with our brain. With any luck, we can pinpoint the extremely beneficial parts of the drug and create new synthetic compounds that aren't rife with the normal side effects of a psychedelic experience. Perhaps we'll be able to give this new compound to people with mental disabilities or conditions which would prevent them from taking a psychedelic of kind. Or if it was safe enough, it might make an entire class of SSRIs obsolete as mushrooms have a beneficial effect on those of us with anxiety and depression. I have anxiety, and while micro-dosing every day would probably solve that problem, a whole host of side effects comes along for the ride that wouldn't really be great for things like my job, so the SSRI works for now. But if you told me I could take 1 pill of $SOME_SYNTHETIC_DERIVED_FROM_PSILOCYBIN every 2 weeks instead of 1 pill of lexapro every day, I'd sign up for that in a heartbeat, and I'm sure everyone else would too.
That doesn't mean 'shrooms would go away, far from it. In fact, I think the more research Big Pharma does on psychedelics, the easier it will be to obtain them. It's already pretty easy (and legal) if you know where to look for spores, and at that point it's just buying some equipment and waiting. I pine for the day that mushroom growing kits are sold that make it totally painless for people to grow their own.
[+] [-] smabie|6 years ago|reply
[+] [-] mirimir|6 years ago|reply
[+] [-] unknown|6 years ago|reply
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[+] [-] robbrown451|6 years ago|reply
[+] [-] kylek|6 years ago|reply
[+] [-] ericmcer|6 years ago|reply
Same thing with mushrooms, preparing the tea for me is a part of the experience.
[+] [-] undersuit|6 years ago|reply
[+] [-] Alex3917|6 years ago|reply
They’re using very large doses in therapy, and there are a lot of unpleasant things that are going to happen already even at the minimum effective dose.
[+] [-] Anoncomposed|6 years ago|reply
[+] [-] tdy721|6 years ago|reply
[+] [-] collyw|6 years ago|reply
[+] [-] ncmncm|6 years ago|reply
[+] [-] steve76|6 years ago|reply
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[+] [-] IgorPartola|6 years ago|reply
I know little of pharmacology but I can see one use of pure compounds: further research. Analyzing how psilocybin affects serotonin receptors could potentially help design other drugs that act on those receptors without psychedelic side effects. It could also help with creating other psilocybin analogs with different effects. And of course having the ability to study in detail the effects that other substances in the psychoactive mushrooms have might help identify other areas of study.
As a software analogy, this is like the debate whether it’s better to have Google Maps vs mapping software and all the underlying data. Of course it’s better to have the latter even if some romanticize the former.
[+] [-] nugga|6 years ago|reply
Similarily, people might be worrying about oversimplifying mushrooms to just psilocybin because mushrooms have more than one chemical in them and they might work in a synergistic way as well.
[+] [-] mistermann|6 years ago|reply
All other things being equal.
[+] [-] andrew_xor_andy|6 years ago|reply
This type of thing always amazes me about nature -- obviously all the ingredients necessary exist in the soil the mushroom is grown in!
Yet the best we can do to mimic nature is get some hard-to-acquire substrates. It's so interesting how, given enough time, the universe can produce a self-replicating organism that can do something with basic building blocks that we can't do with current technology...
(okay, maybe this is a bit romantic, but it's still fun to think about)
[+] [-] ralusek|6 years ago|reply
I can't speak for mushrooms, but for plants, the vast majority of the mass actually comes from carbon in the air (breathes in CO2, takes the carbon, breathes out O2) and obviously water.
[+] [-] vikramkr|6 years ago|reply
[+] [-] scythe|6 years ago|reply
https://www.sigmaaldrich.com/catalog/product/aldrich/524336?...
Presumably this technique could produce psilocybin for much less than $75 per milliliter.
[+] [-] isoprophlex|6 years ago|reply
If your commercialize a compound, you source these starting materials (eg. Bromoindole) directly through manufacturers. You will be able to buy in bulk at 10-1000x lower prices, sometimes. Of course you need to do judicious quality controls yourself, but you likely have the scaling benefits to do.
[+] [-] derefr|6 years ago|reply
There are a lot of bulk reactants that I'd like to buy for chemistry experiments, but can't (because they're controlled, because they can be used to make illegal things), so I have to make them myself from even earlier precursor chemicals; this adds (via labor costs) to the cost of making the final product. Presumably, even big producers like Sigma are in the same situation.
[+] [-] jmkd|6 years ago|reply
For around 1900 years a biannual event took place near Athens known as The Eleusinian Mysteries.[1] This was a real occurrence of which Plato, Socrates, Cicero, Marcus Aurelius and many others wrote about or attended in person. The event culminated in a secret ceremony in which participants invariably reported losing their fear of death [2] Much has been written on the topic, with growing speculation through the 20th century that the initiates took an entheogenic substance, such as psilocybin or ergotamine, from mushrooms, beer or barley. [3]
[1] https://en.wikipedia.org/wiki/Eleusinian_Mysteries [2] https://www.ancient.eu/article/32/the-eleusinian-mysteries-t... [3] PDF https://www.mattioli1885journals.com/index.php/MedHistor/art...
[+] [-] msla|6 years ago|reply
But the first thing I thought when I saw the headline was, "Wow. That's some interesting beer."
[+] [-] farco12|6 years ago|reply
https://reader.elsevier.com/reader/sd/pii/S109671761930401X?...
[+] [-] 0x8BADF00D|6 years ago|reply
[+] [-] tuyiown|6 years ago|reply
[+] [-] collyw|6 years ago|reply
Another point they make is about psylocin. As I understand, as soon as psylocibin hits your stomach acid it gets converted to psylocin anyway. People use lemon to do the process before ingesting in order for it to hit them faster.
[+] [-] crusso|6 years ago|reply
What happens when some of the yeast you capture in the environment is producing psilocybin?
I saw no mention in the article of considerations to keep these genetic modifications contained within the psilocybin manufacturing process.
[+] [-] tehjoker|6 years ago|reply
[+] [-] hatsunearu|6 years ago|reply
[+] [-] tehjoker|6 years ago|reply
[+] [-] kfrzcode|6 years ago|reply
[+] [-] ralusek|6 years ago|reply
Consciousness as a useful frontier, in my opinion, will only have utility as it intersects with neuroscience and artificial intelligence. Producing consciousness with AI will be game-changing. Altering or affecting consciousness with neuroscience, or allowing consciousness to interact with neuroscience in such a way that interfaces with other technologies will be game-changing, sure.
But giving people psychedelics and having them explore their own consciousnesses is not going to catalyze our society forward by leaps and bounds, that has been done since at least the 60s. I obviously don't care if people do whatever they'd like, I just don't see the point in romanticizing them.
[+] [-] toxicFork|6 years ago|reply
[+] [-] refurb|6 years ago|reply
- psilocybin is pretty easy to synthesize with the exception of the phosphorylation (can be hard to purify without degrading it)
- this is a research publication, so of course they put their findings in the best possible light (“finally the synthesis everyone has been waiting for”)