They gave the mice 15mg, which is about a low-medium dose for a human. But humans weigh about 2000 times what mice do, so the effects were observed at about 2k times a reasonable dose.
1) Those mice must have been completely out of it.
2) This probably isn’t helpful to humans unless given under sedation. Or maybe that extreme a dose is equivalent to sedation, I’m not sure anyone has taken 30 _grams_ of psilocybin to tell us?
I’m not an expert so I’ll just ask questions but IIRC, there is no deadly dose of psylocybin.
I would imagine that at some point the effects would plateau. Of course you would be pretty far away in space in multiple dimensions at the same time.
I would be surprised, if this plateau exists, that nobody would have reached it.
In psychedelics space, it’s not unheard of people accidentally taking 100-1000x the expected dose and having the best (or worse) time of their life without further health issues.
Also it seems that set&setting is far more important for the experience than the actual dose.
Another aspect to consider is how quickly tolerance builds. After a few weeks of regular low psilocybin doses, even what's considered a high dose can have little to no noticeable effects. Taking equivalent amounts in the study isn't as far-fetched as it might seem, given a few weeks/months of tolerance building.
The question remains though: would it still have the same effects? The psychological effects are certainly diminished with tolerance, but who knows if this study's findings act on the same/a similar mechanism.
A benzo before or during SSRI treatment and there are no subjective effects. Depending if you want to administer a single dose or an entire course during a certain period of time.
You’d probably do profound psychological damage to yourself. It’s not deadly but that doesn’t mean it won’t affect you permanently to be stuck in some kind of a hell for what will feel like an eternity
Some people have accidentally taken several milligrams of LSD, whose full active dose is 100 ug, and they are fine. Every molecule's effects saturates at some point.
Yes, some people are fine, and some people are not fine at all. Even Terence Mckenna had at least one extremely bad trip(that we know of) on mushrooms that drove him to quit taking them for the rest of his life. That was with a lifetime of experience taking mushrooms and other psychedelics, and at a dose several orders of magntiude lower than the dose suggested by this paper.
And this is not a one-off thing, but a monthly regimen. So we're talking about taking a dose that's way beyond heroic, every month, for the rest of your life. That's so far outside the realm of responsible psychedelic use, I don't think any human has even come close to attempting it. The only thing that's for certain is there's no way of knowing what the psychological effects would be, but I have a hard time believing it wouldn't get extremely ugly.
In general mice need larger doses of most medication candidates. AFAIK this is because they have a faster metabolism compared to humans.
In addition I don't think there is a overdose risk with psychedelics.
I vaguely recall reading that as a rule of thumb, mouse doses of various drugs tend to be equivalent to around ten times higher than human doses in terms of mg/kg. (Don't quote me on that.)
It's not true that there's no overdose risk with psychedelics. Ones that are partial agonists of the serotonin 2A receptor, like LSD and psilocybin, are fairly safe, physiologically. Psychedelics that are full agonists of that receptor, like NBOMe- phenethylamines (which are commonly sold as LSD!), can be deadly vasoconstrictors at dosages not far beyond a pleasant dose. They have killed people. Anyone taking "LSD"/"acid", who didn't make it themself, should be aware of this.
Across species dose adjustment is based on surface area rather than mass.
Mass is proportional to volume. Volume increases super-linearly with respect to area. Therefore area increases sub-linearly compared to volume. Therefore dose increases sub-linearly with respect to volume. Therefore does increases sub-linearly with respect to mass.
It's very difficult to sleep under the influence of a moderate psilocybin dose. Or any other of the classic psychedelics for that matter, like LSD or mescaline.
I'm not sure what the mechanism is but they definitely have a stimulant-like feel sometimes (especially LSD).
I don’t really remember my dreams anymore, but if I go to bed having consumed weed (or one time, a light dose of mushrooms) I end up having a psychedelic version of fever dreams - extremely intense visualisations of thought structures that just keep folding out of themselves, that appear otherwise unfathomly huge and intricate. It’s quite uncomfortable wanting to sleep and rest from your thoughts but the substance won’t let you.
I grew some mushrooms at home for the first time. Ate one at 8pm at a concert tonight. Its now 3am and despite taking melatonin, I cannot get to sleep.
That’s normal. Best to just relax maybe have some food/drink and eventually you’ll sleep but it’s not a party drug if you’re gonna work the next day or something
30 grams of pure psilocybin? that requires eating 3 kilograms of mushrooms, right? usually it's 1% (or less) of dried mass.
well, actually more "doable" than initially I have assumed, but it would quickly lead to vomiting and a pretty guaranteed bad trip, well before ingesting enough.
> 1) ya, at that dose those mice, while unable to parse the Beautiful Mind style mathematical symbols they saw floating by, still understood the true meaning of them in ways the human mind can't begin to imagine
It may be a secondary effect - that the extension of life from reduction of cellular damage was due to the mice being less stressed out mentally after being stoned.
Just got to get it approved for anything and …. well everything will be the same. I’ve seen so many vendors selling professionally packed psilocybin. I’m like “this is like Lion’s Mane..?” Nope, just drugs!
But at least you can talk about it with your family and coworkers more casually
I’m saying that after it gets rescheduled by nature of a clear medical use, the consumer environment will still be the same because its already distributed as if its legal
I used to think I was "awake" because I became intensely aware of my mortality in my early 20s. But actually I feel like that's the norm, these days.
Gen Z seem to take "YOLO" seriously from a young age. Nobody is planning for anything beyond their own lifetimes. Some people still can't resist their biological imperative and have kids, but they're all basically YOLOing their lifestyles and their actions, if not their words, are saying "not my problem, you'll figure it out when I'm gone".
So, yeah, be aware you won't be here forever, but what we need is for people to leave the damn place in a better state than they found it, or at least not worse.
> Gen Z seem to take "YOLO" seriously from a young age. [...] and their actions, if not their words, are saying "not my problem, you'll figure it out when I'm gone".
Can you blame them? Boomers are saying the exact same thing while treating CO2 emissions like they're the main ingredient of a goddamned Werther's Original. Living here is only going to get harder as Gen Z gets older. "Fuck it, enjoy it while it's good" is a rational sentiment when you're born into an ongoing catastrophe that is actively being made worse.
If I take into consideration what I know about history then I'd say times are about as certain and safe as ever. What changed is that we now have an entire industry that thrives on fear and is very, very successful at it.
What "assisted dying" legislation is being introduced for. Start with "humane approach to suffering" end up with "right, you have no savings, and you have been taking your pension for way too long, we suggest a humane termination, here's your goodbye pill"
Assisted dying is legal in several countries and while it is obviously a complex subject and needs well-crafted regulations to ward off some obvious moral pitfalls, it fulfills an important need and right for a society. If I, for whatever reason, feel the need to terminate my life in dignity, I should be able to, without some religious nut interfering, or me exposing anyone assisting me in that endeavor to criminal prosecution.
They gave the mice 15mg, which is about a low-medium dose for a human. But humans weigh about 2000 times what mice do, so the effects were observed at about 2k times a reasonable dose.
1) Those mice must have been completely out of it. 2) This probably isn’t helpful to humans unless given under sedation. Or maybe that extreme a dose is equivalent to sedation, I’m not sure anyone has taken 30 _grams_ of psilocybin to tell us?
I’m not an expert so I’ll just ask questions but IIRC, there is no deadly dose of psylocybin.
I would imagine that at some point the effects would plateau. Of course you would be pretty far away in space in multiple dimensions at the same time.
I would be surprised, if this plateau exists, that nobody would have reached it.
In psychedelics space, it’s not unheard of people accidentally taking 100-1000x the expected dose and having the best (or worse) time of their life without further health issues.
Also it seems that set&setting is far more important for the experience than the actual dose.
Google shows the injected LD50 of psilocybin in mice is 285 mg/kg.
This dose is very much in the range that we should expect some deaths in their test group from overdose based on prior tests.
Edit:
The dose in the study was 15 mg/kg, not 15 mg.
Ahhh! 15mg/kg is much more reasonable!
Another aspect to consider is how quickly tolerance builds. After a few weeks of regular low psilocybin doses, even what's considered a high dose can have little to no noticeable effects. Taking equivalent amounts in the study isn't as far-fetched as it might seem, given a few weeks/months of tolerance building.
The question remains though: would it still have the same effects? The psychological effects are certainly diminished with tolerance, but who knows if this study's findings act on the same/a similar mechanism.
A benzo before or during SSRI treatment and there are no subjective effects. Depending if you want to administer a single dose or an entire course during a certain period of time.
You’d probably do profound psychological damage to yourself. It’s not deadly but that doesn’t mean it won’t affect you permanently to be stuck in some kind of a hell for what will feel like an eternity
Some people have accidentally taken several milligrams of LSD, whose full active dose is 100 ug, and they are fine. Every molecule's effects saturates at some point.
Yes, some people are fine, and some people are not fine at all. Even Terence Mckenna had at least one extremely bad trip(that we know of) on mushrooms that drove him to quit taking them for the rest of his life. That was with a lifetime of experience taking mushrooms and other psychedelics, and at a dose several orders of magntiude lower than the dose suggested by this paper.
And this is not a one-off thing, but a monthly regimen. So we're talking about taking a dose that's way beyond heroic, every month, for the rest of your life. That's so far outside the realm of responsible psychedelic use, I don't think any human has even come close to attempting it. The only thing that's for certain is there's no way of knowing what the psychological effects would be, but I have a hard time believing it wouldn't get extremely ugly.
Ram Dass tried to stay permanently high once, and ended up after some days drinking it from the bottle. Didnt work, still eventually came down.
I don't think Ram Dass ever came down. He blasted through Richard Alpert, and stayed on the other side permanently for the rest of his life.
In general mice need larger doses of most medication candidates. AFAIK this is because they have a faster metabolism compared to humans. In addition I don't think there is a overdose risk with psychedelics.
I vaguely recall reading that as a rule of thumb, mouse doses of various drugs tend to be equivalent to around ten times higher than human doses in terms of mg/kg. (Don't quote me on that.)
It's not true that there's no overdose risk with psychedelics. Ones that are partial agonists of the serotonin 2A receptor, like LSD and psilocybin, are fairly safe, physiologically. Psychedelics that are full agonists of that receptor, like NBOMe- phenethylamines (which are commonly sold as LSD!), can be deadly vasoconstrictors at dosages not far beyond a pleasant dose. They have killed people. Anyone taking "LSD"/"acid", who didn't make it themself, should be aware of this.
The human equivalent dose for a 70 kilo person is around 85mg. See https://pmc.ncbi.nlm.nih.gov/articles/PMC4804402/
Having tried ~80mg once (by mistake) ... it's still a hell of a dose and not a nice experience at all.
Across species dose adjustment is based on surface area rather than mass.
Mass is proportional to volume. Volume increases super-linearly with respect to area. Therefore area increases sub-linearly compared to volume. Therefore dose increases sub-linearly with respect to volume. Therefore does increases sub-linearly with respect to mass.
Dose scales with surface area? This is the first I've heard of that
I have no personal experience with mushrooms, but I never understood why placebo trials aren't done while the patients are asleep.
Just choose research subjects that don't remember their dreams and who sleep a solid 8 hours
I think a trip is much shorter than 8 hours and by the time you wake up you wouldn't be able to tell the difference
It's very difficult to sleep under the influence of a moderate psilocybin dose. Or any other of the classic psychedelics for that matter, like LSD or mescaline.
I'm not sure what the mechanism is but they definitely have a stimulant-like feel sometimes (especially LSD).
So you have it right, just need to take it in the morning before going to work
I don’t really remember my dreams anymore, but if I go to bed having consumed weed (or one time, a light dose of mushrooms) I end up having a psychedelic version of fever dreams - extremely intense visualisations of thought structures that just keep folding out of themselves, that appear otherwise unfathomly huge and intricate. It’s quite uncomfortable wanting to sleep and rest from your thoughts but the substance won’t let you.
I grew some mushrooms at home for the first time. Ate one at 8pm at a concert tonight. Its now 3am and despite taking melatonin, I cannot get to sleep.
That’s normal. Best to just relax maybe have some food/drink and eventually you’ll sleep but it’s not a party drug if you’re gonna work the next day or something
Melatonin is effective ~5 hours later. No need to take more than 0.3 mg.
What you should try is L-Theanine just before going to sleep, it's effective against Caffeine, not sure about Psilocybin.
[dead]
30 grams of pure psilocybin? that requires eating 3 kilograms of mushrooms, right? usually it's 1% (or less) of dried mass.
well, actually more "doable" than initially I have assumed, but it would quickly lead to vomiting and a pretty guaranteed bad trip, well before ingesting enough.
also interestingly LD50 is 280 mg/kg.
> 1) ya, at that dose those mice, while unable to parse the Beautiful Mind style mathematical symbols they saw floating by, still understood the true meaning of them in ways the human mind can't begin to imagine
It's not toxic so someone could try it.
[dead]
See Also:
Psilocybin treatment extends cellular lifespan, improves survival of aged mice (nature.com)
43 points | 1 day ago | 10 comments https://news.ycombinator.com/item?id=44527358
Psilocybin for major depression granted Breakthrough Therapy by FDA (newatlas.com)
1240 points | 6 years ago | 471 comments https://news.ycombinator.com/item?id=21638290
What happens when clergy take psilocybin (nautil.us)
353 points | 25 days ago | 566 comments https://news.ycombinator.com/item?id=44293610
https://news.ycombinator.com/item?id=44525240
It may be a secondary effect - that the extension of life from reduction of cellular damage was due to the mice being less stressed out mentally after being stoned.
Wouldn't this much psycobylin severely affect your personality?
Empathic, schizophrenic, but multiple empathic personalities
As long as one of them can code I’ll be fine
Bonus if the other one can do marketing
I'm not actually interested in anti-aging, but this is still interesting!
Just got to get it approved for anything and …. well everything will be the same. I’ve seen so many vendors selling professionally packed psilocybin. I’m like “this is like Lion’s Mane..?” Nope, just drugs!
But at least you can talk about it with your family and coworkers more casually
Cellular longevity? Lung health? Seems pretty damn useful.
I was thinking, you mean nobody has ever taken a mushroom and thought they were young again?
If not, I would want better mushrooms than that myself :)
Let me know when this is completely well-proven, I have a friend who's an older gentleman . . .
I’m saying that after it gets rescheduled by nature of a clear medical use, the consumer environment will still be the same because its already distributed as if its legal
We need drugs to help people understand they are mortal.
I used to think I was "awake" because I became intensely aware of my mortality in my early 20s. But actually I feel like that's the norm, these days.
Gen Z seem to take "YOLO" seriously from a young age. Nobody is planning for anything beyond their own lifetimes. Some people still can't resist their biological imperative and have kids, but they're all basically YOLOing their lifestyles and their actions, if not their words, are saying "not my problem, you'll figure it out when I'm gone".
So, yeah, be aware you won't be here forever, but what we need is for people to leave the damn place in a better state than they found it, or at least not worse.
It’s a value judgement. The media and culture make a lot of people think that leaving no children will be leaving the planet a better place.
Or that it's questionable to bring children into a world that is increasingly likely to be hostile to human life along several dimensions.
> Gen Z seem to take "YOLO" seriously from a young age. [...] and their actions, if not their words, are saying "not my problem, you'll figure it out when I'm gone".
Can you blame them? Boomers are saying the exact same thing while treating CO2 emissions like they're the main ingredient of a goddamned Werther's Original. Living here is only going to get harder as Gen Z gets older. "Fuck it, enjoy it while it's good" is a rational sentiment when you're born into an ongoing catastrophe that is actively being made worse.
Perhaps that's a result of being born into a world with (unprecedented?) amounts of uncertainty.
Climate change, automation threatening the value of human labor, rise of authoritarianism, "the West" losing it's hegemonic status, wars, genocides.
Hard to make long term plans for your life when the world is changing rapidly and we don't even know how it will look like in 10 years.
If I take into consideration what I know about history then I'd say times are about as certain and safe as ever. What changed is that we now have an entire industry that thrives on fear and is very, very successful at it.
A comment before the resource wars that are likely coming
Arguably the European churches were such an industry for centuries, and were highly effective at it.
This is exactly what the world needs, a bunch of tripping boomers showing us just how wrecked the pension systems are!
What "assisted dying" legislation is being introduced for. Start with "humane approach to suffering" end up with "right, you have no savings, and you have been taking your pension for way too long, we suggest a humane termination, here's your goodbye pill"
Assisted dying is legal in several countries and while it is obviously a complex subject and needs well-crafted regulations to ward off some obvious moral pitfalls, it fulfills an important need and right for a society. If I, for whatever reason, feel the need to terminate my life in dignity, I should be able to, without some religious nut interfering, or me exposing anyone assisting me in that endeavor to criminal prosecution.
so essentially Canada?