14 ms·

Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

82 points by hentrep 5y ago

errcorrectcode 5y ago
Ketamine also. It's already approved. I would prefer all drugs were legalized as in Portugal and regulated because it's impossible for a consumer of illicit drugs to verify their contents and it would cut off criminal profiteering, violence, and the police-prison-industrial-complex from some funding too.
- toomanybeersies 5y ago
  Drugs are not legalised in Portugal, they're decriminalised. Trafficking is still a criminal offence, and personal possession is still punishable with a fine.
  - errcorrectcode 5y ago
    Duh. The word "as" means "like" or "similar," it doesn't mean "is." Prohibition never works, and Portugal doesn't have a consistent approach yet.
icameron 5y ago
I had to look it up to put it in perspective. 25mg pure psilocybin could be around 5g of dried p. cubensis if they are .5% (which varies considerably...) point being this is no microdose. These patients are really tripping! So they are saying a psychedelic experience, which could reconstruct your entire ego, really can be a significant life-changing event.
- constantlm 5y ago
  Terence McKenna called 5 grams an heroic dose.
etaioinshrdlu 5y ago
Wow, 5% reported suicidal ideation or self harm, in a clinical setting. That’s pretty horrible.
- PeterisP 5y ago
  Depression is a quite significant cause of death, above many other major diseases especially for younger people.
- sojournerc 5y ago
  Well, participants were already on anti-depressants, and asked to stop before the trial, so causation isn't clear.
  - darkerside 5y ago
    Well, how did it compare to the control group?
    - deleted 5y ago
      [deleted]
- spaetzleesser 5y ago
  I had one trip where I found peace with the idea of dying. Why keep struggling with life if you can leave it in harmony? Not sure if I would call this suicidal though. But it changed my attitude towards dying. I think if I had a hopeless disease or was close to dying otherwise I wouldn't fight it but try to die in a peaceful and aware way.
alexfromapex 5y ago
Love that it’s randomized and double blinded. Will be hard to cast doubt on it.
spaetzleesser 5y ago
I am pretty prone to depression and I definitely feel it lifting for a while after microdosing or taking a larger dose. Unfortunately I have never experienced a life changing trip that solved all problems as you may want to believe when you read some of the latest articles about the miracle of psilocybin and other psychedelics. Same for Ayahuasca. It seems to help a lot of people but for me it was more just a very interesting experience. For example I think a lot of film makers are/were taking psychedelics. During my trips I noticed so much more detail in my environment and different light reflections which you often see in movies.
- pm90 5y ago
  It’s a pretty well established fact that creatives have to use some mind altering substances to be productive, but it’s hard to believe that claim if you’ve never experienced them personally.
- mettamage 5y ago
  When I meditate hardcore then after a session, I also look differently at light.
PragmaticPulp 5y ago
The trial tested psilocybin combined with therapy. This isn’t equivalent to ad-hoc self treatment with mushrooms. They noticed a response to psilocybin+therapy in about 20-25% of patients depending on the criteria for “sustained response”: > The protocol-defined sustained response* up to week 12 was double, with 20.3% of patients in the 25mg group It’s also notable that about 5% of the psilocybin receivers experienced severe adverse events including suicidal ideation: > There were 12 patients who reported treatment-emergent serious adverse events (TESAEs). These TESAEs included suicidal behaviour, intentional self-injury, and suicidal ideation
- JohnJamesRambo 5y ago
  This sounds pretty crappy right? If I'm understanding the numbers, 25% response is about like what we get with a placebo in most studies if my memory is correct. It sounds like they were tripping balls on 25 mg, so this is definitely in active placebo range. From my memory: Placebo is about 25%. Antidepressants about 35% response rate. Active placebo of something like atropine which makes you feel weird but isn't an antidepressant has about a 35% response rate. https://blogs.scientificamerican.com/cross-check/are-antidepressants-just-placebos-with-side-effects/ https://blogs.scientificamerican.com/cross-check/are-antidep...
  - drooby 5y ago
    I’m not sure if it makes a difference, but this study was conducted on _treatment resistant_ patients.
MrWiffles 5y ago
Some quick points: > 233 patients Very small, can't generalize results based on such a small number. Doesn't mean the study's trash or anything, but don't jump to any conclusions here - good or bad. > "The trial, which had all patients stopping antidepressants before participating, compared two active doses of COMP360, 25mg and 10mg, against a comparator 1mg dose." - COMP360 was, I assume, their therapeutic psilocybin but it's unknown if that differs from raw psilocybin or not, and if so in what way. - Did they TEST and PROVE discontinuation of antidepressants at all stages of the trial? Which kinds of antidepressants did they test for? SSRI? TCA? MAOI? How did they test? Uranalysis? Blood? Or did they just take 233 people's word for it? > "[...] 179 patients reported at least one adverse event — the most common being headaches, nausea, fatigue and insomnia." - Likely unrelated to the medication itself, as those can be caused by hundreds (thousands) of factors. Literally included in every possible side effect list for nearly every medication known to exist. Doubtful that the medication caused any of these. > "There were 12 patients who reported more serious adverse events, such as suicidal behavior, intentional self-injury, and suicidal ideation." - Do we know how many experienced which specific "serious adverse event"? Was it 11 ideations and 1 behavior that could be interpreted as self-injury, for example? - Do we know for certain that none of these 12 had any of those adverse events occur in the last few months prior to starting the medication? --- Again, I'm not crapping on this at all here, but folks should take it with a grain of salt and realize there's more to this, that only 12 adverse events isn't a significant concern unless we can show with high confidence that it was caused by the therapy, and at only 5%, even then it sounds like manageable risk as long as a prescriber would know the patient's history before hand. The announcement - not the study data itself just the press release - is here: https://ir.compasspathways.com/news-releases/news-release-details/compass-pathways-announces-positive-topline-results https://ir.compasspathways.com/news-releases/news-release-de...
- arcticbull 5y ago
  > Very small, can't generalize results based on such a small number. This comes up pretty often, but how many subjects do you need to know getting punched in the face hurts? It's absolutely possible to get statistically significant data from 233 patients, what matters is how the study is designed.
deleted 5y ago
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newbamboo 5y ago
I’m a believer in the potential value but think placebo or blind studies of psychedelics are absurd. You know full well of you’ve eaten an eighth of cubensis. I think to be fair, they should compare psychedelic treatment to other therapies like ECT or a weeklong vacation to Hawaii.
- tasty_freeze 5y ago
  To someone who has done mushrooms before, sure, they can tell. But for people with no psychedelic experience, niacin (a common stand-in) causes flushing and some other effects which a patient can tell "is doing something." IIRC, the famous "Good Friday" psilocybin experiment had some people from the control group believe they were not in the control group.
  - yeetaccount 5y ago
    > IIRC, the famous "Good Friday" psilocybin experiment had some people from the control group believe they were not in the control group. I can find a few people right now that believe that Lord of the Rings is a historical account of medieval Europe.
    - ethanbond 5y ago
      Right but when it comes to questions of placebo, the belief is what matters.
      - yeetaccount 5y ago
        People have sniffed my socks and thought they huffed ether.
- errcorrectcode 5y ago
  9 weeks of TMS should be tried before ECT. ECT is just one away from a lobotomy in terms of brutality and risk.
josh_today 5y ago
Anyone know why their stock dropped? Was this not the best outcome for the trials?
m0zg 5y ago
For me, I get depressed when I feel "stuck" in my circumstances (mostly a directionless project, bad boss, or cancerous working environment, or all of the above). I suppose going on a "trip" would alleviate that significantly, at least for a while. Then you'll get used to it and you'll be back to square one you can't escape without fixing the root cause. So any enthusiasm for this is going to have to be tempered by long term studies and outcomes. Any significant change in one's circumstances can _tactically_ alleviate depression somewhat.
- WalterGR 5y ago
  Do you have clinically diagnosed treatment-resistant depression?
whalesalad 5y ago
Psilocybin has changed my life. It needs to be available to everyone in the world. Pharmaceutical companies will fuck it up (it's coming - very quickly) so learn to grow your own.
- deleted 5y ago
  [deleted]
- azinman2 5y ago
  Legality aside, growing and consuming a fungus to me, someone who knows nothing about them outside the grocery store, sounds very dangerous.
  - spaetzleesser 5y ago
    People eat mushrooms all the time. they aren't dangerous.
  - whalesalad 5y ago
    Make hacker news HACKER news again. We've been eating these for thousands of years and suddenly everyone thinks they are dangerous. It's social conditioning.
ProjectArcturis 5y ago
The thing that's not clear is, how often do you have to do this? It's definitely not an everyday pill like Prozac, but it's not very effective after 6 weeks. Would you trip every 2 months? Seems like that would rapidly run into diminishing returns. No one has even tested a second dose! How is this actually going to work?
amelius 5y ago
29.1% effective Headline could be more informative by including this number.
- kingkawn 5y ago
  That number is misleading without context for how effective other drugs are and in comparison to placebo. Given that placebo was ~8% effective this is a highly promising treatment.
  - wufufufu 5y ago
    I think that was the control group, not placebo. But I didn't read the study in depth.
    - kingkawn 5y ago
      Control groups are given placebos…
- savant_penguin 5y ago
  With the placebo group too "Overall, 29.1% of patients in the highest-dose group were in remission three weeks after treatment, compared to 7.6% of those in the control group, "
  - kemayo 5y ago
    In remission after three weeks is pretty impressive, too. There's many antidepressants which take a lot longer to ramp up to being effective, even assuming they work for you.
- sleepysysadmin 5y ago
  So more effective than antidepressants? Great news!
  - wufufufu 5y ago
efields 5y ago
How does this get commercialized? I can't think of anything that's inherently cheap and easy to produce that you use for a few weeks and then never again that is also a financial cash cow the way most pharmaceuticals are. Disclaimer: I work for a pharma.
- curuinor 5y ago
  They figured out how to jack up the price of ketamine 100x by making it esketamine - find an analog, shove in an acetyl group somewhere, something something chiral something
- rednerrus 5y ago
  The money is in the professional therapists who administer this. It's the same model that's currently working for Ketamine.
- kemayo 5y ago
  It's probably not "a few weeks and then never again" -- I'm not depressed, but anecdotes from people I know who've tried mushrooms at home for this suggest that one trip produces a noticeable improvement that fades over time. It's possible that the full experience with a trained therapist who supervises the trip could produce longer-lasting changes, of course.
- forgotmypw17 5y ago
  Why does it have to be commercialized? Personally, I think the best option is it gets mainstreamed by knowledgeble guides working with individuals through the process, the mushroom growing is done by small-scale growers who do it with the passion and love this Medicine deserves, and the pill-makers are kept far and away from it.
  - spyder 5y ago
    Why does it have to be commercialized? In general it doesn't has to be, but in this case the research is done by a for-profit company which expects to see a return on their investments.
Smooth-Weather 5y ago
This 29.1% effectiveness is awesome considering it is a single dose that was given.
pizzeriafrida 5y ago
There was a great interview between Peter Attia and David Nutt on the research and effectiveness of psychedelics on various disorders https://peterattiamd.com/davidnutt/ https://peterattiamd.com/davidnutt/ He touches on the history of governments banning various drugs through junk science and propaganda (mostly from the US which influences the rest of the world). The scheduling system for drugs is a joke. Also interesting that the inventor of AA credited LSD for his ability to quit drinking. Edit: David Nutt authored this study in the NEJM https://www.nejm.org/doi/full/10.1056/nejmoa2032994 https://www.nejm.org/doi/full/10.1056/nejmoa2032994 which pitted psilocybin against lexapro for the treatment of depression and it showed the same effectiveness (more nuanced than that but you'll have to read or listen). Peter talked about how he is very familiar with Lexapro and it's side effects (libido, a blunting effect on life) in his patients and remarked that what was most exciting about that study is that it showed it could be as effective as Lexapro with less side effects.
- mattwilsonn888 5y ago
  I wasn't aware of the credit the AA inventor gives for his fixing drinking problem to LSD - that's certainly an interesting story, From what I understand the connections one might make considering the religious tones AA has, the common idea of what a high dose LSD experience might entail and the fact that LSD and other psychedelics have proven effective against addiction all together match the science so far - tied together by the interesting fact that for people suffering with depression or addiction who seek out help through psychedelics, religious or spiritual experience, not necessarily dose, is what associates with life improvements including long term. Those who did not have what felt to them a deeply significant experience did not reap the same benefits. I think though the psychedelic community can be somewhat pseudo-sciency (they were of course driven out of main stream science), the reference to psychedelics as a healing tool is apt. It is not the mere ingestion of psychedelics which helps people, but the intense and vivid realizations, visions, and feelings they come to experience which deeply affects them. Its a subtle difference - but I hypothesize that if you put people under anesthesia and gave them a high dose the long term results would be measurable weaker than those who were lucid for the experience.
wufufufu 5y ago
The shrooms community has known about this for a long time, and now it's just about recreating the knowledge in peer-reviewed studies. Although there is a lot of "woo woo" on shrooms usage in the online communities, I do hope that researchers can extract the useful bits. This isn't like an SSRI. 25mg psilocybin isn't something you can just pop at the beginning of a workday. Your setting and "head space" matter a lot for how your "trip" (which we will now rebrand as "treatment") will go. This needs to be accounted for in future studies.
- goodroot 5y ago
  > 25mg psilocybin isn't something you can just pop at the beginning of a workday. I would disagree. For many, 25mg is sub-perceptual. Source: have done this over several year.
  - WalterSear 5y ago
    3-5 grams of mushrooms? I want to work where you work. I hope it doesn't involve heavy machinery.
    - me_me_me 5y ago
      it depend on your weight, and potency of batch. I have settled on 2g every 3rd day. 1g dose seems to work only on empty stomach and I have to pay attention to feel difference in my mood. I can easily see a big guy taking 3-5g and not feeling much beyond mood boost.
  - tayo42 5y ago
    20-something mg of 4aco dmt was pretty wild, psilocybin must be somewhat similar
  - OnACoffeeBreak 5y ago
    I am guessing the 25 mg does here is of pure psilocybin, which is about 2.5 g of dried mushrooms.
  - nobodyofnote 5y ago
cmehdy 5y ago
As somebody who sometimes "treats" severe multi-decades-long depression with psychedelics, I'm not surprised that they'd have a positive impact but the news seems too unclear to my simple mind to make sense of a few things: 1- why is a private group on the stock market doing this, instead of public research & universities? vested interests in seizing a market of illegal drugs in a legal way worry me, because it's easy to completely forget the humans in the process when there's billions to be made 2- is 1mg declared a placebo with enough proof? I'm personally not receptive at all to any kind of "micro-dosing" but I've also seen equally anecdotal comments going exactly the opposite direction and loving that. Is there a study that thoroughly compares the 1mg dose to a fake product looking similar but with no psychoactive substance? 3- as someone keenly aware of an "afterglow" that can happen on psychedelics, I also don't see a proper discussion about (1) the potentially ephemeral nature of the benefits when taking a single dose, as well as (2) the difficulty of taking psychedelics along with pretty much any other treatment for mental health issues (SSRIs, MAOIs, anti-psychotics and so on, which all have their own counter-indications) I very much love all the psychedelic experiences I've had in life, from simple doses to "heroic" and intensely crushing trips, and I've always tried to extract some long-term benefits from them during and post-trip, but even compared to a psychiatric treatment that doesn't help me quite enough (doesn't get rid of anhedonia, brain fog, suicidal ideation, etc etc), I have still come to see those trips as more of a targeted temporary relief for the soul that one should ideally leverage in the window of time post-trip - and not so much as an ongoing treatment in and of itself like what's offered by my meds. At least from my limited perspective it hasn't been so much a treatment for a depression but a temporary relief from it, which offers a window of time to discuss anchoring constructive habits ("job search for an hour every morning", "clean up your house", ...) and having empathy for the self in pragmatic and measurable ways post-trip (cook yourself a meal, get a haircut, commit to physical activities again, etc). I'm not really convinced that we'll turn those substances into long-term treatments, but I could see them becoming a "shock therapy" of sorts.
- JoeAltmaier 5y ago
  I guess the hope is, by figuring out how it helps, the effect can be prolonged?
- 5y ago
WarOnPrivacy 5y ago
Having powerfully beneficial medications locked away is what happens when a law enforcement agency (DEA) decides national medical policy, instead of a qualified medical body.
97jy7h9j89uj 5y ago
> patients who were given [...] 25mg had a significant decrease in depressive symptoms Is that enough to cause impairment?
- maybeOneDay 5y ago
  It's a serious trip, yes. More (by far) than most people would recommend someone do recreationally for their first time - it appears that high doses accompanied by a therapist are what has shown the most promise across various exploratory trials.
shever73 5y ago
In Michael Pollan's fascinating history of psychedelics, "How to Change Your Mind", he explores this. It was interesting to see how governments appeared to have no issue with psychedelics until Timothy Leary came on the scene.
goodroot 5y ago
Have a lot of experience with microdosing psilocybin, as well as with psychedelics like Ayahuasca. My experience with both as a means to remedy depression have been significant. It is analagous to having a lamp in a dark forest. It won't get you through it itself, you need courage, and other tools like meditation (your machete), exercise (your provisions) and intention (your compass) to succeed. But with it, everything is easier. Err -- AMA?
- coding123 5y ago
  If you throw 100M people at this as a solution, do you expect to see most carefully and successfully getting through it like you or would most just become addicted and eventually lose their job and go homeless?
  - ragnese 5y ago
    Addicted and losing your job because of psilocybin? I've not tried it myself, but many of my friends have, and anecdotally, none of them have (to my knowledge) ever even gotten to the point of it being a "habit". I can't say the same for alcohol, cocaine, and even cannabis. I know people who have had problems with all of them.
    - goodroot 5y ago
      Even Terence McKenna, who himself was likely part mushroom given how many he ingested, said time and time again that mushrooms are resistant to abuse. If you take a very high dose, the experience itself can be so difficult and wonderful, that the idea of doing that to yourself again starts to seem ridiculous. :)
  - goodroot 5y ago
    When it comes to something like Ayahuasca, I make a point of not recommending it. I lean into the woo of it, and allow "the ready people" to help realize their calling to it through me. I know, bear with me, but advocating something this wildly, impossibly potent and transformative is something I cannot do, and so I defer to greater wisdom. For small doses of psilocybin, it is - both in my experiences and in a lot of scientific contexts - considered very, very safe. Greater doses, 2.5 dry grams, you start to introduce risk triggering latent psycho-affective disorders. For most people with common neurotic conditions, anxiety, depression, etc, it is very low risk. Out of 100M, I'd say .1% is at risk having a very negative experience due to significant, untreated issues like schizophrenia. All of things things require support. Community, a guiding hand, will truly improve the outcome.
Overtonwindow 5y ago
Psilocybin changed my life. It threw off the wet blanket of depression, which allowed my antidepressant to fully do its job. I can’t really explain it, but imagine if your depression was a jacket, and one day you just took it off.

82 points by hentrep 5y ago

Ketamine also. It's already approved. I would prefer all drugs were legalized as in Portugal and regulated because it's impossible for a consumer of illicit drugs to verify their contents and it would cut off criminal profiteering, violence, and the police-prison-industrial-complex from some funding too.

toomanybeersies 5y ago
Drugs are not legalised in Portugal, they're decriminalised. Trafficking is still a criminal offence, and personal possession is still punishable with a fine.
- errcorrectcode 5y ago
  Duh. The word "as" means "like" or "similar," it doesn't mean "is." Prohibition never works, and Portugal doesn't have a consistent approach yet.

icameron 5y ago

I had to look it up to put it in perspective. 25mg pure psilocybin could be around 5g of dried p. cubensis if they are .5% (which varies considerably...) point being this is no microdose. These patients are really tripping! So they are saying a psychedelic experience, which could reconstruct your entire ego, really can be a significant life-changing event.

constantlm 5y ago
Terence McKenna called 5 grams an heroic dose.

etaioinshrdlu 5y ago

Wow, 5% reported suicidal ideation or self harm, in a clinical setting. That’s pretty horrible.

PeterisP 5y ago
Depression is a quite significant cause of death, above many other major diseases especially for younger people.
sojournerc 5y ago
Well, participants were already on anti-depressants, and asked to stop before the trial, so causation isn't clear.
- darkerside 5y ago
  Well, how did it compare to the control group?
  - deleted 5y ago
    [deleted]
spaetzleesser 5y ago
I had one trip where I found peace with the idea of dying. Why keep struggling with life if you can leave it in harmony? Not sure if I would call this suicidal though. But it changed my attitude towards dying. I think if I had a hopeless disease or was close to dying otherwise I wouldn't fight it but try to die in a peaceful and aware way.

alexfromapex 5y ago

Love that it’s randomized and double blinded. Will be hard to cast doubt on it.

spaetzleesser 5y ago

I am pretty prone to depression and I definitely feel it lifting for a while after microdosing or taking a larger dose. Unfortunately I have never experienced a life changing trip that solved all problems as you may want to believe when you read some of the latest articles about the miracle of psilocybin and other psychedelics. Same for Ayahuasca. It seems to help a lot of people but for me it was more just a very interesting experience. For example I think a lot of film makers are/were taking psychedelics. During my trips I noticed so much more detail in my environment and different light reflections which you often see in movies.

pm90 5y ago
It’s a pretty well established fact that creatives have to use some mind altering substances to be productive, but it’s hard to believe that claim if you’ve never experienced them personally.
mettamage 5y ago
When I meditate hardcore then after a session, I also look differently at light.

PragmaticPulp 5y ago

The trial tested psilocybin combined with therapy. This isn’t equivalent to ad-hoc self treatment with mushrooms. They noticed a response to psilocybin+therapy in about 20-25% of patients depending on the criteria for “sustained response”: > The protocol-defined sustained response* up to week 12 was double, with 20.3% of patients in the 25mg group It’s also notable that about 5% of the psilocybin receivers experienced severe adverse events including suicidal ideation: > There were 12 patients who reported treatment-emergent serious adverse events (TESAEs). These TESAEs included suicidal behaviour, intentional self-injury, and suicidal ideation

JohnJamesRambo 5y ago
This sounds pretty crappy right? If I'm understanding the numbers, 25% response is about like what we get with a placebo in most studies if my memory is correct. It sounds like they were tripping balls on 25 mg, so this is definitely in active placebo range. From my memory: Placebo is about 25%. Antidepressants about 35% response rate. Active placebo of something like atropine which makes you feel weird but isn't an antidepressant has about a 35% response rate. https://blogs.scientificamerican.com/cross-check/are-antidepressants-just-placebos-with-side-effects/ https://blogs.scientificamerican.com/cross-check/are-antidep...
- drooby 5y ago
  I’m not sure if it makes a difference, but this study was conducted on _treatment resistant_ patients.

MrWiffles 5y ago

Some quick points: > 233 patients Very small, can't generalize results based on such a small number. Doesn't mean the study's trash or anything, but don't jump to any conclusions here - good or bad. > "The trial, which had all patients stopping antidepressants before participating, compared two active doses of COMP360, 25mg and 10mg, against a comparator 1mg dose." - COMP360 was, I assume, their therapeutic psilocybin but it's unknown if that differs from raw psilocybin or not, and if so in what way. - Did they TEST and PROVE discontinuation of antidepressants at all stages of the trial? Which kinds of antidepressants did they test for? SSRI? TCA? MAOI? How did they test? Uranalysis? Blood? Or did they just take 233 people's word for it? > "[...] 179 patients reported at least one adverse event — the most common being headaches, nausea, fatigue and insomnia." - Likely unrelated to the medication itself, as those can be caused by hundreds (thousands) of factors. Literally included in every possible side effect list for nearly every medication known to exist. Doubtful that the medication caused any of these. > "There were 12 patients who reported more serious adverse events, such as suicidal behavior, intentional self-injury, and suicidal ideation." - Do we know how many experienced which specific "serious adverse event"? Was it 11 ideations and 1 behavior that could be interpreted as self-injury, for example? - Do we know for certain that none of these 12 had any of those adverse events occur in the last few months prior to starting the medication? --- Again, I'm not crapping on this at all here, but folks should take it with a grain of salt and realize there's more to this, that only 12 adverse events isn't a significant concern unless we can show with high confidence that it was caused by the therapy, and at only 5%, even then it sounds like manageable risk as long as a prescriber would know the patient's history before hand. The announcement - not the study data itself just the press release - is here: https://ir.compasspathways.com/news-releases/news-release-details/compass-pathways-announces-positive-topline-results https://ir.compasspathways.com/news-releases/news-release-de...

arcticbull 5y ago
> Very small, can't generalize results based on such a small number. This comes up pretty often, but how many subjects do you need to know getting punched in the face hurts? It's absolutely possible to get statistically significant data from 233 patients, what matters is how the study is designed.

deleted 5y ago

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newbamboo 5y ago

I’m a believer in the potential value but think placebo or blind studies of psychedelics are absurd. You know full well of you’ve eaten an eighth of cubensis. I think to be fair, they should compare psychedelic treatment to other therapies like ECT or a weeklong vacation to Hawaii.

tasty_freeze 5y ago
To someone who has done mushrooms before, sure, they can tell. But for people with no psychedelic experience, niacin (a common stand-in) causes flushing and some other effects which a patient can tell "is doing something." IIRC, the famous "Good Friday" psilocybin experiment had some people from the control group believe they were not in the control group.
- yeetaccount 5y ago
  > IIRC, the famous "Good Friday" psilocybin experiment had some people from the control group believe they were not in the control group. I can find a few people right now that believe that Lord of the Rings is a historical account of medieval Europe.
  - ethanbond 5y ago
    Right but when it comes to questions of placebo, the belief is what matters.
    - yeetaccount 5y ago
      People have sniffed my socks and thought they huffed ether.
errcorrectcode 5y ago
9 weeks of TMS should be tried before ECT. ECT is just one away from a lobotomy in terms of brutality and risk.

josh_today 5y ago

Anyone know why their stock dropped? Was this not the best outcome for the trials?

m0zg 5y ago

For me, I get depressed when I feel "stuck" in my circumstances (mostly a directionless project, bad boss, or cancerous working environment, or all of the above). I suppose going on a "trip" would alleviate that significantly, at least for a while. Then you'll get used to it and you'll be back to square one you can't escape without fixing the root cause. So any enthusiasm for this is going to have to be tempered by long term studies and outcomes. Any significant change in one's circumstances can _tactically_ alleviate depression somewhat.

WalterGR 5y ago
Do you have clinically diagnosed treatment-resistant depression?

whalesalad 5y ago

Psilocybin has changed my life. It needs to be available to everyone in the world. Pharmaceutical companies will fuck it up (it's coming - very quickly) so learn to grow your own.

deleted 5y ago
[deleted]
azinman2 5y ago
Legality aside, growing and consuming a fungus to me, someone who knows nothing about them outside the grocery store, sounds very dangerous.
- spaetzleesser 5y ago
  People eat mushrooms all the time. they aren't dangerous.
- whalesalad 5y ago
  Make hacker news HACKER news again. We've been eating these for thousands of years and suddenly everyone thinks they are dangerous. It's social conditioning.

ProjectArcturis 5y ago

The thing that's not clear is, how often do you have to do this? It's definitely not an everyday pill like Prozac, but it's not very effective after 6 weeks. Would you trip every 2 months? Seems like that would rapidly run into diminishing returns. No one has even tested a second dose! How is this actually going to work?

amelius 5y ago

29.1% effective Headline could be more informative by including this number.

kingkawn 5y ago
That number is misleading without context for how effective other drugs are and in comparison to placebo. Given that placebo was ~8% effective this is a highly promising treatment.
- wufufufu 5y ago
  I think that was the control group, not placebo. But I didn't read the study in depth.
  - kingkawn 5y ago
    Control groups are given placebos…
savant_penguin 5y ago
With the placebo group too "Overall, 29.1% of patients in the highest-dose group were in remission three weeks after treatment, compared to 7.6% of those in the control group, "
- kemayo 5y ago
  In remission after three weeks is pretty impressive, too. There's many antidepressants which take a lot longer to ramp up to being effective, even assuming they work for you.
sleepysysadmin 5y ago
So more effective than antidepressants? Great news!
- wufufufu 5y ago

efields 5y ago

How does this get commercialized? I can't think of anything that's inherently cheap and easy to produce that you use for a few weeks and then never again that is also a financial cash cow the way most pharmaceuticals are. Disclaimer: I work for a pharma.

curuinor 5y ago
They figured out how to jack up the price of ketamine 100x by making it esketamine - find an analog, shove in an acetyl group somewhere, something something chiral something
rednerrus 5y ago
The money is in the professional therapists who administer this. It's the same model that's currently working for Ketamine.
kemayo 5y ago
It's probably not "a few weeks and then never again" -- I'm not depressed, but anecdotes from people I know who've tried mushrooms at home for this suggest that one trip produces a noticeable improvement that fades over time. It's possible that the full experience with a trained therapist who supervises the trip could produce longer-lasting changes, of course.
forgotmypw17 5y ago
Why does it have to be commercialized? Personally, I think the best option is it gets mainstreamed by knowledgeble guides working with individuals through the process, the mushroom growing is done by small-scale growers who do it with the passion and love this Medicine deserves, and the pill-makers are kept far and away from it.
- spyder 5y ago
  Why does it have to be commercialized? In general it doesn't has to be, but in this case the research is done by a for-profit company which expects to see a return on their investments.

Smooth-Weather 5y ago

This 29.1% effectiveness is awesome considering it is a single dose that was given.

pizzeriafrida 5y ago

There was a great interview between Peter Attia and David Nutt on the research and effectiveness of psychedelics on various disorders https://peterattiamd.com/davidnutt/ https://peterattiamd.com/davidnutt/ He touches on the history of governments banning various drugs through junk science and propaganda (mostly from the US which influences the rest of the world). The scheduling system for drugs is a joke. Also interesting that the inventor of AA credited LSD for his ability to quit drinking. Edit: David Nutt authored this study in the NEJM https://www.nejm.org/doi/full/10.1056/nejmoa2032994 https://www.nejm.org/doi/full/10.1056/nejmoa2032994 which pitted psilocybin against lexapro for the treatment of depression and it showed the same effectiveness (more nuanced than that but you'll have to read or listen). Peter talked about how he is very familiar with Lexapro and it's side effects (libido, a blunting effect on life) in his patients and remarked that what was most exciting about that study is that it showed it could be as effective as Lexapro with less side effects.

mattwilsonn888 5y ago
I wasn't aware of the credit the AA inventor gives for his fixing drinking problem to LSD - that's certainly an interesting story, From what I understand the connections one might make considering the religious tones AA has, the common idea of what a high dose LSD experience might entail and the fact that LSD and other psychedelics have proven effective against addiction all together match the science so far - tied together by the interesting fact that for people suffering with depression or addiction who seek out help through psychedelics, religious or spiritual experience, not necessarily dose, is what associates with life improvements including long term. Those who did not have what felt to them a deeply significant experience did not reap the same benefits. I think though the psychedelic community can be somewhat pseudo-sciency (they were of course driven out of main stream science), the reference to psychedelics as a healing tool is apt. It is not the mere ingestion of psychedelics which helps people, but the intense and vivid realizations, visions, and feelings they come to experience which deeply affects them. Its a subtle difference - but I hypothesize that if you put people under anesthesia and gave them a high dose the long term results would be measurable weaker than those who were lucid for the experience.

wufufufu 5y ago

The shrooms community has known about this for a long time, and now it's just about recreating the knowledge in peer-reviewed studies. Although there is a lot of "woo woo" on shrooms usage in the online communities, I do hope that researchers can extract the useful bits. This isn't like an SSRI. 25mg psilocybin isn't something you can just pop at the beginning of a workday. Your setting and "head space" matter a lot for how your "trip" (which we will now rebrand as "treatment") will go. This needs to be accounted for in future studies.

goodroot 5y ago
> 25mg psilocybin isn't something you can just pop at the beginning of a workday. I would disagree. For many, 25mg is sub-perceptual. Source: have done this over several year.
- WalterSear 5y ago
  3-5 grams of mushrooms? I want to work where you work. I hope it doesn't involve heavy machinery.
  - me_me_me 5y ago
    it depend on your weight, and potency of batch. I have settled on 2g every 3rd day. 1g dose seems to work only on empty stomach and I have to pay attention to feel difference in my mood. I can easily see a big guy taking 3-5g and not feeling much beyond mood boost.
- tayo42 5y ago
  20-something mg of 4aco dmt was pretty wild, psilocybin must be somewhat similar
- OnACoffeeBreak 5y ago
  I am guessing the 25 mg does here is of pure psilocybin, which is about 2.5 g of dried mushrooms.
- nobodyofnote 5y ago

cmehdy 5y ago

As somebody who sometimes "treats" severe multi-decades-long depression with psychedelics, I'm not surprised that they'd have a positive impact but the news seems too unclear to my simple mind to make sense of a few things: 1- why is a private group on the stock market doing this, instead of public research & universities? vested interests in seizing a market of illegal drugs in a legal way worry me, because it's easy to completely forget the humans in the process when there's billions to be made 2- is 1mg declared a placebo with enough proof? I'm personally not receptive at all to any kind of "micro-dosing" but I've also seen equally anecdotal comments going exactly the opposite direction and loving that. Is there a study that thoroughly compares the 1mg dose to a fake product looking similar but with no psychoactive substance? 3- as someone keenly aware of an "afterglow" that can happen on psychedelics, I also don't see a proper discussion about (1) the potentially ephemeral nature of the benefits when taking a single dose, as well as (2) the difficulty of taking psychedelics along with pretty much any other treatment for mental health issues (SSRIs, MAOIs, anti-psychotics and so on, which all have their own counter-indications) I very much love all the psychedelic experiences I've had in life, from simple doses to "heroic" and intensely crushing trips, and I've always tried to extract some long-term benefits from them during and post-trip, but even compared to a psychiatric treatment that doesn't help me quite enough (doesn't get rid of anhedonia, brain fog, suicidal ideation, etc etc), I have still come to see those trips as more of a targeted temporary relief for the soul that one should ideally leverage in the window of time post-trip - and not so much as an ongoing treatment in and of itself like what's offered by my meds. At least from my limited perspective it hasn't been so much a treatment for a depression but a temporary relief from it, which offers a window of time to discuss anchoring constructive habits ("job search for an hour every morning", "clean up your house", ...) and having empathy for the self in pragmatic and measurable ways post-trip (cook yourself a meal, get a haircut, commit to physical activities again, etc). I'm not really convinced that we'll turn those substances into long-term treatments, but I could see them becoming a "shock therapy" of sorts.

JoeAltmaier 5y ago
I guess the hope is, by figuring out how it helps, the effect can be prolonged?
5y ago

WarOnPrivacy 5y ago

Having powerfully beneficial medications locked away is what happens when a law enforcement agency (DEA) decides national medical policy, instead of a qualified medical body.

97jy7h9j89uj 5y ago

> patients who were given [...] 25mg had a significant decrease in depressive symptoms Is that enough to cause impairment?

maybeOneDay 5y ago
It's a serious trip, yes. More (by far) than most people would recommend someone do recreationally for their first time - it appears that high doses accompanied by a therapist are what has shown the most promise across various exploratory trials.

shever73 5y ago

In Michael Pollan's fascinating history of psychedelics, "How to Change Your Mind", he explores this. It was interesting to see how governments appeared to have no issue with psychedelics until Timothy Leary came on the scene.

goodroot 5y ago

Have a lot of experience with microdosing psilocybin, as well as with psychedelics like Ayahuasca. My experience with both as a means to remedy depression have been significant. It is analagous to having a lamp in a dark forest. It won't get you through it itself, you need courage, and other tools like meditation (your machete), exercise (your provisions) and intention (your compass) to succeed. But with it, everything is easier. Err -- AMA?

coding123 5y ago
If you throw 100M people at this as a solution, do you expect to see most carefully and successfully getting through it like you or would most just become addicted and eventually lose their job and go homeless?
- ragnese 5y ago
  Addicted and losing your job because of psilocybin? I've not tried it myself, but many of my friends have, and anecdotally, none of them have (to my knowledge) ever even gotten to the point of it being a "habit". I can't say the same for alcohol, cocaine, and even cannabis. I know people who have had problems with all of them.
  - goodroot 5y ago
    Even Terence McKenna, who himself was likely part mushroom given how many he ingested, said time and time again that mushrooms are resistant to abuse. If you take a very high dose, the experience itself can be so difficult and wonderful, that the idea of doing that to yourself again starts to seem ridiculous. :)
- goodroot 5y ago
  When it comes to something like Ayahuasca, I make a point of not recommending it. I lean into the woo of it, and allow "the ready people" to help realize their calling to it through me. I know, bear with me, but advocating something this wildly, impossibly potent and transformative is something I cannot do, and so I defer to greater wisdom. For small doses of psilocybin, it is - both in my experiences and in a lot of scientific contexts - considered very, very safe. Greater doses, 2.5 dry grams, you start to introduce risk triggering latent psycho-affective disorders. For most people with common neurotic conditions, anxiety, depression, etc, it is very low risk. Out of 100M, I'd say .1% is at risk having a very negative experience due to significant, untreated issues like schizophrenia. All of things things require support. Community, a guiding hand, will truly improve the outcome.

Overtonwindow 5y ago

Psilocybin changed my life. It threw off the wet blanket of depression, which allowed my antidepressant to fully do its job. I can’t really explain it, but imagine if your depression was a jacket, and one day you just took it off.