Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms • Hacker News Board

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#91

Post by goodroot » Wed, Nov 10, 2021, 5:47 PM UTC

lordofgibbons wrote: post #84

goodroot wrote: post #81

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, everythi…

With micro-dosing, doesn't your body get acclimated to the low doses taken over extended periods of time and thus rendering the micro-dose ineffective? I assume you have to cycle with it? Are there any negative effects on your off-cycle days? i.e less creativity or feeling down

Hello!

Your body does build a tolerance. But there is a common misconception that the "psychedelic" presentation is where you find the efficacy. In most microdosing stacks, you combine Psilocybin with lion's mane mushroom and vitamin B12. It is usually 5 on, 2 off. Even if you do not feel any upwelling, it is working.

The process of neurogenesis is very subtle, and that is the mechanism which, when combined with other tools, will help you get over depression when microdosing. It takes time, it is a gradual, slow, re-wiring. The affect of the psychedelic experience can provide creative and mood benefits. But I believe these are separate processes with separate benefits.

Often when speaking with folks, and I notice myself, that there are no withdrawal symptoms. There is always risk of dependency when ingesting any outside substance, but something about the experience itself is resistant to abuse.

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#92

Post by coding123 » Wed, Nov 10, 2021, 5:48 PM UTC

goodroot wrote: post #81

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, everythi…

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?

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#93

Post by e40 » Wed, Nov 10, 2021, 5:48 PM UTC

goodroot wrote: post #81

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, everythi…

This isn't something you can really answer, but I'd be game to try micro-dosing psilocybin, but I have no idea where to get it safely (from LEOs and bad chemistry). It would be great if the local dispensary sold it.

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#94

Post by goodroot » Wed, Nov 10, 2021, 5:50 PM UTC

mayormcmatt wrote: post #87

goodroot wrote: post #81

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, everythi…

This is something I've been interested in for a good while now, and tried a similar LSD microdosing regimen without any exciting results. However, I also didn't pair the practice with meditation or regular exercise (some, not a lot). My main question is, how does one get anything like a regular, precise (micro)dose of the psilocybin? Volumetric dilution with LSD seems simple, because I know how much each tab contains…

In Canada, we are very lucky.

My city produces many laboratory grade mushrooms.

Look! https://www.magicmushroomsdispensary.ca/

There would be a significant variance in potency if we were nibbling on different parts of the fruiting body when measuring a dose. But first, you grind it into powder, measure it on an electronic scale, and then take it.

If you stick to the same supplier and the same type of mushroom, this keeps things very consistent.

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#95

Post by ragnese » Wed, Nov 10, 2021, 5:55 PM UTC

coding123 wrote: post #92

goodroot wrote: post #81

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, everythi…

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?

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.

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#96

Post by cmehdy » Wed, Nov 10, 2021, 5:55 PM UTC

lindsaywaterman wrote: post #77

cmehdy wrote: post #67

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 eas…

1. Pharmaceutical studies are extremely expensive so usually done through private sector. In this case compass has a patent for a certain way to synthesize psilocybin, but not a patent on psilocybin itself. However, the results of the study will generalize to psilocybin of all sources. Win win in my view. 2. There are many studies in the literature that compare "psycholytic" (which tend to accentuate pre-existing men…

Thanks for replying to all those points!

I agree that all news is in principle good news for psychedelics, but the private interests still have a bigger reason to exaggerate the positives for any treatment for financial benefit. We even see this with how prevalent the "latest" SSRIs are vs. treatments that have existed for a long time. New research with fancy articles isn't always better than old research, especially when the people prescribing it to you fall prey to the market pressure of prescribing the costly solution to you vs. older solutions for a tenth of the price, for which on the other hand we'll exaggerate the side effects...

Do you happen to have any interesting link regarding what you mention as being psycholitic and how it relates to a placebo? Because from every page I've been finding on the subject, none seems to indicate that the substance acts specifically as a placebo but only that noticeable psychedelic effects aren't present, which is slightly different. I've done some digging to find something[1] supporting the idea that "microdosing == placebo" but given that there's pretty much only studies that have self-reported data in that domain, I'm not sure I've ever seen anything conclusive regarding microdosing being a placebo, nor at what dosage one can consider each psychedelic substance as microdosing/placebo. I might have very much missed something big in the domain and you seem to know your stuff, so if you happen to know something to link I would happily take a look :)

As for long-term positive effects, are you referring to this study [2] ? It certainly looks interesting for significance over long periods of time, but not necessarily to alleviate depression. I have a few DMT trips in my life that are amongst the most significant moments of my existence, yet I'm into my third decade of debilitating depression - those things don't necessarily have to overlap.

I also agree about concurrent treatments not being absolutely contra-indications, but I think we're being particularly kind to whatever is the new kid on the block and unfairly harsh to old treatments in comparison. I had the chance to meet a psychiatrist who's been doing their job since the 60s, and they were the first to offer trying a RIMA (moclobemide) which significantly helped compared to multiple SSRIs, and had less negative side effects than SSRIs and even some positive ones (libido) - despite a truly horrible reputation everywhere you look, and in young psychiatrists' minds.

I believe there's a good place for psychedelic treatments to contribute to the well-being of a suffering person, but as a pretty experienced "psychonaut" I've always remained keenly aware of the potential for these substances to induce a certain degree of collective delusions too -- even more so if we're talking about a multi-billion dollar new market opening up.

[1] https://www.imperial.ac.uk/news/216134/citizen-scientists-sh... [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050654/

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#97

Post by goodroot » Wed, Nov 10, 2021, 5:57 PM UTC

coding123 wrote: post #92

goodroot wrote: post #81

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, everythi…

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?

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.

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#98

Post by sharadov » Wed, Nov 10, 2021, 6:01 PM UTC

nverno wrote: post #75

abrichr wrote: post #66

Earlier quoted context omitted.

The Huberman Lab podcast episode on depression touches on this. According to Dr. Huberman the quality of the trip is not important, the chemical changes the brain function regardless.

Anecdotally, I've also noticed the most profound lasting positive effects on my mood after the worst trip I ever had- an absolute nightmare for no good reason (same people I'd tripped with before, familiar places, etc), but the following couple weeks I was on cloud 9. There are so many confounding factors, but at the time I was completely convinced the trip was responsible for the following positive period. The exper…

Did you see lasting changes? Or they were mostly temporary.

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#99

Post by fjabre » Wed, Nov 10, 2021, 6:02 PM UTC

cmehdy wrote: post #67

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 eas…

It is because you see the experiences as false compared to the reality you are now immersed in.

If a big trip doesnt manage to completely change your belief system it has mostly failed in its effect.

It is the change in beliefs that lead to a lasting result.

If one leaves the experience denying the new experience and calling it false or calling it just a dream then it will surely fade and results will not last.

This is self evident over time. Effects should not fade but in fact should grow stronger without the further use of psychedelics. Proper integration and meditation do this.

If one takes the experience as truth, a Big trip then has the power to cure. Depression will never return.

Conviction in the experience must be there for it to really work its magic.

To have an experience like this and then to come back calling it just a dream is a tragedy. What a waste. For someone like this they have missed the point. They go back to their lives as normal. Everything is as it is. They simply feel a little better or feel relief for some time, but because they did not accept the new reality they are then forced back down into their old routines and habits. They are put right back in the reality they left and felt relief from after their Big trip. Depression sets in again. Everything goes back to the way it was, the trip becoming a distant memory.

Re: Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms

#100

Post by goodroot » Wed, Nov 10, 2021, 6:09 PM UTC

Dumblydorr wrote: post #85

goodroot wrote: post #81

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, everythi…

Interesting analogy of a dark forest. I'd say the Zen realization is of value here. You can always, at any moment, realize that your sensations and consciousness is all there is. We don't need anything more than to observe what we sense at any moment. I say this because changing our mind doesn't have to be hard arduous work, Zen Buddhists realized that enlightenment is here now, if we have the will to simply see it a…

Reading a book at the moment called "Cutting Through Spiritual Materialism", which are the words of Tibetan Buddhist monk of renown Chögyam Trungpa. He also likens the development of spiritual presence to a blade. The trick with Sam's stated perspective, from this Buddhist perspective, is that it implies attainment of a desire: I meditate to be calm. Meditation can make people calm, and so can breath work. But if you say "I meditate to be calm and ride to wisdom", there are those who would say you are not meditating at all. They would say it is just "I meditate", and then "meditate", in these sort of Buddhist philosophies like Zen and similar.

I do not say this to gatekeep - but experiences have taught me that, absolutely, meditation and the path of spirit is very hard, dangerous and arduous work. Helping others through derealization and psychosis has taught me this lesson time and time again.

In my metaphor, meditation in the psychdelic context is a machete because it is the blade to cut through all the psychedelia, all the woo, all the false notions of personal loftiness from spiritual insight, all the ideas of being healed, all of the mind mess. It simply is the mechanism that you use to cut through, and then "become here and now", to allow yourself to heal beyond stories: depressive stories, happy stories, and into a state of mind that is resilient to the suffering of the times.