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 mental states) to "psychedelic" (which can trigger mystical/insight experiences) doses of psilocybin. I'd say it's reasonable to treat 1 mg as placebo.

3.i. The study followup is ongoing. One of the remarkable aspects of psilocybin treatment is that one dose can lead to lasting (ie >6 mo) effects on mood. See the john hopkins studies.

3.ii. Although the studies all have folks weaning off, concurrent SSRI, MAOI, and anti-psychotic use is not an absolute contraindication. They do not cause serotonin syndrome with psilocybin. But clinically I think this won't be a huge issue as most patients will only be trying psilocyin if 1. their ssri has failed or 2. they are opposed to trying ssris. cheers!

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/

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.

What happens if you were to do two trips in a row, would you then have to change your mind to completely different outcomes each time? Would that one time in the middle be invalidated by the later trip? How do you go about quantifying which trips offer enough change and which don't? How many trips do you then have to do to get there? How do you qualify a new set of beliefs as being the "right" one? Are YOU the person who gets to decide that? And so on.

I appreciate that you find freedom in your personal belief system, and I'm happy for you. But you're definitely getting ahead of yourself if you think that whatever you're holding on to is a universal truth for all that is living. I've had that conversation countless times with people who've also gone through DMT breakthroughs: you're no less in a prison of your own mind when you think this way, you've only shifted your philosophical perspective into a place that anchors different beliefs in place. They appear entirely valid because you perceive less subjective suffering, but generalizing the idea that those beliefs are valid everywhere and for everyone is like believing that a singular value in a system of differential equations give the whole picture. There's a difference between solving your problems and solving everybody's problems, and thankfully the scientific work comes into place to bridge that gap (however slow the process might be).

I appreciate your intentions and I think there are nuggets of truth in what you write (re-integration helps you carry things further, meditation offers relief, a change of beliefs most often does lead to lasting results yes), however some people are allergic to blindly dogmatic thinking and I happen to be one of them. Your entire post could have been written to advocate for religion X, Y or Z btw, and people in each religion have just as valid of a claim as you do when it comes to their belief systems alleviating their suffering.

Mandating that one is bound to find the truth with a big T if one "does it right" is pretty much one of the things that as a guide for others through psychedelics I've never made the mistake of advocating for. Psychedelics are a journey, and like any journey you might come in with who you are and come out with different parts but the more you project rigid expectations the less you'll actually extract from the journey itself. Like any journey, two different people taking the same means of transportation and going to the same place, might extract two entirely different things.

It would do a lot of good to a subset of the psychonaut community to retain empathy and compassion when it comes to sharing about personal journeys.

It is precisely because I care that I commented so that another one may find it.

Just for the sake of clarity I am referring to a level 5 trip.

Two trips in row with different outcomes? This is not a question that would be posed by someone who has experienced a level 5 trip. Why? It becomes self evident. But it is not something I can 'prove' to you. You have to see for yourself.

Regarding outcomes - One has either broken through or not. One will know when they have had an ego death and OBE. It is a very distinct experience. Some will still deny this even but much much fewer can deny an experience that powerful.

I have had many trips that were below a level 5 but only one that I would classify as a level 5 trip - complete loss of ego or ego death.

I was an atheist before that Big trip.

The Psychedelic experience has many common threads. I've read hundreds of big trip reports maybe thousands. The common threads become very obvious after a while. As obvious as the sunrise.

Yes this is my interpretation and the interpretation of some very old religions like Hinduism and its offshoot Buddhism.

They are not dogmatic in that you can believe whatever you want next to them while still considering them as truth.

From One there are many. Surely this does not even escape a mathematician. You cannot deny your own existence yet Science has very little to say about the nature of consciousness. In fact Science really has no clue when it comes to the mystery of consciousness. Its view is that we are meat puppets and the sum of our parts. Nothing more than we can see with our eyes. Why is this accepted as dogma but other belief systems are not?

Science itself is a kind of dogmatic religion. It is one that many take for granted as absolute truth. Older thought systems such as Buddhism have been around for much much longer. To assume they are somehow inferior to Science because of their age is a mistake.

All beliefs are valid. One can worship or believe as they wish to find happiness. It is only that they accept Science's answer as Absolute Truth and not their own direct experience after they have had a big trip. That is the waste. The lack of conviction in their experience as being real.

It is surprising that after such an experience one can walk away without conviction! They would have to try hard to forget and make themselves believe that everything is just as it was and it was all just a dream. That is the difficult part. Believing should be the easy part but the world pulls us back in. Our old concepts rush back in.

We put our belief back in the old way of doing things and back to the world we knew before that Big trip. The world of the 24 hour news cycle and Reddit. The world of our addictions, apps, and waking life. Because we feel comfortable there. It is challenging for us to change our outlook so drastically but that is what a Big trip challenges us to do.

I can only assume you refer to "level 5" from a personal source rather than DMT-Nexus (which only has 3 levels) or PsychonautWiki (which mentions levels rather freely and goes to Levels 8+, also spreading out the descriptions into various categories).

It's going to be impossible to convince you that your subjective experience isn't an absolute truth because it seems like the entire foundation of your approach to the discussion and psychedelics is based on that assumption. What you're entirely wrong about however is regarding the definition of science: science is (1) a set of logically consistent statements for a set of givens, and (2) meant to have its validity tested constantly in order to be invalidated so that a better fitting approximation can be found. Science, down to basic axioms of mathematics, is not debating "Truths" but only relative truths, and is making statements that for assumption A,B,C one will observe logical results X,Y,Z, where it perpetually strives to refine the process such that more logical links can be established and any assumption that leads to incorrect/invalid/uninteresting consequences can be weaned out. When in fairly abstract fields, even those assumptions are usually also explored over time and utilized by people as they see fit (maths without ZFC, relatively quick acceptance of relativity in the world of physics, and so on).

If your insights about science as a whole are so off the mark, I'm frankly not surprised that your assertions come off the way they do. And I happen to disagree with the stance that takes refuge in absolute truths (unless its validity were to ever be proven somehow), and even the mightiest of psychedelic trips of dozens of kinds (including ridiculous doses of DMT, Changa, DOM and what have you) have not fundamentally changed a thing about it since I wasn't susceptible to that belief in the first place. That you can just come out and say "well it was simply not enough drugs you took buddy!" is much more likely to be indicative of your wish for personal bias to be a truth than any alternative. And much like with religions in general, I'll respect your right to dive into your personal belief system, but my perspective will be wildly different from yours (and perhaps not as fixated).

I am not looking to debate or argue. I am simply stating my beliefs. You are free to disagree or take nothing at all from it. To become critical of me or my understanding shows how little you have learned from your experiences.

Depression comes from the same place as your judgement of others.

All experience is subjective. That is my point.

You however limit your experience to the world view of your senses and what science and your cultural background have told you are true. It is as simple as that.

That is valid. But it wont cure Depression. The analytical mind has no clue. That is why. That is my belief. Take what you want or take nothing at all.

> To become critical of me or my understanding shows how little you have learned from your experiences.

That's just an attempt to shield yourself from any kind of external perspective.

> Depression comes from the same place as your judgement of others.

Glad you, on your own, have managed to solve remotely a problem that is a complex combination of multiple traumas, PTSD, neurochemical issues and psychological ones. Or more likely, you've lost all sympathy from me in this response as you've revealed just low little your personal experiences have fundamentally changed in your ability to extend and practice empathy, and therefore the very limited extent to which your experiences retain value in the bigger scheme of things in this discussion.

I too have treated MDD with psychedelics along side CBT therapy (not in official conjunction) and found that my suicidal ideation and anhedonia subsided for about a year after my first big trip. Since then, I've done heroic doses and microdoses and found that the most beneficial to me was infrequent large doses combined with integration in therapy afterwards. I agree with your take that it's more akin to a "shock therapy" than a regular medication.

I'm curious, do you work with a talk therapist? If so, do you feel like the therapy + psychedelics is better than either alone?

I have had limited opportunities to have ongoing talk therapy, but I've done a lot of the heavy lifting of CBT on my own throughout the years (both during psychedelic trips and in my day-to-day life).

For me the psychedelic trips have been an opportunity to focus on a subset of CBT (challenging negative thoughts + behavioural activation), while in the day-to-day CBT I've focused more on keeping in mind the cognitive-behavioural model as well as an index of cognitive distortions to test my flowing thoughts against. It's a bit challenging to try to hold on to your flowing thoughts when under the influence of noticeable doses of psychedelics, and that's why I focused more on specific points of trauma as well as noticeable reactions (literally looking at my face in the mirror at times). I've personally noticed two different moments post-trip: the first few hours to days where clarity of mind is much higher than my baseline and I can transform the work of the trip into something tangible in the long run (like a commitment to the gym), and the next few weeks where I sense an initially sharp and then gradual fading out of any "afterglow" from the trip, which is why I've come to see those trips as shock therapy even when I can extract something positive beyond the horizon of time of that "afterglow". I've also noticed that this whole system worked less and less well with the years, the window of time going from months to weeks to days, even as I spaced apart the psychedelic trips more and more (1/month -> 3-4/year -> 1/year or less).

I used to be a bit wary of inherent bias from researchers all too eager to share positive things with the world, but with the widening of the Overton window regarding psychedelics and the success of the cannabis market in many places in the world I've also started to be wary of financial interests in the subject. Nonetheless, I'm really looking forward to the new research coming out around psychedelics because there's just so much that we don't actually know properly with science to back it up - and more teams to work on the subject will offer more chances to figure out what's going on within that expansive world.

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