5 ms·

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 see

by 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?
lindsaywaterman 5y ago
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!
- cmehdy 5y ago
  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-show-placebo-effect-explain/ https://www.imperial.ac.uk/news/216134/citizen-scientists-sh... [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050654/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050654/
tgittos 5y ago
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?
- cmehdy 5y ago
  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.
fjabre 5y ago
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.
- cmehdy 5y ago
  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.

by cmehdy 5y ago

JoeAltmaier 5y ago

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

lindsaywaterman 5y ago

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!

cmehdy 5y ago
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-show-placebo-effect-explain/ https://www.imperial.ac.uk/news/216134/citizen-scientists-sh... [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050654/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050654/

tgittos 5y ago

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?

cmehdy 5y ago
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.

fjabre 5y ago

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.

cmehdy 5y ago
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.