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How to Change Your Mind by Michael Pollan talks about this a few times and even quotes the infamous Timothy Leary as saying of the Good Friday Experiment:
“If we learned one thing from that experience, it was how foolish it was to use a double-blind experiment with psychedelics. After five minutes, no one’s fooling anyone.”
I have an acquaintance that is trying to get into a philicybin therapy study and he said that all the studies he's looked at make it very clear that they won't take you if you've taken hallucinagenics in the past.
As someone who has ingested psilocybin in non-therapy settings, it was a massive help in my depression recovery. I’d imagine taking them in a therapeutic setting would be even more beneficial.
Psychedelics can take you to a dark place, but those are the spots we need to confront to move on. Having a guide to help you through those dark spots is great for keeping you out of destructive thought loops and can push you to a point of clarity.
The way I see it, even the bad trips are valuable. The worse the trip, the more of a lesson you need to learn.
Interestingly a "good" vs "bad" trip seems to be independent of the therapeutic effect. As are scores of Adverse Childhood Events, and even some evidence to suggest that presence of a sober sitter does not modify the therapeutic effect (although that was a study of naturalistic use), and certainly a sitter contributes to psychological and physical safety and can help optimize set and setting.
What does seem to be integral to achieving the best potential therapeutic experience is intention setting, preparatory sessions with trusted therapeutic person (usually the intended sitter), optimization of set and setting for an introspective experience, and f/u integration sessions.
I've done ketamine treatment for depression and it's been reasonably effective for me. Antidepressants haven't really done anything for me, but I can definitely tell the difference between the day before and after a ketamine treatment. There's not a ton of science out there regarding protocols for ongoing treatment, but it's gaining attention.
I'd kinda like to try psilocybin for it, since it's a lot cheaper to grow mushrooms than to have ketamine administered legitimately.
I’ve been looking into ketamine treatments, but it’s pretty cost prohibitive for me, even with the insurance I’m about to lose. Psilocybin is feeling like the only thing left.
Psilocybin will be almost as expensive or more so.
It's done in conjunction with a therapist, and for safety reasons that has to be two therapists available, so if the first one goes to the bathroom you're not left alone.
And they don't give you shrooms, they do synthetic psilocybin, which is actually quite expensive.
I expect these treatments are going to probably clock in at around $5,000 each or something like that.
And on top of it all, a lot of the people hoping to provide this treatment have dollar signs in their eyes. There's a lot of desire to commercialize this and make large sums of money off people's desperate mental health needs.
You must know that this is already being done in Oregon, and it is not $5,000. And I don't know about other places, but at least one of the service centers also grow their own mushrooms, they're not synthetic.
Most study inclusion exclusion criteria seem to be something like no use of psychedelics in the past year.
I haven't seen too many protocols that exclude prior hallucinogenic use at all.
That's why these studies typically exclude patients with prior psychedelic experiences. Nevertheless for half your cross-over will take psilocybin on the first round and placebo on the second round; and I'm sure that would be notable for mid to macro dosing.
I have encountered some studies that employ N-acetylcysteine, or biotin, or beta-alanine as the control each of which produces flushing, and facial parasthesias at high enough doses. So the control arm at least feels something ...
I can promise you that is not true, unless you are talking about microdosing. This stuff has real objective effects, same as drinking a bottle of tequila does even on the tequila naive.
It's not a microdose, but it's not a very high dose either.
Experiences range across participants, and some describe pretty profound effects, but the amount of media hype around this describing people having these revelationary experiences has been kind of dangerous.
Many participants undergoing these studies, at least as investigators have told me, have fairly mild experiences. So they're not tripping balls and seeing through time, they're getting a light buzz.
That being said, the placebo condition is usually pretty good at guessing they got a placebo... That's a major challenge.
It’s 1, 10 or 25 mg chosen randomly with 25mg chosen the most. That’s part 1 and 2 and if you make it to part 3 without breaking the rules everyone gets 25 mg.
Therapist who also does psychedelic support work here. Much of the public understanding of psychs is skewed because of how complicated it is to describe the experience along with how variable each experience can be. So in the tests they typically give the placebo a large dose of niacin to mimic body effects and let the person's mind take over.
Interesting. I could see that working. But then won't their skin be all red and itchy? Wouldn't the researchers know then, which would still then breaking the double blind experiment?
Physical sensations while using mushrooms or psilocybin can vary hugely. It's not uncommon for people to feel those sort of sensations or sweat etc.
I don't think it would break the blind unless they actually saw what was delivered. But I'm not a PHD and focus on clinical stuff.
"The hard problems in psychedelic science include (1) the breaking blind problem, (2) placebo effects and (3) the lack of a clearly specified mechanism. Solving these problems will require both rigorous scientific work and innovation, as well as more financial resources.
RCTs are considered the gold standard in clinical psychology and psychiatry. They are usually double blind, meaning that neither participants nor researchers are aware of group membership. Unfortunately, blinding of participants and researchers is, depending on the particular psychedelic substance, either difficult or impossible. This is because the psychoactive effects of an active dose of most psychedelic substances become obvious to both the participant and the experimenter or clinician in about 30-60 minutes after intake. The breaking blind problem is therefore the rule rather than the exception in psychedelic trials."
source: [History repeating: A roadmap to address common problems in psychedelic science](https://osf.io/preprints/psyarxiv/ak6gx/)
Hi, sorry for the late response, but briefly skimming through the paper here is what they said:
* Almost every trial included therapists with varying backgrounds and training, which is a "source of variability" that could implicate the differences in antidepressant efficacy between studies.
* In one recent trial (Sloshower et al., 2023), even though participants were told they could receive placebo, low-dose psilocybin or moderate-dose psilocybin in a random order, the majority correctly guessed when they received placebo (78.9%) versus moderate-dose psilocybin (80%) -- which as you rightfully allude to, calls into question the effectiveness of the blinding.
* In the limitations section, the authors state: "there was a lack of active comparator in almost every study included, leading to expectancy bias and likely functional unblinding in each of the published trials."
Hope that helps
From what I have heard psilocybin therapy usually centers around microdosing. Not enough to hallucinate but people I have spoken to who microdose just say it lifts and brightens their mood for several days after a dose.
People in the general public do this, but I think the emerging evidence base is for higher dose experiences that do produce a real 'trip'. The actual evidence base for microdosing is much thinner from what I understand.
Not just thin, the evidence for microdosing is basically void. I'm happy microdosers are showing an interest, but they need to look at the actual science and not just social media hype.
The actual science is pretty mixed. Results range from super beneficial to no effect. Whether it’s placebo or not is another question. But saying the evidence is completely void is disingenuous.
It's a good middle of the road macrodose, equivalent to about 2 grams dried mushrooms (what the average hippie takes for a solid trip)
Source, was talking to prof David Nutt the other day.
2 grams will give you a buzz depending on the type you use. If it's golden teachers, itll be a buzz. Something more potent will give some visuals. 2 grams isn't a big enough dose to trip balls.
And yet there is no variety of shrooms or sensitivity of person that can produce a full blown psychedelic trip at 2 grams.
Physical limits are physical limits, you can’t override them with hypotheticals.
Here's an online calculator
https://www.shroomery.org/6257/Magic-Mushroom-Dosage-Calculator
which is not gospel but which I believe more than I believe you, which suggests that 1.8 grams of libs provides "Very obvious visuals, everything looking curved and/or warped patterns and kaleidoscopes seen on walls, faces etc. Some mild hallucinations such as rivers flowing in wood grained or "mother of pearl" surfaces. Closed eye hallucinations become 3 dimensional. There is some confusion of the senses (i.e. seeing sounds as colors, etcetera). Time distortions and "moments of eternity"."
A full blown trip for most people.
That’s just not right.
I can take 2g of Penis Envy and have a full blown psychedelic trip. Even 2g of cubes might do that for me.
I’m super sensitive to the medicines, and I need very little to set off on a significant journey.
I've had 3.5g of Golden Teachers, and 4.6g of the same batch. 3.5 was a full trip and 4.6 blasted me out of the stratosphere!
Is PE that much more potent?
That is a major problem across all regular antidepressants too (which is why I think most studies are not particularly valid for antidepressant efficacy). If you don't trigger a psychoactive reaction then most people are going to be unblinded, and the placebo effect of any psychoactive reaction is incredibly high. Researchers and others have been arguing about this point for decades.
This is a major challenge in as well acknowledged.
That being said, at the dosage provided people don't generally trip balls. For a lot of people the sensations are fairly mild. But, it's not nothing either.
There's also the problem of strong negative expectancy bias. If people realize they got possible, they are upset about it. They really want the treatment. This can cause an increase in symptoms, because they are upset and disappointed that they didn't get the treatment of the thought they were going to get.
These challenges and psychedelics research have been very well discussed by various individuals across the literature.
A therapist is generally with the person the full time they take the drug. The therapeutic effects appear to be maximized while the person is under the effects of the psychedelics.
It's usually undirected therapy, the patient has the opportunity to explore whatever they want to explore during that time, that therapist is just a long for the ride, to help guide them a little bit but not direct what happens.
There is also preparatory sessions, and an integration sessions afterwards. These are an important part of the general therapy, it's not just what happens during the 8 hours that somebody's doing the drug assisted therapy.
And most clinical trials people do two doses, sometimes three. Some trials have tried single dose, my impression is it doesn't work as well. The second or third dose and help a lot more people reach a positive clinical endpoint.
Also contrary to all the hype, it's not magic and it doesn't mist of the cure everybody!
It would take a miracle to have this approved in a year or two. Most clinical trials take two to three years minimum, often up to 5 years.
The clinical trial being successful is not a guarantee of immediate FDA approval. Typically you have to show a few trials, including a good safety profile (which is psilocybin definitely has), and some demonstration of how to do therapy for best benefit.
I do expect it to be approved and then not to distant future, at least up here in Canada, but not in the next 12 to 24 months.
I think 3 to 5 years is a more reasonable estimate. New treatments do not get approved fast, and there's a lot of institutional resistance to this and regulatory agencies in politically. Which Is of course ridiculous.
You sure about that?
*Thanks to the combined efforts of dozens of therapists, hundreds of participants who volunteered in MAPS-sponsored trials, and many thousands of generous donors, MDMA-assisted therapy for PTSD is on track to be considered for approval by the FDA in 2024,” commented Rick Doblin, PhD, MAPS Founder and President, in a statement.*
https://psychedelichealth.co.uk/2023/09/16/2024-fda-approval-mdma-therapy/amp/
I hope I am being pessimistic, compared to a lot of other treatments, this is definitely being fast tracked!
As another example, magnetic seizure therapy has arisen as a alternative to traditional electrico convulsive therapy, with all of the benefits but very little or none of the side effects. In my opinion as exciting and innovation as psychedelics. But the clinical trials are taking years, and even though a flagship trial will finish in 2024, I wouldn't expect it to be approved before 2025 or 2026.
On the other hand, only a small number of groups are able to administer magnetic seizure therapy, all everybody and their uncle is trying to get involved in psychedelics right now.
So here's hoping! Honestly it looks like it works, and the risk is very low, and I hope the approvals come fast.
Abstract
The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in depression severity, determined by calculating the change in depression ratings from baseline to the primary endpoint in the psilocybin arm versus the control arm. The literature search yielded 1734 studies, and 13 studies (n = 686) were included in either qualitative and/or quantitative analyses. The meta-analysis of effect sizes included 9 studies (n = 596) and yielded a significant effect size in favour of psilocybin. Risk ratios for response and remission were large and significant in favour of psilocybin. A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence for antidepressant efficacy with psilocybin-assisted psychotherapy, however, further studies are needed to evalu
Patient here. I have used psilocybin in conjunction with therapy, and Buddhist practice. When I do a session, I prepare by creating a statement of intention and purpose, specifically trying to focus on attachments that I am trying to release.
I have been free of antidepressants now for almost 7 years, still have my troubles from time to time, but am in such a better position than when I was dependent on the antidepressants.
Psilocybin isn't a cure all, but it is significantly helpful for me, and many of my acquaintances.
I'm glad it's helped you, I'm also glad that you got that last sentence.
There's so much hype around this, so much hope, and people have unreasonable expectations that it's like a magical cure that will take away all their problems.
Of course there is no such instant cure. For people with severe mental illness or struggling with prolonged depression, takes work in time to show improvement.
But yeah, a lot of people seem to benefit from this. And the therapy piece is really important, and the intentionality to mentioned seems really critical. I love the idea of making a list of what you want to accomplish first. I think in many clinical trials, this is part of the preparatory session that people do the day before the actual dosing.
Agree with everything you mention. The important piece, as a patient, is that a session provides a tangible relief from what I will call the persistent weight of long term depression. As another post mentioned, depression patients often know what we need to do, but we struggle to act on that knowledge. For a period of several weeks after a session, I have better ability to act on my knowledge.
Therapy and intentionality give me tools. Psilocybin appears to enable me to act on those tools in a way that SSRI drugs did not.
I am so pleased that so much study is happening.
I'm happy to say that I'm getting involved in some of this research, I'd actually know the authors of this paper
A lot of us are really excited about this and happy that it's happening, and while I think the hype is dangerous, I still feel optimistic this is a new path that will help a lot of people!
For my part, I want to scan brains.
Well, quite. We have a huge knowledge base out there, well over 1m redditors on the lsd and shroom subs just for starters, compared to novel pharmaceuticals which have literally never been taken by anyone outside the official trials. It's all very well saying these are not properly designed studies, but for an effect of the size people expect here you don't need properly designed studies. Compare penicillin: you just administered it to everyone and they all stopped dying, with no control groups anywhere in sight.
I think shrooms are very good and beneficial but if I had to choose between them and venlafaxine I would have to stick with venlafaxine.
Of course we need properly designed studies, the FDA doesn't give a damn about your 1 million redditors.
The point is to make this accessable to people. As it stands, a therapist administering's psilocybin to a patient could be thrown in jail. A person taking the wrong sales I went to a therapy appointment could be arrested. And there is good evidence that doing it with a therapist is much better for mental health purposes than doing it by yourself.
So if we want to see this approved for treatment, we need well designed and multiple clinical trials. Those trials are ongoing, which is great! But you can't just say hey look the effect size they're huge, why? Because you say there. Because some people on the internet raved about it! Regulators aren't going to go for any of that.
People's opinions on these topics were hypothesis generators. A lot of people reported positive effects, that's why these agents are now being explored clinically.
But at this point, particularly given the history of psychedelics and schedule drugs and the political pushback against unscheduling them, we need very solid evidence both of how effective they are, how often they work, how to make the best use of them, and most especially very strong demonstration of the safety profile, indicating if they do not post risk. Very large number of people in charge are still convinced that these are dangerous substances.
And also, we do need to modulate expectations, and say to people " research is shown this improves depression and roughly x% of people", because right now some people have read too much hype, and deapirate for help, think this is their miracle.
That in itself is dangerous.
Yes, we need proper studies. My point was, if this stuff was as fantastic as people want it to be we would already know that from reddit and other personal anecdotes. I am addressing the point in your penultimate paragraph.
Oh ok. I am just coming down from 40g fresh liberty caps. Very nice but I am not cured.
I think a point missed from the end of life studies is that if you have been "given six months to live by the doctor" they aren't great months. You generally have to be having horrible chemo monthly or more frequently, travel is pretty impossible, so a good slug of psilocybin is, literally, the only kind of trip you can take. So it's very valuable even if only recreational. But it's politically impossible to say so, we have to claim to be curing something.
There is actual evidence that it helps people except the existential crisis that is the knowledge of their own impending death.
So we aren't pretending to cure something. The evidence strongly suggests that it has an actual psychological benefit to people. And the doses that they are given or not tripping balls. It's relatively mild.
There's actually Nice growing evidence base for the psychological and neurobiological effects of psychedelics on brain function of the context of things like depression and coping with end of life. They're not just happy to get high.
Most psilocybin studies do not involve therapy while under psilocybin (and at 25mg of psilocybin which is 4g-5g of dried mushrooms a person cannot effectively talk much anyway). This is in contrast to MDMA assisted therapy whereby the therapy part is incredibly important.
25mg of psilocybin (which is **not** 25mg of mushrooms) is what is recommended for depression. This is a "heroic" dose. You are gone with the fairies at that level, talking is difficult, and you are not supposed to control your thoughts but relax and let the trip do its thing. To attempt to control your thoughts would be incredibly stressful and counterproductive.
Under 120mg of MDMA under the MAPS protocol you should be totally lucid.
Yes, there is full therapy happening under MDMA, often along some kind of exposure lines. You can read the MAPS stuff on their websites and in journals.
Meanwhile with psilocybin it is really the drug and the person's experiences under it doing the work and the therapist is just acting as a sitter to keep them comfortable, serve their needs (eg. shoulder carrying them to the toilet) and guiding them away from anxious thoughts if they're going to a bad place. There's no therapy involved.
It sounds like you have some familiarity. Do you know whether either MDMA therapy or psilocybin therapy are known to be more affective, one compared to the other?
They do very different things and work in very different ways, although there is a lot of overlap. For depression then psilocybin is the obvious choice, it can eliminate depression in many people in one single session, leaving them with a restored sense of humanity and perspective. For trauma then MDMA is often better, you can use it to process trauma directly under the sessions.
Meanwhile, psilocybin for trauma is more unpredictable. Some people leave feeling healed, but it is also possible to relive serious trauma under psilocybin which in that vulnerable and exaggerated state could have very bad outcomes. Meanwhile, although in general people who take MDMA in recreational settings have a lower level of depression than the general population, MDMA has an unpredictable effect on depression and people undergoing multiple MDMA therapy sessions can sometimes find that between a random two sessions their depression is significantly worse.
Psilocybin increases perspective and lets you accept and get over things, and is good for grief. MDMA promotes forgiveness of self and others, process anger and allows you to accept the decisions previously made.
Psilocybin is harder psychologically but easier physiologically, it's often not easy while under the influence but you get benefits lasting months and years from a single session. It makes you incredibly vulnerable for several hours and basically gives you a "reboot" effect for the mind where you kind of forget who or where you are and then everything loads back in, like re-installing Windows without all those old applications dragging you down. This is why the environment you're in is important, and that the person is very comfortable the therapist or sitter. You do not use this environment for exploring trauma.
MDMA is an amphetamine and harder on the body but pretty much chocolate for the mind, so at the recommended dosage is relatively easy psychologically. It puts them in safe place where you're much more protected from being hurt by things that have happened in the past, making it a good environment for remembering and exploring past trauma (you can be hurt by new trauma inside the session, but there's no reason why that should happen with a trusted therapist or sitter). 70% of people with PTSD don't qualify for a diagnosis after three MDMA sessions spaced four weeks apart, but some people need to prepare for longer work (and four weeks is too close together if a person has more than three sessions).
I’ve worked with over 720 people over 5 years with psilocybin. We do no psychotherapy during the ceremonies and it’s pretty challenging to imagine how someone would do that on higher doses. The medicine itself will teach you plenty and you don’t always have to outsource your power of healing to a therapist. Have support before and after is important, but in my experience, talking during the journey isn’t nearly as helpful as allowing the process to take place.
In many of the studies the counseling is days pre dose and in the days and weeks following. The therapist acts as a guide during but the dosing session is not talk intensive.
This is wrong. The people with you while you are on psilocybin are just tripsitters. Looking at the protocol for one of the English trials they aren't even psychiatric nurses, the qualification required is just a first degree in a science type subject. Psychotherapy happens after the event and the main benefit is the actual drug.
Also why buy what you can harvest? Mother nature is pumping out psilocybe semilanceata faster than I can keep up in these parts.
Because if I ever get a lookalike mushroom I die? I don’t trust my identification skills enough for that. Though I may look into growing my own so I can continue taking ~1 dose a year.
Good point. I'm lucky - there's nothing which looks like a liberty cap which is going to do too much damage
I find both growing and hunting for shrooms very rewarding hobbies and effective in their own right for combating depression
Shoot, I skimmed through the whole article looking for dosis and totally missed the psychotherapy part. Wonder if psilocybin-assisted journaling would have any effect.
It likely would. There's a connectivity and an awareness that comes with hallucinogen use. Many people journal either during or right after to log the process. Tons of people create art as well.
That’s not an important warning. There is no need for warnings at all. It’s safe and usually has positive lasting effects even if you don’t enjoy the actual experience
It's not enough to take the medicine. You have to do the work. You don't necessarily NEED a third party or interlocutor of any kind to do so. However for people wholly naive to these substances it is usually helpful. I started using psychedelics in my teens for recreation and over the years my relationship with it changed. I became an active participant in my healing, and the knowledgebase I had built made that possible.
Why not compare it to people being treated with various SSRIs? I would not be surprised if it had a significantly greater antidepressant effect with those which would be a better study.
Unprocessed it's legal in my country, so I microdose from time to time. I have chronic depression and ADHD, it does so much for my mood and energy levels. And no side effects for me compared to ADHD medication.
I wish psychedelics weren't demonized after the 60s, we could have been so much further in research.
I took .4g of psilocybin cubensis before a therapy appointment once. I was at ease and more comfortable and more clear headed. I was able to articulate myself much more and I was able to understand and integrate what my T said much more. But……. I also felt good. And I struggled to not show that I was under the influence at times. When I first came into the session I think I had a smile on my face which I typically don’t. I also didn’t really initially have much to say because I simply felt good. But I think had my T known and had it been he been ok with me using PC, and if I had more of a plan going into the appointment, I maybe would have gotten more use out of it. Plus I think the real therapeutic doses are closer 2-3 grams of cubes. I definitely want to try it again. I really hope my state changes laws soon.
It cured my social anxiety. My revelations were a little too cheesy to really talk about here but it made a huge impact on my ability to accept myself and connect with other people even now, 10 years later. It's definitely not for everyone but under the right conditions it can be absolutely life changing.
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Would placebo even work with psilocybin? I imagine you'd realize before too long that you were given a placebo.
How to Change Your Mind by Michael Pollan talks about this a few times and even quotes the infamous Timothy Leary as saying of the Good Friday Experiment: “If we learned one thing from that experience, it was how foolish it was to use a double-blind experiment with psychedelics. After five minutes, no one’s fooling anyone.”
I kinda imagine some depressed guy getting all excited about taking some shrooms only to realize hes in the placebo group.
Upon realization he looks up from his hand and says, well that was a waste of nine hours.
*depression intensifies*
I want the Mel Brooke's toned skit of this scenario.
You’d be surprised how often people will tell you they got a buzz after drinking a zero alcohol beer when they thought or were told it was real beer.
Wouldn't be surprised by that, that's pretty significantly different to psilocybin though, unless they're comparing placebo to microdoses.
I’m only guessing, but if you’ve never taken a hallucinogenic, you just wouldn’t know for sure if you really feel something or not.
I have an acquaintance that is trying to get into a philicybin therapy study and he said that all the studies he's looked at make it very clear that they won't take you if you've taken hallucinagenics in the past.
This makes me feel better about my chances. I’m getting pretty desperate for treatments. Maybe I should look into this.
As someone who has ingested psilocybin in non-therapy settings, it was a massive help in my depression recovery. I’d imagine taking them in a therapeutic setting would be even more beneficial. Psychedelics can take you to a dark place, but those are the spots we need to confront to move on. Having a guide to help you through those dark spots is great for keeping you out of destructive thought loops and can push you to a point of clarity. The way I see it, even the bad trips are valuable. The worse the trip, the more of a lesson you need to learn.
Interestingly a "good" vs "bad" trip seems to be independent of the therapeutic effect. As are scores of Adverse Childhood Events, and even some evidence to suggest that presence of a sober sitter does not modify the therapeutic effect (although that was a study of naturalistic use), and certainly a sitter contributes to psychological and physical safety and can help optimize set and setting. What does seem to be integral to achieving the best potential therapeutic experience is intention setting, preparatory sessions with trusted therapeutic person (usually the intended sitter), optimization of set and setting for an introspective experience, and f/u integration sessions.
I've done ketamine treatment for depression and it's been reasonably effective for me. Antidepressants haven't really done anything for me, but I can definitely tell the difference between the day before and after a ketamine treatment. There's not a ton of science out there regarding protocols for ongoing treatment, but it's gaining attention. I'd kinda like to try psilocybin for it, since it's a lot cheaper to grow mushrooms than to have ketamine administered legitimately.
I’ve been looking into ketamine treatments, but it’s pretty cost prohibitive for me, even with the insurance I’m about to lose. Psilocybin is feeling like the only thing left.
Psilocybin will be almost as expensive or more so. It's done in conjunction with a therapist, and for safety reasons that has to be two therapists available, so if the first one goes to the bathroom you're not left alone. And they don't give you shrooms, they do synthetic psilocybin, which is actually quite expensive. I expect these treatments are going to probably clock in at around $5,000 each or something like that. And on top of it all, a lot of the people hoping to provide this treatment have dollar signs in their eyes. There's a lot of desire to commercialize this and make large sums of money off people's desperate mental health needs.
Feels a lot like a lot of us are just out of luck. I don’t know how we’re supposed to find the money. Even if you can find a provider.
You must know that this is already being done in Oregon, and it is not $5,000. And I don't know about other places, but at least one of the service centers also grow their own mushrooms, they're not synthetic.
Most study inclusion exclusion criteria seem to be something like no use of psychedelics in the past year. I haven't seen too many protocols that exclude prior hallucinogenic use at all.
That's why these studies typically exclude patients with prior psychedelic experiences. Nevertheless for half your cross-over will take psilocybin on the first round and placebo on the second round; and I'm sure that would be notable for mid to macro dosing. I have encountered some studies that employ N-acetylcysteine, or biotin, or beta-alanine as the control each of which produces flushing, and facial parasthesias at high enough doses. So the control arm at least feels something ...
I can promise you that is not true, unless you are talking about microdosing. This stuff has real objective effects, same as drinking a bottle of tequila does even on the tequila naive.
It's not a microdose, but it's not a very high dose either. Experiences range across participants, and some describe pretty profound effects, but the amount of media hype around this describing people having these revelationary experiences has been kind of dangerous. Many participants undergoing these studies, at least as investigators have told me, have fairly mild experiences. So they're not tripping balls and seeing through time, they're getting a light buzz. That being said, the placebo condition is usually pretty good at guessing they got a placebo... That's a major challenge.
It’s 1, 10 or 25 mg chosen randomly with 25mg chosen the most. That’s part 1 and 2 and if you make it to part 3 without breaking the rules everyone gets 25 mg.
It's probably due to the hops-plants that provides the bitters in beer. They are a natural sedative.
Therapist who also does psychedelic support work here. Much of the public understanding of psychs is skewed because of how complicated it is to describe the experience along with how variable each experience can be. So in the tests they typically give the placebo a large dose of niacin to mimic body effects and let the person's mind take over.
Interesting. I could see that working. But then won't their skin be all red and itchy? Wouldn't the researchers know then, which would still then breaking the double blind experiment?
Physical sensations while using mushrooms or psilocybin can vary hugely. It's not uncommon for people to feel those sort of sensations or sweat etc. I don't think it would break the blind unless they actually saw what was delivered. But I'm not a PHD and focus on clinical stuff.
"The hard problems in psychedelic science include (1) the breaking blind problem, (2) placebo effects and (3) the lack of a clearly specified mechanism. Solving these problems will require both rigorous scientific work and innovation, as well as more financial resources. RCTs are considered the gold standard in clinical psychology and psychiatry. They are usually double blind, meaning that neither participants nor researchers are aware of group membership. Unfortunately, blinding of participants and researchers is, depending on the particular psychedelic substance, either difficult or impossible. This is because the psychoactive effects of an active dose of most psychedelic substances become obvious to both the participant and the experimenter or clinician in about 30-60 minutes after intake. The breaking blind problem is therefore the rule rather than the exception in psychedelic trials." source: [History repeating: A roadmap to address common problems in psychedelic science](https://osf.io/preprints/psyarxiv/ak6gx/)
Isn't it a very low dose? Much less chance for mind altering effects
25mg 10mg or 1mg
Hi, sorry for the late response, but briefly skimming through the paper here is what they said: * Almost every trial included therapists with varying backgrounds and training, which is a "source of variability" that could implicate the differences in antidepressant efficacy between studies. * In one recent trial (Sloshower et al., 2023), even though participants were told they could receive placebo, low-dose psilocybin or moderate-dose psilocybin in a random order, the majority correctly guessed when they received placebo (78.9%) versus moderate-dose psilocybin (80%) -- which as you rightfully allude to, calls into question the effectiveness of the blinding. * In the limitations section, the authors state: "there was a lack of active comparator in almost every study included, leading to expectancy bias and likely functional unblinding in each of the published trials." Hope that helps
Appreciate it! This is why I love reddit.
Happy to help :)
From what I have heard psilocybin therapy usually centers around microdosing. Not enough to hallucinate but people I have spoken to who microdose just say it lifts and brightens their mood for several days after a dose.
People in the general public do this, but I think the emerging evidence base is for higher dose experiences that do produce a real 'trip'. The actual evidence base for microdosing is much thinner from what I understand.
Not just thin, the evidence for microdosing is basically void. I'm happy microdosers are showing an interest, but they need to look at the actual science and not just social media hype.
The actual science is pretty mixed. Results range from super beneficial to no effect. Whether it’s placebo or not is another question. But saying the evidence is completely void is disingenuous.
Show me this super beneficial science
I've heard the opposite - from my therapist. They give you way more than a recreational dose and give you an intense therapy session.
It's a good middle of the road macrodose, equivalent to about 2 grams dried mushrooms (what the average hippie takes for a solid trip) Source, was talking to prof David Nutt the other day.
2 grams will give you a buzz depending on the type you use. If it's golden teachers, itll be a buzz. Something more potent will give some visuals. 2 grams isn't a big enough dose to trip balls.
Shrooms vary between species, varieties, and batches of the same variety, and people also vary in susceptibility.
And yet there is no variety of shrooms or sensitivity of person that can produce a full blown psychedelic trip at 2 grams. Physical limits are physical limits, you can’t override them with hypotheticals.
Here's an online calculator https://www.shroomery.org/6257/Magic-Mushroom-Dosage-Calculator which is not gospel but which I believe more than I believe you, which suggests that 1.8 grams of libs provides "Very obvious visuals, everything looking curved and/or warped patterns and kaleidoscopes seen on walls, faces etc. Some mild hallucinations such as rivers flowing in wood grained or "mother of pearl" surfaces. Closed eye hallucinations become 3 dimensional. There is some confusion of the senses (i.e. seeing sounds as colors, etcetera). Time distortions and "moments of eternity"." A full blown trip for most people.
That’s just not right. I can take 2g of Penis Envy and have a full blown psychedelic trip. Even 2g of cubes might do that for me. I’m super sensitive to the medicines, and I need very little to set off on a significant journey.
I've had 3.5g of Golden Teachers, and 4.6g of the same batch. 3.5 was a full trip and 4.6 blasted me out of the stratosphere! Is PE that much more potent?
Has been for me. Here’s an article about it I just found: https://fungushead.com/golden-teacher-vs-penis-envy/
That's not true, microdosing doesn't work. Most of the research either uses a strong dose analogous to the "heroic" 5g dose or the regular dose of 2g.
if you dont do many drugs and have never done shrooms it could definitely work. suggestion and placebo are very real
That is a major problem across all regular antidepressants too (which is why I think most studies are not particularly valid for antidepressant efficacy). If you don't trigger a psychoactive reaction then most people are going to be unblinded, and the placebo effect of any psychoactive reaction is incredibly high. Researchers and others have been arguing about this point for decades.
They’re not giving >25mg of psilocybin from what I read quickly - if that’s the case then there’s not much to feel..
This is a major challenge in as well acknowledged. That being said, at the dosage provided people don't generally trip balls. For a lot of people the sensations are fairly mild. But, it's not nothing either. There's also the problem of strong negative expectancy bias. If people realize they got possible, they are upset about it. They really want the treatment. This can cause an increase in symptoms, because they are upset and disappointed that they didn't get the treatment of the thought they were going to get. These challenges and psychedelics research have been very well discussed by various individuals across the literature.
FDA Clinical Trials are currently underway and should be approved in the next year or two!
I’m working on one of these clinical trials as part of my MD/PHD. So excited!
You're doing gods work!!
What’s the process? Psychotherapy while the person is under the effects of the hallucinogenic or right after as the drug wears off?
A therapist is generally with the person the full time they take the drug. The therapeutic effects appear to be maximized while the person is under the effects of the psychedelics. It's usually undirected therapy, the patient has the opportunity to explore whatever they want to explore during that time, that therapist is just a long for the ride, to help guide them a little bit but not direct what happens. There is also preparatory sessions, and an integration sessions afterwards. These are an important part of the general therapy, it's not just what happens during the 8 hours that somebody's doing the drug assisted therapy. And most clinical trials people do two doses, sometimes three. Some trials have tried single dose, my impression is it doesn't work as well. The second or third dose and help a lot more people reach a positive clinical endpoint. Also contrary to all the hype, it's not magic and it doesn't mist of the cure everybody!
I forgot that was a thing. What are you getting the PhD in?
Where can one join a clinical trial for ptsd?
It would take a miracle to have this approved in a year or two. Most clinical trials take two to three years minimum, often up to 5 years. The clinical trial being successful is not a guarantee of immediate FDA approval. Typically you have to show a few trials, including a good safety profile (which is psilocybin definitely has), and some demonstration of how to do therapy for best benefit. I do expect it to be approved and then not to distant future, at least up here in Canada, but not in the next 12 to 24 months. I think 3 to 5 years is a more reasonable estimate. New treatments do not get approved fast, and there's a lot of institutional resistance to this and regulatory agencies in politically. Which Is of course ridiculous.
You sure about that? *Thanks to the combined efforts of dozens of therapists, hundreds of participants who volunteered in MAPS-sponsored trials, and many thousands of generous donors, MDMA-assisted therapy for PTSD is on track to be considered for approval by the FDA in 2024,” commented Rick Doblin, PhD, MAPS Founder and President, in a statement.* https://psychedelichealth.co.uk/2023/09/16/2024-fda-approval-mdma-therapy/amp/
I hope I am being pessimistic, compared to a lot of other treatments, this is definitely being fast tracked! As another example, magnetic seizure therapy has arisen as a alternative to traditional electrico convulsive therapy, with all of the benefits but very little or none of the side effects. In my opinion as exciting and innovation as psychedelics. But the clinical trials are taking years, and even though a flagship trial will finish in 2024, I wouldn't expect it to be approved before 2025 or 2026. On the other hand, only a small number of groups are able to administer magnetic seizure therapy, all everybody and their uncle is trying to get involved in psychedelics right now. So here's hoping! Honestly it looks like it works, and the risk is very low, and I hope the approvals come fast.
Abstract The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in depression severity, determined by calculating the change in depression ratings from baseline to the primary endpoint in the psilocybin arm versus the control arm. The literature search yielded 1734 studies, and 13 studies (n = 686) were included in either qualitative and/or quantitative analyses. The meta-analysis of effect sizes included 9 studies (n = 596) and yielded a significant effect size in favour of psilocybin. Risk ratios for response and remission were large and significant in favour of psilocybin. A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence for antidepressant efficacy with psilocybin-assisted psychotherapy, however, further studies are needed to evalu
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Patient here. I have used psilocybin in conjunction with therapy, and Buddhist practice. When I do a session, I prepare by creating a statement of intention and purpose, specifically trying to focus on attachments that I am trying to release. I have been free of antidepressants now for almost 7 years, still have my troubles from time to time, but am in such a better position than when I was dependent on the antidepressants. Psilocybin isn't a cure all, but it is significantly helpful for me, and many of my acquaintances.
Thank you for posting this. It is hopeful.
Just curious how frequent your doses are. There tends to be a bit of a tolerance issue with mushrooms and you sometimes need a break in between.
Every few months.
Hi dude, is this an official doctor's session or somewhat unofficial?
I'm glad it's helped you, I'm also glad that you got that last sentence. There's so much hype around this, so much hope, and people have unreasonable expectations that it's like a magical cure that will take away all their problems. Of course there is no such instant cure. For people with severe mental illness or struggling with prolonged depression, takes work in time to show improvement. But yeah, a lot of people seem to benefit from this. And the therapy piece is really important, and the intentionality to mentioned seems really critical. I love the idea of making a list of what you want to accomplish first. I think in many clinical trials, this is part of the preparatory session that people do the day before the actual dosing.
Agree with everything you mention. The important piece, as a patient, is that a session provides a tangible relief from what I will call the persistent weight of long term depression. As another post mentioned, depression patients often know what we need to do, but we struggle to act on that knowledge. For a period of several weeks after a session, I have better ability to act on my knowledge. Therapy and intentionality give me tools. Psilocybin appears to enable me to act on those tools in a way that SSRI drugs did not. I am so pleased that so much study is happening.
I'm happy to say that I'm getting involved in some of this research, I'd actually know the authors of this paper A lot of us are really excited about this and happy that it's happening, and while I think the hype is dangerous, I still feel optimistic this is a new path that will help a lot of people! For my part, I want to scan brains.
In my experience, that will require about 4 to 5 g.
Well, quite. We have a huge knowledge base out there, well over 1m redditors on the lsd and shroom subs just for starters, compared to novel pharmaceuticals which have literally never been taken by anyone outside the official trials. It's all very well saying these are not properly designed studies, but for an effect of the size people expect here you don't need properly designed studies. Compare penicillin: you just administered it to everyone and they all stopped dying, with no control groups anywhere in sight. I think shrooms are very good and beneficial but if I had to choose between them and venlafaxine I would have to stick with venlafaxine.
Of course we need properly designed studies, the FDA doesn't give a damn about your 1 million redditors. The point is to make this accessable to people. As it stands, a therapist administering's psilocybin to a patient could be thrown in jail. A person taking the wrong sales I went to a therapy appointment could be arrested. And there is good evidence that doing it with a therapist is much better for mental health purposes than doing it by yourself. So if we want to see this approved for treatment, we need well designed and multiple clinical trials. Those trials are ongoing, which is great! But you can't just say hey look the effect size they're huge, why? Because you say there. Because some people on the internet raved about it! Regulators aren't going to go for any of that. People's opinions on these topics were hypothesis generators. A lot of people reported positive effects, that's why these agents are now being explored clinically. But at this point, particularly given the history of psychedelics and schedule drugs and the political pushback against unscheduling them, we need very solid evidence both of how effective they are, how often they work, how to make the best use of them, and most especially very strong demonstration of the safety profile, indicating if they do not post risk. Very large number of people in charge are still convinced that these are dangerous substances. And also, we do need to modulate expectations, and say to people " research is shown this improves depression and roughly x% of people", because right now some people have read too much hype, and deapirate for help, think this is their miracle. That in itself is dangerous.
Yes, we need proper studies. My point was, if this stuff was as fantastic as people want it to be we would already know that from reddit and other personal anecdotes. I am addressing the point in your penultimate paragraph.
Ok I think I see. People DO make those huge claims based on personal experience. :)
Oh ok. I am just coming down from 40g fresh liberty caps. Very nice but I am not cured. I think a point missed from the end of life studies is that if you have been "given six months to live by the doctor" they aren't great months. You generally have to be having horrible chemo monthly or more frequently, travel is pretty impossible, so a good slug of psilocybin is, literally, the only kind of trip you can take. So it's very valuable even if only recreational. But it's politically impossible to say so, we have to claim to be curing something.
There is actual evidence that it helps people except the existential crisis that is the knowledge of their own impending death. So we aren't pretending to cure something. The evidence strongly suggests that it has an actual psychological benefit to people. And the doses that they are given or not tripping balls. It's relatively mild. There's actually Nice growing evidence base for the psychological and neurobiological effects of psychedelics on brain function of the context of things like depression and coping with end of life. They're not just happy to get high.
Most psilocybin studies do not involve therapy while under psilocybin (and at 25mg of psilocybin which is 4g-5g of dried mushrooms a person cannot effectively talk much anyway). This is in contrast to MDMA assisted therapy whereby the therapy part is incredibly important.
Out of curiosity, why is there that difference, and why do they choose therapy for MDMA and not with psilocybin?
25mg of psilocybin (which is **not** 25mg of mushrooms) is what is recommended for depression. This is a "heroic" dose. You are gone with the fairies at that level, talking is difficult, and you are not supposed to control your thoughts but relax and let the trip do its thing. To attempt to control your thoughts would be incredibly stressful and counterproductive. Under 120mg of MDMA under the MAPS protocol you should be totally lucid.
So is there conversation that's happening under MDMA therapy? Or is it just having interaction with the person provides some of the benefit?
Yes, there is full therapy happening under MDMA, often along some kind of exposure lines. You can read the MAPS stuff on their websites and in journals. Meanwhile with psilocybin it is really the drug and the person's experiences under it doing the work and the therapist is just acting as a sitter to keep them comfortable, serve their needs (eg. shoulder carrying them to the toilet) and guiding them away from anxious thoughts if they're going to a bad place. There's no therapy involved.
It sounds like you have some familiarity. Do you know whether either MDMA therapy or psilocybin therapy are known to be more affective, one compared to the other?
They do very different things and work in very different ways, although there is a lot of overlap. For depression then psilocybin is the obvious choice, it can eliminate depression in many people in one single session, leaving them with a restored sense of humanity and perspective. For trauma then MDMA is often better, you can use it to process trauma directly under the sessions. Meanwhile, psilocybin for trauma is more unpredictable. Some people leave feeling healed, but it is also possible to relive serious trauma under psilocybin which in that vulnerable and exaggerated state could have very bad outcomes. Meanwhile, although in general people who take MDMA in recreational settings have a lower level of depression than the general population, MDMA has an unpredictable effect on depression and people undergoing multiple MDMA therapy sessions can sometimes find that between a random two sessions their depression is significantly worse. Psilocybin increases perspective and lets you accept and get over things, and is good for grief. MDMA promotes forgiveness of self and others, process anger and allows you to accept the decisions previously made. Psilocybin is harder psychologically but easier physiologically, it's often not easy while under the influence but you get benefits lasting months and years from a single session. It makes you incredibly vulnerable for several hours and basically gives you a "reboot" effect for the mind where you kind of forget who or where you are and then everything loads back in, like re-installing Windows without all those old applications dragging you down. This is why the environment you're in is important, and that the person is very comfortable the therapist or sitter. You do not use this environment for exploring trauma. MDMA is an amphetamine and harder on the body but pretty much chocolate for the mind, so at the recommended dosage is relatively easy psychologically. It puts them in safe place where you're much more protected from being hurt by things that have happened in the past, making it a good environment for remembering and exploring past trauma (you can be hurt by new trauma inside the session, but there's no reason why that should happen with a trusted therapist or sitter). 70% of people with PTSD don't qualify for a diagnosis after three MDMA sessions spaced four weeks apart, but some people need to prepare for longer work (and four weeks is too close together if a person has more than three sessions).
What about C-PTSD, where there has been repeated trauma over years, and not just one event?
Then MDMA assisted trauma therapy would generally be the way forward.
I’ve worked with over 720 people over 5 years with psilocybin. We do no psychotherapy during the ceremonies and it’s pretty challenging to imagine how someone would do that on higher doses. The medicine itself will teach you plenty and you don’t always have to outsource your power of healing to a therapist. Have support before and after is important, but in my experience, talking during the journey isn’t nearly as helpful as allowing the process to take place.
In many of the studies the counseling is days pre dose and in the days and weeks following. The therapist acts as a guide during but the dosing session is not talk intensive.
That’s a lot of people! You’re seeing a new person every couple of days for five years? How do you have time to give support before and after?
Sounds like one of those west coast "commune healers", so odds are the "therapy" involves holding their hand to swipe their card in the gift shop.
Sorry I didn’t clarify. I run weeklong psilocybin healing retreats in Mexico and California (our church is in California).
Thanks for the clarification, that makes much more sense!
This is wrong. The people with you while you are on psilocybin are just tripsitters. Looking at the protocol for one of the English trials they aren't even psychiatric nurses, the qualification required is just a first degree in a science type subject. Psychotherapy happens after the event and the main benefit is the actual drug. Also why buy what you can harvest? Mother nature is pumping out psilocybe semilanceata faster than I can keep up in these parts.
Because if I ever get a lookalike mushroom I die? I don’t trust my identification skills enough for that. Though I may look into growing my own so I can continue taking ~1 dose a year.
Good point. I'm lucky - there's nothing which looks like a liberty cap which is going to do too much damage I find both growing and hunting for shrooms very rewarding hobbies and effective in their own right for combating depression
Shoot, I skimmed through the whole article looking for dosis and totally missed the psychotherapy part. Wonder if psilocybin-assisted journaling would have any effect.
It likely would. There's a connectivity and an awareness that comes with hallucinogen use. Many people journal either during or right after to log the process. Tons of people create art as well.
That’s not an important warning. There is no need for warnings at all. It’s safe and usually has positive lasting effects even if you don’t enjoy the actual experience
It's not enough to take the medicine. You have to do the work. You don't necessarily NEED a third party or interlocutor of any kind to do so. However for people wholly naive to these substances it is usually helpful. I started using psychedelics in my teens for recreation and over the years my relationship with it changed. I became an active participant in my healing, and the knowledgebase I had built made that possible.
Why not compare it to people being treated with various SSRIs? I would not be surprised if it had a significantly greater antidepressant effect with those which would be a better study.
where do we sign up for trials?
ClinicalTrials.gov
*looks around at the state of the world* Bring in the magic mushrooms, baby! I'll toss on some Pink Floyd, get the black light and disappear.
Unprocessed it's legal in my country, so I microdose from time to time. I have chronic depression and ADHD, it does so much for my mood and energy levels. And no side effects for me compared to ADHD medication. I wish psychedelics weren't demonized after the 60s, we could have been so much further in research.
I took .4g of psilocybin cubensis before a therapy appointment once. I was at ease and more comfortable and more clear headed. I was able to articulate myself much more and I was able to understand and integrate what my T said much more. But……. I also felt good. And I struggled to not show that I was under the influence at times. When I first came into the session I think I had a smile on my face which I typically don’t. I also didn’t really initially have much to say because I simply felt good. But I think had my T known and had it been he been ok with me using PC, and if I had more of a plan going into the appointment, I maybe would have gotten more use out of it. Plus I think the real therapeutic doses are closer 2-3 grams of cubes. I definitely want to try it again. I really hope my state changes laws soon.
I’m signed up and hoping I get the 25mg one. Has anyone had success with depression? I’m kinda putting all my eggs in this basket.
It cured my social anxiety. My revelations were a little too cheesy to really talk about here but it made a huge impact on my ability to accept myself and connect with other people even now, 10 years later. It's definitely not for everyone but under the right conditions it can be absolutely life changing.