Once upon a time, I took a (by my standards) pretty large dose of mushrooms while rather depressed (although I did not realize it at the time). The trip itself was rather dark, but the next day, my depression was entirely gone, I was actually happy for the first time in months, and it lasted for quite a while.
The first time I took LSD, my mood was significantly improved for weeks afterwards, even though I don't think I was depressed before. But I did notice that things that normally annoy me tended to annoy me less, and things that made me happy made me happier. Again, this lasted for at least a month.
Considering how often antidepressants tend to be a hit-or-miss game (not to speak of side effects), I am a bit annoyed psychedelics don't get more attention for medical use.
> Considering how often antidepressants tend to be a hit-or-miss game (not to speak of side effects), I am a bit annoyed psychedelics don't get more attention for medical use.
Psychedelics are actually extremely hit-or-miss as well. Anecdotally, psychedelics don't always send someone in the right direction post-trip. If you scroll the comments in any popular psychedelics-for-depression post on Reddit, there are almost as many negative experience reports (including some long-lasting) as there are positive reports. The positive reports receive the bulk of upvotes, though, so you have to scroll down to see them.
Perhaps less anecdotally, any medical professional will see a non-trivial number of people with significant negative effects of psychedelics, from worsening depression to HPPD to existential crises or psychoses. An actual doctor had a great comment on the previous discussion: https://news.ycombinator.com/item?id=30995831
"If you scroll the comments in any popular psychedelics-for-depression post on Reddit, there are almost as many negative experience reports (including some long-lasting) as there are positive reports."
Those trip reports are almost never done in a therapeutic context.
Psychedelic therapy is what research has shown to be very helpful with depression.
When people trip on mushrooms outside of therapy, they often do so:
- with a poor set and setting
- without intention
- with little if any preparation (almost certainly without therapeutic preparation)
- while mixing them with other drugs
- without trusted, experienced trip sitters (much less therapists) there to reassure and help out if need be
- without any integration or therapy afterwards
- without being 100% certain that they were getting real psychedelic mushrooms and not something else (like poisonous mushrooms)
- while believing all sorts of myths about psychedelics (which might be cleared up by trained therapists in the pre-therapy preparation)
So no wonder quite a few people have "bad trips".
Even so, just because someone has a "bad trip" (or difficult/negative experience) doesn't mean that their experience couldn't be of value to them.
It's quite common for people to report that their difficult experiences were actually very valuable to them. My own have been more valuable than my good experiences. The good experiences were fun and all, but the bad ones were incredibly insightful.
When done in a therapeutic context, with trained psychedelic therapists and the right preparation, integration, and followup therapy, there should be many more positive outcomes than in the anecdotal trip reports that you'll read from people tripping casually.
> Those trip reports are almost never done in a therapeutic context.
> Psychedelic therapy is what research has shown to be very helpful with depression.
Exactly right, which is why I mention it. A lot of people are going to read this thread and head off to do some self-experimentation at home, alone. We need to point out that the research and therapy environment is extremely different than DIY.
A McKenna style heroic dose in silent darkness is something I'd recommend any for human, at least once in their life, if they're not at risk of schizophrenia. The experience is profoundly and deeply human.
In a therapeutic context, though, make plans with professionals. Go on a trip to a doctor guided psychedelic session, involve your personal doctors and therapists.
Exploratory, experiential uses of psychedelics aren't appropriate when you're depressed, stressed, or anxious. Psychedelics notoriously kick you into positive feedback loops, which amplify your internal state, sometimes in extreme ways.
Reddit and erowid and tripsit sites aren't rigorous sources of data suitable for science, but they're great for personally understanding the range of possible effects you can experience.
Most doctors have a massive fear of iatrogenic illness. It is understandable - they don't want to be responsible for a problem. So they will allow lots of suffering that cannot be linked to their action. That's the flip side of primum non nocere: suffering is permitted so long as it is not tied to my action.
That's why they opposed cardiac catheterization research and it needed someone who would violate the ethics of the time to invent. Medicine progresses one renegade at a time.
Fortunately, America now has alternatives. We won't suffer for long under the thumb of gatekeepers. The COVID-19 pandemic has moved lots of prescription to online providers who do the bare minimum to diagnose. This has moved power into the hands of patients. For long-tail conditions, this is a superior model to a medical professional.
Since this is necessary to say: I'm not a doctor hater - my parents are both surgeons and almost everyone in the extended family excepting me is in medicine.
EDIT: to vmception, I only said that because there's lots of people who have some sort of grudge against medical professionals for some reason or the other. I don't. I love my family and I'm quite happy in my belief that they're good at it. When I go to a doctor, I usually trust them. Can't reply since rate-limited.
> my parents are both surgeons and almost everyone in the extended family excepting me is in medicine.
I don't think thats necessary to say, I’ve heard the wildest fringe perceptions over the last two years from people who tried to qualify their post the same way, or by mentioning they were a nurse or medical professional.
I think whatever you have to say has enough weight to the people that matter without the disclaimer.
I've had some experience with HPPD but luckily mine went away. My experience ranges from 'oh that is pretty cool to look at' to 'this visual distortion is hurting my ability to focus on an important conversation'. I wish we better understood HPPD.
I'd be curious to see one such thread, but pretty sure you're just talking out your ass. My experience, and recent search, indicates these are usually about 80% positive, and most negative experiences stem from predictable abuse patterns. Of course there are dangers, risks, and bad experiences, but psychedelics might well be qualitatively better for depression than traditional pharmaceuticals.
It was inappropriate language, but I think there is a valid point to be made.
Assuming good faith (ie: not lying) is similar but distinctly different from assuming that someone is speaking truthfully/accurately.
>> Considering how often antidepressants tend to be a hit-or-miss game (not to speak of side effects), I am a bit annoyed psychedelics don't get more attention for medical use.
> Psychedelics are actually extremely hit-or-miss as well. Anecdotally, psychedelics don't always send someone in the right direction post-trip. If you scroll the comments in any popular psychedelics-for-depression post on Reddit, there are almost as many negative experience reports (including some long-lasting) as there are positive reports. The positive reports receive the bulk of upvotes, though, so you have to scroll down to see them.
> Perhaps less anecdotally, any medical professional will see a non-trivial number of people with significant negative effects of psychedelics, from worsening depression to HPPD to existential crises or psychoses. An actual doctor had a great comment on the previous discussion: https://news.ycombinator.com/item?id=30995831
Looking at some of the discrete claims:
> Psychedelics [are actually] [extremely] [hit-or-miss] as well.
This asserts that results (across all instances of usage, not only those that have been studied under formal conditions) are highly random/inconsistent, in fact.
This is highly contrary to my personal experiences, as well as the reading I have done on others' experiences.
(Of course: we should keep in mind that it is unknown what percentage of experiences get posted, whether positive trips are more likely to get posted than negative, etc. - but "both sides" suffer from these problems.)
> Anecdotally, psychedelics don't always send someone in the right direction post-trip.
This true statement notes that they don't always do something positive, but it might be interpreted as being logically supportive of the preceding assertion, even though it is not.
> If you scroll the comments in any popular psychedelics-for-depression post on Reddit, there are almost as many negative experience reports (including some long-lasting) as there are positive reports.
This makes a quantitative claim that is extremely inconsistent with my fairly substantial experiences reading trip reports, which lines up with what /u/rileyphone said:
>> My experience, and recent search, indicates these are usually about 80% positive, and most negative experiences stem from predictable abuse patterns.
-
> The positive reports receive the bulk of upvotes, though, so you have to scroll down to see them.
This seems to imply that the negative trip reports are hard to find, which leads to people having a false impression of what is true. If one reads forums regularly, it seems unlikely that all negative reports were downvoted to oblivion before being seen by regulars, which is inconsistent with my experience on most forum software.
Same experiences. Dropped drinking, started exercising. The LSD dose was much higher and the after effects listed lasted for weeks. However, the mushrooms dosage was lower and while the after effects were similar, it didn’t last as long. Truthfully, I felt a deeper connection with the moment post-LSD.
The LSD trip kind of hurt but after the first few hours, became a solid 6-8 hour span of self reflection. Mushrooms started out chill and evolved into a pretty painful experience before moving into that self reflection stage.
What’s happening during that self reflection stage is best described as a feeling of losing it all. Family, friends, etc. but not so much material items. In that moment, I felt complete loneliness and the fear associated with that loneliness. That fear led to asking what would make me be alone and the answer was my personal ego. It ultimately was a confrontation of personal flaws like narcissism or selfishness. Later in the trip, like 5-8 hours, a feeling of being content with who I am and where I need to improve to not lose the things that truly matter was the result.
I don’t know if I’ll ever try either LSD or mushrooms again but the reset on my personal ego made me value a lot of important things that get backburnered in the grind and stress of life.
> What’s happening during that self reflection stage is best described as a feeling of losing it all.
This reminds me of a passage from Aldous Huxley's Doors of Perception:
We live together, we act on, and react to, one another; but always and in all circumstances we are by ourselves. The martyrs go hand in hand into the arena; they are crucified alone. Embraced, the lovers desperately try to fuse their insulated ecstasies into a single self-transcendence; in vain. By its very nature every embodied spirit is doomed to suffer and enjoy in solitude. Sensations, feelings, insights, fancies - all these are private and, except through symbols and at second hand, incommunicable. We can pool information about experiences, but never the experiences themselves. From family to nation, every human group is a society of island universes...
What's being described in the study is not self-reflection but serotonergic psychedelics' effects on the 5-HT2A receptors in the brain. For example, escitalopram (Lexapro) may help with self-reflection as well but this study was specifically studying patients with treatment-resistant depression.
Your body feels exhausted but your mind is quite awake. So you’re exhausted and energetic at the same time. Your joints can kind of feel tense if you’re not moving. Walking is enough but then you can also feel overheated pretty easily. Hours 1-4 were largely uncomfortable for me on both.
LSD gave me diarrhea for a solid 4 hours. I think that’s rare but I felt better the next day than I had in years. Probably something to do with gut science but I have nothing to back that up other than my story here.
Fair question and yes. Received from a reliable individual and also personally tested. Even still, I’ll admit that even after testing I Googled symptoms of meth use a few times during the early stages of the trip.
You want to go to sleep but the final paper is due in 8 hours and you haven’t started. You are going to write this paper and nothing stops the paper from being written. As you find yourself at hour 4 or 5, well past any joy of ideation, you realize that you must still finish the paper. Caffeine is pounding in your head and you have wrestled the entire day before, now your brain is thinking at full capacity whether you like it or not.
Oh it’s not a pain that can be seen but have a migraine and say that’s not real or work a hard day and have to walk more.
It’s the hurt of causing your brain to be more active than it ever has. Similar to making someone who plays video games all day hike up a mountain. They’re gonna feel it.
I have a pet hypothesis that "curing" depression is an active endeavor, instead of a passive one. Just like being healthy in general requires at least a moderate regard to nutrition and exercising. No amount of medicine can replace those.
From anecdotal reports, it seems that mushrooms forces one into an active thought space (like dropping someone of at the gym with a program for them to follow), such that one is more likely to engage with ones own thoughts, and is capable of interpreting them, recasting them, accepting or letting them go.
The idea of "rewiring" seems a bit too far, since rewiring cannot be achieved instantly.
Have you been depressed? I can tell from experience that a depressed mind is quite active. In a bad way - constantly hurting itself with dark thoughts and hence reinforcing the bad stuff constantly.
You can't exercise depression away. At least for those situations I am familiar with.
Active is a bad word to describe what I meant. I don't mean to say that a depressed mind is not thinking, just that it may not be able to get itself out of the place it is in without "active" effort (as in therapy - self-therapy or mediated by others). The conundrum is that putting in that effort may not possible because all energy is already spent - as you pointed out.
My suggestion is that psychedelics opens space for these thoughts to be actively dealt with in a productive way.
There is also mounting evidence that depression is a symptom and not a single disease, and the symptom may be originating from multiple causes. This view is supported by the extreme between-subject variability seen in imaging studies [1].
That being the case, maybe not all causes would require an "active" approach, just as maybe not all will respond to psychedelics.
To me the point being made is that there will never be a "cure in a pill" for many things, including depression. Medication may help, but really getting past it will also take active effort.
If you're overweight, you can't get lean and fit by taking a pill (much as many would like it to be true). You will have to make some effort by eating less (actively resisting feelings of hunger) and getting more physically active.
Psychedelics used to be a fairly common treatment for depression and addiction in the 50s before the witch hunt of the US government against what was considered "street drugs". Leary didn't do them any favors either as he was essentially telling everyone to load up on psychedelics, which triggered the usual over the top uninformed response our dear elected officials are so fond of.
A similar situation for me. At the beginning of covid I had been struggling with depression and my own mortality. I took a large dose of psilocybin and during my trip I witnessed myself dying, decomposing, growing into flowers, being pollinated, being reborn, etc. Over and over again. The trip itself was uncomfortable and at times terrifying, but the results were immense and lasting. I came to terms with a lot of what I had been struggling with.
Most of my other experiences have been along similar lines. "Oh hey, you know that uncomfortable thing you have been avoiding thinking about and dealing with? Yeah... Buckle up"
I was effectively in isolation for months due to some health issues (pre covid). I knew I was depressed as well and decided to take some LSD. I've taken it a few times before, never had a bad time. This time, I had. I repeated this a few times with the same results, its gonna be some time before I try it again.
Nobody should just expect psychodelics "cure depression". Its possible they can deepen it in some conditions and we do not really understand it (I hope we will thanks to studies like these). They can help, but the lesson I got from this is they cannot replace support from fellow humans.
Best advice I can give is try to only do this with some good company, outside on a sunny day, and it is highly likely it will be an overwhelmingly positive experience.
> They can help, but the lesson I got from this is they cannot replace support from fellow humans.
I think what's lost in the shuffle is that the phrase "guaranteed to" - all drugs are not guaranteed to work for all people, what matters is what is the likelihood that they can help any given individual, also taking into consideration the associated risks (both of taking and not taking).
I'm just noting this because it would be easy for someone to take away from this conversation the notion that psychedelics are necessarily dangerous, as it is possible that they are as safe or even safer than the thousands of other medications people take, and, some people are in situations where not taking a chance could very well end in death (suicide), especially those who live in areas where assisted trips (legal or not) are not available.
Same for me. What happens during the LSD trip may be relatively insignificant from the therapeutic perspective (not always). It's the aftermath when the drug is out of the really interesting system.
I think annealing is a good metaphor for how the process feels. Psychedelics "break the structure" and "shake up" the brain (the trip). Then there is recovery and recrystallization into a state with less internal stresses.
"What happens during the LSD trip may be relatively insignificant from the therapeutic perspective (not always)"
I doubt that's the case, since we know a lot of subconscious material tends to surface during a trip.. and such material can be very fruitful material for all sorts of therapeutic approaches (except maybe behaviorism and its offspring).
The therapeutic effect from the trip seems to happen in first few times or after taking "heroic dose". If you have taken 5 trips over a 1-2 years, I don't think you get much material. Psychedelics seem to have hard limits of what they can reveal.
I have found that the good after effect comes even from low doses. Microdosing or just relatively low dosing that don't bring anything into surface.
"If you have taken 5 trips over a 1-2 years, I don't think you get much material. Psychedelics seem to have hard limits of what they can reveal."
I've never seen any studies to suggest this is the case. Just anecdotes of people saying they stopped taking them after a while because they weren't learning anything new. But usually such anecdotes have no information on just how they were taking them -- with intention? In a therapeutic context? What did you actually deal with in your life and what didn't you deal with?
I suspect that those that stop getting results aren't integrating what they learn during the trip in to their lives, so they're stuck on repeat.
"I have found that the good after effect comes even from low doses."
The research on microdosing is just getting started. It's quite possible that reported effects from microdosing are due entirely to the placebo effect.
May I ask you about the kind of depression ? was it a slowly creeping in or one triggered by a traumatic change (something that is linked to symbols/memories in ones brain though) ?
If it's the 2nd case I'd be even more curious about the effect of shroom chemicals on the upper layers of the brain.
These open-label studies also need to be carefully evaluated within the context of their selection criteria. One of the biggest challenges with open-label studies for psychedelics is that they tend to collect "true believers" who are already convinced that psychedelics will cure their depression. They seek these studies out specifically for the opportunity to receive psychedelics, often because they've read books and news articles telling them it will be successful. Notably, 1/4 of participants admitted to past psychedelic use (and I suspect the actual number is much higher, given that study participants often lie if they think a certain answer might exclude them from receiving the drug they want)
The study also explicitly required treatment-resistant patients to have tried and failed multiple antidepressants in the past, which explains the low response rate to the SSRI arm:
> The open-label trial had the additional criteria of TRD, as defined by no improvement despite multiple courses of antidepressant medication (mean = 4.6 ± 2.6 past medications; range, 2–11)39. Patients were asked whether they had previous experience of using psychedelics. In the open-label trial, 25% had previous experience. Similarly, in the DB-RCT, 31% of patients in the psilocybin arm and 24% in the escitalopram arm had previous experience.
There's also an ongoing problem in the analysis of MRI functional connectivity. About 2010, someone had the idea to apply concepts from graph theory to fcMRI. That is fraught with a number of heroic assumptions (fcMRI correlations do not necessarily represent physical connections, and continuous relationships must be binarized with arbitrary thresholds). But most importantly, there are so many different graph theory metrics, and ways to tweak the analysis, that a determined postdoc is basically guaranteed to find something that can reach statistical significance. I suspect something like that has happened here.
I had dinner with two psychiatrists who are working in this field both with adults as well as one of them who is doing work in paediatric psychiatry. They have both taken LSD, Psilocybin and ketamine as part of their work so they would be able to introduce it to patients properly.
One key component that seems to be missing from a lot of the excitement about these treatments is how important an ongoing therapy or other behavioural support component usually is. A lot of patients find some relief from a ketamine or other therapy but it can open up a host of issues they have not dealt with or it can resurface old behaviours.
One example was a patient who had a long history of abuse which was more or less hidden by their severe depression and suicidal tendencies. They had a series of ketamine treatments by an anesthesiologist and it cracked that past right open. The place they were taking the treatment was not equipped to support that and they did not have immediate access to psychiatric or even good psychological support and it did create a bit of a spiral.
I don't think any of that comes as a surprised to people in the field, but each patient and circumstance is different. The sooner we can bring these treatments in to mainstream health research, the more holistic the approach to patient health can be.
Lots of interesting stuff to learn. I am just bystander-fascinated by it and am not professing any expertise here.
Unfortunately, a lot of people can't afford therapy... and insurance doesn't tend to cover psychedelic therapy.
Hopefully one day it will, but we're not there yet.
This will, at least in the short-term, unfortunately lead to widening inequality, where relatively wealthy people will be able to afford therapeutic treatment, while the poor will be left to their own devices.
> They have both taken LSD, Psilocybin and ketamine as part of their work so they would be able to introduce it to patients properly.
While I think there might be potential for psychedelics in therapy, let's be honest here. That would be like a Wall Street guy saying he snorted 3 lines of cocaine to better advise his clients on investments
I'm not sure what the best way to support it is, but I'm following the progress closely and it isn't getting much coverage - I figure I might as well spread the word whenever I can.
Spreading the word about the bill and also being open with your family, friends, and possibly even coworkers about your own psychedelic use are some of the best ways to support this initiative.
We really need a lot more people to come out of the psychedelic closet.
Also consider contacting and supporting groups like MAPS[1] and Decriminalize Nature[2].
Ending prohibition would mean that criminals would no longer be involved in drugs, because people can buy them at the store.
It doesn't work super well if the regulations and taxes make legal drugs more or as expensive as legal drugs, so that needs to be managed well for things to work.
I was trying to have no presumption about their intent or implication, perhaps there was something frequent in Hmong culture that was relevant...
However, sadly the Hmong are a highly discriminated group (at least my experience in VN), I volunteered at an orphanage for Hmong children and many didn't want them just because of their ethnicity
I can definitely understand giving the benefit of the doubt in most situations, its usually the best move to foster trust and empathy between parties.
When I consider the statement by the OP, I don't know what the reason for including race/nationality could possibly be that isn't malicious. It adds literally no extra context besides the insinuation that 'these people aren't the same as me' ('me' being the OP)
Maybe someone else has a different perspective and they can explain how they see the statement and how it might not be a purely ingroup/outgroup exclusion/racism thing
You can't have a conversation online anymore. If I mention this stuff to people in town, they take it seriously. Just because someone worse exists in the world doesn't make bad people good.
There’s definitely some benefit for some people but this headline is straight sensationalized.
People need to be careful with psychedelics. The afterglow wears off pretty quick. I’ve met many people for which psychedelics actually reinforced “negative” aspects of their person…except now they believe to be enlightened from their trips.
After dozens of trips myself, one of the things I’ve learned is that these drugs induce the feeling of profundity. The experience of a trip FEELS profound, regardless of the actual content of your thoughts. Sometimes it’s great! — When your new idea or outlook is truly beneficial for yourself and others. Not everybody gets that. My cynicism has been magnified.
Absolutely. Psychedelics are incredibly powerful substances and they need to be treated with respect. Everyone considering doing them should educate themselves thoroughly beforehand and use them in maximally safe, constructive ways. James Fadiman's Psychedelic Explorer's Guide[1] has lots of great advice on how to do this.
"The afterglow wears off pretty quick."
It really depends on the substance and how it's used. Ketamine, for example, commonly needs to be readministered relatively frequently (though some people have lasting effects), while many people get very long lasting effects from between one to three therapeutic MDMA or psilocybin sessions (sometimes lasting for years).
It's people who tend to use psychedelics outside of a therapeutic context, to "party" and/or without constructive intention or post-trip integration that tend to lack lasting effects.. but even then it's not at all uncommon for the experiences to be life-changing.
I took a large dose of mushrooms about 11 years ago and haven't had depression since. My life was on track to nowhere and now I'm doing great. Hard to not give mushrooms a bit of the credit, the results were immediate.
Oregon will be formalizing their program to provide therapeutic access to mushrooms in controlled settings soon.
I have mixed feelings and some potential fears about the execution, but it’s still going to be absolutely fascinating to watch and I’ve got my fingers crossed it could become a really positive treatment option for residents here. I bet we’ll see some articles about it on HN in the years to come!
There was another discussion recently about this study because it was also reported in Bloomberg. From my own personal experience, shrooms was the greatest thing that ever happened to me. It was like someone flipped a switch on my depression and the depression magically went away. The study really validates what I experienced, and the truly life-changing effect that it had.
I have a similar experience. I first did shrooms in high school and enjoyed it immensely. But in the few weeks after the trip, I felt great. I was way less nervous talking to people, I felt more confident, and just generally better about myself and life in general.
But if you're interested, be aware: they taste gross and it's pretty common to feel really sick and throw up within the first 30 minutes. But after that, I promise you'll enjoy it, if you are in a good environment of course.
Use a coffee grinder to crush it into a fine powder. Squeeze a lemon into a cup. Put the powder in and stir. Wait 20 minutes, add some orange juice or water and take it down. Activates instantly and you sidestep the nausea from your stomach where it feels like if you move a muscle you'll hurl.
The first time lasted three months of relief. I had a bad day that sent me down the spiral, but a psilocybin chocolate bar brought me back. It’s not a panacea but it certainly ..gives me breathing room to let other therapies work.
when start to feel less motivated - don't want to go out - struggling at work- I take ~3 grams - usually lasts about 2 months or so - find this much better than microdosing personally
For anyone who's never tried mushrooms before, 3 grams is a pretty large dose. If it's your first time start with 1 gram or so. After all, you can always take more, but you can't take less.
Really. Here I was thinking a starting dose was 8 grams (from a documentary about magic truffles in Netherlands). Good thing I never had the opportunity to try mushrooms, that'd probably be a pretty wild, unpleasant trip :))
Three grams of mushrooms is easily 4 to 10 individual mushrooms. Usually people simply weight the entire mushroom and not the exact psilocybin content. This is not ideal since potency will vary but it's enough to give you a good idea of the dose when comparing to previous sessions. However, there are more and more legal services who can provide already weighted product with the exact psilocybin content on the label.
If that was sugar, it's pretty easy for me, as a study participant, to tell whether I've been given mushrooms or not (i.e. am I feeling drugged or not). I suspect that played a part of the reasoning to use a psychoactive compound instead of sugar pills as a placebo.
I think other studies have used Nicotine and other substances to provide an initial flush of feeling like you took something. That being said, "feeling drugged" is pretty dose dependent so plenty of studies could use a truly inactive placebo alongside a lower dose.
Isn't the term "control" more accurate than "placebo" in these contexts? I thought that a placebo was inactive, while a control is used to set a baseline for judging improvement. A placebo is a type of control, but not vice versa.
A placebo does not need to be completely inactive, it merely needs to not exhibit the effect you are trying to test for.
Using an anti-depressant as placebo for a test regarding anti-depressive effects does seem a bit odd, but it is fine if the test is for effects or durations exceeding the capability of placebo drugs.
A placebo doesn't have to be inert, it's more that it has to have no therapeutic value. Meningitis vaccine doesn't protect against covid so it's an effective placebo for testing covid vaccine for example.
Technically an "active control", though the patients appear to be selected to have been SSRI-resistant:
> The open-label trial had the additional criteria of TRD, as defined by no improvement despite multiple courses of antidepressant medication (mean = 4.6 ± 2.6 past medications; range, 2–11)
If i'm reading the study properly (disclaimer: I may not be) then the patients in the open-label trial had already failed an average of 4.6 typical antidepressants. So it's unlikely that they'd be responding to a starter dose of another SSRI (10mg escitalopram, though some were on 20mg perhaps by body weight)
If it's a psychoactive molecule, it's not really a placebo, in my opinion. I don't think the section you linked refutes this:
>Some suggest that existing medical treatments should be used instead of placebos, to avoid having some patients not receive medicine during the trial.
It discusses medical treatments used instead of placebos, rather than as placebos.
I think the more accurate term here would be "control", not "placebo". It arguably could create or enhance a placebo effect with respect to psilocybin, but I think "control" would be less confusing terminology to refer to the non-psilocybin substance. Then again, they're the research university and I'm a random internet commenter, so they probably have more authority on this than I do.
Your opinion is not worth anything regarding this, as it goes against the common understanding of reseachers. The concept of an active placebo is from the 60s and is well know in medical studies.
My understanding is that an active placebo generates some expected effects so that the patient is more likely to believe that they took something: https://en.wikipedia.org/wiki/Active_placebo
>An active placebo is a placebo that produces noticeable side effects that may convince the person being treated that they are receiving a legitimate treatment, rather than an ineffective placebo.
>An example of an active placebo is the 1964 work of Shader and colleagues who used a combination of low-dose phenobarbital plus atropine to mimic the sedation and dry mouth produced by phenothiazines.
>Morphine and gabapentin are painkillers with the common side effects of sleepiness and dizziness. In a 2005 study assessing the effects of these painkillers on neuropathic pain, lorazepam was chosen as an active placebo because it is not a painkiller but it does cause sleepiness and can cause dizziness.
Here, it seems like an example active placebo might be something that induces nausea, since psilocybin is known to induce nausea. SSRIs are not just an active placebo but something that actually attempts to treat the primary symptom: depression. The above paragraph suggests lorazepam would be a good active placebo for testing painkillers because it is not a painkiller; here, an antidepressant is being compared with an antidepressant.
So I was wrong to say that it's not a placebo if it's a psychoactive molecule. I just don't think it is if it's a psychoactive molecule that's treating the primary symptom you're attempting to find a treatment for.
No, in the informed consent document they should describe you will be given an active placebo or the investigational drug. The IRB would approve the specific drug / dose that is administered, as outlined in the trial protocol.
My assumption and this article is badly worded. The wording suggests the second group are not treatment-resistant, and considering the loading and expected timeline of any kind of effect of Escitalopram it may well have been their current medication. Especially as from my experience loading an SSRI has a very unmistakable physical unpleasantness which would be a give-away.
There's also the ethical limitations of taking someone off a medication they need for their wellbeing to try something else, which is largely not allowed which makes trialing certain alternatives difficult and complex.
I guess it's poorly or incompletely worded. This is an "active placebo".
Another example would be determining something about mystic experiences and testing amphetamine against psilocybin. You need something active, because otherwise even a drug-naive participant quickly groks they're on sugar and not an actual drug
placebo controlled studies are not really possible for psychedelics anyways. There's literally no way someone takes a high dose of it and doesn't figure out they have taken psychedelics. You need slightly different tools for this type of studies so I think they are comparing effectiveness instead.
Actually, I've heard a researcher say that in the MDMA studies they ran, some people who were given placebos experienced a full breakthrough, with lots of emotion, crying, and therapeutic benefit and swore that they were given MDMA.
It probably also helped that these were people who'd never tried MDMA.. so they didn't really know what to expect.
Also, in microdosing studies, I think even sugar pills could be very effective placebos.
To help keep it as blind as possible, studies sometimes use something that is better understood and gives you the side-effects you might expect if you weren't on the placebo. Like the Pfizer COVID study used the meningitis vaccine as a placebo IIRC.
edit: see another comment suggesting that control is the right term for this rather than placebo - face palm moment.
Just thinking back to one of my happiest student memories: watching the sea water pouring off the tail of a breaching whale... on a poster on the wall of my friend's digs.
Just from working with a few psychiatrists for the past month, none seemed to be enthused about trialing or studying psychedelics for depressed patients. I think we will need a lot more case studies and a comprehensive list of harms and adverse reactions before convincing them. Worth mentioning this treatment also requires more work on the therapist/psychiatric side. Something that doesn’t need a lot of therapy sessions is ECT which is very effective for treatment resistant depression.
Lastly, psychedelics used to be researched for military purposes and mind control, wondering if this is still a risk factor for patients?
"Just from working with a few psychiatrists for the past month, none seemed to be enthused about trialing or studying psychedelics for depressed patients."
How old are these psychiatrists?
Many psychiatrists grew up during the days of prohibition and paranoia about psychedelics, and their training exclusively focused on treating depression with non-psychedelic antidepressant drugs.. not to mention all the kickbacks that psychiatrists received from the pharma companies peddling those antidepressants.
So I'm not at all surprised to hear skepticism from some of the more conservative ones.
That said, there's been an overwhelming amount of research showing the effectiveness of psychedelics on treatment-resistant depression -- effectiveness that dwarfs the effect of antidepressants. So many other psychiatrists and therapists are much more open to trying them than the psychiatrists you met with.
"psychedelics used to be researched for military purposes and mind control, wondering if this is still a risk factor for patients?"
They were not found to be effective at "mind-control" and the "research" (if it could be called that) was abandoned. All such abuse resulted in was traumatized, broken people. Really horrific stuff. See the history for MKUltra[1] for details.
It's still a concern that you might be unlucky enough to work with an abusive psychiatrist or therapist.. so you should really be vetting the people you work with very carefully. That said, there are training, certification and licensing procedures and organizations that are there to help prevent abuse and deal with it if/when it happens. For example, see: [2]
Also, at least with MDMA therapy the standard is to have two therapists with you at all times, to decrease the chance that one of them will abuse you. Also, at least in the studies, it has been common to videotape the sessions, so there is a record of what happened, which should decrease the risk of people completely getting away with abuse.
But, yeah, it's still a risk and I don't think any therapy will be completely risk free... especially not psychedelic therapy, where the patient is so incredibly vulnerable and suggestible during the session. That's why, again, it's very important that you vet the therapist you're working with to best of your ability before you trust them with your mind.
Both my psychiatrist and therapist are open to the idea. In fact, I'm pretty sure everyone who works in the clinic I go to are open to it. This is in San Francisco though, so YMMV.
And since it's not yet legal in CA, I've thought about joining a UCSF study (last I checked they had 4 ongoing). Haven't acted on it yet though.
The parent comment draws an important difference between the use of psychedelic therapy and, say, ECT. I support this research but "Big Psychiatry just wants the cash!" is a reddit-level of nuance we can do without please.
Funnily, I find the idea that a susbstance can influence your behavior so much rather depressing :( is there anything there that is fundamentally unchangeable no matter the chemistry that could be called a "self".
"is there anything there that is fundamentally unchangeable no matter the chemistry that could be called a "self""
The Buddhists don't think so. One of their fundamental tenets is "anicca" or "impermanence", which is often interpreted to mean that nothing is unchangeable or everlasting.
Many materialists/naturalists/physicalists don't believe there's an unchanging self either.
But those who believe in a soul, in resurrection, or in reincarnation might.
It's not a settled question, and a lot depends on what you mean by "self".
I’m all for this but part of me gets a very “Brave New World” vibe. Are we all going to have to micodose shrooms to tolerate our prosperous progressive society? It’s seeming increasingly likely.
Shrooms had the opposite effect on me, where I suddenly became much more cognizant of the damaging aspects of our society, to an almost unbearable level. It made me overall less capable of operating in society, not more. Can't say I was really a fan of its effects on me.
Psilocybin seems to induce a highly plastic state of mind, and so the results can be somewhat unpredictable.
Did you take them alone? Did you go outside at all? I think your environment really affects your experience. I always tell people to go outside as much as possible, ideally on a nice sunny day. Walk around in a park or the woods and I bet you'd have a different experience. If you're alone and indoors, you'll most likely end up going deep inside your own head, which isn't necessarily a bad thing, but things can definitely start getting dark.
I took them alone, but did go outside. Going outside was the best part of the trip. It wasn't a "bad trip" (had those on DXM before, this was much different). It was more that it opened my mind more fully to the amount of suffering in the world, and how much of it is caused by humans. Something we usually have to suppress in order to function from day to day. It was probably overall a good thing to have those realizations, but it was highly challenging, and it was detrimental to my mental health over the following months. But the lessons were probably just as important as a trip filled with just love and joy (never had one of those).
"Shrooms had the opposite effect on me, where I suddenly became much more cognizant of the damaging aspects of our society, to an almost unbearable level. It made me overall less capable of operating in society, not more."
It's important to connect with others who've had similar realizations of the dysfunction of our society. Together we are stronger, can support each other, and work together for positive change.
I don't know why this doesn't get more attention. It's a classic ethical dilemma in psychiatry, and ultimately the basis for many science fiction works.
Let's say, for the sake of argument, you have a pill that can make people feel really positive and boundless, that they love their lives and nothing could make them feel better. This pill will work regardless of their circumstances. On the other hand, their environment is horrible: they are in poverty due to societal injustices and systemic failures, and loved ones are dying from completely preventable diseases due to those same societal failures.
Works like The Matrix explored this theme in an extreme form, almost to a fault, where the premise is so absurd that it becomes dismissed.
It's difficult to argue about treatments that will help people feel better and be better in their lives, whatever that means for them, but I can't help but be angry, even furious at the paradigm that underlies current behavioral biomedical research, where everything is seen as being a problem within the individual. It's not so much that there's something wrong with doing research like this, it's that other research, focused on more environmental factors, is seen as soft or unsexy, or the domain of some other field, or some such thing.
I can't help but feel that our society is hurtling at astonishing speed toward an ethical crisis that gets almost no attention. What happens when we can alter behavior and experience with extreme precision and power, but still live in a worldview that treats individuals as the primary determinants of their own fate? What happens when withholding treatments or enhancements becomes a salient problem, when opportunity costs become a form of corruption?
You're talking about too many different points in one:
1. How much of someone's suffering and/or depression is due to brain chemical imbalance vs society and environment around them.
2. Would alleviating someone's depression and/or excessive anxiety would make them happy but with indifference to their surrounding, making them oblivious to the environment around them while being in a state of bliss.
3. The ethical dilemma of "fixing" someone by handing them a pill, instead of working on actually improving the real issues that may be contributing to their psychological pain.
I think these are different issues that are not necessarily easy to answer one way or another. Non of these issues are self evidently clear which way should we go about them.
So, I wouldn't argue that no one would benefit from a pill, or that there aren't situations and/or people who need a change of perspective, or an alleviation of pain so they can survive long enough to get through the storm.
It's not so much that I think drugs are bad for treatment of psychological problems; it's that I think that of your issues (3) is radically neglected in contemporary psychiatry.
"Treatment resistant depression" as an idea in studies such as this is sort of telling in that it assumes the problem is the pain, rather than whatever potential external problems someone is dealing with.
A good analogy to me would be someone who keeps coming into the ER with bullets in their body every couple of months (maybe in a conflict zone like Ukraine), but where the case is construed in terms of the pain the bullet causes, rather than the fact there are bullets in their body and the person is in a situation where they keep getting shot at. I don't want to oversimplify things, as the environment and situation is generally attended to, but the paradigm as a field is to treat the disease as the pain the patient is suffering ("depression" as a disease), rather than the scenario as a whole, and to act as if the pain is an attribute of the patient rather than as part of an appropriate response to a problematic situation.
So yes, depression as a phenomenon is a complex mixture of things, but I think in general, at least in the US, it tends to be seen as a disease that's a biological property of the person. There are historical reasons for this, some good and some bad, but I think it's had unintended consequences as a result.
"A good analogy to me would be someone who keeps coming into the ER with bullets in their body every couple of months (maybe in a conflict zone like Ukraine), but where the case is construed in terms of the pain the bullet causes, rather than the fact there are bullets in their body and the person is in a situation where they keep getting shot at."
Interesting analogy, but if my body was ever riddled with bullets and I was taken to the ER, I'd definitely want the doctors to treat the damage the bullets made, remove them from my body, and relieve the pain.
If the ER ignored the bullets in me and assured me they'd instead be sending a police car to the neighborhood in which I was shot then I'd yell, "no! please treat me first!"
There's a lot to be said for symptom relief. Of course, the underlying causes should also be addressed, and there is evidence that psychedelics allow therapists to do just that. In particular, MDMA appears to allow patients to face and deal with their trauma without the pain and aversion that trying to face their trauma ordinarily causes. It also allows many to forgive themselves or their family, to experience love for the first time, and resolve family issues. This is treating the cause, not just the pain.
Of course, traumatising external circumstances must also be changed, when possible. I believe psychedelics can help here too, by making people aware of them (psychedelics often have the effect of opening people's eyes to just how screwed up our society is) and by making people more empathetic and connected to others and to nature.
They will not magically solve all our problems, but they can play an important role in helping us to solve those problems ourselves -- if they are used constructively and in the right context.
What you say is true, but are broken people who are barely able to take care of themselves (and who may be acting out in all sorts of destructive ways) supposed to pull themselves up by their bootstraps and make a positive change in the world (one which often requires a lot of resources, bravery, and long-term commitment)?
Many of our leaders themselves are traumatized and dysfunctional in many ways, and do themselves deserve treatment.. treatment that may open their eyes to how dysfunctional they and the system they're part of has been.
There's a good argument to be made that the in order to heal the world one should heal oneself first. It's like putting on an oxygen mask in a depressurized airplane before putting one on someone else. If you are incapacitated you will be unable to help.
It's healthy, resilient people who will be best suited to both recognizing the problem and helping to fix it in the long-run.
That said, it doesn't have to be one or the other. Those of us who are awake enough already can spread the word about what's wrong with the world, and those of us in good enough shape and with enough motivation to contribute should try to make things right (an important part of which, in my view, is to end the War on Drugs and give affordable access to psychedelic therapy to those who need it).
I would argue that many people today already have their own form of Soma. Alcohol being the most popular one due to its abundant supply. A lot of people just need to step out of their own minds every now and then.
I always understood BNW's soma as a drug that is administered regularly to provide an escape and instill complacency. Modern examples might include alcohol, Netflix, and cushy salaries. Psychedelics are the opposite; they provide perspective and they make you yearn for something greater.
Microdosing - definitely not. Regardless of what the proponents say, even small doses of psychedelics induce some degree of impairment (please don't microdose and drive!)
But you touched on one of the key problems with psychedelics: We can't really expect people to trip every few months forever. If psychedelics are used, I would expect them to be in the context of intense therapy. Many of the studies will require patients to go through 10 or more therapy sessions before, during, and after their psychedelic dose.
Dis you trip while also on other medication? I was on Wellbutrin and Zoloft, but 3 grams didn’t do anything for me. Four grams did, but only mildly, that was enough to have significant therapeutic relief.
I suspect depression medications may inhibit the effect?
Depends on the antidepressant, but SSRIs like Zoloft do suppress the effect. MAOIs, on the other hand, tend to increase the effect. I'm not sure about Wellbutrin.
1. Someone taking SSRI's and psilocybin finds that the dosage... simply doesnt work. I had one individual who ate up to 8! grams before seeing and feeling things that I would see in normal people at about 1.5.
2. This might be really bad for you! There's some evidence that mixing that level of both drugs might be not good for your liver and might get you into toxic levels, and suggests tapering - I honestly dont suggest tapering your anti-depressants unless you are working with a medical professional because well, suicide.
3. If you really want an undenyable trip, just take some salvia (properly), 15 minutes and many of the same after effects.
> I suspect depression medications may inhibit the effect?
When I was on Wellbutrin, it stopped the mental effect of alcohol. When I imbibed, there was no loss of inhibition normally associated with alcohol use. However, I did still lose physical coordination.
In general I think this is most pronounced even within antidepressants of the same class, with similar binding affinities, some people report limited success with one or the other seemingly similar drug.
All this said, wellbutrin is a very different drug than zoloft. It have more dopamine and norepinephrine activity iirc.
Also for anyone else, try to avoid alchohol and wellbutrin or take it knowing that your seizure threshold goes down on wellbutrin so its easy to black out and do worse than you realize (also related to the reported effects above)
Humanity has always been getting intoxicated on drugs and alcohol though. Society practically evolved to organize the brewing of beer in Mesopotamia and Egypt. It's only recently that human societies have gotten so conservative with these things.
Psychedelics caused me to have ongoing dissociative panic attacks. So, you know… it’s not all rainbows :P Hopefully with careful study a safe treatment can be developed.
(Certainly without any study people will keep tripping, so certainly I advocate continuing study!)
It is vital in such a discussion to be mindful of the term "depression".
It is used colloquially as a synonym for being "sad", "grieving" or just
having a sad day.
I am depressed because my mom died.
Usually means
"I am going through natural grief process because someone very dear to be died recently"
Robert Sapolsky explains this much better than I [1]
I have lived with major depression for 3 decades or so.
Treatment is frustrating.
You go through whatever diagnostic process is being used.
Then they throw pills at you.
This one might work, take it for 3 weeks - 3 months and tell us how you feel.
You have to take it for a good amount of time to ensure that it's "fully working".
Some make you more depressed and more suicidal.
Some have other serious side effects.
If the doctor treating, you figure that you tried out one for long enough
they will throw a different pill at you and then you rinse and repeat
until you feel better.
Then they will start to try combinations.
That is even more fun.
I have spent years being a Guiney pig for the most part getting worse
and having to deal with various side effects.
I am not unique in this.
It is common for major depression to have to try and fail, try and fail,
try and fail meds.
We have no physical way to diagnose depression as far as I know.
You can't go to the ER and they measure something and can tell
you if you are or not.
We dont know what causes it, (we have many ideas of things that sometimes do)
and we have no way to measure how much better you are getting.
Its based on talking, filling out endless forms, and being asked if you feel better.
There is no cure. (well death) (Being suicidal)
It is something you cannot run away from.
It is in you, and you can run, but it makes no difference.
(Exercise can be beneficial, but I am not talking about that right now.)
Well-meaning people will suggest all forms of activities that
"Will make you feel better".
It does not.
Then they will nag you about how much better you feel now.
Which you dont.
I just want to urge people to be careful about using the term depression
and dont build up too much hope in people (like me) because this new
drug will fix you all up.
I would take LSD, MDMA, K (all have shown promise).
If prescribed or as part of a study if I could.
It will take massive research over time with plenty of Guiney pigs
to figure out if it works, how it works, for how many it works.
With headlines and discussions on this, we will cause people with major depression
to run out, buy street drugs, self-administer it and in all likelihood end
up with even more problems.
Given the unknowns of street drugs, how pure is it, what else is in it,
how much should you take? It is highly unpredictable.
I had horrific and long lasting negative effects from LSD. My wife absolutely laments that she convinced me to take it the two times I did. I saw mortality and impermanence directly, I felt entirely alone, and also I got extreme motion sickness and was passing out in a mess of white fractals and intensity in my body. I developed severe flashbacks to the trip and every time I had one I became extremely suicidal. The only good thing that came from it is that it pushed me towards an actual solution for me, which is practising zazen (goalless sitting in the Soto Zen tradition of Mahayana Buddhism). Resting in this moment, as Buddha, unmoved by external conditions. If I did not learn this, my life would be over, and indeed taking a break from the practise for 6 months the old grasping mind returned and I found myself heavily desiring death again. I sit and this all goes. My life after LSD was so traumatic that I was forced to find a way. The worst part is that therapists had no idea how to even consider the cosmic horror I felt, they just said it was “weird” and tried to shift the focus to tangible things, but it was the ineffable infinity that I was scared of.
Anyway, I always say that LSD fucked up my life so much that I had to turn to _religion_ to cope!! As a former militant atheist, that’s an incredible thing to say
There's a whole class of therapists who won't dose people on psychedelics because they feel the risks are too high (legally+medically) but will gladly take in people like you to help integrate the experience and helping with coming to some closure and insights.
Might be worth a session or two. Also sounds like you took a really freakin high dose... Yeah acid has its own agenda and lasts waaaaaaaaaaaay too long, there's a reason a lot of the recent research is on psychedelics that don't blow you away for up to 12 hours straight.
Can you believe some of us do that for FUN? Maybe it helps to be spiritually seeking to begin with. I think learning your lesson with these tools is kind of like getting in a fight. You might get your ass kicked but some of us throw hands professionally with a shit eating grin on our faces the whole time.
This is a really unpopular answer, but I whole heartedly support it. Unfortunately, many people are looking for a solution (a quick fix) in a pill. They don't want to hear that perhaps the way they are living or the society they live in is not conducive to happiness.
Perhaps an alternative to intoxication is to work towards a world of human flourishing.
The thing about mushrooms is the effect lasts well after “intoxication”. And the effect of mushrooms is anything but numbing. Scientifically they actually allow the brain to see things in a new light and overcome blocks (they relax the "default mode network" tho I am not a scientist).
Changing your behavior is of course very important but sometimes the mind gets stuck and it seems mushrooms can help get us unstuck.
There are different types of depression. Some are related to how we live, either as a person or the society we find ourselves in. But others are related to physical brain imbalances which will absolutely benefit from medication.
And how many percentage of people suffering from depression do you think have this physical brain imbalance ONLY? Doctors prescribing depression drugs do not care nor do they have the tools to make such a diagnosis.
"Numbing" isn't an accurate description of what psilocybin does to you. It's kind of the opposite, it puts you in closer touch with the thoughts and feeling that were already there. This can be a double edged sword, as it can also surface and magnify highly negative thought processes.
The way these drugs seem to work is they stop serotonin from being blocked in habitual ways. The resulting experience makes people see/feel things as if it was for the first time.
What? Do you mean SSRIs specifically? Or are you including SNRIs, α2 blockers, MAO inhibitors etc? Do you have any evidence to support this or just anecdotes?
This is too broad a statement to support with evidence. This study was specifically about treatment-resistant chronic depression and the measured effects on the brain.
My own impression (and I've been intensely interested in both therapy and psychedelics for several decades) is that psychedelics in combination with therapy (and sometimes even psychedelics alone) can be much more effective than therapy, antidepressants or their combination.
A positive outcome from psychedelic therapy is not guaranteed. Some people don't benefit from it, but many more people benefit from it than other approaches. And when they do benefit, the benefit is often much more pronounced and also typically longer lasting.
There's a lot of research on this, particularly on individuals with treatment-resistant depression.
Psychedelic therapy is not a panacea.. and nothing that operates on your mind is going to magically fix the circumstances you're in or your relationships with others -- you have to do that yourself. But the depression itself can be helped.
Do you have any data on the effectiveness of talk therapy for patients with depression? Any data on how long it takes for the patient to experience any noticeable relief?
I believe a proper summarizing might be closer to "people need therapy AND drugs"
The strongest results across the board are a combination of therapy and medication.
My personal opinion is to vouch for therapy the most, and push hard against the pill narrative.
But I think it adds to the shame of pills to not acknowledge the potential role many people have for pills.
Now disregarding the "ssris are more effective combined with therapy" i also want to point out that most of the psychedelic studies are also combining therapy. My personal conjecture and perhaps some other peoples would be that drugs can help enable the conditions in which talk therapy is more effective.
The classic example is the mdma ptsd therapy trials. Therapists can't apply cognitive therapy techniques if someone's fight or flight kicks in too powerfully. Drugs can help to bring the person to a state where they can get therapy.
I've also seen this with friends --> deep depression, ssris helped elevate to the point that therapy was more successful than deep depression would otherwise have allowed.
The first time I took LSD, my mood was significantly improved for weeks afterwards, even though I don't think I was depressed before. But I did notice that things that normally annoy me tended to annoy me less, and things that made me happy made me happier. Again, this lasted for at least a month.
Considering how often antidepressants tend to be a hit-or-miss game (not to speak of side effects), I am a bit annoyed psychedelics don't get more attention for medical use.