The issue is that what people generally say, like, “oh sometimes you need to encounter your demons,” maybe that will be temporarily traumatizing—in general people recover from that. The real issues are…more complex. More complex than any diagnoses in the DSM can cover. The brain is very complicated, and everyone’s brain is a bit different, and we do not know, really, what goes on in there when you take a drug like Psilocybin. Sometimes something gets a little knocked out of place, and the system doesn’t fully recover.
The last time I took a very high dose of psychedelics I couldn’t think straight for a few weeks after. Thoughts came out of nowhere, I had no control over them; often the constant, unceasing flow of thought was distressing and uncomfortable. Thankfully I could still talk to people—talking made me better. I got plenty of sleep, cut out all drugs, even caffiene, got regular exercise and ate a very healthy diet: about a year and a half later I was back to my old habits. But it wasn’t an easy recovery, and certainly not one any psychiatrist could’ve treated adaquetely. But, now I know to be more careful in the future.
FYI, same goes for SSRIs. The scientific consensus is that the serotonin deficiency theory of depression was wrong. When SSRIs actually work, we still don’t know why.
I’ve had bad trips, too. Very bad, but I still think that psilocybin (in a controlled, supportive setting) is a better bet. My bad trips were all due to being in bad settings and being completely unprepared for what could go wrong. I was young and dumb and just fucking around. But tripping in positive supportive settings was incredibly helpful. And if we do find a way to do this right, then people don’t have to take drugs for the rest of their lives. Psychiatric drugs are generally lifelong sentences, and negative side effects tend to compound over time, which often leads to polypharmacy, and more side effects.
I would know, as my psychedelic mega dose stories are very different from this and also completely unique to me.
I’ve done 500ug of LSD and it was great fun. I scheduled a day off to rest ahead of time and was back to normal after that.
250ug of LSD + 1 full ounce of golden teacher psilocybe cubensis and had a somewhat spiritual experience, took a couple days before I wanted to resume normal life.
+ a dozen or more similar stories
There is a reason why “set and setting” is repeated so heavily when instructing people on how to use these substances. Any discussion of potential subjective benefits or harms of a psychedelic in the context of an experience without specific accounting for that is fundamentally incomplete.
That being said, if my experience sounds ridiculous to you, that’s because it’s unique to me, just as others’ are unique to them. There isn’t really much to be gained by talking about individual experiences other than it’s an entertaining topic of discussion. It gets everybody exactly nowhere closer to establishing the objective clinical value of these things, though.
shrooms feel kind of weak until you get to mega dose territory
I wouldn't recommend a shroom mega dose either, it feels too chaotic to take anything away from
There were indeed some "bad" trips, although I really do not like the term "bad". IMHO there is no bad journey, it is stuff that needs that wants to be seen.
Nor is the journey itself what counts, one cannot expect a quick fix from a 4 or 5 hour journey. What really counts is the preparation (4 to 8 weeks) before, and integration afterwards (again 4 to 8 weeks). In my case I also paired it with years of therapy and meditation.
It takes a lot of courage, especially to continue after an unpleasant experience (fear, grief and loneliness in my case). In my case I kept coming back and allowed myself more and more to let the bad experiences happen. Finally I just learned to be with what is, and accept things and myself the way it all is. With that came a measure of peace and insights I had not experienced before. Along with visions about the structure of existence.
But I'll stress again, just popping a mushroom won't get you there :)
We need to give psychedelics a fair chance, and sure after we can discount them. The article suggests at scale there is potential
As someone who was experienced with psilocybin some 20+ years ago, I always took fairly consistent doses (roughly 3 grams), as I could sense taking much more would be playing with fire. This was pretty much a given amongst my circle of a dozen friends who experienced these trips with me… hero doses were almost never a good or healthy idea. Fun to read about on Erowid though, mostly as cautionary tales.
My time with the substance ended after two bad trips (after a few dozen great ones over a period of 5 years), but neither produced any sort of even minor lasting effect.
Hindsight is 20/20 but often it’s not clear at the time if it’s a bad idea or how bad it can be. I think it’s not such a fair question to someone struggling to find effective treatment for mental health issues to make a mistake on dosing. Especially given both government and medical field have historically not amenable to openly communicating harm reduction or safe guidelines for experimentation with this particular medicine.
The interactions between medications, as well as the patient’s individual response, are hard to predict. These reactions can change over time, too, as bodies and brains adapt, and lifestyles shift.
Yet, you often hear oversimplified statements like "depression means you have too little serotonin," "feeling sluggish means you lack noradrenaline," or "difficulty focusing means you have too little dopamine." These explanations are so reductive that they barely make sense.
The more I read about drug trials, the more I realize how little I — and even many professionals — truly understand about how these medications work and the best way to make informed treatment decisions.
I would like to see some actual data because my assumption has always been that most people have never tried any. I personally have not had any. I have always subscribed to the slippery slope theory of vice.
Me too
Come on over the skiing is great!
I want to touch on this. "You" never have any control of your thoughts, because "you" isn't really a thing. Psychedelics and meditation teach us this if you pay close attention. The thoughts arise from nowhere and we - the imagined, but illusory - self are mere observers along for the ride that is consciousness.
I can imagine that using a substance such a psilocybin could cause your thought patterns to have both short and long term changes in quality (in terms of substance, not of superior gradation), however. It's also possible that your experience led to your paying greater attention to the thoughts that did arise, and over time the feedback loop of consciousness along with taking better care of yourself led to greater moderation of their genesis.
There is voluminous writing in the area of monastic spiritually about this. On the one hand, they affirm that these thoughts aren't chosen, using the vocabulary of sinful thoughts introduced by demons. But it's also clear that change is possible through prayer/meditation (not exactly identical to modern ideas about mindfulness).
No, I stopped mostly after I’d recovered. And I definitely wasn’t “healthier” then, just addled.
I guess people with really bad experiences don’t talk about them as readily as the lucky ones. I don’t know the scale, but there must be some selection bias at work here.
Our selves are not immutable, steady states. Our experiences shape us. It's a lesson learned to guard that carefully and jealously.
Regardless I’ve heard stories of people having severe long term psychological issues from even relatively light doses, simply because of how their body in particular interacted with the drug.
I wrote out a lot more detail for this comment, but pruned to just attempt to make these points 1) generalization here is (generally) not very helpful and also 2) I've come to believe "set, setting, & dosage" are typically listed in that order because that is the order of importance.
“Objection, assuming facts not in evidence”
Evidence based medicine is always better than layman opinions like 'psychedelics are a mental sledgehammer'.
Personally I used psilocybin recreationally back in the days. Got once bad experience and ended up in a psychosis and to hospital. I got better in couple of days and long term effects were nonexistent.
Then I have couple of friends whose basic substances are just legal alcohol and cigarettes, and boy have they fucked their lives with those. It just takes a long time to do it that but psilocybin for sure does not lead to that kind of path.
https://www.frontiersin.org/journals/immunology/articles/10....
The methodology is also kind of strange, the psilocybin group got a total of 20 hours of in-person therapy during their 'treatment' and 6 follow-up skype calls, whereas the SSRI didn't get anything other than the 6 month questionaire. Those 20 hours of personalized therapy while they were dosing had no effect on their psychology? Any change was all a result of the psilocybin and not the 20 hours of therapy?
They also measured results by a self-administered 16 question "quick inventory" depression survey. To enter the study they had to be officially diagnosed with major depression by a doctor, but the results of the study were based completely around a self-reported 16 question questionaire?
They got 'matched' support, which reads to me as 'equivelent': "Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support (‘psilocybin therapy’ or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support (‘escitalopram treatment’ or ET)."
>They also measured results by a self-administered 16 question "quick inventory" depression survey. To enter the study they had to be officially diagnosed with major depression by a doctor, but the results of the study were based completely around a self-reported 16 question questionaire?
This is only the follow up portion, and as secondary measure at 6 weeks. The original study (https://clinicaltrials.gov/study/NCT03429075) says the primary measure was; "Change in blood oxygen level dependent (BOLD) signal during fMRI in response to emotional faces during an emotional faces paradigm done inside the fMRI scanner." at 6 weeks vs baseline.
Statistical significance is based on sample size, and is independent of population size. Let that sink in, doesn't matter if your population is 100K or 8 billion, when you sample you are trying to understand the probabilities in your sample, not in the population.
Therefore, (think about the birthday paradox, doesn't matter how many people in the world, a few dozen in the room with you is an adequate sample), it should not surprise you that statistical significance is achieved through a much smaller sample size than most non-statisticians have intuition for.
This response on the supposed the lack of importance of a sample size is completely wrong on just about every claim. The parent comment had a valid point. Just because a population may fit a certain distribution, does not mean that any given sample size will also fit that distribution. Samples are used to ideally create a representative group of a population, that is smaller than the population. However, the sample size required to come close to a representative distribution can vary between populations and variables being examined. Also, using the birthday paradox is a terrible example and has nothing to do with statistical significance, as the so-called birthday paradox is just a simple function.
It's not, though? Unless you're fine with a very high margin of error... Also the sample in studies like this is hardly ever close to being random anyway.
> it should not surprise you that statistical significance is achieved through a much smaller sample size
Sure... just with a very low confidence level.
Also, what's up with drug studies always having such a low sample size? Is it really that hard to find people who'd volunteer to get free drugs?
They try to make for no comorbidities and and for MDD that is pretty rare. It also means that we’re often studying rare configurations compared to those commonly seen in actual practice. Statistics doesn’t like confounding elements and humans are very confounding. So either you get “bad” statistics, or you get “bad” data. And why you have front line drugs that only have a helpful effect for 33% of people.
Those are design descriptions.
Double blind means that neither patient nor the one administering the treatment knows which is which. Randomized only means that each subject is assigned randomly a treatment group. Controlled trial just means that the study design made sure that other variables that are not under experiment are also under control. Nothing about this preclude actions done to the subjects nor sample sizes.
1: https://slatestarcodex.com/2017/06/05/is-pharma-research-wor...
https://en.wikipedia.org/wiki/Idempotence is the property of certain operations in mathematics and computer science whereby they can be applied multiple times without changing the result beyond the initial application
My few experiences, the first few times, over the course of a year, spread apart by 3-4 months, went from extremely dark to .. just positive, except the last one, where I had no visuals, no bliss at all, and just came to terms with something else in our lives that was going wrong.
The dark ones were rage and anger, and now it seems just gone, like there's nothing there. Like a weight lifted, and seemingly long term.
Congrats on finding a cure for your ailments
However, my personal experience has been that Psilocybin != Psilocybin - the mushroom itself is super important to the process, much like Indica and Sativa have different ways of connecting you to the mind and the aether, Psilocybin (at least for me) VERY much is the same thing, and it's much starker than cannabis is. Getting into woo-woo land here so apologize: I have some concern that just "Psilocybin" isn't a good prescription, that the "spirit" that works on you is unique to the mushroom family, and that both not knowing the mushroom to prescribe and also being clinical about it (Psilocybin vs Mushroom) may not be a good direction to go in to help people with their issues. I also think that about LSD, it might work a bit for a while, but imo it's not the best tool.
A more wholistic approach to health care would be beneficial. For folks looking for more depth or purpose, Psilocybin seems to help reconnect people with a part of themselves they only dimly remember.
I often hear people talk about the risks of psychedelics, which are to be considered, but what’s the risk of doing nothing or withholding the best treatment?
I've commented on this elsewhere, but with psychedelics in particular we wind up in a weird space around our normal approaches to health - for instance, there's a lot of effort right now on finding the chemical mechanisms by which psychedelics affect mood, with the goal of creating substances which have the same impact on depression without the phenomenology of the trip. My suspicion is the trip is the treatment, or at least part of it - that the experience of being in an entirely different mindstate, of reacting to the world in a fundamentally different way using different mental pathways for several hours - is a core part of the treatment. Medicine has a bad habit of ignoring the patient's lived experience - to look at the patient broadly as a mechanism, and particularly as a collection of mechanisms, and to see things like hypertension* as something to be treated with a chemical offset and not a reflection of the full factors of a person's life. My hope is that the psychedelics will help us recognize a paradigm shift here (like, in data leading to changes in practice, not just in their normal way), but I think they've still got too much of the taint of the hippie on them to really be taken seriously.
* I'm using hypertension as just an example of a particular ailment, I'm not making a statement on the treatment hypertension in particular.
Maybe. My personal experience has been that those "negative symptoms" were in fact the entire disorder. I didn't need purpose or depth. I needed to not be so sad that I couldn't function. I needed to be able to hold a coherent thought for 5 minutes without getting stuck into a negative spiral of self loathing.
I want "purpose" and "connection", but those things are what everybody on earth are looking for. The search for those things is the _stuff_ that life is made of. I needed help to get back to a place where I could pursue those things. Pursuing them is my life.
The risk is to make things worse.
And I know that I am preaching to people that are of the opinion that they know better than the FDA, scientists and doctors and are all for self-medicating based off of the echo chamber here and a few cherry-picked, limited and flawed by default (like in the case of this one) studies on the first page of Google.
That risk exists in many medical interventions. We need to quantify that risk and weigh it against the chances of making things better.
Which is more dangerous?
Anyone can have a horrible response with too high of a dose yet with self-medicating theres no sure way to know the amount of medicine you’ve ingested even if weighing.
> 'He added a word of caution for therapists that "psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this."
The long-term consequences of trying to avoid such issues seem considerable, e.g. it might lead to schizophrenia if people try to wall off parts of their memories they find intolerable, though that's just speculation at this point.
Is there science behind this statement?
From what I know, we understanding psychedelics work. We don’t know precisely how.
Seeing mushroom extracts with all the alkaloids included besides psilocybin at gas stations may be a temporary point of stability until I can go to the "21+" store in 2030 to get my preferred arylcyclohexylamine and phenylethylamine variant.
Also, Peter Gasser, a Swiss therapist acquainted with LSD during the 1988-1993 window, was granted approval to carry out the first controlled study of LSD-assisted psychotherapy in more than 40 years. [1]
[0] https://www.swissinfo.ch/eng/science/can-psychedelics-therap...
[1] https://theswisstimes.ch/lsd-and-magic-mushrooms-how-switzer...
https://www.oregon.gov/oha/ph/preventionwellness/pages/psilo...
I've literally walked down Portland and had random homeless people unprompted yell out "Want to buy some shrooms?"
There have been unlicensed openly practicing shrooms businesses which survived far longer than one would expect for such a "regulated" industry.
That being said, there are a number of studies that suggest this is an effective treatment, so I hope this can become more available to those who need it. However, for treatment resistant depression (especially with a catatonia component), intranasal ketamine is very hard to beat. Only topped by ECT in my experience.
This is already a problem for most psychiatric drug trials; studies have found that most people can tell if they’re on an SSRI or in a control group, since the side effects are pretty noticeable.
There is evidence that this skews study results, to the point that some scientists believe that SSRIs may only be “effective” because the obvious side effects make them a good active placebo.
I can see such unreasonable objections being used to prevent it's approval though.
Seems spurious as:
- 1) how do you reliably measure "people could tell"?;
- 2) if people sensed it, likely they can sense when they are on active in a whole range of effective medicines, so seems a biased / moved-goalpost application of the "rules";
- 3) what does it matter if the strength of the drug effect is greater than the strength of the placebo? Ie, surely they can model and subtract and control, so what does it matter if the actual effect is more than placebo?
Ugh...
With the after-glow lasting weeks however, it seems to facilitate/allow a period of self-reflection (using whatever else possibly as an aide) that is notably absent of self-pity.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5...
This statemwnt is true for the people I know who have used it in a recreational manner. This statement is also false for the people I who who have self-treated with it in a controlled setting.
The people in this thread saying things like, "they wear off" or dismissing clinical treatment for depression as "suits ripping people off" are delusional and embodying bad stereotypes. Just because you and your bros took mushrooms, had a few laughs and carried on "working hard on saas" or even had a beneficial, religious-type experience doesn't mean that there aren't also risks or that everyone will have a similarly beneficial experience. It's been known for decades -- both empirically and scientifically -- that psychoactive substances can surface latent or bring about psychological issues (e.g. cannabis and schizophrenia) in some people.
Now, I'm not against use of these substances medicinally or recreationally but to pretend like there is no risk and that they're a one-size-fits-all miracle cure is reckless, naive and dumb. As mushrooms and cannabis become more widely available and more powerful (in the latter case), I suspect we'll be hearing a lot more about this class of issues in the coming years.
Overdosing on SSRIs or using them haphazardly could be pretty detrimental too.
> Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to 'let go', or breathing exercises. The important part is the integration work that comes afterwards," Barba added. [...]
> However, [Rucker] noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants
This is a problem with SSRIs as well; studies have found most people can correctly guess if they’re in the study group or control group.
A true double blind study would require a drug that has similar side effects via an unrelated mechanism, but nobody has attempted that as far as I’m aware.
There was this interesting one though where they deceived patients into believing they were taking an “active placebo” instead of an SSRI, and found that the benefits went away, which is very interesting and raises a lot of questions about the true efficacy of these medications: https://www.nature.com/articles/s41398-021-01682-3.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/
I guess maybe it doesn’t even matter in the end as long as people feel better.
If what they discovered is a particularly powerful way of applying a placebo effect, that could be just as clinically useful. Maybe more so since it could apply to more conditions.
You don't need to. It doesn't really matter whether it's the trip itself that works, the belief that a trip will work, or some other aspect of the molecule. The drug category it's being compared to also has its own placebo effects. It is entirely reasonable to compare the complete holistic experience of taking each.
I rarely see this discussed. I'm not sure why (short of actual cellular test showing it was the drug that did triggered the success some of the success even in the group taking the real meds is still the placebo effect).
Edit: found it https://www.astralcodexten.com/p/does-anaesthesia-prove-keta...
I couldn't disagree more.
Your good friend most likely doesn't have the slightest idea how to handle things if your trip goes south. Especially when they're on their own "ride". That's not to disparage anyone, but just to state the fact that there is training around these things that comes from lots of experience.
And therapists are not "some guy in a suit doing it for the money". You don't get rich doing psychotherapy -- you do it because you genuinely want to help people. And never in my life have I seen a therapist in a suit.
This isn't to say that every therapist is great or that every friend is terrible -- just that the relative success rates of being able to help someone on a bad trip, both during and after, are going to be a lot higher on the side of trained therapists. Because of the training.
Yes they can, everyone experienced can. It's part of having empathy.
>Especially when they're on their own "ride".
The trip sitter doesn't trip while sitting.
It’s a lot harder to accurately dose in its natural form though.
Individual doctors may or may not have this view. I'm talking about "the system." Just consider the incentives. That tells you all you need to know.
If medicine was an honorable industry in the USA the might be more faith.
People worry about various side-effects: I work extremely hard and know others who have done psychedelics and continue with b2b saas and similar.
That said, it’s serious stuff. I think it permanently increased the amount that I like music; other studies show longtitudinal changes to big-five personality traits. Proceed with caution.
For frequency, that depends on a variety of factors I suppose.
Some people are tempted to push the dosage so far as they can take it to experience "ego death", and I don't think that's necessary for therapeutic effects. Not quite sure how safe it is to push the dosage as high as you can either. There's some kind of esoteric belief in some circles that you'll get some magic enlightenment, connecting with another realm if you trip hard enough, but imo that mostly attracts people who already have fragile mental health.
A practical approach is to take about 1.25 grams of dried cubensis, wait about an hour to see how you feel, then try another 0.5 grams if you're up for it, and then another 0.5 in half an hour. By that point you'll have ingested enough to notice effects for sure, and you'll have confidence what your personal right dose is.
Beware of tryptamine tolerance: wait 2 weeks between doses to reset your sensitivity.
Each mushroom contains a different amount of psilocybin. You can calibrate a batch by grinding them all up at once in a coffee grinder and trying a sample. (Always be careful taking powdered mushrooms that someone else has ground up, because you don't know whether anything else has been mixed in.)
Also look up "lemon tek" to prevent tummy upset.
So like pharmaceuticals, you figure out your goals, go with something in the range that works for most people. It doesn't hurt to start very small (0.25g), which some people do every day. There's a lot of variables including strains and even when/what you ate last, where you are in any kind of hormone swing (men have them too), so trial and error is about as best we can get for now (recreationally). This is why I'm really excited by these new pharmaceuticals.
>Post-SSRI sexual dysfunction (PSSD)[62][63] refers to a set of symptoms reported by some people who have taken SSRIs or other serotonin reuptake-inhibiting (SRI) drugs, in which sexual dysfunction symptoms persist for at least three months[64][65][66] after ceasing to take the drug. The status of PSSD as a legitimate and distinct pathology is contentious; several researchers have proposed that it should be recognized as a separate phenomenon from more common SSRI side effects.[67]
>The reported symptoms of PSSD include reduced sexual desire or arousal, erectile dysfunction in males or loss of vaginal lubrication in females, difficulty having an orgasm or loss of pleasurable sensation associated with orgasm, and a reduction or loss of sensitivity in the genitals or other erogenous zones. Additional non-sexual symptoms are also commonly described, including emotional numbing, anhedonia, depersonalization or derealization, and cognitive impairment.[64][68] The duration of PSSD symptoms appears to vary among patients, with some cases resolving in months and others in years or decades;
At least, the mushroom didn't steal my mojo
I've since gotten all my hormones tested (normal), and doctors are suggesting I cycle between TRT HCG & Clomid + Dopamine Agonists
I don't have ED. My symptoms are purely genital numbness/anorgasmia/failure to finish.
I submitted a complaint to the FDA last year. I understand they're currently being sued over this.
I don't understand how SSRIs aren't classified as reproductive toxins.
https://www.reddit.com/r/pssdhealing/comments/10tjyen/a_trea...
An ironclad rule for medically approved drugs is that no fun is allowed - approved drugs must not have any positive effects on mood or well-being or must come with such heavy side effects that no sane healthy person would willingly take them.
For some reason, the medical profession considers the enhancement of one's quality of life beyond some arbitrarily chosen 'healthy' baseline to be forbidden, and is in cahoots with the executive branch to gatekeep it at all costs.
This is all due to scientists having to obscure what they are doing to ameliorate the “don’t clone animals or build nuclear reactors” types.
See the majority on the planet are intolerant religious groups. God has a natural plan types. We’re not to muck with it and to get jobs working for the rich God hand picked.
So we had to invent jobs synthesizing drugs to get around stupid religion and the politics the religious controlled. And those innumerate politicians saw it as a way to make up a political agenda.
There’s a whole lot going on in tech and science that’s just dumb jobs role play. Most of it just normalizing the math of relativity as physical science has bounded human story. Whole lot of people freaking out at that.
System is falling apart with generational churn as experience is not evenly distributed; new people never experienced the past highs and feel the demands to not just use shrooms is corny af since no such ban really exists, it was just social paranoia of a prior generation.
Working as a clinical psychologist, who also reads a lot of research, this study is just another brick in the wall that I am banging my head against when it comes to doing actual evidence-based therapy. I actually read the entire paper and the pre-registration. The title on Medscape and the article are, to me, completely reading the research wrong, and just another example of the actual research design and findings living in a different universe than the press release and subsequent discussion.
Let me try to communicate why I feel this way by summarizing the research in my way, as opposed to the title: "Psilocybin Bests SSRI for Major Depression in First Long-Term Comparison."
Hers my take: Research finds no significant difference between psilocybin and SSRI in the primary outcome from pre-registration (self-reported depression on an emailed form), even when only administering SSRI for 6 weeks, where the maximum effect of SSRI is expected at 12 weeks. As such, this does not even qualify as standard treatment with SSRI. This is after excluding 90% of the applicants for the study. The effectiveness is primary supported by p-hacking, as seen by reporting additional measures not in the registered, where some of them favor psilocybin. And SSRI actually scores BETTER in the main outcome.
Now, someone might come along and call me cynical, mistaken, or worse. But having been through this with biofeedback, metacognitive therapy, light therapy, mindfulness therapy, and ketamine treatment already, I can clearly see the same pattern: lying by omission, p-hacking, not taking into account the "decline effect," borderline acceptable results. It all culminates in a big nothingburger, and any progress for my field remains stagnant. Based on the quality of this study, I am certain that if we just aggressively started treating depression with psilocybin, I just know that it wouldn't make much difference, because I have been through it before with the exact same numbers and effect sizes, just different treatment modalities.
Here is the best indication I found for SSRI: Resistant phobic anxiety (panic attacks that don't stop even after long exposure), and burnout-related depression (person worked normally their whole life but is suddenly just empty of energy and does not look forward to anything with joy). These are examples that very often make a big difference with SSRI, in conjunction with therapy.
Psilocybin seems to work best for existential depression and anxiety that is driven by pathological self-focus (not egotism, but inability to stop focusing on one's own inner states).
But these personal theories are just that, and the studies that keep getting funding are very seldom useful, at least for me, as I genuinely am trying my best to help my patients.
Is there any rigorous operationalization of these concepts, that might be explored in further studies? Unless one can be found, these fuzzy, heavily qualitative descriptions are unlikely to be helpful for future researchers.
We are successfully treating people with this exact kind of indication/operationalization with real success already. For instance, the indication criteria for ECT basically follow the "burnout profile" I described above, with the addition of "treatment resistant to therapy and medication," and it has shown by far the best effectiveness for that kind of depression.
I completely disagree that it's not possible to operationalize the concepts above, for instance with standard BDI or MADRS, supplemented with a ratio with a cutoff to indicate a large fall in everyday functioning. Like an extremely large fall in Global Functioning Scale (GAF) localized to a distinct and pattern-breaking period in a person's life. If you think that these concepts are fuzzy and qualitative, I really hope you have even greater criticism towards this study, not to speak of concepts like anxiety, trauma, and ADHD, which are completely off the rails when it comes to diffuseness and subjectivity.
But even if you are right, that burnout-depression and existential anxiety are not possible to study because of their vagueness, it still would not make this study helpful as it's presented. Or am I mistaken? Do you think it's a good and helpful study, whose implications I should fight for in our clinic? And would I see a marked improvement in our patients, compared to SSRIs for the "Depression" group?
I am willing to admit I am wrong. The only goal is to actually help people.
Maybe it would be more productive to base diagnosis on some kind of brain imaging.
My only bad trip was in a proper, controlled therapy setting — at least that’s how it was presented to me.
Not even getting into the side-effects of SSRIs including PSSD, brain zaps, lethargy, and a whole lot more.
I just don't understand people who do this shit recreationally, as it was quite possibly the worst experience I had in my life.
It's an incredibly scary experience that makes you feel like you're disintegrating in a metaphysical sense. Your mind, perception, body. Yourself. Like you're falling apart, being disassembled and that you will never be able to get yourself together again. You have no agency. And then you are gone. I believe this is what they call "ego death".
And then after you're gone, you're left with all these pieces of yourself. Including a lot of them that you forgot ever existed. Or how they fit together. Or some that you were subconsciously aware of but never perceived them. Like opening a shelf of Legos from your childhood. It's very dream-like.
Then comes the awareness, understanding and grief. I've never cried as much in my life, and I'm not a crying person.
Then comes hope.
And you get to assemble yourself back again. Feels like something between waking up, coming back to reality and a chain-reaction of those "AHA!" moments.
And then you're back, but you're not the same, and you understand more about yourself.
While the next few months were some of the best I had in decades, I'm extremely averse to repeating this experience, as it feels really traumatic.
I was in a controlled, safe, although not a clinical environment, and I am terribly aware how much this can fuck your brain up in ways I can probably never imagine. We have no idea how this machine works and this is basically decompiling an incredibly complex binary during execution, moving code around, recompiling, and hoping it works.
2021: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...
2022: https://www.jwatch.org/na55225/2022/08/16/antidepressants-wo...
2023: https://www.nature.com/articles/s41380-022-01661-0
In any case, I believe that ADHD, Depression and many other “umbrella” psychiatric diagnoses are being overdiagnosed, much like “hysteria” was for hundreds of years (eg 1 in 4 middle-aged women is on antidepressants now, and the opioid epidemic in men was largely exacerbated by the pharma industry, as has the overdiagnosis of ADHD prescribing amphetamines to kids).
To be fair, the actual incidence of phychiatric conditions from ADHD to autism to depression has increased, as well as autoimmune disorders, diabetes etc. although not as much as the pharma industry wants us to believe. It could very well be the result of upstream changes in nutrition (eg wild increases in sugars like fructose across the board, antibiotic overuse on factory farms, buildup of microplastics everywhere etc.), and to a large degree society (including loneliness, dating, relationships, work, etc) and medicating them downstream (eg with amphetamines or opioids) is just a bandaid.
Late stage capitalism has had a direct role in exacerbating this. For example, the tech industry (which many on HN are involved in) has redefined dating, relationships, job searches, political discourse, and much more. All of these affect how people interact. A seminal book even back in 2001 was “Bowling Alone” by Robert Putnam, who noticed Americans aren’t attending communal activities like they used to. Corporations have co-opted many movements (like women’s lib) to make people work harder, neglect their kids, eat unhealthy food, become obese, develop diabetes, lose sleep, and now be part of the gig economy etc.
I like to show this Cadillac commercial from 2014 as a great example of the corporate brainwashing: https://www.youtube.com/watch?v=xNzXze5Yza8
Funny thing is that you can make the arguments that many of those behaviors are actually adaptation to the environment and may sometimes be the future of humanity. That do not please the productivistes who want to extract as much value of every individual as possible, like we do with cattle.
Now they are some very crazy people out there but it's a very small part of the population and you can often trace the problem back to genetics or physical impairement (environmental or else). Solving that sort of thing with drugs or therapy is basically wishful thinking, but it makes money so I guess that's ok...
As far as I can tell the whole field of psychology/psychiatry is basically just one step removed from full on charlatanism. We can learn some stuff about people's behavior, take some moral judgment about what's good or not (changes with time as well as political viewpoint) but the drive to specifically categorize is a bit crazy in itself...
My chronic depression is mostly gone, but I have noticed an uptick in physiological signs of anxiety (though no mental signs).
But more importantly, my gut health is better than it has been in 12 years. I am eating more and losing weight. My energy levels have skyrocketed. My impulsiveness has catered so hard that I was worried my libido was impacted. My executive function issues and ADHD are greatly minimized.
All from a supplement. Utterly life changing.
https://www.mayoclinic.org/diseases-conditions/depression/in...
Also, SSRI can definitely kill your sex life - and by extension your relationship(s) as well. And not just short-term (physiological changes have been observed). SSRIs have never been the best option (except for pharmaceutical companies).
From my personal experience, SSRI (zoloft) felt like a temporary coffee-like stimulant. Psilocybin (or easier to handle synthetic analog 4-aco-dmt) provided short-acting relief from depression and some new perspectives. But ketamine is truly a magic pill if done right. After glow is about a month, and the trip takes 2-3 hrs max. FDA-approved, see Spravato. I feel like at some point ketamine therapy at scale would make SSRIs obsolete, it's just better and faster.
https://www.thelancet.com/action/showPdf?pii=S2589-5370%2824...
Study design and methods:
> "All the patients provided written informed consent and after discontinuing any pre-trial antidepressants, enrollees received two oral doses of psilocybin (1 mg or 25 mg) with accompaniment from two experienced therapists for ∼6–8 h, separated by 3 weeks, as well as daily pills (escitalopram 10–20 mg or placebo capsules). Thirty patients were randomised to PT and 29 to ET."
> 'The PT condition consisted of two high-dose (25 mg) treatment sessions with the serotonergic psychedelic psilocybin, administered with support from two study therapists...and daily placebo capsules. The ET condition consisted of daily doses of the selective serotonin reuptake inhibitor (SSRI) escitalopram - 10 mg for three weeks followed by 20 mg for a further three weeks—as well as equivalent psychological support including dosing sessions with placebo-like doses of psilocybin (1 mg)."
This is an interesting way to address the placebo issue, giving a noticeable microdose of psilocybin (1 mg) versus the active dose (25 mg) for the non-control group.
Fundamentally I think psilocybin's main overall psychological effect is to push subconscious issues up into the mind's conscious processing space. Large doses can generate visual hallucinations related to those subconscious issues which can be unpleasant, even terrifying, for many people, so that's why caution is warranted. Extremely large doses cause complete dissociation from external sensory input, which is of course very dangerous for the unprepared individual in an uncontrolled situation - an experience unlikely for any herbivore to want to repeat, hence the evolutionary selection pressure for biosynthesis of such compounds by plants and fungi.
Great idea to compare a new trendy treatment with promise of potential financial windfalls to another treatment that barely works. If you kept feeding them cocaine under medical supervision, they'd probably report feeling slightly better, too. They're recreational drugs. People take them because they feel good. The most common symptom of depression is to take refuge in drug consumption.
Shrooms sadly do not agree with my digestive system.
Bio:
- Late 30s.
- Long history of depression my entire life. "Melancholic" child. Bad drunk teenager. Suicidal in college (failed attempt).
- No drugs except alcohol until I was in my mid 20s.
I've been prone to major bouts of depression my entire life. I went to therapy multiple times a week for years and got on SSRI's towards the end of university as a response to a failed (but serious) suicide attempt.
SSRI's never did anything for me except make me feel like shit (and not be able to take one). Eventually I went off them and sort of got by, and I managed to stay safe by drinking no alcohol. Therapy twice a week was an utter waste of time and money.
Then, sort of on a whim, I grew some mushrooms at home with my then fiancée and we took them together. I was mid 20s and had no prior experience with any drug but alcohol. Not knowing what I was doing, we took a BIG dose. I had a trip that was fun at first and then became quite unenjoyable.
For the next twelve months I felt like myself again. The change was subtle but, over a long term, quite obvious.
After about 18 to 24 months, my depression came back. We took mushrooms again and the same thing happened. A year of well being in exhcange for 2 fun hours and 6 tough ones.
So about every two years I'll take a big (2-4g dry) dose of mushrooms and...it's like magic. I feel like myself again. I'm "back." Life is not happy, none of my problems go away, but I feel like I'm an agent in my own life as opposed to a spectator.
The well being lasts about a year or 18 months (less if I've been drinking alcohol). It's almost never as bad as when I was suicidal, but it still sucks. For me depression is like being a professional chef and one day your taste buds make everything taste like ash. Or a painter and one day you see colors less and less.
Last year I went into a VERY deep depression, so deep that I refused to take mushrooms until my wife basically forced me to. Same thing. The very next day I felt like "I was back."
Those things changed my life.
I've since had fun with other drugs maybe 5 times. Acid a couple times, molly a couple times. Cheap (wtf) fun for a half a day, but nothing like the impact mushrooms have on my mind.
I've had one bad trip while taking mushrooms recreationally. I don't understand who would take those things for fun, at night.
Strictly during the day, well-rested, with loved ones, and in nature!
I'm also convinced that the impact they have on me is purely chemical. It has nothing to do with "facing my demons" or "connecting with a higher spirit" or anything like that. I just get off my stupid rut.
"Neurons that fire together wire together" as they say, and when I'm depressed it's the stupid neurons that fire together. Mushrooms makes a whole different set fire, and fire hard, and that seems to be enough.
The deepeest lesson I've gotten while on shrooms is:
"I'm trying my best. Everything is actually fine."
Pretty good lesson.
"How to Change Your Mind" by Michael Pollan
There's also a Netflix doc series based on the book.
one time much later i was in the hospital because i had a bad fever. maybe i was being kind of paranoid for going in. but as i was laying in the hospital bed my fever suddenly broke. and a wave of intense depression, unmistakable, washed over me. i thought this might be turning into an emergency but soon enough it passed as if nothing had happened. it was very useful to know about the connection between inflammation and depression during that little journey.
why is the connection between inflammation and various psychiatric diseases not taken seriously by the medical establishment? because its too complicated of a subsystem for a statistical study to tease it out. even if it were the sole cause of depression it still wouldnt lend itself to any study that is not exploring directly the biochemical mechanism. expect some breakthroughs in this area.
The primary outcome of depression symptoms (QIDS-SR-16) was not significantly different between the groups. The sample size is small and unrepresentative of the real-world population of depression patients - the trial participants are very disproportionately male and university-educated. There are obvious and much-discussed issues with blinding in psychedelic trials.
These results point to a treatment that may be superior to treatment-as-usual for a minority of patients, but the results certainly aren't revolutionary. There is still the potential for significant risk in wider clinical populations who may have psychiatric comorbidities that would exclude them from trials like this, and in delivering psychedelic treatments in more normal clinical settings that are likely to be far less carefully controlled than a clinical trial.
