The abstract spells it out: "This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions."
They are comparing the effectiveness of SSRIs and psilocybin on depression by analyzing brain activity and the response to faces with different emotions (both agents work on serotonin receptors). Their conclusion is that while SSRIs lessens reaction to negative emotions, while psilocybin helps people think through their reactions. They conclude “Psilocybin represents a novel intervention for major depression that appears to be safe, rapid and potentially enduring in its antidepressant action.”
The last sentence of the abstract does a good job of this:
>"Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions."
This hypothesis was borne out in the data produced by the experiment.
Essentially, they were able to increase empathy in their patients which enabled the patients to experience less isolation, thus relieving (some/most of) their depression.
Sounds like an alternative might then be loving kindness meditation which is basically a mental workout plan for opening up and feeling kindness to yourself, other people, and human experience in general.
While researching microdosing last year I learned that psilocybin and SSRIs have similar mechanisms of action, so I’m very happy they did this research. Anti-depressants are very popular drugs, and psychedelics have been suppressed culturally and legally, much like marijuana. I think there is definitely a place for ‘medicinal mushrooms ‘. Like MDMA, it’s an amazing substance psychologically.
> psilocybin and SSRIs have similar mechanisms of action
This is incorrect. An SSRI is a selective serotonin reuptake inhibitor[1]. It works through decreasing the reuptake of serotonin from the synaptic cleft back into the presynaptic cell, effectively increasing utilization of existing serotonin. It has limited short-term psychoactive side-effects compared to psilocybin, which is mostly a powerful agonist of certain serotonin receptors and can have considerable psychoactive effects[2]. You can't really "trip" from an antidepressant, but you definitely can from psilocybin.
Also just so you know, while MDMA has promise in certain psychological issues, it is also neurotoxic when used regularly and can cause some severe long-term problems[3]. It's an interesting drug for sure, but just claiming it's "amazing" is being reductionist.
Similar as in 'act on serotonin', which is close enough for me and most people. Like the article says, they actually have somewhat of an opposite mechanism. Thanks for the details.
Your analysis of SSRIs is detailed, but not of psilocybin - saying they make you 'trip' and that's all is a bit reductionist too, wouldn't you say? They do have lasting psychological effects beyond that, and thankfully research such as this is elucidating what those effects are in detail.
By 'amazing', I'm referring to how many researchers, users and therapists refer to properties of, the potential of, and experiences with MDMA, not my own perception, usage or beliefs. I agree that something called 'methylene dioxy methamphetamine' is a serious drug that should be only used under the direction of a professional. As far as safety of long term effects and neurotoxicity, I'd question that about many current, legal prescription drugs such as SSRIs.
> saying they make you 'trip' and that's all is a bit reductionist too, wouldn't you say?
That's not all I said. First I compared the pharmacodynamics of the two(reuptake inhibition leading to better utilization of existing serotonin of SSRI vs direct serotonin receptor agonism of psilocybin), then I compared the psychological effects(fewer acute psychiatric effects in SSRI vs the "trip" of psilocybin). I personally don't believe that's reductionist.
> As far as safety of long term effects and neurotoxicity, I'd question that about many current, legal prescription drugs such as SSRIs.
There may be undiscovered negative effects of drugs like SSRIs, but suggesting that the negative effects of such drugs compare to the already recognized dose-dependent neurotoxic effects of MDMA is a stretch. Its combination of monoamine release and reuptake inhibition causes much more severe neurotoxic effects than SSRIs.
I don't doubt that one would not want to take MDMA daily or regularly, and I doubt it will ever be prescribed or used like that - at least not in recreational doses. Their potential in large doses seems to be in therapeutic intervention.
If you know, I'd love to hear more about the mechanisms of psilocybin in the way you described SSRIs - I've done some reading but my understanding is certainly at the layman level.
Hopefully we will see research about related substances that exhibit therapeutic qualities with less toxic drawbacks.
> I'd love to hear more about the mechanisms of psilocybin in the way you described SSRIs
Sure, but keep in mind that 1) I'm just a hobbyist and what I think may be wrong, and 2) most of what I studied was a few years ago, things may have changed since then.
Serotonin is a neurotransmitter that acts upon serotonin(5-HT) receptors. Modification of these receptors by serotonin help control several systems of the brain, many of which are still being researched. Not all serotonin receptors are the same, and those different receptors affect different systems of the body differently, as well as interact with drugs differently. Examples of these are 5-HT1A, 5-HT2A, 5-HT2B, and many many others.
Psilocybin partially activates(aka partially agonizes[1]) several serotonin receptors, mostly 5-HT2B and 5-HT2C receptors, but also 5-HT2A. 5-HT2C regulates regulates mood, anxiety, feeding, and reproductive behavior[2], while 5-HT2A links to the visual cortex and orbitofrontal cortex[3]. Agonism of these receptors modifies those systems they're linked to, causing emotional, behavioral, and visuospacial changes.
Note how different this is from an SSRI. SSRIs basically increase existing serotonin, while this drug activates the receptors of the brain itself.
A big reason psilocybin isn't physically dangerous(you can't die from OD) is because it's just a partial agonist, meaning it doesn't fully link into the receptor and activate it. There do exist full agonists like 25C-NBOMe that are psychedelic, but are also incredibly dangerous. You can die from those. If you are interested in psychedelics, IMO it's _super_ interesting to read about the history of the 2C generation of drugs.
> but just claiming it's "amazing" is being reductionist.
This seems a bit parochial. The results that MDMA is showing for PTSD can certainly be called "amazing," even when the dangers are taken into consideration. That's why it has been given Breakthrough Therapy designation by FDA. So it seems reasonable to summarize this as "it's an amazing substance psychologically."
evidence indicates that psilocybin with psychological support may be effective for treating depression
On its own, psychological support may be effective for treating depression. If you're depressed, a reasonable starting point for clinical treatment is clinical treatment. The abstract does not suggest that self-medication with magic mushrooms may be effective. Deciding to consume psilocybin on one's own is an orthogonal decision and the study might provide a new rationalization for the practice. But it's just a rationalization for shrooming outside of a clinical setting.
Contemporary clinical practice tends toward conservation of everyone's time. The days of weekly appointments with a Freudian analyst are largely past, if they ever were for anyone other than well off clients who could afford such things. Contemporary clinical practice for treating depression tends toward prescriptions for clinically tested anti-depressants. Many of the mild main stream anti-depressants have moderately positive effects quickly for many people (though not all of them and not for everyone).
Don't get me wrong, if you want to eat mushrooms it's fine by me. Just be clear that the abstract does not indicate clear clinical efficacy in treating depression and the possible evidence it suggests is in conjunction with psychological support. It does not suggest evidence of efficacy as self medication outside of a clinical setting.
On a related topic, a friend of mine with treatment-resistant depression has been undergoing ketamine treatments from a doctor. He says there isn't a dramatic improvement but it helps alleviate catastrophic thinking. The hour-long treatments themselves are relaxing, he says, almost like a trip to a spa. The sessions are expensive, even when partially covered by insurance.
does he do cbt? does he do regular light cardiovascular exercise? does he do mindfulness mediation? all of this has proven effectiveness. sure, try ketamin, but also try the stuff that's known to work
Joins other studies from NYU investigating psilocybin mitigation of anxiety in advanced stage cancer patients. As well as a comprehensive survey by psychiatrists at Johns Hopkins showing 84% of those who tripped describing the experience as somewhat beneficial:
Survey study of challenging experiences after ingesting psilocybin mushrooms
As federal dollars may face a difficult path to providing the funding for psychedelic research. This represents an enormous opportunity for privately funded as well as citizen oriented science. Indeed, MAPS, the Multidisciplinary Association for Psychedelic Studies was just gifted 111 BTC from two free thinking philanthropists as part of its Pinapple Fundraising campaign!
No and most likely there won't be. It is still thought that psychedelics can trigger or worsen schizophrenia in those people - it is certainly possible, though nobody knows - and all studies will try to play it on the safe side and exclude them. Remember these are still Schedule 1 illegal drugs, so anyone trying to get them rescheduled wants to avoid controversy.
I wonder how such drugs can make patient take different treatment options for cancer. My uncle did his best after being diagnosed with terminal cancer, at times he wanted to try things but very often he ended up rejecting ideas.
Anecdotally, one-time use of LSD(which acts similarly to psilocybin, primarily through 5-ht2a agonism) set me on a path to self improvement. I had depression for years during my puberty, teens, and early adulthood. I contemplated suicide regularly and had a pessimistic outlook on life. I dropped out of college in my first semester despite taking and passing multiple AP classes in high school because I didn't see the point of college.
Then I took a large dose of LSD once. It was a very unpleasant experience. The changes weren't immediate, but in the following months, my outlook started to change. I started caring about life again, quit smoking and started exercising, and went back to college. Now, I'm completely drug free, have a wife and a degree, and am optimistic for the future. I wouldn't recommend other people try it, because my experience made me understand why some people go insane from it. I believe, though, that it put me on a path of self-improvement, and should absolutely continue to be studied.
Also anecdotally, I took a fairly large amount of magic mushrooms once, and it was an awful episode that left me with anxiety attacks for many months afterwards.
I saw no life improvement from this experience, and regret having ever dabbled recreationally.
This is why I want more research, but don't necessarily recommend it. "Bad trips" are common enough and can cause a strong enough negative reaction to make its use very risky.
Actually no, the inclusion criteria for this study were major (unipolar) depression and no improvement despite two courses of antidepressants (6 weeks minimum each), I think this is exactly what SSRI are used for.
Which is exactly what I'm talking about, against your original claim that "SSRIs are used to treat a different class of depression" sorry if this wasn't clear enough from my post, English is not my first language.
It's not treatment resistant depression until the other stuff hasn't worked. Treatment resistant depression isn't a more exact diagnosis: it's an admission that the previous diagnosis was wrong, and the disease is a different one, with a different etiology and a different form of treatment - both pharmaceutical and from the standpoint of therapy.
Yes, and the other stuff that didn't work is most of the time SSRI.
Treatment resistant depression is not a class of depression like bipolar or psychotic. It can be any depression that resisted the given treatment - that does not mean that the previous diagnosis was wrong. Exactly like when you diagnose a particular cancer and the the treatment does not work. It's still the same cancer. It has not morphed into something else, it has not jumped to a different type of cell. It just means your treatment options are limited and in this case they didn't work.
This is fascinating as this is the plague of our generation. depression is such a debilitating condition, and in the UK mental health care has fallen to the level where it doesn't really exist outside of prescription medication.
There was an earlier study in the UK [0] which showed similar effects, again on a small sample. The following interested me
> A clinical trial, which took years and significant money to complete due to the stringent regulatory restrictions imposed around the class 1 drug
This seems insane. Lots of other prescription drugs would be illegal for me to buy, why is this reserved for mushrooms that grow in our lawn? It makes me wonder if the real resistance to this research is that an unmodified mushroom medicine would not be patentable, and it would be financially catastrophic to big pharma if people stopped taking their medication and grew their own more effective ones.
I note that many people are concerned about the side effects of magic-mushrooms. Perhaps you could consider that weighed against the side effects of the Seroxat[1] which amongst other things can stop a man reaching orgasm, or stop you dreaming(!) for years after taking it, is addictive and clouds your judgment. It can turn you suicidal or homicidal.
I wont bother to list any of the others and their side effects, but I know I would try the mushrooms first, and I would urge my family to do the same if they needed help.
> It makes me wonder if the real resistance to this research is that an unmodified mushroom medicine would not be patentable, and it would be financially catastrophic to big pharma if people stopped taking their medication and grew their own more effective ones.
Many of the antidepressant and psychoactive/psychedelic effects are caused by 5-ht2a receptor agonism, and many novel 5-ht2a agonists have been made[1], most of which could be patented. The issue is abuse potential. Most of these drugs can be used to "trip," or have a psychedelic experience, meaning it would likely be made illegal very quickly.
> The issue is abuse potential. Most of these drugs can be used to "trip," or have a psychedelic experience, meaning it would likely be made illegal very quickly.
But why is tripping considered abuse? Particularly in cases where overdosing is difficult or impossible (like with marijuana). These requirements just seem asinine.
This is ultimately politics, and it is easy to scare with images of people who behave in entirely unpredictable ways.
One underutilized method to fight this, IMHO, is illustrating how terrible that line of thought is when you can compare it favorably to getting drunk in almost every way—but most of all judgement. Drunk people are already ethical black holes.
Because in the late 60s and 70s, US politicians needed scapegoats to blame for the social unrest, and the psychedelic movement with prominent figureheads like Timothy Leary was an easy target. Demonizing and criminalizing their drugs of choice gave them cause to imprison them and break up their social movements. So campaigns and institutions were established to proselytize the dangers of whatever drugs they were using, and laws were written and regulations established which simultaneously criminalized those drugs. Because the US political system is very slow moving and hard to course-correct, those institutions, regulations, and propaganda continue to this day.
> But why is tripping considered abuse? Particularly in cases where overdosing is difficult or impossible (like with marijuana). These requirements just seem asinine.
It's heavily associated with '60s counterculture in general, and more specifically hippies. Some users were starting to talk about entirely new (to them) kinds of spiritual experiences that didn't fit with Western religious traditions. Prohibition was seen as a valid tool for keeping these "subversive" people under control and blunting their effect on wider society.
To all replied here with "politics" as a reason. How do you explain the fact there are harsh policies in the ex-USSR countries, where no racism existed, no hippies, no minorities to put in jail, etc?
The communist regimes just banned anything which didn't adhere to the new man utopian concept. Blue jeans, males with long hair, narcotics, being gay, being unemployed etc. Alcohol wasn't banned for some reason, although Gorbatchev tried to limit alcohol use and failed.
No racism? In the early USSR, racism was state policy, with people being deported to Siberia or scattered around the USSR in order to dillute their culture. Ukraine was also subjected to genocide through famine, which killed 7-10M people.
Sounds questionable. Many substances with high abuse potential are used by medicine, and alcohol has no medical benefits that I know of but creates loads of problems everywhere I look. I don’t feel like I’m making any non-obvious points.
You can abuse mushrooms if you take them in lower dosages. This keeps the antidepressant effect, but doesn't allow you to trip.
I had done this - nothing bad happened to me, but not suggesting to try this at home. The point still stands though: please don't misinform people around you since that just reinforces the negative agenda around theses substances.
Curious as someone who has considered micro dosing - what would you say the effects of taking the lower dosages repeatedly were that would put it in the 'abuse' category?
It’s the general anti-depressant effect. Over a course of a few days you get used to the fact that your mood is more swingy - that would be “your ups are higher and the downs are lower”.
Now you get used to it, and returning to a less emotional state of mind would be similar to stopping “wake and bake’ing” - there’s no physical dependence, but there’s a routine of keeping yourself more moody every day.
I noticed no effect from microdosing mushrooms (0.5g per day for a few days) but I don't suffer from depression. How long did microdosing take to make a meaningful effect?
A low baseline is common in bipolar disorder, too. It was (and to a lesser but unfortunate degree, still is) very commonly misdiagnosed as depression because of this. It reacts quite differently to drugs than depression; many anti-depressants pose a high suicide risk when taken by bipolar individuals. While the overall effect during depressive periods (which can last years) in bipolar seems the same, it seems to have a different underlying cause. Normally you wouldn’t get cycling that fast, but AFAIK, there is even less research so far about how psilocybin affects bipolar disorder. I’m not trying to diagnose anyone... just something to think about for anyone who thinks they might be suffering from depression. I think I was misdiagnosed for many years, leading to decades of ineffective treatments.
By the way, certain combinations tend to highlight the fact that you have indeed dosed and it’s not placebo: try making a coffee with the same 0.5g dosage and you’d see that the stimulating effect of the coffee is way more expressed at +1H.
The abusive component is where you forget that life isn’t as impressive as it is on shrooms. It gets harder to return to life full of paler colours (or let’s say - you start reacting to the fact, that compared to being a bit high, life isn’t as impressive).
Also don’t forget that there’s next to no studies about long-term (let’s say: microdosing for a month) effect of shrooms.
Currently, there is an application at the European Medicines Agency (EMA) for a large clinical trial of psilocybine therapy for the treatment of otherwise treatment-resistant depression, 400 patients in 8 European countries. As far as I know, it has not yet been approved, but I am optimistic.
It will be trivial to "modify" the mushroom and then put it in pill form, and it will be easy to patent it when they do it. Big pharma will happily make money selling us what we could be growing in our backyards, and there is nothing wrong with that.
Many people with depression, also would like to avoid the trip (especially people who have to work), and if Big Pharma spends millions creating a non psychoactive effective treatment regimen derived from mushrooms, that would be fantastic. And that won't be something we could ever hope to grow in our backyards without the help of the pharmaceutical industry.
To some degree, it absolutely is. At the very least, your reality needs to shift. That's the whole idea of healing depression... there are things in your reality that need shifting.
I'm also sure that psilocybin isn't the only molecule involved. And I'm also sure that if someone isn't ready to take active ownership of their mental health into taking psilocybin could be just as moot as any other substance.
Healing is a deeply embedded, embodied process. If you're experiencing depression, there's probably more than one switch that needs to get flipped on the switchboard, and a lot of dials that need to get retuned, along with habits, beliefs and perspectives that need questioning.
Depression is bred out of dehumanizing norms in belief and habit. You can't just continue to go about practicing the very same things that feed your depression, take a magic pill and suddenly feel well adapted. There's going to have to be profound realization.
That's exactly what a "trip" is. If you don't want to get jarred by your own realizations, you can microdose. You won't "trip" in a heavy sense, but you very well might uncover some painful things you've been neglecting for a very long time. Hopefully then you will do what you've been needing to do for a long time: grieve.
> To some degree, it absolutely is. At the very least, your reality needs to shift. That's the whole idea of healing depression
Hold on now, you're deciding what the mechanism of action is without merit. Consider some of the studies being done for depression with Ketamine. In those studies, they're finding that the psychoactive component isn't the one causing the improvement- just a byproduct of it created during metabolism[0]. Patients can get the same effects by just consuming that metabolite instead without any high or trip.
What this study is finding is that there are specific mental changes after taking psilocybin. It isn't saying anything yet about the mechanism. I'm not saying that your interpretation is wrong, just that it's without any proof beyond your beliefs.
For psilocybin it looks like the more powerful experience means more pronounced and longer lasting therapeutic effect:
"Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience."
https://www.ncbi.nlm.nih.gov/pubmed/29119217
And there are more and more studies about the mechanism of psychedelics such ad psilocybin and LSD coming out, essentially telling the same story.
That's correlation, not causation. What if the more intense experience comes from the same root cause as the more pronounced effect (ie: maybe some people are just wired differently and it has multiple effects?)
More study is needed before we go off saying that the psychedelic experience is the cause of the improvement, in my view.
Yes, my comment is based on reading essentially all the studies that came out during last few years (since about 2008). I am pretty sure there is a causal relationship, but to prove it is a different task (and one that is not strictly needed for medical approval).
You might be right. I think that the "trip" might be necessary, is a solid theory.
But there were many people who thought the same things as you (that psycho activity was necessary) about the positive effects of marijuana. And it turned out that CBD (the non trip version of marijuana) had the same pain relief benefits for a lot of people without the high.
Despite being intensely skeptical of anything veering towards association as causation, I have always insisted that a psilocybin trip when I was 20 years old was overwhelming responsible for a series of achievements and positive changes in my life in the years following.
My lack of words or explanation for this has left me embarrassed to talk about it. Seeing these studies is bringing up a lot of dormant curiosity.
I wouldn't feel bad about this at all. I'm comfortable that there are many very important things that can be understood but cannot be conveyed to others using language. You can tell someone the capital of France, but not what it was like when your child was born, maybe because one is a concept and the other is an experience. I've had a lot of indescribable but very valuable experiences too (LSD).
My anecdotal and totally non scientific experience about 6 months ago with psilocybin is similar to yours, i suspect. A positive trip completely changed my outlook on.. well, everything. It's almost as if I see everything in a different light. Instead of being pessimistic and negative about things (by things, I mean pretty much everything under the sun) I just feel hopeful and positive and thankful instead. I really cannot find enough words to describe how much better I have been feeling. How long will it last? I don't know. While it lasts, I have at least been dealing with things better.
It really is hard to explain. But I think you might know how I feel.
This is a reddit quality comment. On what basis do you justify classifying the treatment as brutal? Or that the dose was high enough that the test subjects underwent ego death? Were you just exaggerating for comic effect and didn't really have anything to add?
have you done them? i would say its a pretty accurate description of my experience. every time ive done them, ive found aspects extremely uncomfortable, but by the end i almost feel a sense of accomplishment. i know people read comments like this and imagine an idiot who is easily swayed by bullshit, so ill offer what i thought of as the most tangible interesting things that comes from taking mushrooms: many things that happen automatically in your brain seem to stop when you take mushrooms. for instance, it was no longer obvious to me what time of day it was, or what day of the week. it was very interesting to experience this, because it had never been something id been without, and it had never even occurred to me as a thing that could not be obvious. so seeing that it was a process like anything else is very eye opening.
You sound very agitated and sensitive about this topic. Have you considered eating several grams of psilocybin mushrooms and involuntarily thinking about how your behavior is or isn't serving you for a few hours? I hear it increases amygdala response!
Quality and humor are not mutually exclusive. I'm experienced enough in this area to be both excited by this study and amused by this tongue-in-cheek characterization of the psychedelic experience. Not only is it worth pointing out that psychedelic experiences can be disorienting or scary as well as benign and thrilling, it may be that much or all of the therapeutic value comes from getting through those negative experiences.
I can vouch for the antidepressant properties of psilocybin, as well as it's nearly miraculous efficacy at stopping cluster headaches.
If any of you are unaware of cluster headaches, they are also called suicide headaches, because the pain is so great that many people just kill themselves. The pain level has few peers, it's been compared to amputation without anaesthetic. For me, the bulk of the sensation is of one of my eyes being crushed while a hot poker is run through it. The cluster part comes from the fact that they occur in clusters that can last weeks, months, or years.
It is debilitating to know that at any moment you could suddenly, and with very little warning, start experiencing the worst pain of your life. I had panic attacks at the first hint of symptoms.
During my last cluster I took mushrooms, and it completely eradicated them. The literature I read said it could stop them for a year, but it's been almost 4 years now and I'm still clear of them. I'd prefer to dose again for peace of mind, but mushrooms are illegal and hard to find.
It was also very nice for my depression, I had an elevated mood for several months.
I wish it was legal, it scares me a lot less than the actual antidepressant medications, and it's the only effective treatment for preventing cluster headaches.
Illegal in most of europe (we banned analogs years ago when the legal drug thing boomed). I am generally not the biggest fan of psychodelic analogs, have had bad experience with some of them. There is a reason real shrooms, acid and DMT are still the king of the scene :) [not entirely true for LSD, as 1P-LSD and AL-LAD are virtually the same as LSD-25]
After the first time I took LSD, I, too, noticed an elevated mood for several weeks afterwards.
I was not depressed at the time - I might have been a little down - but my mood was better - things that used to annoy me now annoyed me much less, while things that used to make me happy made me even happier.
Since LSD and Psilocybin are so similar in their effects, I would not be surprised if the mechanism turns out to be the same.
Now that I think if of it, I remember a mushroom experience when I was maybe 19 or 20 years old, and, at the time, quite unhappy about my life, quite likely even depressed. I did mushrooms with a friend whose parents were on vacation. The trip itself was very depressing. But when I woke up the next morning, I was happier than I had been in months, and that, too, lasted several weeks.
The problem with acid is that you believe everything you think, so be careful what you think :)
Aside from LSD's longer duration[^1] and increased potency[^2] acid also has a dopaminergic action, whereas psilocin[^3] is primarily a serotonergic drug. It is the dopaminergic action that can result in the obsessive quality or "looping" experience of LSD trips.
When you eat magic mushrooms, you are essentially taking yourself for an existential ride by voluntarily staring into the abyss. The trip itself is primarily "weird" and euphoric, but IME, what many people refer to as a "rough trip" is actually the existential rebound that begins 1.5-2 hours in. During this serotonin recoil, you can face the heart of darkness: the realization of all potential simultaneous chaos and creativity.
This state can include a ton of beauty, but also a reminder of your own inevitable demise. This visitation to a more "eternal" mode of thought has the same effect as surviving a face-off with any dangerous unknown: radical personal transformation. Self-knowledge necessarily feeds back into your world-view, thus changing you (usually for the better, but not always).
Nowadays, when I embark on a shroom trip, I do so in the knowledge that I will have to stare into the abyss. Sometimes you have to chew glass while doing so, e.g. a friend enters a psychotic state, or somebody dies and you have to be useful. Nevertheless, you become vulnerable and have the opportunity to learn something, help someone, or be helped and form new relationships.
Advice for brave mushroom eaters:
- be well-rested, preferably in nature
- don't trip alone, but keep it under 6 people
- have music, or an instrument nearby
- don't eat more than you can handle (0.7g is potent. 2.4g is effective. 4g is high. 10g is godlike and dangerous)
[^1]: LSD duration is 8-12 hours. Anything less than 8h is not LSD.
[^2]: psychoactive LSD dose is 25µg and up, hence LSD-25.
[^3]: the primary psychoactive metabolite of psilocybin
I believe the name LSD-25 comes from the active form we know today being the 25th incarnation of whatever substance it was that Hoffman et al were trying to create.
It is incredible to see the pain these individuals go through (sometimes for an hour every two hours - 12 times a day). It is even more impressing how resilient some humans are and the pain they can endure.
Although nowadays I am rather conservative regarding recreative use of entheogenics Azarius ships their growkits seemingly to entire Europe [1]. Anecdata: it is fairly easy to grow champignons and psilos. The kits I used were complete with straightforward guides.
I wrote "psilos" because there is also A. Muscaria, though it has less severe effects care must be taken when plucking food in the wild (and I am unsure if they'd be an option for your specific use case). There are some great guides out there allowing you to distinct species but as Sean Penn's Into The Wild [2] shows one mistake can be fatal. There's a Dutch community on FB about plucking mushrooms in the wild, but its focusing on its culinary usage. As I said, there's also some guides (in the form of books) available.
BTW, do you know if and why psilocybin works (better) than LSD for your use case?
On the legal front I'm less concerned about punishment than I am about convenience. I don't really care to get into growing mushrooms just to have one dose every year or two, just wish I could easily purchase them ready to go.
I actually don't know if psilocybin works better. I was unclear when I said it was the only effective treatment, I just meant psychedelics in general. I actually prefer LSD, but at the time I could only get mushrooms.
According to everything I've read they seem pretty equal for cluster headache treatment.
Oh, and "Into the Wild" definitely made me wary of attempting to identify wild plants to eat.
Honestly, if there are diseases like this- im for a all in approach, every human being free to try whatever might stick.
The thing is, we dont have that one type of humans. We have many - different Neuro-types, and what might be a salvation for one, might send another to a different hell altogether.
I find this problematic not really addressed in most studies. Thus i take them with a grain of salt that is- find out first, via a independet third observer, whether you are a similar type of neuro-type to the one who recived the mircale cure.
Last but not least:
Be aware that some drugs might prevent negative experience testimony by rendering the person unable to testify. If you are send over the edge and become a schizophrenic living in a cardboard box- you are unlikely to ever testify against the remedy you took.
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[ 4.1 ms ] story [ 191 ms ] thread>"Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions."
This hypothesis was borne out in the data produced by the experiment.
Essentially, they were able to increase empathy in their patients which enabled the patients to experience less isolation, thus relieving (some/most of) their depression.
This is incorrect. An SSRI is a selective serotonin reuptake inhibitor[1]. It works through decreasing the reuptake of serotonin from the synaptic cleft back into the presynaptic cell, effectively increasing utilization of existing serotonin. It has limited short-term psychoactive side-effects compared to psilocybin, which is mostly a powerful agonist of certain serotonin receptors and can have considerable psychoactive effects[2]. You can't really "trip" from an antidepressant, but you definitely can from psilocybin.
Also just so you know, while MDMA has promise in certain psychological issues, it is also neurotoxic when used regularly and can cause some severe long-term problems[3]. It's an interesting drug for sure, but just claiming it's "amazing" is being reductionist.
[1] https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
[2] https://en.wikipedia.org/wiki/Psilocybin#Pharmacology
[3] https://en.wikipedia.org/wiki/MDMA
Your analysis of SSRIs is detailed, but not of psilocybin - saying they make you 'trip' and that's all is a bit reductionist too, wouldn't you say? They do have lasting psychological effects beyond that, and thankfully research such as this is elucidating what those effects are in detail.
By 'amazing', I'm referring to how many researchers, users and therapists refer to properties of, the potential of, and experiences with MDMA, not my own perception, usage or beliefs. I agree that something called 'methylene dioxy methamphetamine' is a serious drug that should be only used under the direction of a professional. As far as safety of long term effects and neurotoxicity, I'd question that about many current, legal prescription drugs such as SSRIs.
That's not all I said. First I compared the pharmacodynamics of the two(reuptake inhibition leading to better utilization of existing serotonin of SSRI vs direct serotonin receptor agonism of psilocybin), then I compared the psychological effects(fewer acute psychiatric effects in SSRI vs the "trip" of psilocybin). I personally don't believe that's reductionist.
> As far as safety of long term effects and neurotoxicity, I'd question that about many current, legal prescription drugs such as SSRIs.
There may be undiscovered negative effects of drugs like SSRIs, but suggesting that the negative effects of such drugs compare to the already recognized dose-dependent neurotoxic effects of MDMA is a stretch. Its combination of monoamine release and reuptake inhibition causes much more severe neurotoxic effects than SSRIs.
If you know, I'd love to hear more about the mechanisms of psilocybin in the way you described SSRIs - I've done some reading but my understanding is certainly at the layman level.
Hopefully we will see research about related substances that exhibit therapeutic qualities with less toxic drawbacks.
Sure, but keep in mind that 1) I'm just a hobbyist and what I think may be wrong, and 2) most of what I studied was a few years ago, things may have changed since then.
Serotonin is a neurotransmitter that acts upon serotonin(5-HT) receptors. Modification of these receptors by serotonin help control several systems of the brain, many of which are still being researched. Not all serotonin receptors are the same, and those different receptors affect different systems of the body differently, as well as interact with drugs differently. Examples of these are 5-HT1A, 5-HT2A, 5-HT2B, and many many others.
Psilocybin partially activates(aka partially agonizes[1]) several serotonin receptors, mostly 5-HT2B and 5-HT2C receptors, but also 5-HT2A. 5-HT2C regulates regulates mood, anxiety, feeding, and reproductive behavior[2], while 5-HT2A links to the visual cortex and orbitofrontal cortex[3]. Agonism of these receptors modifies those systems they're linked to, causing emotional, behavioral, and visuospacial changes.
Note how different this is from an SSRI. SSRIs basically increase existing serotonin, while this drug activates the receptors of the brain itself.
A big reason psilocybin isn't physically dangerous(you can't die from OD) is because it's just a partial agonist, meaning it doesn't fully link into the receptor and activate it. There do exist full agonists like 25C-NBOMe that are psychedelic, but are also incredibly dangerous. You can die from those. If you are interested in psychedelics, IMO it's _super_ interesting to read about the history of the 2C generation of drugs.
[1] https://en.wikipedia.org/wiki/Partial_agonist
[2] https://en.wikipedia.org/wiki/5-HT2C_receptor
[3] https://en.wikipedia.org/wiki/5-HT2A_receptor
[4] https://en.wikipedia.org/wiki/25C-NBOMe
This seems a bit parochial. The results that MDMA is showing for PTSD can certainly be called "amazing," even when the dangers are taken into consideration. That's why it has been given Breakthrough Therapy designation by FDA. So it seems reasonable to summarize this as "it's an amazing substance psychologically."
On its own, psychological support may be effective for treating depression. If you're depressed, a reasonable starting point for clinical treatment is clinical treatment. The abstract does not suggest that self-medication with magic mushrooms may be effective. Deciding to consume psilocybin on one's own is an orthogonal decision and the study might provide a new rationalization for the practice. But it's just a rationalization for shrooming outside of a clinical setting.
Don't get me wrong, if you want to eat mushrooms it's fine by me. Just be clear that the abstract does not indicate clear clinical efficacy in treating depression and the possible evidence it suggests is in conjunction with psychological support. It does not suggest evidence of efficacy as self medication outside of a clinical setting.
Survey study of challenging experiences after ingesting psilocybin mushrooms
http://journals.sagepub.com/doi/full/10.1177/026988111666263...
As federal dollars may face a difficult path to providing the funding for psychedelic research. This represents an enormous opportunity for privately funded as well as citizen oriented science. Indeed, MAPS, the Multidisciplinary Association for Psychedelic Studies was just gifted 111 BTC from two free thinking philanthropists as part of its Pinapple Fundraising campaign!
https://www.maps.org/
Then I took a large dose of LSD once. It was a very unpleasant experience. The changes weren't immediate, but in the following months, my outlook started to change. I started caring about life again, quit smoking and started exercising, and went back to college. Now, I'm completely drug free, have a wife and a degree, and am optimistic for the future. I wouldn't recommend other people try it, because my experience made me understand why some people go insane from it. I believe, though, that it put me on a path of self-improvement, and should absolutely continue to be studied.
I saw no life improvement from this experience, and regret having ever dabbled recreationally.
SSRIs, and their more recent variants, would almost invariably comprise that first and second courses of treatments.
It's not treatment resistant depression until the other stuff hasn't worked. Treatment resistant depression isn't a more exact diagnosis: it's an admission that the previous diagnosis was wrong, and the disease is a different one, with a different etiology and a different form of treatment - both pharmaceutical and from the standpoint of therapy.
Treatment resistant depression is not a class of depression like bipolar or psychotic. It can be any depression that resisted the given treatment - that does not mean that the previous diagnosis was wrong. Exactly like when you diagnose a particular cancer and the the treatment does not work. It's still the same cancer. It has not morphed into something else, it has not jumped to a different type of cell. It just means your treatment options are limited and in this case they didn't work.
There was an earlier study in the UK [0] which showed similar effects, again on a small sample. The following interested me
> A clinical trial, which took years and significant money to complete due to the stringent regulatory restrictions imposed around the class 1 drug
This seems insane. Lots of other prescription drugs would be illegal for me to buy, why is this reserved for mushrooms that grow in our lawn? It makes me wonder if the real resistance to this research is that an unmodified mushroom medicine would not be patentable, and it would be financially catastrophic to big pharma if people stopped taking their medication and grew their own more effective ones.
I note that many people are concerned about the side effects of magic-mushrooms. Perhaps you could consider that weighed against the side effects of the Seroxat[1] which amongst other things can stop a man reaching orgasm, or stop you dreaming(!) for years after taking it, is addictive and clouds your judgment. It can turn you suicidal or homicidal.
I wont bother to list any of the others and their side effects, but I know I would try the mushrooms first, and I would urge my family to do the same if they needed help.
[0]https://www.theguardian.com/science/2016/may/17/magic-mushro... [1]https://www.theguardian.com/uk/2001/jun/11/highereducation.m...
Many of the antidepressant and psychoactive/psychedelic effects are caused by 5-ht2a receptor agonism, and many novel 5-ht2a agonists have been made[1], most of which could be patented. The issue is abuse potential. Most of these drugs can be used to "trip," or have a psychedelic experience, meaning it would likely be made illegal very quickly.
[1] https://en.wikipedia.org/wiki/5-HT2A_receptor#Agonists
But why is tripping considered abuse? Particularly in cases where overdosing is difficult or impossible (like with marijuana). These requirements just seem asinine.
One underutilized method to fight this, IMHO, is illustrating how terrible that line of thought is when you can compare it favorably to getting drunk in almost every way—but most of all judgement. Drunk people are already ethical black holes.
It's heavily associated with '60s counterculture in general, and more specifically hippies. Some users were starting to talk about entirely new (to them) kinds of spiritual experiences that didn't fit with Western religious traditions. Prohibition was seen as a valid tool for keeping these "subversive" people under control and blunting their effect on wider society.
No racism? In the early USSR, racism was state policy, with people being deported to Siberia or scattered around the USSR in order to dillute their culture. Ukraine was also subjected to genocide through famine, which killed 7-10M people.
I had done this - nothing bad happened to me, but not suggesting to try this at home. The point still stands though: please don't misinform people around you since that just reinforces the negative agenda around theses substances.
Now you get used to it, and returning to a less emotional state of mind would be similar to stopping “wake and bake’ing” - there’s no physical dependence, but there’s a routine of keeping yourself more moody every day.
But in my case I would be dosing 0.5g several times a day over the course of three days; knowing that the effect keeps for around 3 hours at +1H.
On the other hand at that point of time I did suffer from depression and they would kick me out of the relatively low-peak baseline.
I have repeated this a few times.
Also don’t forget that there’s next to no studies about long-term (let’s say: microdosing for a month) effect of shrooms.
http://www.appliedclinicaltrialsonline.com/compass-pathways-...
Many people with depression, also would like to avoid the trip (especially people who have to work), and if Big Pharma spends millions creating a non psychoactive effective treatment regimen derived from mushrooms, that would be fantastic. And that won't be something we could ever hope to grow in our backyards without the help of the pharmaceutical industry.
I'm also sure that psilocybin isn't the only molecule involved. And I'm also sure that if someone isn't ready to take active ownership of their mental health into taking psilocybin could be just as moot as any other substance.
Healing is a deeply embedded, embodied process. If you're experiencing depression, there's probably more than one switch that needs to get flipped on the switchboard, and a lot of dials that need to get retuned, along with habits, beliefs and perspectives that need questioning.
Depression is bred out of dehumanizing norms in belief and habit. You can't just continue to go about practicing the very same things that feed your depression, take a magic pill and suddenly feel well adapted. There's going to have to be profound realization.
That's exactly what a "trip" is. If you don't want to get jarred by your own realizations, you can microdose. You won't "trip" in a heavy sense, but you very well might uncover some painful things you've been neglecting for a very long time. Hopefully then you will do what you've been needing to do for a long time: grieve.
Hold on now, you're deciding what the mechanism of action is without merit. Consider some of the studies being done for depression with Ketamine. In those studies, they're finding that the psychoactive component isn't the one causing the improvement- just a byproduct of it created during metabolism[0]. Patients can get the same effects by just consuming that metabolite instead without any high or trip.
What this study is finding is that there are specific mental changes after taking psilocybin. It isn't saying anything yet about the mechanism. I'm not saying that your interpretation is wrong, just that it's without any proof beyond your beliefs.
[0]https://www.nimh.nih.gov/news/science-news/2016/ketamine-lif...
And there are more and more studies about the mechanism of psychedelics such ad psilocybin and LSD coming out, essentially telling the same story.
More study is needed before we go off saying that the psychedelic experience is the cause of the improvement, in my view.
But there were many people who thought the same things as you (that psycho activity was necessary) about the positive effects of marijuana. And it turned out that CBD (the non trip version of marijuana) had the same pain relief benefits for a lot of people without the high.
there are clear withdrawal symptoms (no one should drop this treatment without gradual dose lowering) but addiction seems the wrong word
My lack of words or explanation for this has left me embarrassed to talk about it. Seeing these studies is bringing up a lot of dormant curiosity.
I wouldn't feel bad about this at all. I'm comfortable that there are many very important things that can be understood but cannot be conveyed to others using language. You can tell someone the capital of France, but not what it was like when your child was born, maybe because one is a concept and the other is an experience. I've had a lot of indescribable but very valuable experiences too (LSD).
It really is hard to explain. But I think you might know how I feel.
It allows you to view things with fewer of your own biases and default thought patterns coloring your perception.
If any of you are unaware of cluster headaches, they are also called suicide headaches, because the pain is so great that many people just kill themselves. The pain level has few peers, it's been compared to amputation without anaesthetic. For me, the bulk of the sensation is of one of my eyes being crushed while a hot poker is run through it. The cluster part comes from the fact that they occur in clusters that can last weeks, months, or years.
It is debilitating to know that at any moment you could suddenly, and with very little warning, start experiencing the worst pain of your life. I had panic attacks at the first hint of symptoms.
During my last cluster I took mushrooms, and it completely eradicated them. The literature I read said it could stop them for a year, but it's been almost 4 years now and I'm still clear of them. I'd prefer to dose again for peace of mind, but mushrooms are illegal and hard to find.
It was also very nice for my depression, I had an elevated mood for several months.
I wish it was legal, it scares me a lot less than the actual antidepressant medications, and it's the only effective treatment for preventing cluster headaches.
I was not depressed at the time - I might have been a little down - but my mood was better - things that used to annoy me now annoyed me much less, while things that used to make me happy made me even happier.
Since LSD and Psilocybin are so similar in their effects, I would not be surprised if the mechanism turns out to be the same.
Now that I think if of it, I remember a mushroom experience when I was maybe 19 or 20 years old, and, at the time, quite unhappy about my life, quite likely even depressed. I did mushrooms with a friend whose parents were on vacation. The trip itself was very depressing. But when I woke up the next morning, I was happier than I had been in months, and that, too, lasted several weeks.
Aside from LSD's longer duration[^1] and increased potency[^2] acid also has a dopaminergic action, whereas psilocin[^3] is primarily a serotonergic drug. It is the dopaminergic action that can result in the obsessive quality or "looping" experience of LSD trips.
When you eat magic mushrooms, you are essentially taking yourself for an existential ride by voluntarily staring into the abyss. The trip itself is primarily "weird" and euphoric, but IME, what many people refer to as a "rough trip" is actually the existential rebound that begins 1.5-2 hours in. During this serotonin recoil, you can face the heart of darkness: the realization of all potential simultaneous chaos and creativity.
This state can include a ton of beauty, but also a reminder of your own inevitable demise. This visitation to a more "eternal" mode of thought has the same effect as surviving a face-off with any dangerous unknown: radical personal transformation. Self-knowledge necessarily feeds back into your world-view, thus changing you (usually for the better, but not always).
Nowadays, when I embark on a shroom trip, I do so in the knowledge that I will have to stare into the abyss. Sometimes you have to chew glass while doing so, e.g. a friend enters a psychotic state, or somebody dies and you have to be useful. Nevertheless, you become vulnerable and have the opportunity to learn something, help someone, or be helped and form new relationships.
Advice for brave mushroom eaters:
- be well-rested, preferably in nature - don't trip alone, but keep it under 6 people - have music, or an instrument nearby - don't eat more than you can handle (0.7g is potent. 2.4g is effective. 4g is high. 10g is godlike and dangerous)
[^1]: LSD duration is 8-12 hours. Anything less than 8h is not LSD. [^2]: psychoactive LSD dose is 25µg and up, hence LSD-25. [^3]: the primary psychoactive metabolite of psilocybin
Where can I learn more about that?
Relevant talk from Horizons:
https://vimeo.com/10918637
It is incredible to see the pain these individuals go through (sometimes for an hour every two hours - 12 times a day). It is even more impressing how resilient some humans are and the pain they can endure.
Although nowadays I am rather conservative regarding recreative use of entheogenics Azarius ships their growkits seemingly to entire Europe [1]. Anecdata: it is fairly easy to grow champignons and psilos. The kits I used were complete with straightforward guides.
I wrote "psilos" because there is also A. Muscaria, though it has less severe effects care must be taken when plucking food in the wild (and I am unsure if they'd be an option for your specific use case). There are some great guides out there allowing you to distinct species but as Sean Penn's Into The Wild [2] shows one mistake can be fatal. There's a Dutch community on FB about plucking mushrooms in the wild, but its focusing on its culinary usage. As I said, there's also some guides (in the form of books) available.
BTW, do you know if and why psilocybin works (better) than LSD for your use case?
[1] https://azarius.net/smartshop/magic-mushrooms/grow-kits/ (Disclaimer: I'm not affiliated, used to be a customer back in the '00s)
[2] http://www.imdb.com/title/tt0758758/
I actually don't know if psilocybin works better. I was unclear when I said it was the only effective treatment, I just meant psychedelics in general. I actually prefer LSD, but at the time I could only get mushrooms.
According to everything I've read they seem pretty equal for cluster headache treatment.
Oh, and "Into the Wild" definitely made me wary of attempting to identify wild plants to eat.
I wonder if you could put yourself into high morphine diet until the pain goes away but right now I'm just very happy you found a trick
The thing is, we dont have that one type of humans. We have many - different Neuro-types, and what might be a salvation for one, might send another to a different hell altogether. I find this problematic not really addressed in most studies. Thus i take them with a grain of salt that is- find out first, via a independet third observer, whether you are a similar type of neuro-type to the one who recived the mircale cure.
Last but not least: Be aware that some drugs might prevent negative experience testimony by rendering the person unable to testify. If you are send over the edge and become a schizophrenic living in a cardboard box- you are unlikely to ever testify against the remedy you took.