22 ms·

Psilocybin repairs 'brains cells damaged by depression' in mice: study

403 points by pmoriarty 5y ago

dylan604 5y ago
Would love to know the dosages they are using in the trials. Obviously, we're not talking McKenna level doses, but are we in milligrams or even as little as micrograms?
- squid_demon 5y ago
  I would love to know, too! Oh. A search engine. What's this? "Eighty participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo."
  - anonydsfsfs 5y ago
    That is not the study referenced in the article. That's an older study.
    - squid_demon 5y ago
      You are right. That is not the same study. Thanks for pointing that out.
  - taneq 5y ago
    Is this the "new study" the article is referring to with "a single dose of psilocybin given to mice"? Oh. Some text. What's this? > Eighty participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo. I'm not convinced these participants are mice. (As an aside, I love the way they talk about double blind conditions as if you're not going to be able to tell whether that pill was 25mg of psilocybin.).
    - yarg 5y ago
      It's possible to have a blind participant if they've not had psilocybin before and they are going to receive either psilocybin or one of a multitude of other psychoactive substances (at least that's how Johns Hopkins did it).
  - dylan604 5y ago
    You go to all the trouble to type up a smart ass response to show how smart you are with being able to use a search engine, yet you totally fail to provide the link which you found. This quote is meaningless without context of what study you found.
    - squid_demon 5y ago
      I'm pretty sure you can find the link using Google, also.
- anonydsfsfs 5y ago
  > we chose to use 1 mg/kg – the inflection point of the dose-dependence curve – to assess psilocybin’s effect on structural plasticity. https://www.biorxiv.org/content/10.1101/2021.02.17.431629v1.full https://www.biorxiv.org/content/10.1101/2021.02.17.431629v1....
- nosmokewhereiam 5y ago
  For psilocin, 25 milligrams is enough for many (or a good start...). Just like with THC though, it's tough to gauge how much is appropriate per person per experience per environment. A tenth of a gram may not be enough if you've previously consumed it the day(s) before.
- jk888 5y ago
  Johns Hopkins uses pure psilocybin about the equivalent of 2.5 grams of dried mushrooms.
  - dylan604 5y ago
    2.5 grams? That's enough for an exeperienced psychonaut to have a good time. That's way higher than what I would believe a therapy session would be going for, so I'm not buying these numbers one bit.
SamoyedFurFluff 5y ago
*in mice
straw_hat 5y ago
"Shrooms" are illegal here and I'm skeptical about eating "discovered" fungus grown in cow feces, particularly in raw/uncooked form. I'm not a chemist, either, so extracting psilocybin seems daunting. What's a safe way to consume psilocybin from such a "discovery", in terms of psychoactive dosage and for avoiding unwanted ancillary poisons?
- redisman 5y ago
  The dark web or travel to a state that is doing experimental treatments and has lax laws. Oregon and Denver have state/local laws decriminalizing them at least
  - straw_hat 5y ago
    Can you elaborate? I won't make an illicit online purchase. Prefer instead to consume safely from a post-rain visit to a manure pile. edit: comment I replied to initially just said "the dark web" and the additional info was added after I replied.
    - redisman 5y ago
      It would be illicit purchases so I guess that’s out
    - cartoonworld 5y ago
      You can make a totally legal purchase of microspscopy specimens in the form of millions of cubenses spores in a sterile solution, several of them for about Fifty dollars of whichever currency we are discussing. They will helpfully include a microscope slide so you can enjoy your microscopy hobby immediately. It may be the case that when accidentally applied to a sterile growth medium, such as brown rice flour in a mason jar which was autoclaved in a regular pressure cooker for about 45 minutes, that after a few weeks the microscopy specimens will provide you with a new way to look at the world. Be careful though, It's really easy to inadvertently drop the mason jars face down in a plastic tub that you use to store perlite that you bought from walmart, dislodging this nondescript white rubbery substance onto some tinfoil squares or better yet a metal rack suspended just above the perlite. If you forget about the mistake you made with the mason jars and the plastic tub for a few more weeks, and the conditions remain humid enough somehow, you will sometimes find a complex biological reaction has occurred in the chamber. Its important not to harvest them just before the veil is broken, chopping them up with a sharp knife and stirring them into a pot of water set to a low simmer for about 20-30 minutes. In any case, if you discover that you, despite your best efforts, have still made this error, you should strain the chopped peices out and discard the water, or "tea", in a way that conforms to local and federal law. Some lemon juice and/or Numi brand morroccan mint tea helps with the disposal. You might need some friends to help with that part though, it can take about 6-8 hours. You'll likely have a little trouble sleeping after all that work, so make sure to leave the next day open. I also recommend getting a bit stoned first using recreationaly legal marijuana.
Gatsky 5y ago
(I work in healthcare) There is something very odd or perhaps magical about these agents. I don’t really understand why they exist. What purpose do they serve to the mushroom? And how is it that similar agents exist in fungi, plants (ayehuasca) and amphibians (DMT from toad venom)? And also how do they produce such dramatic effects (generally beneficial when used judiciously) in humans with seemingly very little toxicity? There are basically no other molecules like this in the biosphere.
- selcuka 5y ago
  It is also possible that the answer lies somewhere in our evolution, not the mushroom's.
- rantwasp 5y ago
  it’s not really though. The mushrooms evolved independently a neurotransmitter that also just happens to work on humans. Fungi and humans have a common ancestor roughly 450 million years ago. It’s also possible that they evolved this by accident and the mushrooms that were mostly successful got carried away further and reproduced more because of this secondary utilization humans had for them.
  - jlawson 5y ago
    Not just humans - animals may respond to these compounds as well. Like humans, or in a different way.
  - wskish 5y ago
    Terrance McKenna entertained us with the theory that psilocybin catalyzed human language "on the mushroom dotted plains of Africa". https://www.amazon.com/Food-Gods-Original-Knowledge-Evolution/dp/0553371304?tag=inverse03-20 https://www.amazon.com/Food-Gods-Original-Knowledge-Evolutio... https://en.wikipedia.org/wiki/Terence_McKenna https://en.wikipedia.org/wiki/Terence_McKenna https://www.youtube.com/watch?v=FdaMVuswNrg https://www.youtube.com/watch?v=FdaMVuswNrg
    - rantwasp 5y ago
nszceta 5y ago
Another method which any able-bodied individual can try at home is multi day salt water fasting with multivitamin supplementation. Elevated levels of autophagy after fasting result in the elimination of senescence-like neurons. Individual neurons of this type can negatively influence the extracellular environment and may promote induction of the same phenotype in surrounding cells, as well as driving aging and age-related diseases.
- tomrod 5y ago
  Citation(s)?
  - TimSchumann 5y ago
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/ With the obligatory 'In Mice' addendum.
    - tomrod 5y ago
      Thanks.
    - dna_polymerase 5y ago
      Also worth checking out in the context: https://peterattiamd.com/the-mouse-trap-lost-in-translation/ https://peterattiamd.com/the-mouse-trap-lost-in-translation/
- el_dev_hell 5y ago
  That sounds really interesting. Do you have any book recommendations that explain this process (ideally targeted at a non-medical audience)?
  - lugged 5y ago
    Not a book but this does a good job exlaining it, https://youtu.be/FGoLcJxApCA https://youtu.be/FGoLcJxApCA
ArcturianDeath 5y ago
The arcturians, anshar/anunaki, and possibly other aliens have used the intoxication of psilocybin mushrooms upon the human brain to facilitate psychic attack. They tried to get me to do them, but I declined, they succeeded in getting another targeted individual to do them twice, to which they orchestrated a gangstalking and psychic attack to etch terror and cause physical organ damage for the sake of propaganda.
yarg 5y ago
I've suffered from this shit for ~20 years, and have damned near zero hope that the government's going to so much as acknowledge the medicinal utility of psilocybin, let alone legalise mushrooms. But here's a patented little pill that you can take every day for the rest of your life just to feel human. Pill a day, pill a day...
- AnIdiotOnTheNet 5y ago
  Honestly, even taking psilocybin is basically just another "fix you" pill for what I'm convinced is a deeply serious societal problem we keep refusing to address.
  - sparkie 5y ago
    You can't address societal problems before you address your own problems. And who is "we"? You should always ask this question when you see the word. Most people use it incorrectly because they falsely assume it includes people who would prefer to not be included in their statement.
    - AnIdiotOnTheNet 5y ago
      > You can't address societal problems before you address your own problems. To me this just sounds like more of the same stuff our societies keep pushing: that all the problems are ones of individual responsibility, not systemic flaws. You're depressed because there's something wrong with you, not the world you live in, so fix yourself instead of trying to make the world better. > And who is "we"? I guess any society where >10% of the population, and growing, is on an antidepressant.
      - haram_masala 5y ago
        Thanks for bringing some sanity and perspective to this discussion. Just like we judge some ancient civilizations for human sacrifice as a way of securing prosperity (or whatever), someday people will look back on our use of psychiatric drugs with the same amazement and revulsion.
elromulous 5y ago
dang - can we add "in mice" to the title?
- dang 5y ago
  Yup, always up for that. almost tempted to write some code to try automating it
  - mercer 5y ago
    Haha first proper laugh of the day
  - failwhaleshark 5y ago
    Every study works in mice. Human trials, not so much. Also, who would volunteer for depression + psychedelics before and after brain biopsies to prove this thesis? Maybe try it on the "before" sample in vitro first?
    - wavefunction 5y ago
      This seems like something that could be measured with at least one of the scanning techniques we already employ. It seems like an MRI could provide a rough result that could lead to further and more direct testing.
      - failwhaleshark 5y ago
        Gross structural scanning is essentially worthless when it comes to pathway functions.
    - taneq 5y ago
      Of course it doesn't. The fact that we don't hear about all the trials that don't produce a significant result in mice is more to do with the state of science publication than to do with mice.
  - elromulous 5y ago
myrandomcomment 5y ago
So I have a family member that suffers from depression. At some point at a party we convinced her to drink some mushroom tea. She was amazingly together for 6 months after. Magic mushrooms should be legal.
- Trasmatta 5y ago
  For anyone else reading this and considering it -- you really need to be careful before recommending this for someone with depression. If they are not prepared for the experience it can be deeply destabilizing. Bad trips are real. Shroom tea is generally very strong too. It absolutely can work for depression sometimes, just be careful and intentional, and don't just talk somebody into it who may not be ready for it.
  - Milner08 5y ago
    This is critical. You cant/shouldn't just go out on a whim and take shrooms. Either find someone who knows what they're doing and can walk you through it or do your own research and take it slow. Know how much your taking (as best you can) and don't over do it first time. Bad trips _suck_ and aren't going to help anyone.
  - mylons 5y ago
    thank you for posting this.
  - pmoriarty 5y ago
    Completely agree that it's not for everyone, and that those that do try it should thoroughly (and I mean really thoroughly) educate themselves on what they're getting themselves in to and how to maximize their chances of having a good experience. For this I'd recommend "The Psychedelic Explorer's Guide"[1] by James Fadiman as a good start. Erowid[2] and PsychonautWiki[3] are good for experience reports and reference. People with pre-existing health and psychiatric conditions, and young people should be doubly careful. The physical and sometimes psychological effects of some substances can be dangerous, especially when mixed with other drugs (alcohol is a particularly bad one to mix with). Psilocybin mushrooms are some of the safest psychedelics around, but at the very least be absolutely sure you got the right kind (have them identified by experts or grow your own)... and starting with lower doses, in a good set and setting, with someone more experienced than you who you like and trust is prudent. Have some quiet days to integrate the experience afterwards, maybe with a therapist. [1] - https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeutic-Journeys/dp/1594774021 https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeut... [2] - https://erowid.org https://erowid.org [3] - https://psychonautwiki.org/wiki/Main_Page https://psychonautwiki.org/wiki/Main_Page
fourstar 5y ago
There's a free psych investor conference tomorrow (https://psych.global/agenda/ https://psych.global/agenda/) for people interested in what companies are working in the psychedelic space. California just voted in favor of a bill that would allow those 21 and older to possess for personal use and social sharing LSD, mescaline and the psilocybin. I suspect a lot of consolidation and new players entering, but it's definitely in its infancy and will be exciting to watch it mature. One company called Braxia Scientific is opening ketamine clinics throughout Canada and plans to do so in the US. They also just received funding from the Canadian government to study the effects so some of these companies are legit. https://www.yahoo.com/lifestyle/braxia-scientific-awarded-government-canada-113000840.html https://www.yahoo.com/lifestyle/braxia-scientific-awarded-go...
- pmoriarty 5y ago
  I'm kind of ambivalent about commercial interests entering the psychedelic space. Hopefully some way will be found to keep the providers small, local, employee-owned, and ethical... maybe non-profit even.
fractallyte 5y ago
Psychedelics (and all mind-altering substances) are analogous to camera (or Photoshop) filters. A filter works by taking an image, and processing it... The processed image typically loses information in pursuit of an 'effect'. It's an illusion! The original is always richer, more nuanced, detailed, colorful and REAL. Humans seem to be obsessed with the illusion of mind 'enhancement', whether through drugs, alcohol or caffeine. It all reduces to this: an inablity to appreciate reality.
- foolfoolz 5y ago
  i think a better analogy is rotating an image in photoshop. it lets you see the picture in a different perspective. psychedelics make it easier to view yourself from a different perspective
- chickenpotpie 5y ago
  Reality isnt always worth appreciating
- sebmellen 5y ago
  Insisting that the reality a depressed person experiences is "reality" is myopic. How many filters affect your experience that you're completely unaware of? Tons!!! What is really real, and how can you ascertain what's "reality" and what isn't? Now, the way I think of psychedelics (and the way they worked for me) was that they removed a shroud — a bad filter, if you will — from my depressed mind. I was at -2 exposure, and with the help of psychedelics and a psychologist I was able to get back to right around 0. Now, I'm actually able to appreciate "reality", or at least what I see of it. What's wrong with that?
- halotrope 5y ago
  Thats not really how psychedelics work. I would say the experience can teach you a lot about how you mind operates. I hear things like “ego”, “categories” or “meaning” start to dissolve on Psilocybin for instance. The experience is apparently quite exhausting and not really suitable to “enhance” reality for any stretch of time. What I think happens you learn something about yourself and that can also teach you something about your relationship with reality.
guerrilla 5y ago
> The research found that the compound increases the density of dendritic spines, small protrusions found on nerve cells that aid in the transmission of information between neurons. Chronic stress and depression are known to reduce the number of these neuronal connections. How well is the latter known? Is that consensus? Also, is it just an effect or a possible cause of depression? If it's just an effect, why would reparation be an effective treatment for depression?
operator-name 5y ago
This is quite an interesting topic, and as a non neuroscientist recently I've been going down the rabbit hole. Although depression is not well understood, there are some theories/interpretations of the data. One of which is the differences of mechanism behind 5-HT_1A and 5-HT_2A: SSRIs are (stronger) antagonists for 5-HT_1A which is theorised to increase "passive coping". Psychadelics are (stronger) antagonists for 5-HT_2A which is theorised to increase "active coping". The original paper that proposes this is "Serotonin and brain function: a tale of two receptors" by Harris and Nutt, hopefully my simplification has been accurate enough. This is quite interesting as it mirrors not only what I've experienced but also the conversations I've had with other. The following is obviously the anecdotal opinion of a single person. Firstly neither SSRIs or Psychadelics by themselves "fix the problems with the world" - if being in debt living paycheck to paycheck or having a bad relationship is a contributing factor then taking medication doesn't magically make that go away. Whilst on SSRIs, although there was an objective decrease in symptoms subjectively it it became increasingly difficult to continue the course of medication. This is not uncommon, as can be seen in "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis" by Andrea Cipriani et al. In contrast psychadelics and the "mania", flexible thinking, decreased pessimism they induced combined with the subjective contrast was extremely insightful - "oh yeah, I can be happy". Although objectively my actions did not change much, subjectivly they were no longer "shameful", I didn't need to ruminate and accepted them. But it should be said, taking psychadelics when not in a good mental state is incredibly dangerous, especially if it is the first time. This is mirrored in this review of a review (https://astralcodexten.substack.com/p/on-cerebralab-on-nuttcarhart-harris https://astralcodexten.substack.com/p/on-cerebralab-on-nuttc...). To quote the original review: > I found it curious that people who take psychedelics for introspection usually end up as religious cranks or burnouts. While people that take psychedelics because "they are fun" don't seem to experience many negative side effects. Under this framework, it makes perfect sense, activate highly conceptual functions in the cortex and tell them to solve an intrinsic and emotional, you'll end up with some very weird conceptual scaffolding.
- adammunich 5y ago
  Anecdotally I found that psilocybin reduced my feelings of depression to a state of… nothing. This allowed me the space to think about how I should build an identity I was happier with. Another time (LSD) I had an experience so terrifying that nothing in the mortal world compares. It destabilized me for a bit, however, the experience helped me recognize the volatility bounds of “normal” life emotions and that keeps them in perspective.
masterbit 5y ago
https://www.drbronner.com/all-one-blog/2019/12/dr-bronners-support-psychedelic-therapy-drug-policy-reform/ https://www.drbronner.com/all-one-blog/2019/12/dr-bronners-s... ... Dr. Bronner is supporting research in that area for a while.
immmmmm 5y ago
got me cured. acted in 15 minutes. 4 years of pain gone. i have no words to explain the relief.
- doublejay1999 5y ago
  i'm so tempted.
  - immmmmm 5y ago
    it should be noted that this not recommended doing this out of a medical context.
    - Leparamour 5y ago
      > it should be noted that this not recommended doing this out of a medical context. How could you even do that? As buying and possession of psychedelics is illegal in most countries.
      - pmoriarty 5y ago
        There are both underground and licensed therapists who will work with patients who use psychedelics. Discretely ask around and you might find them. Try asking around at psychedelic conferences and psychedelic meetups. Also try contacting MAPS[1] and CIIS[2] (which has a training program for psychedelic therapists), and related organizations. Contacting people doing research in to psychedelics might also be fruitful. [1] - https://maps.org/ https://maps.org/ [2] - https://www.ciis.edu/ https://www.ciis.edu/
        staticman2 5y ago
        The idea of a licensed therapist who does psychedelics is something of an oxymoron because even if they are licensed for doing therapy they aren't doing anything that they were taught to do in school so I don't see the point of looking for someone with a license. You could just have a friend you trust babysit.
mettamage 5y ago
Psilocybin's effect can be amazing, but there were moments when I took truffles in Amsterdam that almost made me commit suicide. The sane part -- whatever was left of it -- recognized it and found an immediate way to stop it. So what actually happened is that I locked myself up in an empty room and cried (I couldn't harm myself there, because I didn't know how to get out until I sobered up a bit). After one hour of crying I started noticing the magical effects of "we're all connected" etc. So after the bad part of my trip, the amazing things came. I don't mind that I cried, but I do mind that I was acting on a suicidal tendency that I never experienced sober. I think I overdosed on it, being quite an inexperienced user. Because the first time I took half a dose, that was an amazing experience and it allowed me to reconnect to true child-like wonder (measured in units of whatever the smart shops in Amsterdam sell). N = 1, I know. All I'm saying is: be careful, have a trip sitter and a good set and setting. Don't go all out simply because you see a few positive papers.
- voisin 5y ago
  What dose on that first experience? Anyone know if dose needs to be scaled with body weight?
  - mettamage 5y ago
    First experience: half Bad experience: a whole one Smart shops in Amsterdam have a pretty standardized dose that they sell. I forgot the actual amount of grams.
    - staticman2 5y ago
      This does not match my experience. I've found they have beginner, intermediate, or advanced truffles, presumably types with different natural dosages of psilocybin in the different types of Truffles. I've only taken the beginner ones and had a good time.
      - mettamage 5y ago
        I think in both cases we took an intermediate one. But I don't fully remember tbh.
lucasnorth 5y ago
"in mice". stop wasting our time with this junk science
jb1991 5y ago
Having experienced psilocybin a few times and agree it does have some of these positive, possible (but not guaranteed) effects, I also believe that similar effects are possible through entirely sober means, though harder to achieve for most people (proper meditation, talk therapy, certain relationships with natural surroundings).
ixtal 5y ago
In my opinion the main problem of the using of psilocybin, LSD and other psychedelics in medicine is unpredictable effect that depends on not only the status of a pacient but on entourage too. One time you have a good trip, but next time you get into TRUE HELL.
- pmoriarty 5y ago
  Recent research in to psychedelics has proven that we've learned how to control set and setting so that the overwhelming majority of people who do psychedelics with trained therapists have positive results. Some people still have difficult experiences, but with the aid of properly trained therapists even those experiences can be constructive, and people can come out healed on the other side of even the worst trips.
  - ixtal 5y ago
    I do not known such researches but I agree that it can work for some people, especially for suggestible people or who strongly trust in therapist. But in general we do not be able to control it. Any psy trip is similar to sailing in ocean.
    - pmoriarty 5y ago
      It's not just about trust in the therapist. Music plays a huge role. In fact, I've recently heard a psychedelic researcher say that he now thinks of psychedelic therapy as a form of music therapy done with psychedelics. It's also important to be in a safe, comfortable place, without people you don't intimately trust around, at a time when you can just focus on yourself on the day of the experience and ideally at least a day or two afterwards.
      - ixtal 5y ago
        These are necessary but insufficient conditions. A bad trip may be triggered by a fleeting recollection/thought. I believe that a medical procedure cannot be based on such precarious approaches.
myth_drannon 5y ago
I wonder what is the effect on neuro mascular conditions like cerebral palsy. It's more of dead neurons than connections between them but still if it increases the number of connections/strength between the existing neurons it can compensate the fact of having less nodes in the network.
- pmoriarty 5y ago
  Same question regarding other neurodegenerative diseases like Alzheimer's. It could be revolutionary if they make a difference. Unfortunately, I haven't heard of any studies of this except for a study in to microdosing LSD as a potential treatment for Alzheimer's.[1][2] This is a wide open area, and I hope some patients' advocacy groups start seriously funding research in to this and demanding that governments remove the many regulatory hurdles that still stand in the way. [1] - https://www.forbes.com/sites/abbierosner/2020/02/21/microdosed-lsd-may-finally-be-the-breakthrough-for-alzheimers-disease/ https://www.forbes.com/sites/abbierosner/2020/02/21/microdos... [2] - https://pubmed.ncbi.nlm.nih.gov/32973482/ https://pubmed.ncbi.nlm.nih.gov/32973482/
hereme888 5y ago
A 10% increase in synaptic density and strength can be good or bad. Are these new connections rooted and grounded in useful things that pertain to reality, or are they connections rooted in halluconations? Or what? Magnesium-L-Threonate (Magtein) also increases synaltic density but without hallucination. However it doesn't offer the serotonin effects of psilocybin. Aerobic exercise regimens offer both, but without the hallucinogenic benefits of having a new perspective on things.
jk888 5y ago
I wrote a piece here about avoiding bad trips. Maybe it can be useful to someone. https://www.eleusiniaretreat.com/how-to-avoid-a-bad-trip/ https://www.eleusiniaretreat.com/how-to-avoid-a-bad-trip/

403 points by pmoriarty 5y ago

Would love to know the dosages they are using in the trials. Obviously, we're not talking McKenna level doses, but are we in milligrams or even as little as micrograms?

squid_demon 5y ago
I would love to know, too! Oh. A search engine. What's this? "Eighty participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo."
- anonydsfsfs 5y ago
  That is not the study referenced in the article. That's an older study.
  - squid_demon 5y ago
    You are right. That is not the same study. Thanks for pointing that out.
- taneq 5y ago
  Is this the "new study" the article is referring to with "a single dose of psilocybin given to mice"? Oh. Some text. What's this? > Eighty participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo. I'm not convinced these participants are mice. (As an aside, I love the way they talk about double blind conditions as if you're not going to be able to tell whether that pill was 25mg of psilocybin.).
  - yarg 5y ago
    It's possible to have a blind participant if they've not had psilocybin before and they are going to receive either psilocybin or one of a multitude of other psychoactive substances (at least that's how Johns Hopkins did it).
- dylan604 5y ago
  You go to all the trouble to type up a smart ass response to show how smart you are with being able to use a search engine, yet you totally fail to provide the link which you found. This quote is meaningless without context of what study you found.
  - squid_demon 5y ago
    I'm pretty sure you can find the link using Google, also.
anonydsfsfs 5y ago
> we chose to use 1 mg/kg – the inflection point of the dose-dependence curve – to assess psilocybin’s effect on structural plasticity. https://www.biorxiv.org/content/10.1101/2021.02.17.431629v1.full https://www.biorxiv.org/content/10.1101/2021.02.17.431629v1....
nosmokewhereiam 5y ago
For psilocin, 25 milligrams is enough for many (or a good start...). Just like with THC though, it's tough to gauge how much is appropriate per person per experience per environment. A tenth of a gram may not be enough if you've previously consumed it the day(s) before.
jk888 5y ago
Johns Hopkins uses pure psilocybin about the equivalent of 2.5 grams of dried mushrooms.
- dylan604 5y ago
  2.5 grams? That's enough for an exeperienced psychonaut to have a good time. That's way higher than what I would believe a therapy session would be going for, so I'm not buying these numbers one bit.

SamoyedFurFluff 5y ago

*in mice

straw_hat 5y ago

"Shrooms" are illegal here and I'm skeptical about eating "discovered" fungus grown in cow feces, particularly in raw/uncooked form. I'm not a chemist, either, so extracting psilocybin seems daunting. What's a safe way to consume psilocybin from such a "discovery", in terms of psychoactive dosage and for avoiding unwanted ancillary poisons?

redisman 5y ago
The dark web or travel to a state that is doing experimental treatments and has lax laws. Oregon and Denver have state/local laws decriminalizing them at least
- straw_hat 5y ago
  Can you elaborate? I won't make an illicit online purchase. Prefer instead to consume safely from a post-rain visit to a manure pile. edit: comment I replied to initially just said "the dark web" and the additional info was added after I replied.
  - redisman 5y ago
    It would be illicit purchases so I guess that’s out
  - cartoonworld 5y ago
    You can make a totally legal purchase of microspscopy specimens in the form of millions of cubenses spores in a sterile solution, several of them for about Fifty dollars of whichever currency we are discussing. They will helpfully include a microscope slide so you can enjoy your microscopy hobby immediately. It may be the case that when accidentally applied to a sterile growth medium, such as brown rice flour in a mason jar which was autoclaved in a regular pressure cooker for about 45 minutes, that after a few weeks the microscopy specimens will provide you with a new way to look at the world. Be careful though, It's really easy to inadvertently drop the mason jars face down in a plastic tub that you use to store perlite that you bought from walmart, dislodging this nondescript white rubbery substance onto some tinfoil squares or better yet a metal rack suspended just above the perlite. If you forget about the mistake you made with the mason jars and the plastic tub for a few more weeks, and the conditions remain humid enough somehow, you will sometimes find a complex biological reaction has occurred in the chamber. Its important not to harvest them just before the veil is broken, chopping them up with a sharp knife and stirring them into a pot of water set to a low simmer for about 20-30 minutes. In any case, if you discover that you, despite your best efforts, have still made this error, you should strain the chopped peices out and discard the water, or "tea", in a way that conforms to local and federal law. Some lemon juice and/or Numi brand morroccan mint tea helps with the disposal. You might need some friends to help with that part though, it can take about 6-8 hours. You'll likely have a little trouble sleeping after all that work, so make sure to leave the next day open. I also recommend getting a bit stoned first using recreationaly legal marijuana.

Gatsky 5y ago

(I work in healthcare) There is something very odd or perhaps magical about these agents. I don’t really understand why they exist. What purpose do they serve to the mushroom? And how is it that similar agents exist in fungi, plants (ayehuasca) and amphibians (DMT from toad venom)? And also how do they produce such dramatic effects (generally beneficial when used judiciously) in humans with seemingly very little toxicity? There are basically no other molecules like this in the biosphere.

selcuka 5y ago
It is also possible that the answer lies somewhere in our evolution, not the mushroom's.
rantwasp 5y ago
it’s not really though. The mushrooms evolved independently a neurotransmitter that also just happens to work on humans. Fungi and humans have a common ancestor roughly 450 million years ago. It’s also possible that they evolved this by accident and the mushrooms that were mostly successful got carried away further and reproduced more because of this secondary utilization humans had for them.
- jlawson 5y ago
  Not just humans - animals may respond to these compounds as well. Like humans, or in a different way.
- wskish 5y ago
  Terrance McKenna entertained us with the theory that psilocybin catalyzed human language "on the mushroom dotted plains of Africa". https://www.amazon.com/Food-Gods-Original-Knowledge-Evolution/dp/0553371304?tag=inverse03-20 https://www.amazon.com/Food-Gods-Original-Knowledge-Evolutio... https://en.wikipedia.org/wiki/Terence_McKenna https://en.wikipedia.org/wiki/Terence_McKenna https://www.youtube.com/watch?v=FdaMVuswNrg https://www.youtube.com/watch?v=FdaMVuswNrg
  - rantwasp 5y ago

nszceta 5y ago

Another method which any able-bodied individual can try at home is multi day salt water fasting with multivitamin supplementation. Elevated levels of autophagy after fasting result in the elimination of senescence-like neurons. Individual neurons of this type can negatively influence the extracellular environment and may promote induction of the same phenotype in surrounding cells, as well as driving aging and age-related diseases.

tomrod 5y ago
Citation(s)?
- TimSchumann 5y ago
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/ With the obligatory 'In Mice' addendum.
  - tomrod 5y ago
    Thanks.
  - dna_polymerase 5y ago
    Also worth checking out in the context: https://peterattiamd.com/the-mouse-trap-lost-in-translation/ https://peterattiamd.com/the-mouse-trap-lost-in-translation/
el_dev_hell 5y ago
That sounds really interesting. Do you have any book recommendations that explain this process (ideally targeted at a non-medical audience)?
- lugged 5y ago
  Not a book but this does a good job exlaining it, https://youtu.be/FGoLcJxApCA https://youtu.be/FGoLcJxApCA

ArcturianDeath 5y ago

The arcturians, anshar/anunaki, and possibly other aliens have used the intoxication of psilocybin mushrooms upon the human brain to facilitate psychic attack. They tried to get me to do them, but I declined, they succeeded in getting another targeted individual to do them twice, to which they orchestrated a gangstalking and psychic attack to etch terror and cause physical organ damage for the sake of propaganda.

yarg 5y ago

I've suffered from this shit for ~20 years, and have damned near zero hope that the government's going to so much as acknowledge the medicinal utility of psilocybin, let alone legalise mushrooms. But here's a patented little pill that you can take every day for the rest of your life just to feel human. Pill a day, pill a day...

AnIdiotOnTheNet 5y ago
Honestly, even taking psilocybin is basically just another "fix you" pill for what I'm convinced is a deeply serious societal problem we keep refusing to address.
- sparkie 5y ago
  You can't address societal problems before you address your own problems. And who is "we"? You should always ask this question when you see the word. Most people use it incorrectly because they falsely assume it includes people who would prefer to not be included in their statement.
  - AnIdiotOnTheNet 5y ago
    > You can't address societal problems before you address your own problems. To me this just sounds like more of the same stuff our societies keep pushing: that all the problems are ones of individual responsibility, not systemic flaws. You're depressed because there's something wrong with you, not the world you live in, so fix yourself instead of trying to make the world better. > And who is "we"? I guess any society where >10% of the population, and growing, is on an antidepressant.
    - haram_masala 5y ago
      Thanks for bringing some sanity and perspective to this discussion. Just like we judge some ancient civilizations for human sacrifice as a way of securing prosperity (or whatever), someday people will look back on our use of psychiatric drugs with the same amazement and revulsion.

elromulous 5y ago

dang - can we add "in mice" to the title?

dang 5y ago
Yup, always up for that. almost tempted to write some code to try automating it
- mercer 5y ago
  Haha first proper laugh of the day
- failwhaleshark 5y ago
  Every study works in mice. Human trials, not so much. Also, who would volunteer for depression + psychedelics before and after brain biopsies to prove this thesis? Maybe try it on the "before" sample in vitro first?
  - wavefunction 5y ago
    This seems like something that could be measured with at least one of the scanning techniques we already employ. It seems like an MRI could provide a rough result that could lead to further and more direct testing.
    - failwhaleshark 5y ago
      Gross structural scanning is essentially worthless when it comes to pathway functions.
  - taneq 5y ago
    Of course it doesn't. The fact that we don't hear about all the trials that don't produce a significant result in mice is more to do with the state of science publication than to do with mice.
- elromulous 5y ago

myrandomcomment 5y ago

So I have a family member that suffers from depression. At some point at a party we convinced her to drink some mushroom tea. She was amazingly together for 6 months after. Magic mushrooms should be legal.

Trasmatta 5y ago
For anyone else reading this and considering it -- you really need to be careful before recommending this for someone with depression. If they are not prepared for the experience it can be deeply destabilizing. Bad trips are real. Shroom tea is generally very strong too. It absolutely can work for depression sometimes, just be careful and intentional, and don't just talk somebody into it who may not be ready for it.
- Milner08 5y ago
  This is critical. You cant/shouldn't just go out on a whim and take shrooms. Either find someone who knows what they're doing and can walk you through it or do your own research and take it slow. Know how much your taking (as best you can) and don't over do it first time. Bad trips _suck_ and aren't going to help anyone.
- mylons 5y ago
  thank you for posting this.
- pmoriarty 5y ago
  Completely agree that it's not for everyone, and that those that do try it should thoroughly (and I mean really thoroughly) educate themselves on what they're getting themselves in to and how to maximize their chances of having a good experience. For this I'd recommend "The Psychedelic Explorer's Guide"[1] by James Fadiman as a good start. Erowid[2] and PsychonautWiki[3] are good for experience reports and reference. People with pre-existing health and psychiatric conditions, and young people should be doubly careful. The physical and sometimes psychological effects of some substances can be dangerous, especially when mixed with other drugs (alcohol is a particularly bad one to mix with). Psilocybin mushrooms are some of the safest psychedelics around, but at the very least be absolutely sure you got the right kind (have them identified by experts or grow your own)... and starting with lower doses, in a good set and setting, with someone more experienced than you who you like and trust is prudent. Have some quiet days to integrate the experience afterwards, maybe with a therapist. [1] - https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeutic-Journeys/dp/1594774021 https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeut... [2] - https://erowid.org https://erowid.org [3] - https://psychonautwiki.org/wiki/Main_Page https://psychonautwiki.org/wiki/Main_Page

fourstar 5y ago

There's a free psych investor conference tomorrow (https://psych.global/agenda/ https://psych.global/agenda/) for people interested in what companies are working in the psychedelic space. California just voted in favor of a bill that would allow those 21 and older to possess for personal use and social sharing LSD, mescaline and the psilocybin. I suspect a lot of consolidation and new players entering, but it's definitely in its infancy and will be exciting to watch it mature. One company called Braxia Scientific is opening ketamine clinics throughout Canada and plans to do so in the US. They also just received funding from the Canadian government to study the effects so some of these companies are legit. https://www.yahoo.com/lifestyle/braxia-scientific-awarded-government-canada-113000840.html https://www.yahoo.com/lifestyle/braxia-scientific-awarded-go...

pmoriarty 5y ago
I'm kind of ambivalent about commercial interests entering the psychedelic space. Hopefully some way will be found to keep the providers small, local, employee-owned, and ethical... maybe non-profit even.

fractallyte 5y ago

Psychedelics (and all mind-altering substances) are analogous to camera (or Photoshop) filters. A filter works by taking an image, and processing it... The processed image typically loses information in pursuit of an 'effect'. It's an illusion! The original is always richer, more nuanced, detailed, colorful and REAL. Humans seem to be obsessed with the illusion of mind 'enhancement', whether through drugs, alcohol or caffeine. It all reduces to this: an inablity to appreciate reality.

foolfoolz 5y ago
i think a better analogy is rotating an image in photoshop. it lets you see the picture in a different perspective. psychedelics make it easier to view yourself from a different perspective
chickenpotpie 5y ago
Reality isnt always worth appreciating
sebmellen 5y ago
Insisting that the reality a depressed person experiences is "reality" is myopic. How many filters affect your experience that you're completely unaware of? Tons!!! What is really real, and how can you ascertain what's "reality" and what isn't? Now, the way I think of psychedelics (and the way they worked for me) was that they removed a shroud — a bad filter, if you will — from my depressed mind. I was at -2 exposure, and with the help of psychedelics and a psychologist I was able to get back to right around 0. Now, I'm actually able to appreciate "reality", or at least what I see of it. What's wrong with that?
halotrope 5y ago
Thats not really how psychedelics work. I would say the experience can teach you a lot about how you mind operates. I hear things like “ego”, “categories” or “meaning” start to dissolve on Psilocybin for instance. The experience is apparently quite exhausting and not really suitable to “enhance” reality for any stretch of time. What I think happens you learn something about yourself and that can also teach you something about your relationship with reality.

guerrilla 5y ago

> The research found that the compound increases the density of dendritic spines, small protrusions found on nerve cells that aid in the transmission of information between neurons. Chronic stress and depression are known to reduce the number of these neuronal connections. How well is the latter known? Is that consensus? Also, is it just an effect or a possible cause of depression? If it's just an effect, why would reparation be an effective treatment for depression?

operator-name 5y ago

This is quite an interesting topic, and as a non neuroscientist recently I've been going down the rabbit hole. Although depression is not well understood, there are some theories/interpretations of the data. One of which is the differences of mechanism behind 5-HT_1A and 5-HT_2A: SSRIs are (stronger) antagonists for 5-HT_1A which is theorised to increase "passive coping". Psychadelics are (stronger) antagonists for 5-HT_2A which is theorised to increase "active coping". The original paper that proposes this is "Serotonin and brain function: a tale of two receptors" by Harris and Nutt, hopefully my simplification has been accurate enough. This is quite interesting as it mirrors not only what I've experienced but also the conversations I've had with other. The following is obviously the anecdotal opinion of a single person. Firstly neither SSRIs or Psychadelics by themselves "fix the problems with the world" - if being in debt living paycheck to paycheck or having a bad relationship is a contributing factor then taking medication doesn't magically make that go away. Whilst on SSRIs, although there was an objective decrease in symptoms subjectively it it became increasingly difficult to continue the course of medication. This is not uncommon, as can be seen in "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis" by Andrea Cipriani et al. In contrast psychadelics and the "mania", flexible thinking, decreased pessimism they induced combined with the subjective contrast was extremely insightful - "oh yeah, I can be happy". Although objectively my actions did not change much, subjectivly they were no longer "shameful", I didn't need to ruminate and accepted them. But it should be said, taking psychadelics when not in a good mental state is incredibly dangerous, especially if it is the first time. This is mirrored in this review of a review (https://astralcodexten.substack.com/p/on-cerebralab-on-nuttcarhart-harris https://astralcodexten.substack.com/p/on-cerebralab-on-nuttc...). To quote the original review: > I found it curious that people who take psychedelics for introspection usually end up as religious cranks or burnouts. While people that take psychedelics because "they are fun" don't seem to experience many negative side effects. Under this framework, it makes perfect sense, activate highly conceptual functions in the cortex and tell them to solve an intrinsic and emotional, you'll end up with some very weird conceptual scaffolding.

adammunich 5y ago
Anecdotally I found that psilocybin reduced my feelings of depression to a state of… nothing. This allowed me the space to think about how I should build an identity I was happier with. Another time (LSD) I had an experience so terrifying that nothing in the mortal world compares. It destabilized me for a bit, however, the experience helped me recognize the volatility bounds of “normal” life emotions and that keeps them in perspective.

masterbit 5y ago

https://www.drbronner.com/all-one-blog/2019/12/dr-bronners-support-psychedelic-therapy-drug-policy-reform/ https://www.drbronner.com/all-one-blog/2019/12/dr-bronners-s... ... Dr. Bronner is supporting research in that area for a while.

immmmmm 5y ago

got me cured. acted in 15 minutes. 4 years of pain gone. i have no words to explain the relief.

doublejay1999 5y ago
i'm so tempted.
- immmmmm 5y ago
  it should be noted that this not recommended doing this out of a medical context.
  - Leparamour 5y ago
    > it should be noted that this not recommended doing this out of a medical context. How could you even do that? As buying and possession of psychedelics is illegal in most countries.
    - pmoriarty 5y ago
      There are both underground and licensed therapists who will work with patients who use psychedelics. Discretely ask around and you might find them. Try asking around at psychedelic conferences and psychedelic meetups. Also try contacting MAPS[1] and CIIS[2] (which has a training program for psychedelic therapists), and related organizations. Contacting people doing research in to psychedelics might also be fruitful. [1] - https://maps.org/ https://maps.org/ [2] - https://www.ciis.edu/ https://www.ciis.edu/
      - staticman2 5y ago
        The idea of a licensed therapist who does psychedelics is something of an oxymoron because even if they are licensed for doing therapy they aren't doing anything that they were taught to do in school so I don't see the point of looking for someone with a license. You could just have a friend you trust babysit.

mettamage 5y ago

Psilocybin's effect can be amazing, but there were moments when I took truffles in Amsterdam that almost made me commit suicide. The sane part -- whatever was left of it -- recognized it and found an immediate way to stop it. So what actually happened is that I locked myself up in an empty room and cried (I couldn't harm myself there, because I didn't know how to get out until I sobered up a bit). After one hour of crying I started noticing the magical effects of "we're all connected" etc. So after the bad part of my trip, the amazing things came. I don't mind that I cried, but I do mind that I was acting on a suicidal tendency that I never experienced sober. I think I overdosed on it, being quite an inexperienced user. Because the first time I took half a dose, that was an amazing experience and it allowed me to reconnect to true child-like wonder (measured in units of whatever the smart shops in Amsterdam sell). N = 1, I know. All I'm saying is: be careful, have a trip sitter and a good set and setting. Don't go all out simply because you see a few positive papers.

voisin 5y ago
What dose on that first experience? Anyone know if dose needs to be scaled with body weight?
- mettamage 5y ago
  First experience: half Bad experience: a whole one Smart shops in Amsterdam have a pretty standardized dose that they sell. I forgot the actual amount of grams.
  - staticman2 5y ago
    This does not match my experience. I've found they have beginner, intermediate, or advanced truffles, presumably types with different natural dosages of psilocybin in the different types of Truffles. I've only taken the beginner ones and had a good time.
    - mettamage 5y ago
      I think in both cases we took an intermediate one. But I don't fully remember tbh.

lucasnorth 5y ago

"in mice". stop wasting our time with this junk science

jb1991 5y ago

Having experienced psilocybin a few times and agree it does have some of these positive, possible (but not guaranteed) effects, I also believe that similar effects are possible through entirely sober means, though harder to achieve for most people (proper meditation, talk therapy, certain relationships with natural surroundings).

ixtal 5y ago

In my opinion the main problem of the using of psilocybin, LSD and other psychedelics in medicine is unpredictable effect that depends on not only the status of a pacient but on entourage too. One time you have a good trip, but next time you get into TRUE HELL.

pmoriarty 5y ago
Recent research in to psychedelics has proven that we've learned how to control set and setting so that the overwhelming majority of people who do psychedelics with trained therapists have positive results. Some people still have difficult experiences, but with the aid of properly trained therapists even those experiences can be constructive, and people can come out healed on the other side of even the worst trips.
- ixtal 5y ago
  I do not known such researches but I agree that it can work for some people, especially for suggestible people or who strongly trust in therapist. But in general we do not be able to control it. Any psy trip is similar to sailing in ocean.
  - pmoriarty 5y ago
    It's not just about trust in the therapist. Music plays a huge role. In fact, I've recently heard a psychedelic researcher say that he now thinks of psychedelic therapy as a form of music therapy done with psychedelics. It's also important to be in a safe, comfortable place, without people you don't intimately trust around, at a time when you can just focus on yourself on the day of the experience and ideally at least a day or two afterwards.
    - ixtal 5y ago
      These are necessary but insufficient conditions. A bad trip may be triggered by a fleeting recollection/thought. I believe that a medical procedure cannot be based on such precarious approaches.

myth_drannon 5y ago

I wonder what is the effect on neuro mascular conditions like cerebral palsy. It's more of dead neurons than connections between them but still if it increases the number of connections/strength between the existing neurons it can compensate the fact of having less nodes in the network.

pmoriarty 5y ago
Same question regarding other neurodegenerative diseases like Alzheimer's. It could be revolutionary if they make a difference. Unfortunately, I haven't heard of any studies of this except for a study in to microdosing LSD as a potential treatment for Alzheimer's.[1][2] This is a wide open area, and I hope some patients' advocacy groups start seriously funding research in to this and demanding that governments remove the many regulatory hurdles that still stand in the way. [1] - https://www.forbes.com/sites/abbierosner/2020/02/21/microdosed-lsd-may-finally-be-the-breakthrough-for-alzheimers-disease/ https://www.forbes.com/sites/abbierosner/2020/02/21/microdos... [2] - https://pubmed.ncbi.nlm.nih.gov/32973482/ https://pubmed.ncbi.nlm.nih.gov/32973482/

hereme888 5y ago

A 10% increase in synaptic density and strength can be good or bad. Are these new connections rooted and grounded in useful things that pertain to reality, or are they connections rooted in halluconations? Or what? Magnesium-L-Threonate (Magtein) also increases synaltic density but without hallucination. However it doesn't offer the serotonin effects of psilocybin. Aerobic exercise regimens offer both, but without the hallucinogenic benefits of having a new perspective on things.

jk888 5y ago

I wrote a piece here about avoiding bad trips. Maybe it can be useful to someone. https://www.eleusiniaretreat.com/how-to-avoid-a-bad-trip/ https://www.eleusiniaretreat.com/how-to-avoid-a-bad-trip/