Psilocybin bests SSRI for major depression in first long-term comparison • Hacker News Board

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#251

Post by londons_explore » Sat, Oct 12, 2024, 9:35 PM UTC

Affric wrote: post #242

notfed wrote: post #240

Earlier quoted context omitted.

If that's true, I'm confused how this is a "double-blind, randomized, controlled trial"? Also, what's up with drug studies always having such a low sample size? Is it really that hard to find people who'd volunteer to get free drugs?

Often you’re not allowed on your medication for any of your other health issues.

We need a new approach to randomly controlled trials.

I propose a new approach: Rather than given treatment vs not given treatment, we instead vary the dose slightly, and we include the whole world in the trial.

Ie. instead of taking 100mg of Advil, instead you will receive somewhere between 95mg and 105mg of Advil. You won't be told how much you got - but the barcode on the box will encode that info. That already might be the case due to allowed inaccuracies, but now we're gonna measure and record it.

Later, the data of which box was dispensed is combined with any other relevant medical records, and across the hundreds of millions of people involved, any benefit/disadvantage of a small increase or decrease in dose will become apparent.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#252

Post by andoando » Sat, Oct 12, 2024, 9:37 PM UTC

notfed wrote: post #240

thegrim33 wrote: post #173

The results are based on a grand total of 25 people in the psilocybin group and 21 people in the SSRI group. The sample size is pretty small. The methodology is also kind of strange, the psilocybin group got a total of 20 hours of in-person therapy during their 'treatment' and 6 follow-up skype calls, whereas the SSRI didn't get anything other than the 6 month questionaire. Those 20 hours of personalized therapy whil…

If that's true, I'm confused how this is a "double-blind, randomized, controlled trial"? Also, what's up with drug studies always having such a low sample size? Is it really that hard to find people who'd volunteer to get free drugs?

Its expensive. Statistically speaking its really not that small. You can always argue p hacking but these are always useful as a means to do further research

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#253

Post by beardedwizard » Sat, Oct 12, 2024, 9:37 PM UTC

DiscourseFan wrote: post #82

Ok like most of you I’ve taken psychedelic drugs. I’ve had bad experiences sure, but I’m fine now. The issue is that what people generally say, like, “oh sometimes you need to encounter your demons,” maybe that will be temporarily traumatizing—in general people recover from that. The real issues are…more complex. More complex than any diagnoses in the DSM can cover. The brain is very complicated, and everyone’s brain…

This is a real risk I see overlooked and minimized often. People should not assume it can't happen to them.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#254

Post by andoando » Sat, Oct 12, 2024, 9:38 PM UTC

neom wrote: post #21

Psilocybin saved my life. I'm no longer suicidal, I'm no longer a practicing alcoholic, and outside of a few things here and there, I'm generally at peace with my life. I cannot express how grateful I am for psilocybin.

Can you share some info on how much you took, and in what setting you took them, what you did on the trip, etc? I have a bunch of shrooms sitting in my cabinet but I havent had got any life altering effect out of them.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#255

Post by andoando » Sat, Oct 12, 2024, 9:39 PM UTC

neom wrote: post #38

agumonkey wrote: post #25

Earlier quoted context omitted.

Is it something that you still take here and there or was it a time limited therapy ? Congrats on finding a cure for your ailments

I did 3 sessions of 8 grams in silent darkness for 3 weekends in a row and that basically "beat the devil out of me" as they say - it was very very difficult, and a lot of work, but well worth it.I've only felt the "brain haze" (I call it) once since then, I took a gram and went for a long walk in the forest, back to no haze. It's been about 7/8 months and I can feel the "haze" building in my mind again, so I plan to…

8 grams in one sitting? Im not even so worried about the psychological response but even a gram can give me extreme stomach pain and nausea that ruins the whole thing.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#256

Post by andoando » Sat, Oct 12, 2024, 9:48 PM UTC

tristanMatthias wrote: post #163

neom wrote: post #38

Earlier quoted context omitted.

I did 3 sessions of 8 grams in silent darkness for 3 weekends in a row and that basically "beat the devil out of me" as they say - it was very very difficult, and a lot of work, but well worth it.I've only felt the "brain haze" (I call it) once since then, I took a gram and went for a long walk in the forest, back to no haze. It's been about 7/8 months and I can feel the "haze" building in my mind again, so I plan to…

Totally agree. The variance between species can be dramatic! 2.5 grams of Golden teacher was a standard trip, vs 0.5 grams of PES Amazonian was enough to send my friend into a full blown “awakening” (physical responses and everything). It’s fascinating how they can hit different. Also important to keep in mind the same dose can hit someone different each time depending on surrounding life conditions. I’m a big believ…

It's really hard to say because your mental state of being, how tired/hungry/etc you are, and thr environment you take it in are huge factors.

Taking it alone vs with friends is going to be a dramatic difference on its own, just because of what neural pathways are active when you take them.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#257

Post by AI_beffr » Sat, Oct 12, 2024, 9:51 PM UTC

in 2020 i was very interested in psychedelics because of the breakthrough with PTSD and MDMA via MAPS. so i read pihkal and tihkal and i started reading a biochemistry textbook and generally took an intense interest in that area. and i went to oakland when i had the chance to be back in the bay area and i went to zide door and bought a small amount of psilocybin. at a bohemian friends house (it has since been cleaned out and sold, perhaps the last such house in the bay area at the time!) i took the little capsule in my palm and contemplated if i really wanted to take the risk. and i did. it was not a large enough dose to produce a psychoactive effect -- i think i had read that a psychoactive dose was not necessary to see benefits in mental health. there is one effect that i remember very clearly. it was when it got later into the night that i noticed something subtle but extremely strange. i felt awake or energized in some way. and i realized that my whole life, during the evening and late hours i would be sort of depressed and not feeling good. and so that was the first time that i felt lucid and energized after dusk. my whole life i had always known that i feel very depressed and agitated at dusk. but this experience really showed me how abnormal it was. later on i made a connection that is very oddly absent in medical circles that explains this. you know how when someone is having a deadly allergic reaction they are meant to use what is known as an "epi-pen?" thats because epinephrine, whats inside the pen, reduces inflammation. but what isnt mentioned or connected anywhere to anything is that when you go to sleep at night your body massively reduces the level of epinephrine that circulates in your blood so that you can sleep. inflammation therefore must increase. and inflammation is implicated in many psychiatric disorders including and perhaps most of all with depression.

one time much later i was in the hospital because i had a bad fever. maybe i was being kind of paranoid for going in. but as i was laying in the hospital bed my fever suddenly broke. and a wave of intense depression, unmistakable, washed over me. i thought this might be turning into an emergency but soon enough it passed as if nothing had happened. it was very useful to know about the connection between inflammation and depression during that little journey.

why is the connection between inflammation and various psychiatric diseases not taken seriously by the medical establishment? because its too complicated of a subsystem for a statistical study to tease it out. even if it were the sole cause of depression it still wouldnt lend itself to any study that is not exploring directly the biochemical mechanism. expect some breakthroughs in this area.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#258

Post by luckydata » Sat, Oct 12, 2024, 9:53 PM UTC

thegrim33 wrote: post #173

The results are based on a grand total of 25 people in the psilocybin group and 21 people in the SSRI group. The sample size is pretty small. The methodology is also kind of strange, the psilocybin group got a total of 20 hours of in-person therapy during their 'treatment' and 6 follow-up skype calls, whereas the SSRI didn't get anything other than the 6 month questionaire. Those 20 hours of personalized therapy whil…

Therapy is such a wash statistically that I'm not particularly confused or concerned by that, and everyone that has ever taken psylocibin knows the results are typical.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#259

Post by radlad » Sat, Oct 12, 2024, 9:56 PM UTC

SoftTalker wrote: post #219

dingnuts wrote: post #201

Earlier quoted context omitted.

funny, I could have written the same post but about boring old general anesthesia given before surgery

How long ago? Every general anesthesia I've had was basically "OK you'll start to get sleepy now" and then "ok we're finished" and zero awareness of any elapsed time.

The paper here is worth a look: https://news.ycombinator.com/item?id=36323275

Also this post has stuck with me through the years: https://news.ycombinator.com/item?id=24566568

Be sure to scroll down to the comment thread started by myself248.

Re: Psilocybin bests SSRI for major depression in first long-term comparison

#260

Post by arcticbull » Sat, Oct 12, 2024, 10:05 PM UTC

luckydata wrote: post #258

thegrim33 wrote: post #173

The results are based on a grand total of 25 people in the psilocybin group and 21 people in the SSRI group. The sample size is pretty small. The methodology is also kind of strange, the psilocybin group got a total of 20 hours of in-person therapy during their 'treatment' and 6 follow-up skype calls, whereas the SSRI didn't get anything other than the 6 month questionaire. Those 20 hours of personalized therapy whil…

Therapy is such a wash statistically that I'm not particularly confused or concerned by that, and everyone that has ever taken psylocibin knows the results are typical.

It’s kinda interesting you say that because studies show that SSRIs are not much better than placebo for treating depression, and that therapy plus SSRIs is the best treatment available right now.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592645/