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

#271

Post by throwup238 » Sat, Oct 12, 2024, 11:22 PM UTC

fsckboy wrote: post #266

M4v3R wrote: post #37

Earlier quoted context omitted.

Thanks for sharing this, you’re not the only one. I have a close friend who tried LSD as a last resort to get the best of his severe depression and suicidal thoughts (after being on SSRIs for his entire life) and just one session completely removed his suicidal thoughts for months . After this experience he repeats this whenever he feels the dark thoughts are coming back and it always curbs them down almost completel…

just consider, if it's so powerful in adjusting his brain, it's probably equally powerful in adjusting anybody's brain, and what if your brain doesn't need adjustment? there's no reason to think it's "idempotent" so to speak. https://en.wikipedia.org/wiki/Idempotence is the property of certain operations in mathematics and computer science whereby they can be applied multiple times without changing the result beyond…

I suspect there’s a lot of self selection at work already. The vast majority of people don’t jump straight into psilocybin and LSD, they progress to them by taking softer drugs like alcohol and cannabis. I think a lot of people who don’t need “adjustment” figure out drugs don’t do much for them and stop before they take the intense psychedelics, or they figure it out at lower doses and stop before they take the intense dose.

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

#272

Post by drilbo » Sat, Oct 12, 2024, 11:32 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…

>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.

They got 'matched' support, which reads to me as 'equivelent': "Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support (‘psilocybin therapy’ or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support (‘escitalopram treatment’ or ET)."

>They also measured results by a self-administered 16 question "quick inventory" depression survey. To enter the study they had to be officially diagnosed with major depression by a doctor, but the results of the study were based completely around a self-reported 16 question questionaire?

This is only the follow up portion, and as secondary measure at 6 weeks. The original study (https://clinicaltrials.gov/study/NCT03429075) says the primary measure was; "Change in blood oxygen level dependent (BOLD) signal during fMRI in response to emotional faces during an emotional faces paradigm done inside the fMRI scanner." at 6 weeks vs baseline.

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

#273

Post by [deleted] » Sat, Oct 12, 2024, 11:34 PM UTC

appplication wrote: post #211

brandall10 wrote: post #203

Earlier quoted context omitted.

Why did you take a very high dose? As someone who was experienced with psilocybin some 20+ years ago, I always took fairly consistent doses (roughly 3 grams), as I could sense taking much more would be playing with fire. This was pretty much a given amongst my circle of a dozen friends who experienced these trips with me… hero doses were almost never a good or healthy idea. Fun to read about on Erowid though, mostly…

> Why did you take a very high dose? Hindsight is 20/20 but often it’s not clear at the time if it’s a bad idea or how bad it can be. I think it’s not such a fair question to someone struggling to find effective treatment for mental health issues to make a mistake on dosing. Especially given both government and medical field have historically not amenable to openly communicating harm reduction or safe guidelines for…

[deleted]

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

#274

Post by advael » Sat, Oct 12, 2024, 11:34 PM UTC

refulgentis wrote: post #261

londons_explore wrote: post #251

Earlier quoted context omitted.

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 m…

This doesn't sound very helpful

I mean it sounds like a way to trick people into letting a giant company build a surveillance system, and I imagine aliens observing humans in this moment in history might conclude that's what we want, but for science or the benefit of the people "surveyed" it's mostly downsides

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

#275

Post by Wytwwww » Sat, Oct 12, 2024, 11:37 PM UTC

fsckboy wrote: post #264

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…

> The results are based on a grand total of 25 people in the psilocybin group and 21 people in the SSRI group. Statistical significance is based on sample size, and is independent of population size. Let that sink in, doesn't matter if your population is 100K or 8 billion, when you sample you are trying to understand the probabilities in your sample, not in the population. Therefore, (think about the birthday paradox…

> few dozen in the room with you is an adequate sample

It's not, though? Unless you're fine with a very high margin of error... Also the sample in studies like this is hardly ever close to being random anyway.

> it should not surprise you that statistical significance is achieved through a much smaller sample size

Sure... just with a very low confidence level.

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

#276

Post by standardUser » Sat, Oct 12, 2024, 11:39 PM UTC

romseb wrote: post #213

standardUser wrote: post #91

Earlier quoted context omitted.

I've have done a lot of drugs and know a lot of people who have done a lot of drugs, and psilocybin is far and away the substance that is most loved and gets the best reviews. It's not even close.

What are the more preferred plants/substances for personal growth and mental health?

If someone is unfamiliar with psychoactive drugs, I would suggest they eat a single mushroom cap in a safe, private, comfortable environment and with another person who has some experience. I think it is a more pleasurable and worthwhile experience than marijuana, which can actually be more intense and is more prone to generating anxiety and paranoia. There's lots of resources online and there are communities in a lot of cities that advocate mushroom use.

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

#277

Post by taurath » Sat, Oct 12, 2024, 11:41 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?

> Also, what's up with drug studies always having such a low sample size? Is it really that hard to find people who'd volunteer to get free drugs?

They try to make for no comorbidities and and for MDD that is pretty rare. It also means that we’re often studying rare configurations compared to those commonly seen in actual practice. Statistics doesn’t like confounding elements and humans are very confounding. So either you get “bad” statistics, or you get “bad” data. And why you have front line drugs that only have a helpful effect for 33% of people.

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

#278

Post by idunnoman1222 » Sat, Oct 12, 2024, 11:45 PM UTC

dontwearitout wrote: post #195

cubefox wrote: post #56

Unfortunately it's hardly possible to do proper case control studies with psilocybin, since the psychedelic effects cause unblinding. The participants know whether they are in the treatment or control group. > Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to 'let go', or b…

I've never found it compelling that blinding isn't possible for drug-naive patients. There are other drugs that could induce a "trip" and an unfamiliar individual could mistake for a minor psychedelic experience.

Really? name one.

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

#279

Post by fsckboy » Sat, Oct 12, 2024, 11:47 PM UTC

yieldcrv wrote: post #269

fsckboy wrote: post #266

Earlier quoted context omitted.

just consider, if it's so powerful in adjusting his brain, it's probably equally powerful in adjusting anybody's brain, and what if your brain doesn't need adjustment? there's no reason to think it's "idempotent" so to speak. https://en.wikipedia.org/wiki/Idempotence is the property of certain operations in mathematics and computer science whereby they can be applied multiple times without changing the result beyond…

everyone considers that, but because they’ll be dead by the time the studies narrow down anything they chose the substance that moves them towards results - or doesn’t everyone can perceive that psychedelic is doing many highly variable things at once and probably shouldn't be recommended, so they just say their experience

the vast majority of people who try psychedelics are not trying to escape untreatable clinical depression, they are doing it recreationally, for a roller coaster ride which they believe connects them with the Almighty or the Unknowable or the Dao or the All-loving Everpresent or the "insert word that sounds profound" These people are inspired—perhaps by the Almighty, i'm not judging—to preach The Gospel of psychedelics and praise any confirmation of these miracles. I'm simply pointing out that what appears to be the Omnipotence of the Almighty might very well be Selling Your Soul to the Devil for all you know. I'm an atheist, simply using metaphor to get the point across to you.

When you talk about how powerful medication is in warping the brain to cure intractable mental problems, that is not at all an endorsement of recreational use. Heroin makes you feel like your mother not only loves you, but makes up for her not loving when she abandoned you as a baby. Is heroin therefore a good idea? (and if you say "that's chemical dependency", you completely miss the point)

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

#280

Post by Wytwwww » Sat, Oct 12, 2024, 11:47 PM UTC

iknowSFR wrote: post #231

Sharlin wrote: post #221

Earlier quoted context omitted.

When "the system" subsidizes your therapy and your prescription drugs (as in most civilized societies), and indeed pays for your medical leave and loses value in the form of lost workdays, it definitely doesn't have much of an incentive to keep you in therapy or on drugs.

I get the impression that there’s misalignment on what “the system” is to each commenter here. One side views it as the larger society and the other as the pharmaceutical industry.

> society and the other as the pharmaceutical industry

The market is huge and executives usually care much more about short-term (or at the most medium-term) growth. A company that actually found some magical cure for depression they would have no reason to not undercut their competitors and still make massive amounts of money even if that would destroy their target market would disappear over the next 10-20 years.

Also aren't pretty much all the most popular antidepressants and related drugs relatively very chip. Nobody is making that much money selling SSRIs. Why would pharmaceutical companies forego hundreds of billions on purpose?