[HN Gopher] Single-Dose Psilocybin for Major Depressive Disorder...
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       Single-Dose Psilocybin for Major Depressive Disorder: Randomized
       Clinical Trial
        
       Author : bookofjoe
       Score  : 62 points
       Date   : 2023-12-09 13:22 UTC (9 hours ago)
        
 (HTM) web link (jamanetwork.com)
 (TXT) w3m dump (jamanetwork.com)
        
       | bjoli wrote:
       | There is a fantastic interview of David Nutt where they talk in
       | depth on the subject: https://youtu.be/UWhk2LMDwCc
        
       | Sakos wrote:
       | > Results A total of 104 participants (mean [SD] age, 41.1 [11.3]
       | years; 52 [50%] women) were randomized (51 to the psilocybin
       | group and 53 to the niacin group). Psilocybin treatment was
       | associated with significantly reduced MADRS scores compared with
       | niacin from baseline to day 43 (mean difference,-12.3 [95% CI,
       | -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean
       | difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin
       | treatment was also associated with significantly reduced Sheehan
       | Disability Scale scores compared with niacin (mean difference,
       | -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43.
       | More participants receiving psilocybin had sustained response
       | (but not remission) than those receiving niacin. There were no
       | serious treatment-emergent AEs; however, psilocybin treatment was
       | associated with a higher rate of overall AEs and a higher rate of
       | severe AEs.
        
         | readthenotes1 wrote:
         | AE=adverse events
        
       | jokoon wrote:
       | Some scientists have bridges to sell
        
         | dang wrote:
         | Maybe so, but please don't post unsubstantive comments to
         | Hacker News.
        
           | wredue wrote:
           | The anti-science brigading in hacker news of late has been on
           | another level.
           | 
           | At least once a week we are seeing massive pushes to
           | discredit science. Ominous "JAQing off" standard rabble like
           | "how can I trust science after news like this that I am
           | responding to on a device that exists only because science
           | exists!"
           | 
           | It's tiresome how quickly and efficiently the alt-right is at
           | taking over websites, and even more annoying how willing
           | moderators and administrators are to let it happen.
           | 
           | Unfortunately for this poster above, this post isn't going to
           | generate the rage bait necessary to rile up the alt-right
           | discord brigades.
        
       | ogogmad wrote:
       | There are concerning risks:
       | https://en.wikipedia.org/wiki/Hallucinogen_persisting_percep...
       | 
       | How does the paper address this? Haven't checked.
       | 
       | [EDIT]
       | 
       | Ctrl+f on "HPPD" and "disorder" found nothing relevant.
        
         | zoklet-enjoyer wrote:
         | I doubt the number of people experiencing this is anywhere
         | close to what Wikipedia says it is. I know a lot of people who
         | have used a lot of psychedelics from their late teens to
         | 30s/40s and none of them have had HPPD
        
           | schmichael wrote:
           | Only one of the studies Wikipedia included had concerning
           | results, and it was a survey of users. Such studies are good
           | indicators of where future research should be done, but only
           | demonstrate a loose correlation between psychedelics and
           | HPPD. There's no differentiating users who are "self-
           | medicating" the issue from psychedelics _causing_ the issue.
        
           | lambdaba wrote:
           | AFAIK this is not something that's seen with psilocybin,
           | maybe with frequent high dose LSD... Anyway, I wish people
           | didn't even bring this up because it'd be a shame if that
           | dissuaded anyone to try psilocybin.
        
         | schmichael wrote:
         | While I do hope these issues are researched, I'm not sure why
         | you find them "concerning." According to Wikipedia only 1 of
         | the 2 studies really seems well done, and that one reported no
         | HPPD.
         | 
         | Since SSRIs are extremely widely prescribed already and seem
         | capable of causing HPPD as well, I'm not sure what's making you
         | find them concerning for psilocybin in particular.
        
         | tpm wrote:
         | That's mostly a risk for recreational users I'd say.
         | Anecdotally, from people with psychedelic experience I know,
         | only massive multidrug abusers experience this sort of issues.
        
         | deepnotderp wrote:
         | Most HPPD is just floaters or tracers, and SSRIs can cause them
         | too.
         | 
         | The magnitude of HPPD and the frequency/prevalence need to be
         | studied, but I think seeing some extra floaters in exchange for
         | having a will to live is a trade most would take.
        
         | zug_zug wrote:
         | It addresses it as such "Visual perceptual effects (assessed
         | following resolution of acute drug effects) were reported by
         | 22/50 (44%) psilocybin participants on the day of dosing and by
         | 3/50 (6%) after the dosing day, all resolved by study
         | conclusion (See Table 3 for details)." [table shows it resolved
         | by day 9]
         | 
         | However the study also shows 2 people in the experiment group
         | (1 in the control) had an adverse effect that required
         | psychiatric attention. Unclear what that means (admitted to a
         | hospital or a phonecall with the therapist?)
        
       | underseacables wrote:
       | _Participants taking psychotropic agents who otherwise met
       | inclusion /exclusion criteria were eligible following medication
       | taper._
       | 
       | I have heard that people who are currently on an anti-depressant
       | have to take a larger dose of psilocybin. It was not surprising
       | to see that they'd want to taper the medication to maximize the
       | effect of the psilocybin.
        
         | blcknight wrote:
         | Not just a larger dose, most people on SSRI's won't trip no
         | matter how much psilocybin they consume.
        
           | akomtu wrote:
           | I'll make a guess that SSRIs act by inhibiting or even
           | destroying connections between neurons, creating the effect
           | of dullness, while mushrooms activate connections that were
           | previously dormant.
        
       | makeworld wrote:
       | How does the 25 mg used compare to what average non-research
       | users are ingesting?
        
         | zoklet-enjoyer wrote:
         | Probably about average? An 1/8 has around 35mg according to
         | this website https://pabcounseling.com/how-to-dose-psychedelic-
         | mushrooms/
        
       | Euphorbium wrote:
       | It has been the best antidepresant in the history of life, just
       | legalize it.
        
       | Eumenes wrote:
       | If it keeps people off poison like SSRIs, I'm all for it.
        
         | staticautomatic wrote:
         | What makes you say SSRIs are poison?
        
       | ec109685 wrote:
       | Interesting that so many people in study have taken psychedelics.
       | I wonder how that compares to general population?
       | 
       | " Mean (SD) participant age was 40.4 (10.9) years in the
       | psilocybin group and 41.8 (11.7) years in the niacin group; half
       | were men and the majority (89%) were White. Ten participants
       | (19.6%) in the psilocybin group and 13 (24.5%) in the niacin
       | group reported previous lifetime use of a psychedelic"
        
         | cubefox wrote:
         | I think US Americans generally take a lot of drugs.
        
       | cubefox wrote:
       | The problem with studying psychoactive substances is that they
       | can't realistically rule out a placebo effect. Psilocybin has
       | strong side effects, but niacin (the placebo for the control
       | group) has no side effects, so people know whether they are in
       | the treatment group or control group. The apparent positive
       | impact of psilocybin could just be a placebo effect.
       | 
       | A better idea would perhaps be to test two different psychoactive
       | drugs with similar effects, like LSD and psilocybin, so people
       | don't know which they got.
        
         | zug_zug wrote:
         | Great point, and the study even admits that point
         | 
         | "Limitations: First, the success of allocation blinding was not
         | assessed, and it is likely that the acute psychoactive effects
         | of psilocybin produced some degree of functional unblinding
         | that may have contributed to the observed effect in psilocybin-
         | treated participants and the increased dropout rate in niacin-
         | treated participants."
         | 
         | Unblinding = participants figure out if they got the real thing
         | 
         | I think a recent ketamine study found a lot of the clinical
         | effect went away if participants weren't awake/aware of the
         | treatment. Wonder if that could be used here.
        
           | amanaplanacanal wrote:
           | It's also possible that the conscious experience of the
           | effect is part of what makes it work. I'm not sure how you
           | would test that out.
        
           | cubefox wrote:
           | Yeah, though perhaps it is the trip itself that causes the
           | antidepressive effect, so if you prevent the trip via sleep,
           | the effect goes away.
        
         | Notatheist wrote:
         | >they can't realistically rule out a placebo effect.
         | 
         | Kind of like every other treatment for depression? Not being
         | funny here but I don't think we gave the control groups in
         | clinical trials for MAOIs brutal kicks to their blood pressure
         | every morning.
        
       | zug_zug wrote:
       | My take on these studies -- either read the whole study or don't
       | take it as evidence of anything. If you aren't motivated enough
       | to read 20-30 pages, then you probably shouldn't be willing to
       | risk your health around it.
       | 
       | For example title is great, but there's a bunch of other stuff to
       | be aware of in there. E.G. "the most common solicited AE was
       | headache in 33 of 50 participants (66%) receiving psilocybin and
       | 13 of 54 participants (24%) receiving niacin."
       | 
       | Also this study was only 6 weeks. I think the obvious question is
       | "Then what, do you redose, or hope it lasts?"
       | 
       | Lastly, anecdotally, I know a lot of people who recommended
       | hallucinogens personally, and many/most of them seemed believably
       | happier, but perhaps had other negative side-effects that a study
       | like this wouldn't measure (e.g. do you friends think you're
       | acting kinda weird now?). Some of these people seemed overly
       | invested in convincing me in a way that made me uncomfortable and
       | uncertain of their objectivity.
       | 
       | There's an interesting reply-all episode about microdosing LSD.
       | https://gimletmedia.com/shows/reply-all/2oh933
        
         | cubefox wrote:
         | People with depression probably don't care about headaches.
        
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       (page generated 2023-12-09 23:00 UTC)