[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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