
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf] - dtawfik1
https://www.nature.com/articles/s41598-017-13282-7.pdf
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ComputerGuru
Before self-medicating based on this combined with a self-diagnosis, consider
that LSD and psilocybin have a nasty tendency of triggering latent
psychological conditions if not taken in the appropriate dosage and in a
controlled environment.

[ref:
[http://www.nationaldrugstrategy.gov.au/internet/drugstrategy...](http://www.nationaldrugstrategy.gov.au/internet/drugstrategy/publishing.nsf/Content/FE16C454A782A8AFCA2575BE002044D0/$File/mono71.pdf)
]

~~~
cheshire_cat
I'd definitely advise anyone thinking about this to do their research but the
risk doesn't seem to be as large as often suggested. There was a large US
study that showed no correlation between lifetime psychedelic use and mental
health problems.

"[...] lifetime use of LSD, psilocybin, mescaline, or peyote, or past year use
of LSD, was not associated with a higher rate of mental health problems."

[https://www.nature.com/news/no-link-found-between-
psychedeli...](https://www.nature.com/news/no-link-found-between-psychedelics-
and-psychosis-1.16968)
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747247/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747247/)

~~~
CardenB
“Life time use” and “one time use triggering latent psychological conditions”
are very different. Of course those who use over a long period of time aren’t
showing adverse conditions. The ones who were triggered stayed away.

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mulvya
“Life time use” != "use over a long period of time"

In epidemiological surveys, lifetime use == reports using at least once.

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Alex3917
> In epidemiological surveys, lifetime use == reports using at least once.

Not necessarily. For smoking you need to smoke 100 cigarettes before
qualifying for lifetime use.

~~~
clappski
100 cigarettes seems like a very low threshold, that’s 5 packs of 20, even
moderate smokers (>10 per day) could go through 200 in a month.

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trgv
Assuming that psilocybin is effective at treating depression, I find myself
wondering whether actual conscious experience (that is, being high) is an
essential part of its effectiveness or not.

To put this another way, imagine someone takes whatever dose of psilocybin and
then is rendered unconsciousness until the perceptual effects wear off. Will
there be any difference in its effectiveness as a treatment for depression?

~~~
delegate
Being conscious during the trip is an essential part of the healing process.
In fact, healing comes from the realization of what consciousness really is,
that death is not the end, how my little self is just a stubborn part of a
larger infinite consciousness that is the Universe thinking itself into
existence, etc. You 'remember' what you really are and that's liberating.

One theory that I subscribe to is that the drug increases the brain's
neuroplasticity, allowing for new pathways to be created between sometimes
unrelated parts of the brain.

Being conscious allows one to guide (but not control heh) this process, where
the user can pick a subject to think about and immerse oneself into a
audiovisual/emotional/cognitive hallucinatory experience that follows related
to that subject. Inevitably the most pressing issues of one's life will
surface, allowing the user to examine them from all these different angles -
accept, forgive, love and heal.

~~~
CuriouslyC
Psychedelics absolutely increase neuroplasticity, via triggering the release
of BDNF. They are also extremely potent anti-inflammatories.

Regarding the value of the trip itself, you pretty much hit the nail on the
head. It always makes me chuckle when scientists talk about trying to isolate
the antidepressant effect from the psychedelic nature of the experience. That
is a sure sign that the people studying the compound lack significant first-
hand experience with it.

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adammunich
Anecdotally, I've seen psilocybin to be an excellent assistant, but not
treatment per say, for depression. It can temporarily free people from
negative thought patterns; but lasting change only comes from persistent self-
reflection and actualization.

~~~
uoaei
Anecdotally, this is precisely my experience. It'll start the engine, but you
have to navigate the course.

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gt_
I still don't have the words to explain how, but I insist that psilocybin
played a major role in the most successful period of my life. I am generally a
highly skeptical person and remain a little frustrated that I can't articulate
better such an impactful correlation.

~~~
anythingnonidin
Can you share any more details?

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debarshri
My girlfriend has treatment resistant depression. Most of her life doctors
prescribed SSRI based drugs which didn't really work. A lot of money was also
spent on psychiatrist for CBT. Based on a youtube videos and blogpost, read
about 5HTP.

I think 5htp supplements really works in cases where depression is genetic or
the depression exists since childhood, where the cause of depression is not
known. You can actually see the result and change in personality within few
week. I think 5HTP should be the first medication before any other
psychoactive medications are consumed.

~~~
jonnycomputer
Depression is such a broad spectrum disorder (or put another way, a highly
variable cluster of symptoms), that its hard to generalize in any way.

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beagle3
Is Psilocybin and/or Ayahuasaca and/or any other DMT source legal anywhere in
the world? I would expect at least _some_ places make it legal, possibly have
hundreds/thousands of years of experience that might be interesting to read
alongside modern studies.

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atom-morgan
I believe Psilocybin is legal enough (decriminalized?) to purchase in
Amsterdam right? I remember watching a Vice piece on truffles.

~~~
hellofunk
Mushrooms were made illegal in the netherlands a few years ago, but "magic
truffles" are a loophole in the law because they are not mushrooms, so they
are still for sale. It's a bid of a shady distinction.

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DenisM
From the abstract:

[...] Quality pre and post treatment fMRI data were collected from 16 of 19
patients. Decreased depressive symptoms were observed in all 19 patients at
1-week post-treatment and 47% met criteria for response at 5 weeks. [...]

~~~
discordance
N=19 is a very small sample size. I would be careful forming opinions based on
this study.

~~~
pizza
even if it were e.g. sixteen or seventeen, for all of them to report lessened
depression a week after is a fairly strong finding, at least enough to merit
someone else attempting to reproduce the research. present depression
medication barely works better than placebo

~~~
DanBC
> present depression medication barely works better than placebo

That depends on quite a few things, and so far none of the psilocybin
treatments are controlling for those. It's possible (likely, even) that if
psilocybin is approved for treatment and used as often as other meds we'll see
effectiveness plummet.

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anythingnonidin
It is absolutely shocking to me that research into psychedelics isn't swamped
with funding. I'd imagine that some wealthy people must find this stuff
extremely intriguing - Yuri Milner is spending $100 million on space
exploration, and a psilocybin phase 3 research trial needs ~$10 million and
finds it really hard to raise money?

Psychedelics have extremely high therapeutic potential, and are also just
interesting in a similar same way as space exploration is interesting.

~~~
diogenescynic
>It is absolutely shocking to me that research into psychedelics isn't swamped
with funding.

I find it more shocking that we as a society put up with it. All the
pharmaceutical companies would much rather find synthetic alternatives they
can patent/control. Follow the money, as always, and it makes perfect sense.

~~~
sannee
> I find it more shocking that we as a society put up with it. All the
> pharmaceutical companies would much rather find synthetic alternatives they
> can patent/control. Follow the money, as always, and it makes perfect sense.

Why are not pharmaceutical companies pushing synthetic psychedelics then? The
whole {P,T}IHKAL is full of them, it surely isn't a large problem to cook up
another variant to patent.

~~~
anythingnonidin
Good question. My guess at first pass is that {P,T}IHKAL has explored the easy
search space? But, I'm not very certain here.

Also, the Usona Institute had a job posting for a psychedelic chemist doing
just that earlier this year. They are the group supporting the psilocybin
phase 3 trials.

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rubatuga
I think it would make a trip to a psychologists office much more exciting

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lighttower
What makes this go into Nature rather than a regular medical journal?

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avodonosov
Heroin, BTW, helps from cough.

[https://en.wikipedia.org/wiki/Heroin#History](https://en.wikipedia.org/wiki/Heroin#History)

> From 1898 through to 1910, diamorphine was marketed under the trademark name
> Heroin as a non-addictive morphine substitute and cough suppressant.

~~~
snvzz
>heroin

>non-addictive

I'm confused.

~~~
askvictor
> marketed as

Anti depressants are addictive in the classical sense. But the pharmaceutical
companies don't call it 'withdrawl' but rather 'discontinuation syndrome' when
you're coming off them. Looks like not much as changed in 100 odd years of
pharmaceutical marketing.

~~~
DanBC
> Anti depressants are addictive in the classical sense.

No, they are not. addiction in the classic sense requires:

1) pre-occupation and seeking

2) tolerance

3) dependence

Anti depressant meds don't have any of these. But even if you call
discontinuation effects "dependence" you still don't have tolerance or drug
seeking and preoccupation.

