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Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

nature.com

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Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#31

Post by hwillis »

trgv wrote: post #10

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 depres…

Serotonin and brain function: a tale of two receptors by Robin Carhart-Harris and David Nutt[1] suggests that the main affects are due to the conscious impacts on behavior, but that those impacts don't depend on the experience of being high so much as the long-lasting effects of the stimulation. It basically comes down to whether or not you believe them though.

[1] http://slatestarcodex.com/2017/10/10/ssc-journal-club-seroto...

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#32

Post by [deleted] »

cheshire_cat wrote: post #9
ComputerGuru wrote: post #4

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... ]

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.co…

[deleted]

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#33

Post by notduncansmith »

trgv wrote: post #10

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 depres…

Doubtful, but I'm sure you could find a way if you really tried, maybe with someone to talk to you while you sleep.

Euphoria is only one of several effects on the consciousness, and in many cases the deliberate cognitive processes that are enabled/invited by that combination of effects are the real treatment. This is when the issues causing the depression are thought patterns, which can sometimes be more effectively examined and dealt with under the influence of ego-fear-dissolving euphoria, dissociativity, form constant hallucinations, etc.

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#34

Post by mulvya »

CardenB wrote: post #30
cheshire_cat wrote: post #9

Earlier quoted context omitted.

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.co…

“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.

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

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

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#36

Post by drvdevd »

trgv wrote: post #10

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 depres…

I’m not going to look for references right now, but there is current research into the anti-inflammatory effects of classical psychedelics.

Anecdotally, it has been speculated by researchers that it is in fact this effect that produces many of the observed benefits, apart from the psychedelic experience itself.

And so people are looking at analogs that can have some of the same receptor affinity profiles without causing psychedelic effects, or with much diminished psychedelic effects.

Personally I think a protocol such as what you suggest is a better approach and would work.

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#37

Post by ssijak »

trgv wrote: post #10

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 depres…

Hallucinacions are part of the healing with any psychedelic for me. Set yourself in a pleasant environment with cool people, and the experience that you get will be long lasting and behavior changing. Not always life changing, but it always added something positive to my views, thinking or overall scence of wellbeing. At it is the same for mushrooms, lsd and ayahuasca

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#38

Post by anythingnonidin »

ComputerGuru wrote: post #4

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... ]

Tendency: "an inclination toward a particular characteristic or type of behavior." "a strong chance that something will happen in a particular way"

> “Since the early 1990s, approximately 2000 doses of psilocybin (ranging from low to high doses) have been safely administered to humans in the United States and Europe, in carefully controlled scientific settings, with no reports of any medical or psychiatric serious AEs, including no reported cases of prolonged psychosis or HPPD (Studerus et al., 2011).”1

Then, to address 'controlled environment':

> “Lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81 (0.72–0.91)), past year suicidal thinking (weighted OR=0.86 (0.78–0.94)), past year suicidal planning (weighted OR=0.71 (0.54–0.94)), and past year suicide attempt (weighted OR=0.64 (0.46–0.89))”13

And

> According to US government statistics, magic mushrooms have been used by 22.8 million Americans at least once.12

https://tripsafe.org/shrooms/

While they can lead to this, tendency doesn't seem to be the right word to use.

I'm quite passionate about this topic and I think it's very important that people writing publicly and sharing opinions on these substances are accurately informed, and try to present statics and put references into context.

Does the above change your mind on this? If not, what would change your mind a little bit towards thinking that they don't have a tendency to do this?

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#39

Post by zamalek »

sdfin wrote: post #12
ComputerGuru wrote: post #4

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... ]

Is there proof that they have a tendency of triggering "latent" conditions, instead of generating the conditions? How can it be demonstated that conditions were latent before the use? Could it also be the case that people with potential mental illnesses is more likely to try drugs? Therefore being a correlational relationship instead of a causal one?

"Reefer Madness" is inconclusive [1] (so far as agitating an underlying psychosis). Many proponents would regard this as a affirmative result, however it does go both ways.

> Is there proof that they have a tendency of triggering "latent" conditions, instead of generating the conditions?

Personally, I've had panic attacks (originating from paranoia) bought on by historical heavy use - the correlation isn't subtle at all. Did my paranoia drive me to the initial peace associated with the drug? I'd have a hard time arguing otherwise - it really, really helped at first. My life was altered positively days after the previous dosage. If I take it now the situation becomes unbearable in less than 5 seconds. Anecdote disclaimer, as well as not being the same psychoactive drug (but it is psychoactive).

[1]: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...

Re: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

#40

Post by anythingnonidin »

trgv wrote: post #10

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 depres…

I believe we already have an answer for this - which is that most of the benefits of psilocybin on depression (and most other things) rely on the patient being conscious so that they are able to have a 'mystical-type experience.'

In almost all psilocybin studies, the effect is mediated by the degree to which the participant has a 'mystical-type experience.'

I don't imagine this could be experienced while unconscious, and so assuming that's correct, then it would be substantially less effective if someone was unconscious.

I would expect a small anti-depressant effect of psilocybin alone, possibly related to the serotonin 2A receptor and it's impact on well-being. But, to be very clear - the active experience of a 'mystical trip' is what causes a reduction in depression.

See:

http://journals.sagepub.com/doi/full/10.1177/026988111773127...

'Determinants of enduring effects were psilocybin-occasioned mystical-type experience'

http://journals.sagepub.com/doi/full/10.1177/026988111667551...

'The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression.'

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