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Author: Subject: Ayahuasca psychedelic tested for depression
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[*] posted on 21-5-2015 at 10:22


Quote: Originally posted by Nicodem  

I already cited the Carhart-Harris and Nutt, et al. studies for the fMRI measurments that were crucial to determine the mechanism of action of psychedelic drugs (in short, the inhibition of certain brain hubs that direct or filter out information from being processed; see also their new study on DMT and ayahuasca DOI: 10.1523/JNEUROSCI.2063-13.2013). The same group also uses magnetoencephalography (MEG) and EEG.
See also Vollenweider's studies that managed to connect brain scanning results with psychometric results, particularly nicely with the psychological indicator for mystic experiences (so called "oceanic boundlessness").



I have to look that up.
For whatever reason it is these "map" studies that I can relate to the best. It's most likely because I can put an image to an idea. Further on in that paragraph you also mentioned hormones. I have to read more on this as well.

What you stated for Vollenweider is what I believe I am most interested in. Making the connections between these combined brain scans, and other human sciences. There HAS to be a simple, demonstrable approach to seeing exactly what happens, and why. (mystical experience)


Quote: Originally posted by Nicodem  

Are you asking if neuroses cause detectable changes in the receptor density, neuronal firing frequency, and so on, all the way to neuronal plasticity? Of course they do. That is how the brain works. Every event, every piece of information, every neural signal that enters your brain, can and generally does physically alter the brains. There is no such thing as the concepts of hardware and software to be applied for the brains. Regardless of how complex the animal and its brain is, neuronal plasticity is at the very base of its functionality. In fact, that external information causes physical and observable changes in the brain was first discovered in some simple slugs, if I remember correctly.




I think I was a little too far off the base here. I already knew the answer to this one...

I was married to a crazy gal. I mean REAL crazy. (bi-polar, paranoid, schizophrenic) Her doctor(s) kept switching/combining medications, and the girl went thru hell with all the changes. Physically, and emotionally.
I kept asking why the wouldn't do some simple brain scans to see what was happening physically to her. Not while they had her all doped up but when she was clean of all the drugs.
Not one of them ever had a satisfactory answer. One flat out said it was too expensive to run these sort of tests, and they might not be conclusive even if they were run.
My reply was "Is it any less expensive to keep treating her with different combos, and HOPE to find something that worked? Is it less expensive to have her committed 4-7 times a year due to episodes, and reactions? What about the peripheral costs? What about her children? Her family?

Point is since they know certain base line patterns, isn't it easier to SEE what is wrong before assuming what is wrong?


Quote: Originally posted by Nicodem  

Quote:
It would all seem to be less of a "shotgun" approach if there were more constants in the studies. As in every study had to use the same methods for comparison.


Would you mind to cite these studies with "shotgun" approaches so that we at least know what you are talking about.

[Edited on 21/5/2015 by Nicodem]



Well what I mean here is what I addressed above. Does anyone really sit down, and think all of this thru logically? In my x-wifes case... A simple comparison of the known factors should easily point to a potential solution.
It seams to me that these issues have been studied for centuries yet there is no correlated solution.
We understand a rat will swim till it dies or just drown depending on what it's brain tells it to do. We know how to change what the brain tells it to do. We know the mechanisms... Why are there so many holes in this research?

I get the fact that ONE scientist can not possibly correlate all the known data. Hell, even entire institutes have enough combined data to stifle their own results. Something is always lost.
What about computer analysis? Has anyone developed a program to correlate all the know data to seek the commonalities? Sort of a code breaker for the brain. I get the fact that computers only do what they are programmed to do, and can not "think" but it would seem an easy task to at least search for commonalities.

I appreciate you fellas keeping this thread going. This is really the most interesting field in science IMHO.




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[*] posted on 21-5-2015 at 15:39


Zombie, I think part of the problem is that you may be conflating CSF and brain bloodflow chemistry with the neural connections themselves. If you want to measure the chemicals in the solution around regions of the brain, you use in vivo microdialysis. If you want to see what happens in each cell or neuron due to drug activity, there is not really a good way to do this now. Some techniques such as patch clamp techniques can show what electrical differences are occuring on various scales (single channel, multicell, etc.) but they have limitations. If want to look at what neuronal activity does in response to to a drug, which tells a lot about the pathways involved, you use MEG, EEG, fMRI, etc. To get a taste of how some of these techniques can work together, read what Nicodem has linked and the Riegel and Kalivas article on benzodiazepine addiction and dependence in PMID: 20148025. It's a fantastic article resolving what was, at once, a mystery in neuropharmacology and drug addiction.

These techniques all tell you different things. They have subtly different implications in terms of longterm effects. You can manipulate each of these by applying different drugs, transcranial magnetic simulation, electrical impulses. It is the context that is important, as gene expression, neural connections, hormonal chemistry, etc. all change in normal, healthy humans. They change on circadian rhythms to assist with sleep regulation (timless/period genes and per, tim, clock proteins). They vary in addiction, such as the imbalance in CRF/cAMP/NPY feedback loop in chronic alcoholic abusers.

Finding/knowing the exact right molecule you want to adjust in an animal of person is just not possible. Knowing how to specifically adjust it in one particular region of the brain is not possible. Being sure you don't affect other parts of the body is definitely not possible. Even knowing what was cause vs. effect is very difficult in these complex systems.
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[*] posted on 21-5-2015 at 18:04


Born a hundred years too soon I guess... It seems it should all be so simple.



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[*] posted on 21-5-2015 at 20:26


Zombie, part of the reason it is simple to you is that you don't understand the resolution or scope of the data, the difficulty in normalizing data to be quantifiably comparable to different experiments even with different equipment and parameters, and the fidelity of some of these experiments. Sometimes we just know what pathways interact, but not what they say, or where in the neuronal game of telephone a particular operation takes place. Reversible cryo-lesioning studies in animals can tell us more about what regions of a neuronal pathway actually do things, but these are not that precise, and again have their own problems.

You asked about some kind of big data analysis center. I knew a small agency that tried automated literature and data analysis for topics including these types of issues... and let's just say the tens of millions of tax dollars wasted could have bought a lot of real science. That is not to say a better implementation with more collaboration wouldn't work, but it is far from easy. Fortunes and lots of intellect has hammered away at it to little avail thusfar.
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[*] posted on 21-5-2015 at 20:39


Zombie, part of the reason it is simple to you is that you don't understand the resolution or scope of the data, the difficulty in normalizing data to be quantifiably comparable to different experiments even with different equipment and parameters, and the fidelity of some of these experiments. Sometimes we just know what pathways interact, but not what they say, or where in the neuronal game of telephone a particular operation takes place. Reversible cryo-lesioning studies in animals can tell us more about what regions of a neuronal pathway actually do things, but these are not that precise, and again have their own problems.

You asked about some kind of big data analysis center. I knew a small agency that tried automated literature and data analysis for topics including these types of issues... and let's just say the tens of millions of tax dollars wasted could have bought a lot of real science. That is not to say a better implementation with more collaboration wouldn't work, but it is far from easy. Fortunes and lots of intellect has hammered away at it to little avail thusfar.
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[*] posted on 21-5-2015 at 21:03


Well I kind of understand chipping away at large projects simultaneously. You keep at it until everything comes together.

Now isn't it similar in (I guess this is molecular medicine?) , and neuroscience? I do get the scope you are talking about. I thought that the tiny little things were all nailed down.
I mean I thought that the brain scan techniques described in the articles were real?

Is part of the problem in allocation to resources? Like who gets to play w/ the baseball but I don't want it getting dirty cause it's mine?

Yeah we did cover this, I just have a hard time accepting it.
Forget about things like dinosaurs, moon rocks, growing corn in space stations, WAR, and volcanoes for awhile. Work on medicine. I think it's a reasonable request.

Maybe it's an overall complacency in humanity... we're not going to survive this anyway. Why bother.




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[*] posted on 23-5-2015 at 07:45


After doing some reading about it, I found out that the sub-threshold to threshold dosing of psychedelic drugs is quite popular among some people. They call it "microdosing" (named after the pharmacological method for safe pharmacokinetics probing of new drug candidates). This is not exactly the chronic microdosing that Zombie proposes, however there is some information that comes close to that. Apparently, it is possible to continously microdose using a protocol of 2 days at about 10-20 micrograms LSD, followed by a recovering third day and then all over again. This is supposedly enough to prevent tolerance. Interestingly, even though 10 micrograms is generally considered a sub-threshold dose in regard to the psychotropic effects (30 micrograms is the typical threshold), it was found to improve mood, performance, creativity and is is self-reported as generally beneficial. Until I see scientific results on a longterm study, I rather remain skeptical on how healthy this is supposed to be.

James Fadiman did some research on the application of microdosing in problem solving and creativity enhancement while it was still allowed 5 decades ago and then kept on researching by gathering information from psychedelics users. He has written about it in his books, particularly in the "The Psychedelic Explorer's Guide" and has a nice web site with all his interviews in video and audio formats:
http://jamesfadiman.com/watch-hear.html
For now, I have only listened to his interview for the "The Tim Ferriss Show", but I was seriously impressed.

In regard to interviews and other video materials, here are a few other suggestions:

The LondonReal interviews in relation to psychedelics. They managed to make some excellent interviews with interesting people (I highly recommend the interview with R. Doblin, D. Nutt and R. Carhart-Harris). They also have there several very interesting first hand accounts of ayahuasca and DMT experience. So far, all the episodes I watched were totally interesting.

Hear also the interview with David E. Nichols at Horizons'08.

TEDx: Roland Griffiths on psilocybin and his lecture "The Mystical Experience and Psilocybin Research". See also the account of two of the Johns Hopkins study subjects (participant 1 and participant 2). These are excerpts from the documentary "The Substance" which is an excellent film that I highly recommend (its torrent is easy to find).

BBC Horizon: Psychedelic Science is another excellent documentary.

Inside LSD is a National geographic documentary. Unfortunately it is made in a very lousy style. It looks like some documentary that is made specifically only for the USA public and therefore brings sensationalism in front of factuality, but might be worth seeing.

How do psychedelic drugs work on the brain? is a lecture from R. Carhart-Harris.

Neurobiology of Psychedelics: Implication for Mood Disorders is a lecture from F. Vollenweider about his Swiss group's work on psilocybin, MDMA, ketamine and other related compounds.

[Edited on 23/5/2015 by Nicodem]
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[*] posted on 23-5-2015 at 10:33


Thank you for posting all of those links.

I have seen 2-3 of them, and others are new to me.
Your statements about self reported improvements in creativity, problem solving, and an overall improvement in the quality of life (my term) are really spot on for my own experience with psilocybin.
I can only assume that others have realized that taking these drugs to threshold, and beyond is not needed unless you are only looking for recreational use. Same for most other mis-used, and abused drugs.

Getting back to DMT... Since it is so similar to psilocybin my hope is it can have similar effects if taken in moderation, and I again hope that the effect can be much more profound. Meaning it can help with MORE self reported symptoms.

The only drawback, and thing that prevents me from experimenting with it is the need for it to be smoked or injected for it to be active on it's own.
I have no use for needles due to all the potential complications, and smoking something off in a corner just feels wrong. That's a bad way to preface a "treatment"

I have considered extracting MAOIs, and DMT to experiment with oral dosing. My life long diet, and other potential complications prevent this.

I sort of feel like a poor kid that found the Sears Xmas book in the mailbox. All of this potentially life changing stuff out there, and you wind up in prison for trying to improve your quality of life yet crack, and dope slingers pay off patrol cops or entire prescient-s to hawk their wares. Please don't comment on that statement...

It's rather sad really... If your life is more comfortable then it only follows that others around you can not help but to reap the benefits. Why oh why is something so simple, so very complex.

I'm going to have a long night watching those vids.
Thanks Nickodem.




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[*] posted on 5-8-2015 at 05:49


It appears that Jim Fadiman stirred quite some interest in "microdosing" with his latest study on self-reported effects of microdosing of psychedelics. It appears this topic become quite fashionable since the discussion in this thread. Several media reports talk about it:

Reset me, 21. May: Benefits Of Microdosing With LSD And Psilocybin Mushrooms

Raw Story, 17. June: Microdosing — a new, low-key way to use psychedelics

The Fix, 30. June: 'Microdosing' Psychedelics in Daily Life Shows Increased Focus, Emotional Clarity

Live science, 8. July: Short Trip? More People 'Microdosing' on Psychedelic Drugs

The Vice, 8. July: Can a Low Dose Go a Long Way?

-------------

As an interesting side note, at least one pharmaceutical company is considering a new application of ketamine for treating depression, however it appears they cannot figure out the mechanism of action and posted this problem as an Innocentive challenge. Ketamine is perfect as it is an already registered drug, so a company only needs to provide a final dosage form for use in a new therapy and skips the most expensive part of the development. But apparently they cannot figure out how this drug can cure depression upon a single application. Looks like their scientist never heard of neuronal plasticity.

Boehringer Ingelheim Challenge: Understanding the Antidepressant Effect of Ketamine

The challenge just got awarded (it was still active last month when I checked). I wish I could see the awarded solution. Ketamine is technically not a psychedelic. It is a dissociative, but just like psychedelics it is well known for facilitating the mystical state.




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[*] posted on 20-8-2015 at 13:26


Nicodem,

Thanks for providing all these links. I've only recently returned to the forums after a 7-year hiatus, and it's certainly a breath of fresh air to see the interest in non-recreational uses of psychotropics.

Indeed, I've had a renewed desire to try these micro-dosing experiments after struggling with clinical depression in recent years, so all these discussions have a massive personal benefit for me. I've always been skeptical of the results though, despite the amount of research poured into exploring psychedelics as therapeutics in more controlled medical environments. I mean, you would think that someone would have been investigating low-dosing much earlier in the century...

But the question that tripping-level dosages brings about the changes that lead to long-term neurological/psychological improvement is something I've really hotly debated for myself in my experiences with psychedelics. The weeks and months after the high certainly FEEL like I'm doing better, but without sustained effort in some way, like better lifestyle or improved relationships, the brain certainly can't keep up the feeling. Since then, I've steered away from them - I've essentially associated my ecstatic experiences with the rise of my mood disorder. IMHO, and a subjective perspective, of course. For all I know, some laced substance wore away the neurological circuitry. Or just plain damn genetic luck. Now I'm rambling.

Zombie, I certainly agree with you on your perspective. As more and more information comes out, I feel like I'm just sitting here twiddling my thumbs before an actual full-blown therapeutic legally hits the market.

If you don't mind sharing, Zombie, what sort of dietary problems would you have to face if you wanted to go the gastro-MAOI route for DMT? Milk, bread and meat seem to be the major problem foods, if I recall correctly.




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[*] posted on 1-12-2015 at 20:56


Few month ago my velociraptor tried micro-dosing.

Some of you guys might have seen some articles about micro-dosing psychedelics recently.. and my baby velociraptor tried it out.

I dont know if the SCM community likes this, but i found my velociraptor's diary and here is what it wrote. I found it pretty interesting.


---------


11:00 am - my pet velociraptor took between 20-30 ug of LSD-25.

1:00 pm - my pet velociraptor told me it felt slight body high from the dose. it told me it might been too much of a dose for micro-dosing, it said a good dose is probably 15-20 ug. However no obvious visuals were experienced

2pm - my pet velociraptor finishes all his homework and was surprised that an hour passed. For a long time i saw my velociraptor sitting really focused on its work, it told me it felt like around 10 minutes.

4pm - my pet velociraptor really wanted to go out for a walk because the sun is setting and the world is beautiful.

5pm - my pet velociraptor had a meal and drank some coffee for its soccer game in a dinning hall, it told me it can clearly listen to multiple conversations even though it was really quite, as if its ears were enhanced.

7pm - my pet velociraptor played some soccer, it told me it forgot the outside universe existed during the event because it was too focused in the game. My velociraptor assisted on goal in the game and its team beat some other velociraptors 1-0. I was told the addition of adrenaline into its body made him feel very calm, and slight tunnel vision was experienced.

8pm - my pet velociraptor thought the effects were almost none.

My pet velociraptor said today was a good day, he suggests its a little over whelming for him because he felt over-dosed for daily activities and 10-20ug was probably enough. He would love to do it again once in a while, especially if he would go out side for a long walk, because my velociraptor kept thinking about its life and questioning its existence.
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[*] posted on 3-3-2020 at 02:19
Makes you wonder what they're up to now


www.yahoo.com/news/did-the-ci-as-notorious-mind-control-prog...


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A scientist who experiments on other people is called a pioneer.


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