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Offlinedemetris castaneda
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Hallucinogen actions on human brain
    #19239918 - 12/07/13 08:54 AM (10 years, 1 month ago)

From NCBI---->PubMedCentral: Hallucinogen actions on human brain revealed
Hyeong-Min Lee and Bryan L. Roth
With regard to hallucinogens like psilocybin—an ingredient of so-called “magic mushrooms” (e.g., Psilocybe cubensis)—it may be high time to reconsider long-standing hypotheses related to their actions in the human brain.

Although psilocin (the active metabolite of psilocybin) (Fig. 1A) and other classical hallucinogens like lysergic acid diethylamide (LSD) have complex pharmacologies with high affinities for multiple neurotransmitter receptors (1), it has long been appreciated that their psychedelic actions correlate best with 5-HT2A–serotonin receptor agonism (2). Indeed, in 5-HT2A knockout mice, classical hallucinogens are devoid of activity (3, 4). Importantly, the psychedelic actions of psilocybin in humans are abolished by pretreatment with relatively selective 5-HT2A antagonists (5, 6). Taken together, these findings support the hypothesis that psilocybin and other classical hallucinogens exert their psychedelic actions in humans via activating 5-HT2A serotonin receptors.

psilocybin diminishes brain activity and connectivity. (A) Psilocybin, which is inactive, is metabolized to the active ingredient psilocin. Psilocin then activates many neurotransmitter receptors (B) to modulate activity on excitatory pyramidal and inhibitory ...
Although there is consensus regarding the pharmacological actions of classical hallucinogens, the neuronal mechanisms responsible for the psychedelic actions of hallucinogens remain controversial. Thus, some investigators have observed that LSD-like hallucinogens can enhance pyramidal neuron activity by activating 5-HT2A serotonin receptor signaling (7, 8) (Fig. 1). These findings that hallucinogens activate glutamatergic neurotransmission are consistent with many other studies demonstrating that 5-HT2A receptors were enriched on Layer V glutamatergic neurons (9) although we and others have noted that 5-HT2A receptors are also found on GABA-ergic interneurons (10–12). Indeed, 5-HT2A agonists can also augment inhibitory neuronal activity (13). Taken together, these previous findings have implied that the actions of hallucinogens such as psilocybin might be due to a mixture of actions on both excitatory (e.g., pyramidal) and inhibitory (e.g., GABA-ergic interneuronal) neuronal circuits (Fig. 1C). Conceivably, then, hallucinogens like psilocybin could induce their psychedelic effects via augmenting either excitatory or inhibitory neuronal activity in humans. Unfortunately, because of medical, legal, human use, and societal concerns, well-controlled studies of hallucinogen actions in humans have languished since the early 1960s.

In PNAS, Carhart-Harris et al. (14) successfully execute an important study that begins to fill in our gaps regarding hallucinogen actions in humans. Surprisingly, they demonstrate that psilocybin decreases surrogate markers for neuronal activity [cerebral blood flow and blood oxygen level-dependent (BOLD) signals] in key brain regions implicated in psychedelic drug actions. They also report that psilocybin appears to decrease brain “connectivity” as measured by pharmaco-physiological interaction.

To perform these studies, Carhart-Harris et al. (14) recruit 15 experienced hallucinogen users for arterial spin labeling (ASL) perfusion and BOLD fMRI studies. The individuals were scanned before and after receiving i.v. doses of placebo or psilocybin (2 mg). Individuals were also rated for the subjective effects of psilocybin or placebo. Not surprisingly, psilocybin exerted a robust psychedelic effect with individuals reporting alterations in consciousness, time perception, and visual perceptions within minutes of psilocybin administration.

Coincident with these profound perceptual alterations, decreases in cerebral blood flow were observed in key brain regions long implicated in psychedelic drug actions—the anterior and posterior cingulate cortices and thalamus. Intriguingly, the intensity of the psychedelic experience significantly correlated with decrements in blood flow in the thalamus and anterior cingulate cortex. Carhart-Harris et al. (14) also report what they refer to as decreases in “functional connectivity” between the ventral medial.
    Psilocybin appears to decrease brain “connectivity” as measured by pharmaco-physiological interaction.

prefrontal cortex and other regions that they interpret to indicate an overall diminished connectivity.

Overall, these findings are consistent with the hypothesis that psilocybin diminishes activity in key brain regions and networks implicated in hallucinogen actions. These provocative findings are important because they challenge many long-held models regarding hallucinogen actions that have focused mainly on their ability to enhance excitatory neurotransmission and overall brain activity.

The findings of Carhart-Harris et al. are also important because they provide a nice proof that, provided appropriate safeguards are in place, psychedelic drug actions can once again be rigorously deconstructed in normal human volunteers. Psychedelic drugs are unique in their abilities to profoundly alter human awareness and perception, and these studies provide important hints regarding the neuronal substrates of human consciousness.


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OfflineGreySatyr
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Re: Hallucinogen actions on human brain [Re: demetris castaneda]
    #19240241 - 12/07/13 10:30 AM (10 years, 1 month ago)

Huxley already said that in much less words and with less advanced technology at his disposal. He basically took mescaline and told us what it did to his brain without any science malarkey.


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Offlinedemetris castaneda
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Re: Hallucinogen actions on human brain [Re: GreySatyr]
    #19240445 - 12/07/13 11:26 AM (10 years, 1 month ago)

yeah..as many others..but any scientific approach can only help our  practical knowledge of what our brain seems to be and how compounds as psylocin can interact with it.i think most of the people blame all our useless technology, but they are involved into it. Technology is a product of scientific research, and we should use it to get our research easier and optimized. Technical language could appear boring, as also obviously less emphatic than Huxley's verses,  but in my opinion there's to be a scientific approach to understand the mechanisms of mysterious  molecules as psylocin/psylocibin and how our thoughts can be wonderfully 'changed' because of them.


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Offlinedemetris castaneda
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Re: Hallucinogen actions on human brain [Re: GreySatyr]
    #19240514 - 12/07/13 11:48 AM (10 years, 1 month ago)

oops, but you studied philosophy. Got it now,have usually this discussion with 2 friends of mine that studied philosophy. we could never stop :tongue: Well man, think the best way to make our mind take a look further, is to weave humanistic and scientific methods and fields into one only uniform way of think. As Egyptians, they were astronomers and priests, as Archimedes was a thinker and a scientist, let's not separate in white and black...great things could come up. :mushroom2:


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OfflineGreySatyr
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Re: Hallucinogen actions on human brain [Re: demetris castaneda]
    #19241689 - 12/07/13 04:26 PM (10 years, 1 month ago)

Science is a double edged sword. It creates more problems than it solves. I love a good scientific approach but I also see the problems it could entail.


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...also, go to hell, huh?


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OfflinePrimalSoup
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Re: Hallucinogen actions on human brain [Re: demetris castaneda] * 1
    #19241878 - 12/07/13 05:30 PM (10 years, 1 month ago)

Quote:

demetris castaneda said:
From NCBI---->PubMedCentral: Hallucinogen actions on human brain revealed
Hyeong-Min Lee and Bryan L. Roth...




Why do people keep throwing this up like it's news????

These results have been superseded recently, especially the "suppression of brain function".  The results were incomplete at best and the timeframe only looking at the comeup phase.  Much more interesting results along the lines of what anybody who trips would expected are reported from studying autobiographical recall over longer term administration.  Look in this thread:  http://www.shroomery.org/forums/showflat.php/Number/18536889 and read http://bjp.rcpsych.org/content/200/3/238.full

:peace:PS


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if you stand too close to the machine it'll start to eat you
Primal's simple tested teks and projects: :awesomenod: Wheat Prep 2.0  Acidic Tea Tek  Potency Project! 


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Offlinehealing
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Re: Hallucinogen actions on human brain [Re: GreySatyr]
    #19242890 - 12/07/13 10:32 PM (10 years, 1 month ago)

Quote:

GreyMorph said:
Science is a double edged sword. It creates more problems than it solves. I love a good scientific approach but I also see the problems it could entail.




There is no quality of scientific approach. There is the scientific approach and everything else. I'm not saying that someone who calls their approach scientific is correct, to be clear.

The problem with science and its effects on our existence is that science doesn't care if you live or die, it doesn't care if you're happy or sad. Science is despite your humanity, so it often challenges our humanity. How we respond to the prompting of scientific research is not a problem of science, but a problem of people. Just read a little bit about Alfred Nobel.


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Open mind, open heart, open book.



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Invisibleredgreenvines
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Re: Hallucinogen actions on human brain [Re: PrimalSoup]
    #19243771 - 12/08/13 06:15 AM (10 years, 1 month ago)

Quote:

PrimalSoup said:
Quote:

demetris castaneda said:
From NCBI---->PubMedCentral: Hallucinogen actions on human brain revealed
Hyeong-Min Lee and Bryan L. Roth...




Why do people keep throwing this up like it's news????

These results have been superseded recently, especially the "suppression of brain function".  The results were incomplete at best and the timeframe only looking at the comeup phase.  Much more interesting results along the lines of what anybody who trips would expected are reported from studying autobiographical recall over longer term administration.  Look in this thread:  http://www.shroomery.org/forums/showflat.php/Number/18536889 and read http://bjp.rcpsych.org/content/200/3/238.full

:peace:PS



I like the links here - particularly some of the graphic support:
such as this one

please note that the psilocybin affected series shows that activation has spread beyond the placebo series.
this is the essence of tripping,
going farther,
the idea is sustained in mind longer, so
before fading, more associations have opportunity of chiming in to the idea that has been raised.

each chime is also an idea, so in that way we expect spreading,

experientially,
in that longer lasting - wider spreading way, every momentary node of consciousness seems to have more dimensionality that in turn connects to more.

(the photos appear to be averaged from many samples, but that they show anything at all is impressive, since the events we are discussing are in the range of seconds, and these exposures relate to blood flow over a longer duration)


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:confused: _ :brainfart:🧠  _ :finger:


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OfflinePrimalSoup
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Re: Hallucinogen actions on human brain [Re: redgreenvines]
    #19243853 - 12/08/13 07:34 AM (10 years, 1 month ago)

Well said.  It's taking a while for researchers to figure out what trippers have known forever. :awecid:

:peace:PS


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

if you stand too close to the machine it'll start to eat you
Primal's simple tested teks and projects: :awesomenod: Wheat Prep 2.0  Acidic Tea Tek  Potency Project! 


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Offlinedemetris castaneda
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Re: Hallucinogen actions on human brain [Re: PrimalSoup]
    #19255718 - 12/10/13 02:38 PM (10 years, 1 month ago)

found also this one, very interesting..  Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.
Catlow BJ, Song S, Paredes DA, Kirstein CL, Sanchez-Ramos J.
Source
Lieber Institute for Brain Development, Baltimore, MD, USA.
Abstract
Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.


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