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brain_guy
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Registered: 03/27/23
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Neuroscience of DMT and other psychedelics
#28249481 - 03/27/23 03:20 PM (10 months, 29 days ago) |
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I'm a neuroscientist with an interest in the mechanism of altered states of consciousness. I may come at this topic from a specific technical background but am interested in how the emerging brain science of psychedelics overlies with the experience of others from different perspectives:
A new study dropped last week looking at brain imaging of the effects of DMT, the active ingredient in ayahuasca, used as a psychedelic for thousands of years in religious and ceremonial rituals. DMT produces vivid visual imagery, sense of alternate reality, communication with "beings" or "entities", and profound experiences of meaning and pleasure (and in some cases fear and dysphoria).
This is an extraordinary study, and for those interested I'll give my more technical take on the results and implications below. Robin Carhart-Harris and colleagues have done absolutely extraordinary work on brain imaging of psychedelics, and this study is IMO their capstone piece so far. I see it as the most thoughtful, complete, and informative study of psychedelics and the brain to date.
Here is the study (open access):
https://www.pnas.org/doi/10.1073/pnas.2218949120
1) DMT has essentially the same mode of action as psilocybin (magic mushrooms) and LSD; it is an agonist of the serotonin 5HT2A receptor. While these three drugs have different time course of action, they are far more similar than different in their biological action and produce many similar effects. Many of the differences can be related to dosing and duration of the effects, which vary in time.
2) This study is so informative because although it is most commonly ingested (ayahuasca and hundreds of native plants), it has a powdered form that can be administered intravenously with effects within minutes. This makes it ideal to study with modern brain imaging techniques since we know exactly when it begins and can make appropriate within subject controls. 3) Another experimental design element was adding EEG simultaneously to fMRI. This gets around some important theoretical confounds with effects on blood vessels and also gives us access to both high resolution signals across the brain and in time which are complementary. These studies are incredibly complex studies to perform (I've done them) and difficult to analyze. I can't say enough about how much useful data is here to study because of this design.
I'm trying below to skip some of the technical elements and describe the results in more colloquial language. Apologies for anything that gets lost in translation:
How do psychedelics work in the brain?
Simple answer is the 5HT2A receptor. But this receptor has evolved to be expressed in very specific brain regions which arrived on the scene late in human evolution which are strongly associated with our most high-level functions of thinking, memory, pattern recognition, and social function.
Psychedelics work by causing these brain regions to become more active, and to become connected to the rest of the brain. This increased "global connectivity" of the brain is tightly correlated to intensity of the experience. The perception of geometric visual patterns and synaesthesia (sounds interpreted as colors or other sensory phenomena for example) are most tightly connected to this global connectivity that arises.
The normal (non psychedelic) function of the brain is characterized by 2 high-level brain networks fighting for control. The "default mode network" is dominant when you are thinking or talking to yourself, using language, or checking in on your internal state. the "attention control network" dominates when you are paying attention to sounds, sights, or planning movements. A portion of this network also controls your response to novelty, pleasure, and automatic emotional responses that dominate our actions most of the time.
Each of these 2 networks shuts the other down. When you are lost in thought, you are oblivious to sensations in the world around you. When you are paying close attention to sounds or sights or touch, the voice in your head shuts off.
In depression, these rigid networks become even more antagonistic, and the voice in your head goes largely unchecked by the world around you lost in thought and increasingly detached from pleasure networks in the brain, producing obsessive thoughts that don't shut off.
The effect of psychedelics is to activate these global networks increasingly together instead of separate. Gone is the autonomous function of the default mode network and the usual running narrative in our heads. At high doses this gives the sense of ego-dissolution, or losing our identity as self and taking on a new more expanded consciousness temporarily.
This new study gives us much more detailed information about the time course (I'm lumping together effects over time into 3 stages - the study showed minute by minute evolution and I'm taking the most salient shifts in pattern to my eye):
Stage 1: The voice in our head and attention to stimuli simultaneously become more connected to the visual part of our brain, producing heightened awareness of light and colors, and producing sometimes hallucinatory effects of complex geometric designs, texture and patterns.
Stage 2: The voice in our head and attention to stimuli simultaneously focus on somatosensory networks and subcortical brain networks related to dopamine and pleasure. We have heightened response to touch, and increasing discoordination of fine motor control.
Stage 3: The 2 high-level brain networks focus their attention on each other. The voice in your head has access to information that before was strictly "black box." You become aware with emotional information in the more primitive, automatic brain, gain access to new insights about the emotions driving your behavior, and experience cooperation between these two networks as the "awareness" network gives language and voice to emotions and inner states of which you may not have been aware. Sometimes this can be coming to grips with fears or unpleasant emotions, although the coactivation of the ventral striatum tips this interaction to be much more commonly a positive experience. This is probably the core of the medicinal properties of psychedelics where people talk about making personal breakthroughs or gaining radical new insights that may take otherwise years of therapy.
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redgreenvines
irregular verb


Registered: 04/08/04
Posts: 37,847
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Re: Neuroscience of DMT and other psychedelics [Re: brain_guy] 1
#28250462 - 03/28/23 06:35 AM (10 months, 29 days ago) |
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Brain Guy, welcome to the forum I am sure you are going to have a fun ride here today.
The roller coaster obtains accelerative thrills by cranking the rolling mass up to a very high point and then chanelling the accumulated potential energy in downhill curving flourishess of screaming riders.
I have cranked this up and would encourage you to click on the in my sig below. feel free to scream, evryone does, you are still safely belted in.
Quote:
brain_guy said: ... Psychedelics work by causing these brain regions to become more active, and to become connected to the rest of the brain. This increased "global connectivity" of the brain is tightly correlated to intensity of the experience. The perception of geometric visual patterns and synaesthesia (sounds interpreted as colors or other sensory phenomena for example) are most tightly connected to this global connectivity that arises.
The normal (non psychedelic) function of the brain is characterized by 2 high-level brain networks fighting for control. The "default mode network" is dominant when you are thinking or talking to yourself, using language, or checking in on your internal state. the "attention control network" dominates when you are paying attention to sounds, sights, or planning movements. A portion of this network also controls your response to novelty, pleasure, and automatic emotional responses that dominate our actions most of the time....
Yes and no.
Taking a step back from the lofty achievements of Neuro-chemistry, Neuro-Biology, Neuro-physics, Theory of Mind, The dualism of Decartes, all the way to Socrates, one of history's greatest philosophers, who doubted his omniscience and famously stated โall I know is that I know nothingโ, I have to say that we still, as a body of science know nothing.
By that I mean, we do not know what knowing is, I mean, as a group, no group yet has a good theory of mind that washes with the findings of the SERT receptors and the DMN and the Doors of Perception which Huxley claimed open up on psychedelics.
What I am telling you is that we could have already put it together with the findings that we already have, but as an extremely fragmented group, Neuroscience has not yet put it together.
At the center of the mysterious miracle of memory is the associative linkage of "what fires together wiring together". We know the following facts (some of these facts are over 100 years old (observed and recorded by Santiago Ramรณn y Cajal) and still ignored but still true) eg: a) multiple neuron types and wiring arrangements are in the cortex: ---Cortical Neurons with tufts of dendrites above receive axon feed from thalamic neurons and send their axons in a feedback loop to the same thalamic neurons. This makes every sensory activation a feedback ride of a series of pulses and local dendritic energy field bursts. ---Pyramidal Neurons with up to 100,000 axon branches distribute their activation charge widely to all parts of the cortex both locally and into different lobes via aggregate white matter bundles. ---Interneurons and glia have localized connections and may perform high speed processing with varied functions editing and shunting signals and suppressing or allowing Cortico-Thalamic feedback (C-T looping) b) when both the cortical neuron and the pyramidal neurons fire synchronously the juncture (minisynapse) where one of 100,000 pyramidal axon branchlets forms an ARC protein spine (if one is not already there from previous experience - this is the act of memory formation (on an associative voxel basis)). c) when a plurality of activated axon branchlets reach a resting cortical neuron it becomes re-activated and re-starts the C-T loop firing with the thalamus (this is the perceptive reflex (on an associative voxel basis)). d) the C-T loop has to be active for 3 cycles to form memory which is performed at ~10hz during waking consciousness and ~8hz during REM sleep: --- the first 1/10 second pulse causes cortical neuron dendritic back propagation of an electrical field which activates nearby Pyramidal neurons. --- the second pulse keeps the cortical neuron active so that spines can form whenever an active pyramidal axon branchlet connects with the active cortical neuron.(associative memory formation of synchronous mental contents) --- the third pulse keeps the engram pattern alive to extend memory formation to associatively include the next frame of experience which provides the facility for sequence memory.
SERT and other receptors do make the Cortical neurons more responsive, and what that typically means is that the C-T loop runs with full impact longer than 3 cycles.
This causes the overlapping of frames of experience. The same effect which is generated by SERT and other psychedelic receptor activation also happens naturally under limbic emotional activation but is more thalamically related, but the net effect in both cases is that with psychedelics or emotional or absorptive meditation states C-T looping is extended.
The additional activity, observed on EEG and fMRI metrics etc is localized increased C-T looping.
Frame stacking is what produces the enhanced or layered sensations, but also the more widely ramified perceptions (extraordinarily beatific or scary - increase the "Number of Thalamo-Cortical Feedback loop cycles" in my JavaScript demo higher than 3 to see that kind of thing in a small scale).
Frame stacking is also what confuses the sense of time passing. Up to 3 seconds can be stacked when really stoned, beyond that we black out, but sequence memory of 3 seconds can go back much farther making it seem like time is stopped or even going in reverse.
We can take this discussion further, but I want to suggest also that what is seen in the hoopla about mapped "networks" is like night time time-lapse photography of the lights of vehicles streaming on highways and city streets. It is not clear evidence of any specific thing other than the fact that some active mental contents are in the areas shown. As such what we take for DMN activity is not explicative in the ways people imagine it to be. I would suggest that researchers focus more on the matter of memory formation, and perception and build their theories of mind outward from that base.
 this image goes together with the demo linked under my brainfart below which you can see and play with to explore.
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Blue_Lux
ฯฯ ฮบแพฐฯแพฐฯฮตฯฯฯฮบฯฯ ฯฯฮฟฮฝฯฮนฯฯฮฎฯ



Registered: 12/07/19
Posts: 2,655
Loc: chillin' on Charon's skiff
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Re: Neuroscience of DMT and other psychedelics [Re: redgreenvines]
#28250746 - 03/28/23 09:43 AM (10 months, 29 days ago) |
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ipse se, nihil scire, id unum sciat CICERO
-------------------- โโฎโ
โI โก the music, not the blingโโ
โฎโ https://rictornorton.co.uk/eighteen/1730news.htm ๐ด๐ ๐๐๐๐๐๐ ๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐. Comibus est oculis alliciendus amor. Love is to be attracted by kind eyes โจ lured with alluring eyes Ovid
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redgreenvines
irregular verb


Registered: 04/08/04
Posts: 37,847
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Re: Neuroscience of DMT and other psychedelics [Re: Blue_Lux]
#28250779 - 03/28/23 09:58 AM (10 months, 29 days ago) |
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yeah well that moves into a different set of ideas and a different empire, Roman confusion after Greek delusion.
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Blue_Lux
ฯฯ ฮบแพฐฯแพฐฯฮตฯฯฯฮบฯฯ ฯฯฮฟฮฝฯฮนฯฯฮฎฯ



Registered: 12/07/19
Posts: 2,655
Loc: chillin' on Charon's skiff
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Re: Neuroscience of DMT and other psychedelics [Re: redgreenvines]
#28250788 - 03/28/23 10:05 AM (10 months, 29 days ago) |
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What you said reminded me of what Oliver sacks said in this video about memory at 26 minutes 30 seconds, he is asked how memory is 'stored.'
-------------------- โโฎโ
โI โก the music, not the blingโโ
โฎโ https://rictornorton.co.uk/eighteen/1730news.htm ๐ด๐ ๐๐๐๐๐๐ ๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐. Comibus est oculis alliciendus amor. Love is to be attracted by kind eyes โจ lured with alluring eyes Ovid
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Blue_Lux
ฯฯ ฮบแพฐฯแพฐฯฮตฯฯฯฮบฯฯ ฯฯฮฟฮฝฯฮนฯฯฮฎฯ



Registered: 12/07/19
Posts: 2,655
Loc: chillin' on Charon's skiff
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Re: Neuroscience of DMT and other psychedelics [Re: redgreenvines]
#28250798 - 03/28/23 10:12 AM (10 months, 29 days ago) |
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ipse se (he himself) nihil scire (to know nothing) id unum sciat (only thing he may know [subjunctive]) Transl- "Nothing is the only thing he himself claimed to know." Cicero was talking about Socrates and thats just 1 of the first examples of it being quoted succinctly in written history
-------------------- โโฎโ
โI โก the music, not the blingโโ
โฎโ https://rictornorton.co.uk/eighteen/1730news.htm ๐ด๐ ๐๐๐๐๐๐ ๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐. Comibus est oculis alliciendus amor. Love is to be attracted by kind eyes โจ lured with alluring eyes Ovid
Edited by Blue_Lux (03/28/23 10:31 AM)
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redgreenvines
irregular verb


Registered: 04/08/04
Posts: 37,847
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Re: Neuroscience of DMT and other psychedelics [Re: Blue_Lux]
#28250871 - 03/28/23 11:00 AM (10 months, 29 days ago) |
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Quote:
Blue_Lux said: What you said reminded me of what Oliver sacks said in this video about memory at 26 minutes 30 seconds, he is asked how memory is 'stored.'
good, YES - the speaker Sacks (or Huxley?) is right on target!
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Blue_Lux
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Registered: 12/07/19
Posts: 2,655
Loc: chillin' on Charon's skiff
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Re: Neuroscience of DMT and other psychedelics [Re: redgreenvines]
#28251172 - 03/28/23 01:35 PM (10 months, 29 days ago) |
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Haha Dr. Oliver Sacks RIP
-------------------- โโฎโ
โI โก the music, not the blingโโ
โฎโ https://rictornorton.co.uk/eighteen/1730news.htm ๐ด๐ ๐๐๐๐๐๐ ๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐๐๐ ๐๐๐๐๐. Comibus est oculis alliciendus amor. Love is to be attracted by kind eyes โจ lured with alluring eyes Ovid
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