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Science paper: LSD flattens the brain’s energy landscape

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downwardsfromzero

downwardsfromzero

Boundary condition
Pretty interesting work, pre-published recently here

"LSD flattens the brain’s energy landscape: evidence from receptor-informed network control theory"
S. Parker Singleton, Andrea I. Luppi, Robin L. Carhart-Harris, Josephine Cruzat, Leor Roseman, Gustavo Deco, Morten L. Kringelbach, Emmanuel A. Stamatakis, Amy Kuceyeski
Abstract

Psychedelics like lysergic acid diethylamide (LSD) offer a powerful window into the function of the human brain and mind, by temporarily altering subjective experience through their neurochemical effects. The RElaxed Beliefs Under Psychedelics (REBUS) model postulates that 5-HT2a receptor agonism allows the brain to explore its dynamic landscape more readily, as suggested by more diverse (entropic) brain activity. Formally, this effect is theorized to correspond to a reduction in the energy required to transition between different brain-states, i.e. a “flattening of the energy landscape.” However, this hypothesis remains thus far untested. Here, we leverage network control theory to map the brain’s energy landscape, by quantifying the energy required to transition between recurrent brain states. In accordance with the REBUS model, we show that LSD reduces the energy required for brain-state transitions, and, furthermore, that this reduction in energy correlates with more frequent state transitions and increased entropy of brain-state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors, we demonstrate the specific role of this receptor in flattening the brain’s energy landscape. Also, in accordance with REBUS, we show that the occupancy of bottom-up states is increased by LSD. In addition to validating fundamental predictions of the REBUS model of psychedelic action, this work highlights the potential of receptor-informed network control theory to provide mechanistic insights into pharmacological modulation of brain dynamics.

Significance Statement
We present a multi-modal framework for quantifying the effects of a psychedelic drug (LSD) on brain dynamics by combining functional magnetic resonance imaging (fMRI), diffusion MRI (dMRI), positron emission tomography (PET) and network control theory. Our findings provide support for a fundamental theory of the mechanism of action of psychedelics by showing that LSD flattens the brain’s energy landscape, allowing for more facile and frequent state transitions and more temporally diverse brain activity. We also demonstrate that the spatial distribution of serotonin 2a receptors - the main target of LSD - is key for generating these effects. This approach could be used to understand how drugs act on different receptors in the brain to influence brain function.
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downwardsfromzero said:
Pretty interesting work, pre-published recently here

"LSD flattens the brain’s energy landscape: evidence from receptor-informed network control theory"
S. Parker Singleton, Andrea I. Luppi, Robin L. Carhart-Harris, Josephine Cruzat, Leor Roseman, Gustavo Deco, Morten L. Kringelbach, Emmanuel A. Stamatakis, Amy Kuceyeski
Quote:
Abstract

Psychedelics like lysergic acid diethylamide (LSD) offer a powerful window into the function of the human brain and mind, by temporarily altering subjective experience through their neurochemical effects. The RElaxed Beliefs Under Psychedelics (REBUS) model postulates that 5-HT2a receptor agonism allows the brain to explore its dynamic landscape more readily, as suggested by more diverse (entropic) brain activity. Formally, this effect is theorized to correspond to a reduction in the energy required to transition between different brain-states, i.e. a “flattening of the energy landscape.” However, this hypothesis remains thus far untested. Here, we leverage network control theory to map the brain’s energy landscape, by quantifying the energy required to transition between recurrent brain states. In accordance with the REBUS model, we show that LSD reduces the energy required for brain-state transitions, and, furthermore, that this reduction in energy correlates with more frequent state transitions and increased entropy of brain-state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors, we demonstrate the specific role of this receptor in flattening the brain’s energy landscape. Also, in accordance with REBUS, we show that the occupancy of bottom-up states is increased by LSD. In addition to validating fundamental predictions of the REBUS model of psychedelic action, this work highlights the potential of receptor-informed network control theory to provide mechanistic insights into pharmacological modulation of brain dynamics.

Significance Statement
We present a multi-modal framework for quantifying the effects of a psychedelic drug (LSD) on brain dynamics by combining functional magnetic resonance imaging (fMRI), diffusion MRI (dMRI), positron emission tomography (PET) and network control theory. Our findings provide support for a fundamental theory of the mechanism of action of psychedelics by showing that LSD flattens the brain’s energy landscape, allowing for more facile and frequent state transitions and more temporally diverse brain activity. We also demonstrate that the spatial distribution of serotonin 2a receptors - the main target of LSD - is key for generating these effects. This approach could be used to understand how drugs act on different receptors in the brain to influence brain function.
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Thanks for study downwardsfromzero. Study shows that LSD reduces the energy required for brain-state transitions.

I also read in the book Return to the Brain of Eden by Tony Wright & Graham Gynn with forward by Dennis Mckenna, Ph.D. that LSD, Ayahuasca, shrooms, ibogaine, mescaline, and this includes the now researched tetrahydroharmine found in Caapi, all "light up the right hand side of the brain".

This is the side of the brain involved with creativity, spirituality, empathy, art & music appreciation, visualization, feelings of spiritual joy...and that earlier in human history we used our right brain a lot more than we do now.

The world is moving in the direction of the Left Brain: technology and science. What the world needs is to move in the direction of Right Brain development: empathy, spirituality, connectedness. I think these entheogens not only reduce the energy needed to transition between brain states but are also smart-nutrients or smart-drugs for the right side of the brain.

My grandmother was an oil painter, and taught me to use the "right side of my brain" by teaching me to paint when I was young.
 
Loverofallthings said:
Very interesting. Thank for posting this; it’s the kind of stuff I love finding in the nexus.
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I found it in the Guardian (UK newspaper) online and traced it back to source :lol: It's good when newspapers actually provide that information.

So, how does flattening of my brain's energy landscape lead to eight hours of convulsive laughter? Is it that practically any and all of the assumptions underpinning culture are inherently ridiculous?
 
Well with that, I think someone is gonna start microdosing a little Lucy to see how it helps with productivity and speed in changing tasks and establishing focus after said task change. Thank you for sharing this gem of info.

One love
 
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