MSCA blog - cont'd

The optogenetics of psychedelic drug action

5/12/2020

Gentle reader,

As a part of our Marie-Skłodowska-Curie-Actions outreach strategy, I presented the first of our exciting findings on the "optogenetics of psychedelic drug action" at the 2019 Breaking convention congress (see youtube.com).

In our project, we use highly refined techniques of optogenetic electrophysiology to reveal how the primary key targets of psychedelic drugs (namely cortical pyramidal cells) respond while mice engage in the so-called "psychedelic signature move". The psychedelic signature move is a very brief tingle-like body-shake, which mammals off and on show when they are under the influence of a psychedelic drug.

The mechanism of this psychedelic specificum is little understood, all the more significant, as it constitutes the 5-HT2Aergic bridge from animals to humans. Our project is the first to ever shed light into the cortex as pyramidal cells and peripyramidal haemodynamics orchestrate while animals go off and on showing the enigmatic signature of behavioural psychedelia.

Enjoy :)

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Psychedelic 5-HT2A activity neither starts nor ends with a pyramidal cell

2/18/2020

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Gentle reader,

Psychedelics mediate their mind-altering effects my activation of serotonin 2A (5-HT2A) receptors. 5-HT2A receptors are proteins that are abundantly expressed by so-called pyramidal cells of the brain’s cortex. It is these pyramidal-cellular 5-HT2A receptors, which in fact are thought to constitute the “molecular doorway” for the psyche to enter psychedelia.

However, 5-HT2A receptors are by far not restricted to cortical pyramidal cells. They can be found in a lot of other regions of the mammalian central nervous system and the periphery; in the spinal cord, the retina, the liver, the intestines, the platelets, the vessels, and even in the bones. What do 5-HT2A receptors do here and beyond the brain in general?

Although it is unlikely that all of these non-brain 5-HT2A populations play a role in psychedelia, chances are that they play out in the overall physiology as the psychedelic travels the body. But let us take a step back and reconsider a 5-HT2A function that is more imminent to the brain (and thus psychedelia?):

Using 25CN-NBOH (a mescaline-derivative which selectively activates 5-HT2A receptors), we in our most recent research show how 5-HT2A receptors affect different parameters of blood-blow in brain-supplying neck-arteries. Mind you blood does not only carry oxygen and nutrition to the brain, but also distributes cell-derived warmth across the body. It might therefore not be surprising if environmental temperature conditions did have some say in psychedelic blood flow regulation, too…

Green open access. Enjoy :)

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Isolating 5-HT2A

4/2/2018

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Gentle reader,

I am happy to announce our recent open-access publication Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN-NBOH in Mice. In this paper we use 25CN-NBOH (see figure), a newly developed tool of pharmacology, and describe it in terms of its basic behavioural dynamics.

Gaining insights into the mechanism of action of serotonergic hallucinogens is difficult because most of the representatives of this class of drugs have the tendency to bind to various target proteins within the brain. Serotonergic hallucinogens bind to these so-called "receptor" proteins located in the membrane of the brain cells, and thereby affect the cells' communication patterns. Given their structural similarity to brain inherent monoaminergic neurotransmitters (which represent the "dialects" neurons use to communicate), serotonergic hallucinogens show a particular preference for receptors belonging to the monoamine neurotransmitter family (most notably those of serotonin, dopamine, and noradrenaline).

Although all binding to the individual receptors is likely to affect the brain in one or another way, not all of the receptors are thought to be primarily involved in the psychedelic action of serotonergic hallucinogens. Instead, a specific member of the serotonin receptor family, namely the 5-HT2A receptor, seems to play a predominate role. With all the noise created by the other receptors, though, it remains an unabated challenge of science to actually tell apart what is 5-HT2A, and what it is that marks this protein out and makes it so peculiar when it comes to conscious experience and the mechanism of action of serotonergic hallucinogens.

25CN-NBOH is a newly developed drug that bypasses a multitude of non5-HT2 receptors and selectively addresses 5-HT2A receptors. Characterising the behavioural and physiological profile of this drug, and tracing it back to its very origins in the brain might therefore help and write a new chapter in the delineation of serotonin as to one of the key narrators of consciousness.

Best, Tobias

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Welcome

7/16/2016

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Gentle reader,

I am a German Psychologist and I do neuroscientific research on serotonergic hallucinogens (sHGs), including lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT). Being a Psychologist, I consider the psyche one of the most fascinating entities that exist, and I think that helping to decipher its ancient secrets has the potential to harbor good and benefit to each and every aspect of human health and society.
Trying to understand an entity as volatile and impalpable as the psyche, multiple disciplines (incl., Psychology, Pharmacology, Neuroscience, Biology, Medicine, Philosophy...) need to come together and in the consent of their different methodological approaches trace the hidden psychic paths and re-sculpture what these possibly are made of.

Believing in the synergistic might of interdisciplinarity, I ran my PhD project in Neuroscience at the Institute of Pharmacology and Toxicology at the OvG University in Magdeburg and now have come to continue my research in Optogenetics and Circuit Dynamics at the Imperial College in London.

Being awarded the highly reputed Marie Skłodowska-Curie Actions (MSCA) Individual Fellowship, my research is supported by the European Commission (Horizon 2020), and I now have the fortunate opportunity to learn from one of the pioneers and world-leading experts in the field of voltage imaging with genetically encoded voltage indicators (GEVIs), Prof. Dr. Thomas Knöpfel, and through his guidance bring my scientific journey to the next level.

This blog is meant to give you an insight into my research and, as to this, make science more transparent to you. I will try and update it regularly. If you are interested, I'd be glad to welcome you here once in a while.

Best, Tobias

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The optogenetics of psychedelic drug action

Psychedelic 5-HT2A activity neither starts nor ends with a pyramidal cell

Isolating 5-HT2A

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