Jackson Cionek
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Neurochemical Underpinnings of Psychedelic-Induced Ego Dissolution

Neurochemical Underpinnings of Psychedelic-Induced Ego Dissolution

Neurochemical Underpinnings of Psychedelic-Induced Ego Dissolution
Neurochemical Underpinnings of Psychedelic-Induced Ego Dissolution


Ego dissolution is a phenomenon frequently reported during psychedelic experiences, in which one's sense of self temporarily disintegrates or becomes greatly diminished. It's commonly experienced with substances like LSD, psilocybin, DMT, and others. Understanding the neurochemical underpinnings can help demystify this experience and provide insights into the functioning of the human brain and consciousness.

1. 5-HT2A Receptor Activation:

The primary action of most classic psychedelics, such as LSD and psilocybin, is the activation of the 5-HT2A receptor subtype in the brain. This receptor is a type of serotonin receptor.

Activation of 5-HT2A receptors alters the usual patterns of serotonin transmission, a neurotransmitter linked to mood, cognition, and perception.

This receptor is particularly abundant in the cortex and plays a pivotal role in the modulation of cortical activity and connectivity.

2. Changes in Brain Network Connectivity:

Studies using functional MRI (fMRI) have shown that psychedelics dramatically change the way different brain regions communicate with each other.

Normally, various brain networks (like the Default Mode Network - DMN, which is associated with self-referential thoughts and the sense of "self") have their own defined, largely separate patterns of activity. Psychedelics appear to increase connectivity between these typically segregated networks.

The DMN, in particular, becomes less cohesive under the influence of psychedelics, which some researchers believe may underlie the experience of ego dissolution.

3. Reduced Activity in the Default Mode Network (DMN):

The DMN, as previously mentioned, is heavily involved in maintaining our sense of personal identity or ego. When its activity is diminished or disrupted, as seen during psychedelic experiences, the boundaries between self and other can blur.

This decreased integrity of the DMN is one of the most consistent findings in neuroimaging studies of psychedelics and is thought to play a significant role in the ego dissolution experience.

4. Increase in Entropy:

Psychedelics seem to make the brain's activity more chaotic or entropic. This can be understood as increasing the diversity of possible brain states.

Such an increase in entropy might explain why psychedelics can induce a vast array of subjective experiences, including ego dissolution.

5. Neuroplasticity:

There's some evidence to suggest that psychedelics can promote neuroplasticity, the ability of the brain to rewire and form new neural connections. This could contribute to the profound shifts in consciousness and perception observed.

6. Other Neurotransmitter Systems:

While the serotonergic system (particularly the 5-HT2A receptor) is most often implicated in the effects of psychedelics, other neurotransmitter systems might also play roles. For instance, there's some evidence to suggest interactions with the glutamate system.

Ego dissolution, by blurring the boundaries of the self, can lead to feelings of interconnectedness, unity, and oneness with the environment and universe. Understanding the neurochemical bases of these experiences not only provides insights into the effects of psychedelics but also sheds light on the neural substrates of self-consciousness and the construction of personal identity.


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Jackson Cionek

New perspectives in translational control: from neurodegenerative diseases to glioblastoma | Brain States