Psilocin and LSD Approach the 5-HT2A Binding Pocket
Serotonergic psychedelics cross the blood-brain barrier and reach cortical neurons.
- 5-HT2A: Primary target (placeholder receptor subtype note)
- Tryptamine: Ligand class (placeholder chemical class note)
- ~20-40 min: Onset (placeholder timing note)
- Oral: Route (placeholder administration note)
Molecular diffusion and receptor approach
Placeholder: ligand crosses membrane and drifts toward receptor.
Binding pocket recognition
Placeholder: tryptamine scaffold matches orthosteric pocket residues.
Placeholder highlight: structural similarity to serotonin enables binding.
Conformational Activation of the 5-HT2A GPCR
Agonist binding triggers a conformational switch in the receptor.
- Gq/PLC: Signaling (placeholder pathway note)
- β-arrestin: Second path (placeholder bias note)
- IP3/DAG: Effect (placeholder cascade note)
- Layer V: Location (placeholder cortical layer note)
G-protein coupled activation
Placeholder: receptor recruits Gq protein and activates PLC.
Downstream second messengers
Placeholder: IP3 and DAG trigger calcium release in neuron.
Placeholder highlight: apical dendrite excitability rises sharply.
Layer V Pyramidal Neurons Become Hyperexcitable
Activated neurons fire more frequently and release more glutamate.
- ↑ Elevated: Firing rate (placeholder physiology note)
- ↑ Release: Glutamate (placeholder neurotransmitter note)
- Prefrontal: Cortex region (placeholder region note)
- ↓ Alpha power: EEG marker (placeholder EEG note)
Increased pyramidal firing
Placeholder: neurons cross threshold more often under agonism.
Network-wide desynchronization
Placeholder: cortical rhythms lose their usual synchrony.
Placeholder highlight: entropy of cortical signals increases measurably.
Default Mode Network Connectivity Loosens and Rewires
Hub regions of the default mode network lose their tight coupling.
- mPFC/PCC: DMN hubs (placeholder region note)
- ↓ Decreased: Connectivity (placeholder fMRI note)
- ↑ Integration: Cross-network (placeholder network note)
- fMRI/MEG: Measure (placeholder imaging note)
Hub decoupling
Placeholder: mPFC and PCC coupling weakens under agonism.
Emergent cross-network links
Placeholder: normally segregated networks begin to communicate.
Placeholder highlight: reduced DMN integrity correlates with ego dissolution.
Global Brain Dynamics Shift Toward an Entropic State
The whole-brain network becomes flatter, more flexible, less hierarchical.
- ↑ Increased: Entropy (placeholder dynamics note)
- Altered: Experience (placeholder subjective note)
- 4-8 hrs: Duration (placeholder duration note)
- REBUS: Model (placeholder theory note)
Relaxed belief hierarchies
Placeholder: top-down predictive control over cortex relaxes.
Subjective altered state
Placeholder: perception, mood, and self-referential thought change.
Placeholder highlight: effects resolve as receptors desensitize over hours.