Psychedelics are a class of compounds that temporarily alter consciousness, leading to profound changes in perception, cognition, and mood. These substances, which include naturally occurring compounds like psilocybin and synthetic ones such as LSD, can induce complex imagery, a heightened sense of connection, and sometimes synesthesia, where senses blend. The term “psychedelic” itself means “mind-manifesting,” reflecting their capacity to reveal aspects of the mind.
Neurochemical Foundation
Classic psychedelics primarily exert their effects by interacting with the brain’s serotonin system, specifically targeting the serotonin 5-HT2A receptor. Serotonin is a neurotransmitter, a chemical messenger that transmits signals between nerve cells. Psychedelics like psilocin, the active metabolite of psilocybin, are chemically similar to serotonin and act as agonists, meaning they bind to and activate these receptors.
While the 5-HT2A receptor is the main target, psychedelics do not bind exclusively to it; for example, LSD can interact with most serotonin receptor subtypes, as well as dopamine and adrenergic receptors. However, evidence indicates that the activation of 5-HT2A receptors is necessary to produce hallucinogenic effects. Newer research is exploring how psychedelics activate multiple intracellular pathways through the 5-HT2A receptor, which may help differentiate their therapeutic benefits from their hallucinogenic properties. Some non-hallucinogenic compounds have been developed that still activate the 5-HT2A receptor but without causing hallucinations, suggesting different pathways can be engaged.
Targeted Brain Networks and Structures
Psychedelics impact several key brain regions and networks, leading to their unique effects on perception and self-awareness. A prominent network affected is the Default Mode Network (DMN), a collection of interconnected brain regions active during states of rest, self-referential thought, and introspection. Under the influence of psychedelics, activity within the DMN decreases, and its internal connectivity is reduced. This reduction in DMN activity is correlated with subjective effects and may contribute to a decreased sense of self or “ego dissolution” reported by users.
The thalamus, often described as the brain’s sensory filter, also undergoes changes with psychedelic use. This structure normally relays sensory information to the cortex and plays a role in filtering out irrelevant stimuli. Psychedelics can disrupt this filtering mechanism, leading to an increased flow of information from the thalamus to cortical areas. This disruption can result in an overload of unfiltered sensory information reaching the cortex, contributing to altered perceptions.
The prefrontal cortex, involved in executive functions like planning, decision-making, and self-control, also experiences altered activity. Changes in this region, alongside the DMN, contribute to the cognitive and perceptual shifts observed during a psychedelic experience. For example, the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), both key nodes of the DMN, show decreased functional connectivity under psychedelics.
Altered Brain Connectivity and Perception
The effects of psychedelics extend beyond individual brain regions, altering the communication and connectivity between different brain networks. While activity within established networks like the Default Mode Network decreases, there is often an increase in connectivity between brain regions that do not communicate extensively. This “cross-talk” or “hyperconnectivity” creates a more fluid and less modular brain state, where information flows more freely across previously segregated areas.
This altered connectivity contributes to various subjective experiences, including synesthesia, such as seeing sounds or hearing colors. The disruption of typical brain organization can also lead to novel insights and changes in self-perception, described as a sense of unity or oceanic boundlessness. The increased communication across the brain, particularly between lower-order sensory processing regions, and the decreased connectivity within higher-order interpretive regions, may explain the vivid perceptual changes experienced during a psychedelic state. This reorganization allows for new psychological insights and a reframing of one’s perception of reality.