How classic psychedelics act

Established Classic psychedelics such as psilocybin, LSD and DMT act mainly as agonists at serotonin 5-HT2A receptors, which are dense in the cortex. Blocking these receptors largely prevents their subjective effects in human studies.

The entropic brain

Debated Imaging studies led by Robin Carhart-Harris and colleagues found that psychedelics increase the diversity, or “entropy”, of brain activity and loosen the usual boundaries between brain networks. Later, with Karl Friston, Carhart-Harris proposed the REBUS model: psychedelics relax the brain’s high-level prior beliefs, letting bottom-up information reshape experience.

Ego dissolution

Debated At higher doses many people report a dissolution of the boundary between self and world. Some studies associated this with reduced integrity of the default mode network, linked to self-related thought. It interests consciousness researchers because it suggests that the sense of being a self is a construction that can be partly taken apart.

The clinical-trial context

Controlled trials of psilocybin with psychological support for treatment-resistant and major depression have reported promising results, but they are relatively small, hard to blind and still under regulatory evaluation. Positive trial results do not imply that use outside these settings is safe.