The oneirogen hypothesis: modeling the hallucinatory effects of classical psychedelics in terms of replay-dependent plasticity mechanisms
eLife January 13, 2026 Colin Bredenberg, Fabrice Normandin, Blake Richards et al.
Classical psychedelics produce complex visual hallucinations that are coherent at low levels but surreal at high levels, resembling dream-like states. The oneirogen hypothesis proposes that these perceptual effects arise because psychedelics induce neural activity states similar to dreaming. By simulating psychedelics' effects on neural network models trained with the Wake-Sleep algorithm—which alternates between a perceptual (wake) phase and a generative (dream) phase—partially shifting the model to the 'Sleep' state (increasing top-down connections, consistent with effects on apical dendrites) captures observed phenomena: hallucinations, increased stimulus-conditioned variability, and large synaptic plasticity increases. The hypothesis offers testable predictions for validation.