Modeling the hallucinatory effects of classical psychedelics in terms of replay-dependent plasticity mechanisms.
Colin Bredenberg, Fabrice Normandin, Blake Richards, Guillaume Lajoie
Elife April 21, 2026 DOI: 10.7554/elife.105968 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Neuroplasticity |
| Keywords | Humans Hallucinations Hallucinogens Dreams Sleep Neuronal plasticity Models, neurological Neural networks, computer Machine learning Memory consolidation None Psychedelics |
| Key points | Proposes that classical psychedelics' perceptual effects result from pharmacologically inducing neural activity states similar to dreaming, as simulated by shifting a neural network model toward the 'Sleep' phase. |
Abstract
Classical psychedelics induce complex visual hallucinations in humans, generating percepts that are coherent at a low level, but which have surreal, dream-like qualities at a high level. While there are many hypotheses as to how classical psychedelics could induce these effects, there are no concrete mechanistic models that capture the variety of observed effects in humans, while remaining consistent with the known pharmacological effects of classical psychedelics on neural circuits. In this work, we propose the ‘oneirogen hypothesis,’ which posits that the perceptual effects of classical psychedelics are a result of their pharmacological actions inducing neural activity states that truly are more similar to dream-like states. We simulate classical psychedelics’ effects via manipulating neural network models trained on perceptual tasks with the Wake-Sleep algorithm. This established machine learning algorithm leverages two activity phases: a perceptual phase (wake) where sensory inputs are encoded, and a generative phase (dream) where the network internally generates activity consistent with stimulus-evoked responses. We simulate the action of psychedelics by partially shifting the model to the ‘Sleep’ state, which entails a greater influence of top-down connections, in line with the impact of psychedelics on apical dendrites. The effects resulting from this manipulation capture a number of experimentally observed phenomena, including the emergence of hallucinations, increases in stimulus-conditioned variability, and large increases in synaptic plasticity. We further provide a number of testable predictions which could be used to validate or invalidate our oneirogen hypothesis.
Comparable studies
Other theoretical and historical papers on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic Potential? | 2021 | Theoretical or philosophical paper | |
| A complex systems perspective on psychedelic brain action. | 2023 | Theoretical or philosophical paper | |
| Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy | 2021 | Theoretical or philosophical paper | |
| Therapeutic mechanisms of psychedelics and entactogens. | 2023 | Theoretical or philosophical paper |
Citations in the library
Cites 27
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
and 22 more in the library