Persisting perceptual abnormalities in psychedelic users are associated with conditioned hallucinations and impaired sensory processing

Serotonergic psychedelics (SP) are increasingly used in clinical research and naturalistic settings, but their psychotic-like side effects, including persisting perceptual abnormalities (PPAs), are poorly understood. Psychosis-associated hallucinations are associated with susceptibility to conditioned hallucinations and computationally-estimated overweighting of perceptual expectations, or priors. However, SPs are widely argued to reduce prior weighting.

We surveyed 186 naturalistic SP users on prior SP use, SP-associated PPA history, and current PPAs. Participants completed the visual conditioned hallucinations (VCH) task, in which conditioning induces perception of absent stimuli. Behavioral data were used to fit parameters of a computational model to estimate latent states driving percepts and responses.

Past and current PPAs were associated with younger age at first use and higher SP doses, lower visual thresholds, higher VCH rate and confidence, and reduced sensory discrimination. Among model parameters, however, only reduced decision precision tracked both measures and mediated the dose-PPA relationship; relative prior weighting rose equivocally, as expected when priors and sensory evidence gain precision together. SP-related PPAs may therefore arise from a noisy visual system biased toward detection, in which priors act as templates that convert sensory noise into expected percepts.

These findings may point to a tractable model for how psychotic-like perception emerges. The authors would like to thank Kayla Morgan, Gabby Hernandez, and Sara Azzi for assisting in data collection, quality control, and advertisement. We thank Dustin Bufford and Mica Chayro for generously offering to advertise our study.

We also thank all of the reddit moderators who allowed us to advertise our study: r/psychonaut, r/LSD, r/DMT, r/Mescaline, r/5MeODMT, r/Ayahuasca, r/HPPD, and r/LSD, r/Shrooms, r/Drugs, and r/RationalPsychonaut. We especially thank the consortium of moderators at r/Drugs who created a centralized review system for advertising research studies across multiple subreddits. We also want to thank Bluelight.org and Dr.

Monica Barratt for allowing us to advertise on their website and Discord. We want to especially thank the DMT Nexus and Shroomery.org who promoted the study on their websites. We wish to thank Silas Keeter, who assisted in deployment of the VCH task online.