410. Comparative neurophysiological signatures of psychedelics, stimulants and anesthetics in rodent cortical activity
B Richardson, J O'Byrne, V Bruno, Stefano Comai, R Carhart-Harris, Gabriella Gobbi
International Journal of Neuropsychopharmacology September 9, 2026 DOI: 10.1093/ijnp/pyag040.152 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rodents |
| Interventions | Psilocybin LSD 5-MeO-DMT Lisuride D-amphetamine Propofol |
| Dose | Psilocybin 6 mg/kg, LSD 0.2 mg/kg, 5-MeO-DMT 10 mg/kg, lisuride 0.5 mg/kg, d-amphetamine 5 mg/kg, propofol 100 mg/kg |
| Measures | Electrocorticography (ECoG), electromyography (EMG), Lempel-Ziv complexity, Higuchi fractal dimension, spectral entropy |
| Key findings | Psilocybin and LSD broadly desynchronized cortical activity, whereas 5-MeO-DMT and lisuride increased delta and gamma power, resembling a stimulant-like state. Lisuride uniquely increased signal complexity, and propofol showed minimal changes. The authors propose that serotonergic psychedelics exhibit compound-specific neural signatures. |
Abstract
Abstract Background Psychedelics induce altered states of consciousness (AOC) with profound perceptual, cognitive, and emotional shifts, often linked to positive therapeutic outcomes. Although serotonergic psychedelics such as psilocybin, LSD, and 5-MeO-DMT share receptor targets, they differ in behavioral and neural effects. How these compounds alter cortical dynamics relative to other consciousness-modulating agents, including dopaminergic stimulants and anesthetics, remains unclear. Aims & Objectives We aimed to delineate the compound-specific neurophysiological signatures of serotonergic psychedelics, dopaminergic stimulants, and anesthetics by examining cortical oscillations, muscular activity, signal complexity, and spectral entropy.
Method: Rodents received i.p. injections of psilocybin (6 mg/kg), LSD (0.2 mg/kg), 5-MeO-DMT (10 mg/kg), lisuride (0.5 mg/kg), d-amphetamine (5 mg/kg), or propofol (100 mg/kg). Electrocorticography (ECoG) and electromyography (EMG) recorded cortical and muscular activity. Analyses included absolute and relative power across canonical delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13Hz), beta (13-30Hz), and gamma (30-40 Hz) bands, Lempel-Ziv complexity (LZ) and Higuchi fractal dimension (HFD) to assess signal diversity, and spectral entropy to quantify frequency-specific unpredictability. Principal component and clustering analyses identified compound-specific patterns.
Results: Psilocybin reduced cortical power across delta (-21.4 ± 5.7 %, p < 0.05), theta (-27.1 ± 5.4 %, p < 0.01), alpha (-34.9 ± 2.9 %, p < 0.001), beta (-33.6 ± 3.5 %, p < 0.001), and gamma (-40.3 ± 3.8 %, p < 0.001) bands and decreased EMG (-28.3 ± 7.5 %, p < 0.05), reflecting cortical desynchronization and reduced arousal. LSD produced similar cortical reductions, but EMG increased early (76.0 ± 21.3 %, p < 0.05). In contrast, 5-MeO-DMT and lisuride, like d-amphetamine, elevated delta (96–180 %, p < 0.05–0.001) and gamma (106–136 %, p < 0.05) power, indicative of synchronized, high-amplitude cortical activity. Only lisuride uniquely increased complexity (LZ +0.02 ± 0.005, HFD +0.05 ± 0.009, p < 0.05–0.01) and modulated theta and gamma biphasically and transiently. D-amphetamine decreased mid-frequency relative power early, then increased beta and gamma spectral entropy (0.005–0.0075 ΔSE, p < 0.05), consistent with sustained high-frequency engagement. Propofol showed minimal changes, with modest delta suppression (-16.6 ± 4.0 %, p < 0.05) and alpha elevation (+1.72 ± 0.42 %, p < 0.05). Principal component analysis segregated serotonergic psychedelics (LSD and psilocybin) and propofol from d-amphetamine and 5-MeO-DMT based on absolute gamma, delta and beta and total power, highlighting neurophysiological signatures driven by cortical power, EMG, and frequency-specific entropy. Discussion & Conclusions Serotonergic psychedelics exhibit distinct, compound-specific neural signatures. Psilocybin and LSD induce broadband cortical desynchronization, whereas 5-MeO-DMT resembles a high-arousal, stimulant-like state. Lisuride demonstrates biphasic modulation and transient complexity increases. These findings reveal mechanistic heterogeneity among psychedelics and provide a multivariate framework for understanding the electrophysiological basis of altered consciousness states.