2026 ECNP Congress

PS02-2062

Temporal mapping of electroencephalographic dynamics during intravenous psilocin administration in binge eating disorder: a case study

Sean Carruthers — H. Pedersen, S. Rossell, C. Finkelstein, T. Nguyen, A. Miller, R. Iyer, D. White, H. Byrne, M. Pena, J. Pincombe, D. Castle · Swinburne University of Technology, Centre for Mental Health and Brain Sciences, Hawthorn, Australia

2026 ECNP Congress

Introduction

Binge eating disorder (BED) is the most prevalent eating disorder, characterised by recurrent compulsive overconsumption, loss of control and significant psychological distress, with limited effective pharmacotherapies [1] Psilocin, the active metabolite of psilocybin, has demonstrated therapeutic potential across multiple psychiatric conditions when administered with psychedelic-assisted psychotherapy [2]. As a centrally acting serotonergic agonist, psilocin directly mediates the neural processes underlying the psychedelic state [3]. However, electroencephalographic (EEG) biomarker characterisation during dosing has been constrained by the pharmacokinetic variability inherent to oral administration [4]. Intravenous (IV) delivery of psilocin enables precise dose-onset alignment of neural activity, providing a methodological advance that may resolve the temporal structure of drug-induced neural reorganisation with high temporal precision and reduced inter-individual pharmacokinetic variability, and has not yet been exploited in clinical psychedelic EEG research.

Aims

To characterise the temporal profile of EEG oscillatory changes during IV psilocin (TRP-8803) administration in a participant with BED enrolled in a Phase I open-label clinical trial.

Methods

Resting EEG was recorded at baseline (eyes closed and open) and continuously throughout an IV psilocin dosing session (~100 min). Raw data were preprocessed using a standardised pipeline including high-pass filtering (1 Hz), 50 Hz notch filtering, bad channel interpolation and independent component analysis (ICA)-based artefact rejection. A broad metric set including theta-beta ratio (TBR), relative band powers, frontal alpha asymmetry (FAA), peak alpha frequency (PAF), signal complexity and phase-based connectivity was extracted per 1-minute non-overlapping epoch. Changes were compared across dose-aligned windows: pre-dose, acute (0–20 min) and late (>40 min post-dose), with magnitude of change quantified relative to baseline.

Results

IV dose-onset alignment revealed a temporally structured oscillatory reorganisation across the dosing period. The earliest signal was an acute rise in TBR, peaking approximately 24 minutes post-dose, reflecting rapid relative elevation of slow-wave over fast frequency activity. This was followed by sustained and progressive suppression of relative alpha and beta power, both reaching their nadir in the late dosing window, consistent with a broadband spectral shift toward low frequency dominance. PAF declined gradually from dose onset through the late dosing period, indicating progressive slowing of the dominant cortical rhythm. Together, these metrics describe two temporally distinct neurophysiological states: an early acute shift in slow:fast spectral balance and a sustained late-dosing reorganisation characterised by low frequency spectral dominance and cortical slowing.

Conclusions

IV psilocin induces temporally structured EEG changes characterised by progressive spectral slowing, with converging signals across oscillatory, complexity and connectivity domains. Precise IV dose-onset alignment reveals temporally anchored acute and late neurophysiological states, a resolution not achievable with oral routes due to absorption variability. These preliminary findings from a single BED case establish a methodological framework for clinical psychedelic EEG biomarker research and motivate replication across the full BED-IV cohort to determine whether these neural signatures relate to clinical outcomes.

References

  1. Guerdjikova, A. I., Mori, N., Casuto, L. S., & McElroy, S. L. (2021). Binge eating disorder. Psychiatric Clinics of North America, 40(2), 255–266.
  2. Carhart-Harris, R., & Goodwin, G. M. (2017). The therapeutic potential of psychedelic drugs: Past, present, and future. Neuropsychopharmacology, 42(11), 2105–2113.
  3. Madsen, M. K., Fisher, P. M., Burmester, D., Dyssegaard, A., Stenbæk, D. S., Kristiansen, S., Johansen, S. S., Lehel, S., Linnet, K., Svarer, C., Erritzoe, D., Ozenne, B., & Knudsen, G. M. (2019). Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(7), 1328–133.4
  4. Meshkat, S., Al-Shamali, H., Perivolaris, A., Tullu, T., Zeifman, R. J., Zhang, Y., Burback, L., Winkler, O., Greenshaw, A., Husain, M. I., C Reichelt, A., Vermetten, E., Jha, M. K., Jetly, R., Loebenberg, R., & Bhat, V. (2025). Pharmacokinetics of Psilocybin: A Systematic Review. Pharmaceutics, 17(4), 411.