Electrophysiological effects of psilocybin co-administered with midazolam.
Michael H Sutherland, Christopher R. Nicholas, Richard C Lennertz, Cody J. Wenthur, Bryan M Krause, Christina J. Sauder, Brady A. Riedner, Richard F Smith, Paul R. Hutson, Charles L. Raison, Matthew I Banks
Translational Psychiatry February 14, 2026 DOI: 10.1038/s41398-026-03894-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open label pilot study Open-label Peer reviewed |
|---|---|
| Interventions | Psilocybin Midazolam |
| Dose | 25 mg |
| Topics | Psilocybin |
| Key points | Psilocybin's effects on EEG measures, including increased LZCn and spectral exponent and decreased broadband power, are maintained in the presence of midazolam. |
Abstract
The serotonergic psychedelic psilocybin induces neural plasticity and profoundly alters consciousness. The benzodiazepine midazolam blunts neural plasticity and induces conscious sedation and amnesia at low doses. In our recent open label pilot study, we administered oral psilocybin (25 mg) along with intravenous midazolam at doses allowing a full psychedelic experience while blunting memory for the experience. We previously reported preliminary results from high density scalp electroencephalography (EEG) recorded during the dosing session. Here, we examined changes in EEG band power, normalized Lempel Ziv complexity (LZCn), and spectral exponent. We used linear mixed effects models that incorporated time and the subjective effects of midazolam and psilocybin, measured with the Observer's Assessment of Arousal and Sedation (OAA/S) and selected items from the Altered States of Consciousness (ASC) questionnaire, respectively. At 15-30 min, when midazolam but not psilocybin was at its targeted effect site concentration, we observed increased beta power and decreased spectral exponent. As the subjective effects of psilocybin commenced and over the next six hours, we observed increased LZCn and spectral exponent and decreased broadband power, with the most prominent power reductions in the delta, theta, and alpha frequency bands. OAA/S improved model fits for alpha power while ASC improved model fits for LZCn and spectral exponent. While recognizing limitations inherent to the small sample size and variability in dosages of midazolam, these data are further evidence that the effects of psilocybin are maintained in the presence of midazolam, supporting its utility in mechanistic studies of psilocybin's therapeutic activity.
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |
Citations in the library
Cites 40
- A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behavior Science Translational Medicine August 14, 2013
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology December 1, 2011
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
and 35 more in the library