Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience.
Christopher R. Nicholas, Matthew I Banks, Richard C Lennertz, Cody J. Wenthur, Bryan M Krause, Brady A. Riedner, Richard F Smith, Paul R. Hutson, Christina J. Sauder, John D. Dunne, Leor Roseman, Charles L. Raison
Translational Psychiatry September 12, 2024 DOI: 10.1038/s41398-024-03059-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Healthy participants |
| Interventions | Psilocybin Midazolam |
| Dose | 25 mg |
| Topics | Psilocybin |
| Keywords | Psychedelics Mental health therapy Memory Therapeutic outcomes |
| Citations | 10 |
| Key findings | Memory impairment from midazolam tended to associate with reduced salience, insight, and well-being induced by psilocybin, suggesting memory contributes to psilocybin's therapeutic behavioral effects. |
Abstract
Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.
Comparable studies
Other experimental studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... | 2015 | Validation study using pooled data from five laboratory experiments | n = 184 |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... | 2020 | Long-term within-subjects follow-up analysis | n = 15 |
| Enzymatic Synthesis of Psilocybin | 2017 | Laboratory study |
Citations in the library
Cited by 10
- The ketamine chameleon: history, pharmacology, and the contested value of experience. Expert Review of Clinical Pharmacology March 1, 2025
- Psychedelic research, assisted therapy and the role of the anaesthetist: A review and insights for experimental and clinical practices. British Journal of Clinical Pharmacology December 1, 2024
- How to set up a psychedelic study: Unique considerations for research involving human participants. Neuroscience & Biobehavioral Reviews July 1, 2026
- The entropic brain today Brain December 12, 2025
- Commentary on Methods for Addressing Functional Unblinding and Mechanistic Uncertainty in Clinical Trials of Psychedelic-Assisted Treatments Current Treatment Options in Psychiatry November 11, 2025
and 5 more in the library
Cites 74
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 69 more in the library