Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience
This open-label study (n=8) co-administered psilocybin (25mg) with the amnestic benzodiazepine midazolam to assess the role of memory in the therapeutic effects of psilocybin. It finds that midazolam partially impaired memory while allowing a conscious psychedelic experience, with memory impairment inversely associated with salience, insight, and well-being induced by psilocybin, suggesting a role for memory in its therapeutic effects.
Authors
- Leor Roseman
- Charles Raison
- Christopher Nicholas
Published
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.
Research Summary of 'Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience'
Introduction
Serotonergic psychedelics such as psilocybin produce acute subjective experiences that have been linked to durable improvements in mental health and wellbeing. Prior studies report that particular features of the psychedelic session—often characterised as mystical, insight, or breakthrough experiences—predict longer‑term therapeutic benefit. However, it remains unclear whether those benefits arise from the immediate phenomenology of the session itself, from the neural plasticity induced during the acute drug action, or from subsequent memory and integration of the experience. Distinguishing the contribution of experience versus its memory is important for mechanistic models of psychedelic‑assisted therapy and for understanding how post‑dosing integration supports durable change. Nicholas and colleagues aimed to separate the occurrence of a psychedelic experience from its later recollection by co‑administering the amnestic benzodiazepine midazolam with psilocybin in a small pilot dose‑finding study. Their objective was to identify a midazolam dosing strategy that would permit a conscious psychedelic experience while partially impairing memory for that experience, enabling subsequent tests of whether memory mediates persistent behavioural effects. The study therefore focused on feasibility, safety, and initial signals relating midazolam dose, subjective experience during dosing, and post‑dosing memory and wellbeing measures.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Nicholas, C. R., Banks, M. I., Lennertz, R. C., Wenthur, C. J., Krause, B. M., Riedner, B. A., Smith, R. F., Hutson, P. R., Sauder, C. J., Dunne, J. D., Roseman, L., & Raison, C. L. (2024). Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience. Translational Psychiatry, 14(1). https://doi.org/10.1038/s41398-024-03059-8
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