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.