Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience

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....

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Published inTranslational psychiatry Vol. 14; no. 1; pp. 372 - 11
Main Authors Nicholas, Christopher R, Banks, Matthew I, Lennertz, Richard C, Wenthur, Cody J, Krause, Bryan M, Riedner, Brady A, Smith, Richard F, Hutson, Paul R, Sauder, Christina J, Dunne, John D, Roseman, Leor, Raison, Charles L
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 12.09.2024
Subjects
Adult
Anesthesia
Benzodiazepines
Drug dosages
Female
Hallucinogens - administration & dosage
Hallucinogens - pharmacology
Health care
Humans
Male
Medicine
Memory
Memory - drug effects
Midazolam - administration & dosage
Midazolam - pharmacology
Psilocybin - administration & dosage
Psilocybin - pharmacology
Psychedelic drugs
Psychiatry
Public health
Young Adult
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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.
AbstractList 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.
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.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.
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.
ArticleNumber 372
Author Lennertz, Richard C
Riedner, Brady A
Hutson, Paul R
Sauder, Christina J
Dunne, John D
Roseman, Leor
Krause, Bryan M
Banks, Matthew I
Wenthur, Cody J
Raison, Charles L
Nicholas, Christopher R
Smith, Richard F
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Snippet Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved...
Abstract Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and...
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StartPage 372
SubjectTerms Adult
Anesthesia
Benzodiazepines
Drug dosages
Female
Hallucinogens - administration & dosage
Hallucinogens - pharmacology
Health care
Humans
Male
Medicine
Memory
Memory - drug effects
Midazolam - administration & dosage
Midazolam - pharmacology
Psilocybin - administration & dosage
Psilocybin - pharmacology
Psychedelic drugs
Psychiatry
Public health
Young Adult
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Title Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience
URI https://www.ncbi.nlm.nih.gov/pubmed/39266503
https://www.proquest.com/docview/3103678751/abstract/
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Volume 14
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