A Phase 1 interventional study of Psilocybin and Midazolam in Psychedelic Experiences and Amnesia, sponsored by University of Wisconsin, Madison. Completed at 1 site in United States. Open to participants aged 21 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-05-19.
Sponsored by University of Wisconsin, Madison · Phase 1, Interventional, and Treatment
The primary objective of the RECAP Study Program is to investigate the role played by conscious experience in the antidepressant effects of the psychedelic agent psilocybin. This pilot dosing study (PILOT RECAP) is designed to determine the optimal dose of midazolam that allows a psychedelic experience to occur while inducing amnesia for the experience. This is an essential step required for subsequent evaluation of the role of memory for the psychedelic experience in the antidepressant effects of psilocybin in the full RECAP study.
The PILOT RECAP Study will investigate the effect of co- administering the amnestic agent midazolam with a single 25 mg dose of psilocybin on the induction of a psychedelic experience and subsequent memory for the experience with the goal of identifying an optimal dosing regimen of midazolam that will allow a psychedelic experience to occur while also inducing amnesia for the experience. Identifying this midazolam dosing regimen will allow us in a subsequent stage of the RECAP program to test whether memory for the psychedelic experience is required/important for psilocybin to produce longer-term antidepressant effects. This is a phase 1 study in psychiatrically and medically healthy volunteers. Given this, there is no disease background for PILOT RECAP per se. However, the purpose of PILOT RECAP is to identify an optimal midazolam dosing schedule to be used in a subsequent study (RECAP) in patients with major depressive disorder (MDD).
The investigational treatment for PILOT RECAP is a single 25 mg dose of psilocybin combined with repeated intravenous (IV) boluses of midazolam dosed at levels known to maintain conscious experience while inducing subsequent amnesia for the experience upon its conclusion. Because PILOT RECAP is the first study to examine this drug combination, no data are currently available on this approach. Psilocybin + midazolam will be administered within a "Set and Setting" (SaS) protocol that provides psychoeducation and therapeutic support prior to, during, and following psychedelic dosing, and that has been standard procedure for recent studies of psilocybin in humans. It is believed that this SaS approach enhances clinical efficacy and safety. SaS is an integral component of the PILOT RECAP intervention.
The PILOT RECAP study will not enroll vulnerable populations. During this study, participants are asked to:
Refrain from using legal psychoactive substance for the following defined time periods (the exception is caffeine):
22 studies on the registry are indexed under Amnesia; 2 are open to participants now.
This study's enrollment of 8 is below the median of 62 across 19 interventional studies indexed under Amnesia.
Browse Amnesia studies →University of Wisconsin, Madison is the lead sponsor of 1,188 studies on the registry; 181 are open to participants now.
Of its 157 completed or terminated interventional studies of FDA-regulated products, 118 (75%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Medically and psychiatrically healthy adults ages 21 to 65 years will receive a single 25 mg dose of psilocybin combined with repeated boluses of midazolam administered in a clinically supportive setting.
Drug: Psilocybin and Midazolam
Drug pages: Psilocybin · Midazolam
The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. The midazolam in this study will be administered intravenously. The total dose administered to a given subject is dependent on the individual's level of amnesia, sedation scale score, age, and weight.
Also known as: Psilocybine, Psilocibin, benzodiazepine
Number of participants scoring >50 percent of normative scores on selected questions from the Altered States of Consciousness (ASC) questionnaire asked during the dosing session Day 0.
Participants will complete a selection of several questions from the ASC questionnaire that strongly associate positively or negatively with later antidepressant effect of psilocybin in patients with treatment resistant depression or capture classic features of the psychedelic experience. During the dosing session, investigator will repeatedly ask selected items from the ASC scale to get a "real time" measure of what the participants are experiencing. Each of these items will be scored separately. Higher score are indicative of a more intense psychedelic experience.
Time frame: On Day 14
Number of participants scoring < 50 percent on post-dosing Day 1 of the mean normative score of ASC data from healthy volunteers administered the ASC questionnaire post-dosing
To assess the degree to which midazolam has induced amnesia for the psychedelic experience, participants will complete the full ASC. The ASC is a 94 item questionaire. In response to each item, participants are asked to mark their experience somewhere between 'No, not more than usual' to 'Yes, much more than usual'. Normal waking consciousness corresponds to a mark at the very left end of the scale, i.e. 'No, Not more than usual'. Responses marked more towards right side of the range are considered high on psychedelic experience.
Time frame: On Day 15
Accuracy on post-dosing Day 1 in recognizing ASC items asked during the dosing session Day 0 (number of correct versus distractor items)
Participants will undergo a yes-no ASC recognition task regarding their memory for internally and externally focused phenomenological content of their experience.
Time frame: On Day 15
Safety of psilocybin-midazolam co-administration assessed by number of adverse event incidences in each severity grade.
Adverse event grading will be done using Common Terminology Criteria for Adverse Event (CTCAE)Adverse events will be graded from Grade 1-5 depending on severity. Grade 1 - mild, grade 2 - moderate, grade 3 - severe, grade 4 - Life threatening, grade 5 - Fatal. Adverse events will be collected on an Adverse Event Log throughout the study.
Time frame: up to 4 weeks
Safety of psilocybin-midazolam co-administration assessed by number of participants requiring medical attention due to adverse events
Time frame: up to 4 weeks
Safety of psilocybin-midazolam co-administration assessed by number of participants requiring psychiatric attention due to adverse events
Time frame: up to 4 weeks
Safety of psilocybin-midazolam co-administration assessed by number of participants leading to withdrawal from study due to adverse events
Time frame: up to 4 weeks
Safety of psilocybin-midazolam co-administration assessed by number of participants with severe adverse events
Time frame: up to 4 weeks
Safety of psilocybin-midazolam co-administration assessed by number of participants with new concomitant medication due to adverse events
Time frame: up to 4 weeks
Plan to share: No
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This study is completed, as verified in May 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Psilocybin · Midazolam
University of Wisconsin, Madison →