PsilocybinPhase 1NCT06692192
The RECAP2 Study: Midazolam and Psilocybin
A Phase 1 study testing Psilocybin, Midazolam and Saline in people with Psilocybin, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn about the role that inducing neuroplasticity (the brain's ability to adapt and change) plays in the behavioral effects of psilocybin in people who have experienced a mild decline in emotional wellbeing. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Psilocybin
- What is being tested?
- Psilocybin, Midazolam and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2025to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years at screening, of any identified gender and racial/ethnic group
- Physically healthy; does not meet criteria for an exclusionary medical condition
- English-speaking (able to provide consent and complete questionnaires)
- Modest decrement in self-reported wellbeing without the presence of a DSM-5 Axis I mood or anxiety disorder
- Able to undergo magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS)
Who cannot join
- Exclusionary DSM-5 psychiatric diagnosis and/or active suicidal ideation
- Exclusionary medical conditions
- Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)
- Clinically significant electrocardiogram (ECG)
- Use of psychotropic or CNS-altering medications within 3 months of screening
- Hypertension or tachycardia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UW School of Medicine and Public Health
Madison, Wisconsin, 53792
About this study
Official title: Role of Experience, Conscious Awareness, and Plasticity in Psilocybin's Behavioral Effects - Follow-Up Study (The RECAP 2 Study)
The goal of this clinical trial is to learn about the role that inducing neuroplasticity (the brain's ability to adapt and change) plays in the behavioral effects of psilocybin in people who have experienced a mild decline in emotional wellbeing.
Researchers will compare different doses of psilocybin combined with midazolam or placebo to see what dose induces increased wellbeing.
Participants will:
- Receive one of four possible combinations of medications
- Undergo an MRI
- Complete questionnaires
- Undergo transcranial magnetic stimulation (TMS) and EEG
Read the detailed description
The purpose of this study is to investigate the role that inducing neuroplasticity plays in the behavioral effects of psilocybin in people with modest decrements in emotional wellbeing.
- Conditions
- Psilocybin
- Being tested
- Psilocybin, Midazolam, Saline
- Keywords
- sub-optimal wellbeing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Also called Psilocybine, Psilocibin
25mg of psilocybin
PsilocybinDrug
Also called Psilocybine, Psilocibin
1mg of psilocybin
MidazolamDrug
The goal of the midazolam dosing regimen is to induce amnesia of the psychedelic experience without inducing over-sedation during the dosing session.
SalineDrug
Saline will be administered as a placebo for midazolam
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Psilocybin and intravenous (IV) midazolam | Experimental | Psilocybin (25 mg) + IV midazolam Receives: Drug: Psilocybin; Drug: Midazolam |
| Group 2: Psilocybin and IV saline | Experimental | Psilocybin (25 mg) + IV saline (placebo for midazolam) Receives: Drug: Psilocybin; Drug: Saline |
| Group 3: Psilocybin and IV midazolam | Experimental | Psilocybin (1 mg/control) + IV midazolam Receives: Drug: Psilocybin; Drug: Midazolam |
| Group 4: Psilocybin and IV saline | Experimental | Psilocybin (1 mg/control) + IV saline Receives: Drug: Psilocybin; Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Warwick-Edinburgh Mental wellbeing Scale (WEMWBS)
WEMWBS is a 14-item questionnaire in which participants describe their experience of each item. It is scored on a 5-point Likert scale, possible range of 14-70 where higher scores indicate higher levels of wellbeing.
Measured: Baseline to 7 days post-dose
Change in Brief Experiential Avoidance Questionnaire (BEAQ)
The BEAQ is a 15-item questionnaire assessing participants agreement with wellbeing statements. It is scored on a 6-point Likert scale, ranging from 15-90 with higher scores indicating a greater tendency towards experiential avoidance
Measured: Baseline to 7 days post-dose
Change in Probabilistic Reversal Learning (PRL)
Participants are presented with two stimuli or options and learn which one is more likely to be associated with a reward based on feedback after each trial. After a certain number of trials, the reward contingencies are reversed, meaning the previously advantageous option becomes less likely to be rewarded, and vice versa. The task assesses how quickly and effectively individuals can adapt to these changes in reward contingencies. Researchers analyze various performance metrics, such as the speed of reversal, the number of errors, and the patterns of choices (e.g., win-stay, lose-shift).
Measured: Baseline to 7 days post-dose
Change in transcranial magnetic stimulation evoked potential (TEP) amplitude
TEP measures neural excitability in the stimulated region of the brain.
Measured: Baseline to 7 days post-dose
Secondary outcomes (7)
Change in WEMWBS
WEMWBS is a 14-item questionnaire in which participants describe their experience of each item. It is scored on a 5-point Likert scale, possible range of 14-70 where higher scores indicate higher levels of wellbeing.
Measured: Baseline to 28 days post-dose
Change in BEAQ
The BEAQ is a 15-item questionnaire assessing participants agreement with wellbeing statements. It is scored on a 6-point Likert scale, ranging from 15-90 with higher scores indicating a greater tendency towards experiential avoidance
Measured: Baseline to 28 days post-dose
Change in PRL
Participants are presented with two stimuli or options and learn which one is more likely to be associated with a reward based on feedback after each trial. After a certain number of trials, the reward contingencies are reversed, meaning the previously advantageous option becomes less likely to be rewarded, and vice versa. The task assesses how quickly and effectively individuals can adapt to these changes in reward contingencies. Researchers analyze various performance metrics, such as the speed of reversal, the number of errors, and the patterns of choices (e.g., win-stay, lose-shift).
Measured: Baseline to 28 days post-dose
Change in TEP amplitude
TEP measures neural excitability in the stimulated region of the brain.
Measured: Baseline to 28 days post-dose
Altered States of Consciousness (ASC) questionnaire
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.
Measured: Dosing 1 day
Emotional Breakthrough Inventory (EBI)
The EBI is a 6-item scale that assesses the presence and severity of emotionally challenging/distressing experiences that occur during a psychedelic experience. Participants rate to what extent the statements apply to their experience by marking a single line across each scale. Scale ranges from not at all to very much so. Higher scores (more slashes toward the 'very much so' end) on the scale have been associated with enhanced well-being following psychedelic use
Measured: Dosing 1 day
Psychological Insight Questionnaire (PIQ)
The PIQ is a 23-item instrument designed to query self-perceived attainment of insight during a psychedelic medicine session. Items are rated on a 6-point Likert scale, 0 = no not at all and 5 = extremely. Possible scares range from 0-115, with higher scores indicating greater insight.
Measured: Dosing 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2024
- Study start7 Aug 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PsilocybinStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Vail Health Foundation, Advanced Research Projects Agency for Health (ARPA-H)
- Responsible party
- Sponsor
- Investigators
- Charles Raison, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06692192
- Sponsor's protocol ID
- 2024-0852
- Other IDs
- A538900, SMPH/PSYCHIATRY/PSYCHIATRY, Protocol Version 7/22/2026
- Status last verified
- Mar 2026
- First submitted
- 14 Nov 2024
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Experience, Conscious Awareness, and Plasticity in Psilocybin's Behavioral Effects - Follow-Up Study (The RECAP 2 Study)
- ClinicalTrials.gov ID
- NCT06692192
- Acronym / sponsor ID
- 2024-0852
- Conditions
- Psilocybin
- Keywords
- sub-optimal wellbeing
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Vail Health Foundation, Advanced Research Projects Agency for Health (ARPA-H)
- Study start
- 7 Aug 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 18 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn about the role that inducing neuroplasticity (the brain's ability to adapt and change) plays in the behavioral effects of psilocybin in people who have experienced a mild decline in emotional wellbeing.
Researchers will compare different doses of psilocybin combined with midazolam or placebo to see what dose induces increased wellbeing.
Participants will:
- Receive one of four possible combinations of medications
- Undergo an MRI
- Complete questionnaires
- Undergo transcranial magnetic stimulation (TMS) and EEG
Detailed description
The purpose of this study is to investigate the role that inducing neuroplasticity plays in the behavioral effects of psilocybin in people with modest decrements in emotional wellbeing.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: Psilocybin and intravenous (IV) midazolam | Experimental | Drug: Psilocybin, Drug: MidazolamPsilocybin (25 mg) + IV midazolam |
| Group 2: Psilocybin and IV saline | Experimental | Drug: Psilocybin, Drug: SalinePsilocybin (25 mg) + IV saline (placebo for midazolam) |
| Group 3: Psilocybin and IV midazolam | Experimental | Drug: Psilocybin, Drug: MidazolamPsilocybin (1 mg/control) + IV midazolam |
| Group 4: Psilocybin and IV saline | Experimental | Drug: Psilocybin, Drug: SalinePsilocybin (1 mg/control) + IV saline |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 to 65 years at screening, of any identified gender and racial/ethnic group
- Physically healthy; does not meet criteria for an exclusionary medical condition
- English-speaking (able to provide consent and complete questionnaires)
- Modest decrement in self-reported wellbeing without the presence of a DSM-5 Axis I mood or anxiety disorder
- Able to undergo magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS)
Key exclusion criteria (6 listed)
- Exclusionary DSM-5 psychiatric diagnosis and/or active suicidal ideation
- Exclusionary medical conditions
- Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)
- Clinically significant electrocardiogram (ECG)
- Use of psychotropic or CNS-altering medications within 3 months of screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PsilocybinAlso: Psilocybine, Psilocibin25mg of psilocybin | Drug | Group 1: Psilocybin and intravenous (IV) midazolam, Group 2: Psilocybin and IV saline |
| PsilocybinAlso: Psilocybine, Psilocibin1mg of psilocybin | Drug | Group 3: Psilocybin and IV midazolam, Group 4: Psilocybin and IV saline |
| MidazolamThe goal of the midazolam dosing regimen is to induce amnesia of the psychedelic experience without inducing over-sedation during the dosing session. | Drug | Group 1: Psilocybin and intravenous (IV) midazolam, Group 3: Psilocybin and IV midazolam |
| SalineSaline will be administered as a placebo for midazolam | Drug | Group 2: Psilocybin and IV saline, Group 4: Psilocybin and IV saline |
Primary outcome
Change in Warwick-Edinburgh Mental wellbeing Scale (WEMWBS)
Time frame: Baseline to 7 days post-dose
WEMWBS is a 14-item questionnaire in which participants describe their experience of each item. It is scored on a 5-point Likert scale, possible range of 14-70 where higher scores indicate higher levels of wellbeing.
Change in Brief Experiential Avoidance Questionnaire (BEAQ)
Time frame: Baseline to 7 days post-dose
The BEAQ is a 15-item questionnaire assessing participants agreement with wellbeing statements. It is scored on a 6-point Likert scale, ranging from 15-90 with higher scores indicating a greater tendency towards experiential avoidance
Change in Probabilistic Reversal Learning (PRL)
Time frame: Baseline to 7 days post-dose
Participants are presented with two stimuli or options and learn which one is more likely to be associated with a reward based on feedback after each trial. After a certain number of trials, the reward contingencies are reversed, meaning the previously advantageous option becomes less likely to be rewarded, and vice versa. The task assesses how quickly and effectively individuals can adapt to these changes in reward contingencies. Researchers analyze various performance metrics, such as the speed of reversal, the number of errors, and the patterns of choices (e.g., win-stay, lose-shift).
Change in transcranial magnetic stimulation evoked potential (TEP) amplitude
Time frame: Baseline to 7 days post-dose
TEP measures neural excitability in the stimulated region of the brain.
7 secondary outcomes
Change in WEMWBS
Time frame: Baseline to 28 days post-dose
Change in BEAQ
Time frame: Baseline to 28 days post-dose
Change in PRL
Time frame: Baseline to 28 days post-dose
Change in TEP amplitude
Time frame: Baseline to 28 days post-dose
Altered States of Consciousness (ASC) questionnaire
Time frame: Dosing 1 day
Emotional Breakthrough Inventory (EBI)
Time frame: Dosing 1 day
Psychological Insight Questionnaire (PIQ)
Time frame: Dosing 1 day
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Take the pre-screening surveyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Charles Raison, MD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Psilocybin, Midazolam and Saline in people with Psilocybin, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact RECAP Study Contact (608-263-4852, recap2@psychiatry.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Warwick-Edinburgh Mental wellbeing Scale (WEMWBS) (time frame: Baseline to 7 days post-dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.