About this trial

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

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

Psilocybin
Drug
25mg of psilocybin
Psilocybin
Drug
1mg of psilocybin
Midazolam
Drug
The goal of the midazolam dosing regimen is to induce amnesia of the psychedelic experience without inducing over-sedation during the dosing session.
Saline
Drug
Saline will be administered as a placebo for midazolam

Treatment groups

60 Participants

are divided into 4 treatment groups

Group A: Group 1: Psilocybin and intravenous (IV) midazolamExperimental treatment 2 interventions

Group B: Group 2: Psilocybin and IV salineExperimental treatment 2 interventions

Group C: Group 3: Psilocybin and IV midazolamExperimental treatment 2 interventions

Group D: Group 4: Psilocybin and IV salineExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame

Baseline to 7 days post-dose

2

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

Time frame

Baseline to 7 days post-dose

3

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).

Time frame

Baseline to 7 days post-dose

4

Change in transcranial magnetic stimulation evoked potential (TEP) amplitude

TEP measures neural excitability in the stimulated region of the brain.

Time frame

Baseline to 7 days post-dose

Secondary outcomes

1

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.

Time frame

Baseline to 28 days post-dose

2

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

Time frame

Baseline to 28 days post-dose

3

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).

Time frame

Baseline to 28 days post-dose

4

Change in TEP amplitude

TEP measures neural excitability in the stimulated region of the brain.

Time frame

Baseline to 28 days post-dose

The RECAP2 Study: Midazolam and Psilocybin

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts