Pilot RECAP Study in Healthy Volunteers
Condition: Psychedelic Experiences; Amnesia
MeSH terms: Amnesia
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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 use of psychotropic medications. Use of such medications prior to
           psilocybin/midazolam dosing will result in a participant being discontinued from the
           study.

        -  Refrain from use of any illegal psychoactive substances from screening until study
           termination.

        -  Refrain from using legal psychoactive substance for the following defined time periods
           (the exception is caffeine):

             -  Tobacco and Nicotine: from screening until study termination

             -  Alcohol: 72 hours prior to the Dosing Visit
    

Intervention name(s): Psilocybin and Midazolam
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): Psilocybine; Psilocibin; benzodiazepine
Intervention MeSH terms: Midazolam; Psilocybin
Intervention model: Single Group Assignment
Intervention model description: Open trial of a single 25 mg dose of psilocybin combined with repeated boluses of midazolam in medically and psychiatrically healthy volunteers.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Memory; Amnesia; Healthy Volunteer