2 x 2 Factorial, Double-blind, Randomized Trial of 'Set and Setting': a Translational Study in Healthy Volunteers
Overview
- Phase
- Phase 2
- Intervention
- Psilocybin
- Conditions
- Not specified
- Sponsor
- Robin Carhart-Harris, PhD, MA
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Challenging Experience Questionnaire (CEQ) subscales score
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
One hundred twenty healthy participants, ages 21 to 70, who experience moderate-to-lower-than-average mental well-being will be evenly randomized into four different study arms, using a 2x2 factorial design. Depending on the study arm, participants will either receive an inactive placebo or up to 25mg psilocybin (oral dose), in one of two set and setting conditions; drug administration contexts that are predicted to modulate drug effects.
The purpose of this study is to evaluate any interaction effects between an oral dose of psilocybin and the surrounding context (set and setting).
Detailed Description
Recent research posits that psychedelic medicine is best employed as a combination treatment, i.e., as drug x psychological support or psychotherapy referred to for simplicity as 'psychedelic therapy'. It is assumed that positive outcomes via psychedelic therapy critically depend on a synergistic relationship between drug-induced brain and mind plasticity and supportive contextual factors (Carhart-Harris et al., 2018; Carhart-Harris and Friston, 2019). These contextual factors have been referred to as 'set and setting' (Leary et al., 1963) or 'extrapharmacological'- highlighting elements beyond the drug that contribute to relevant outcomes (Hartogsohn, 2016). The proposed experiment is a double-blind, randomized between-subjects 2 x 2 factorial study in 120 volunteers who experience low psychological well-being at baseline and have limited prior experience with psychedelics (1:1:1:1, n = 30 per condition). The main aim of the study is to assess the contribution of a select number of pre-defined contextual variables (both 'set' and 'setting') on the nature and trajectory of effects linked to a single dosing session with either psilocybin (oral, 25mg) or placebo (oral, inert). The study will have four primary outcomes, two pertaining to mental health, namely: changes in psychological well-being - as measured via the Warwick-Edinburgh Mental Wellbeing Scales (WEMWBS), from baseline to 4 weeks post dosing session (primary endpoint) and changes in the Watts Connectedness Scale (WCS) at consistent timepoints. The two primary outcomes indexing the quality of the acute experience will be: Emotional Breakthrough - measured via mean scores on the Emotional Breakthrough Inventory (EBI), and Challenging experience (CE) - defined and measured here as scores on the following four sub-factors of the Challenging Experience Questionnaire (CEQ): fear, insanity, isolation, and paranoia.
Investigators
Robin Carhart-Harris, PhD, MA
Professor
University of California, San Francisco
Eligibility Criteria
Inclusion Criteria
- •Participants will be considered for inclusion if they:
- •Are between 21 and 70 years of age
- •Are fluent in speaking and reading English
- •Are able to swallow pills/capsules
- •If able to become pregnant, must be non-lactating, have a negative pregnancy test at study entry and prior to each Experimental Session and must agree to an adequate form of birth control over the course of the study. Adequate forms of birth control include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Unable to become pregnant is defined as documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, and/or tubal ligation), permanently sterile by medical device such as Essure, postmenopausal, or assigned male sex at birth.
- •Able and willing to provide informed consent
- •Able and willing to use computers and tablets or phones to enter electronic data
- •Agree to inform the investigators within 48 hours of any new or changed medical conditions.
- •Have an identified support person
- •For those dosed with psilocybin, their prior consent to be accompanied home (or to an otherwise safe destination) by a support person, chosen by them - ahead of time, or by a member of the study team.
Exclusion Criteria
- •Participants will be excluded if they:
- •Have a current diagnosed psychiatric disorder that, in the opinion of the study clinician or PI, renders to person psychologically unstable or unduly vulnerable, or interferes with activities of daily living, or could impact attendance at or participation in study activities
- •Have a medically significant condition that renders the person unsuitable for the study
- •Give a positive alcohol breathalyzer test result on any study visit
- •A positive urine drug screen to any excluded substances prior to an Experimental Session, which warrants exclusion based on concerns that it may compromise safety or confound outcomes
- •Are breastfeeding, or have a positive pregnancy test at screening or at any point during the course of the study
- •Systolic and diastolic BP values exceeding 139 SBP and exceeding 89 DBP and heart rate exceeding 90 bpm would result in exclusion from the study.
- •Present with a exceeding 450 msec or with evidence of cardiac damage, ischemia, or heart disease.
- •Have received an investigational drug within 30 days of the screening visit
- •Have an allergy or intolerance to any of the materials contained in either drug product or setting components, such as certain scents.
Arms & Interventions
Psilocybin C1
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of up to 25mg psilocybin in a context (Context 1) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Psilocybin
Psilocybin C1
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of up to 25mg psilocybin in a context (Context 1) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Context 1
Psilocybin C2
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of up to 25mg psilocybin in a context (Context 2) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Psilocybin
Psilocybin C2
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of up to 25mg psilocybin in a context (Context 2) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Context 2
Placebo C1
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of an inactive placebo in a context (Context 1) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Context 1
Placebo C1
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of an inactive placebo in a context (Context 1) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Placebo
Placebo C2
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of an inactive placebo in a context (Context 2) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Context 2
Placebo C2
Following screening and a baseline assessment visit, healthy volunteers will receive one dose of an inactive placebo in a context (Context 2) that is hypothesized to modulate acute and post-acute drug effects.
Intervention: Placebo
Outcomes
Primary Outcomes
Challenging Experience Questionnaire (CEQ) subscales score
Time Frame: Eight hours post-dose.
The Challenging Experience Questionnaire is designed to measure challenging psychological experiences associated with the acute effects of psilocybin. For this study, the combined score across four our of its seven subscales will be used as a primary outcome: Fear, Insanity, Isolation, and Paranoia, excluding Grief, Physical Distress, and Death subscales. Scaled scores range from 0 to 100. Higher scores indicate higher levels of challenging experience (worse outcome).
Change in Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) score from Baseline to 28 days post-dose
Time Frame: Baseline to 28 days post-dose.
The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) was developed to enable the monitoring of mental wellbeing in the general population and the evaluation of projects, programmes and policies which aim to improve mental wellbeing. Scores range form 14 to 70. Higher scores indicate higher levels of mental well-being (better outcome).
Change in Watts Connectedness Scale (WCS) scores from Baseline to 28 days post-dose
Time Frame: Baseline to 28 days post-dose.
The WCS is a 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. Scores range from 0 to 100. Higher scores indicate higher levels of connectedness (better outcome).
Emotional Breakthrough Inventory (EBI) score
Time Frame: Eight hours post-dose.
The Emotional Breakthrough Inventory was developed to assess emotional breakthrough, an important and distinct component of the acute psychedelic experience. Scores range from 0 to 100. Higher scores indicate higher levels of emotional breakthrough (better outcome).
Secondary Outcomes
- Travelling waves via Electroencephalography (EEG)(Pre-dose; 2, 4, and 6 hours post-dose)
- Changes in resting state BOLD activity viafunctional magnetic resonance imaging (fMRI)(Baseline to 28 days post-dose.)
- Acute Lempel Ziv Complexity (LZC) via Electroencephalography (EEG)(Pre-dose; 2, 4, and 6 hours post-dose)
- Transfer entropy and integrated information via Electroencephalography (EEG)(Pre-dose; 2, 4, and 6 hours post-dose)
- Changes in BOLD activity during emotional processing via functional magnetic resonance imaging (fMRI)(Baseline to 28 days post-dose.)
- Structural brain changes via magnetic resonance imaging (MRI)(Baseline to 28 days post-dose.)
- Synergistic and redundant activity patterns via Electroencephalography (EEG)(Pre-dose; 2, 4, and 6 hours post-dose)
- Changes in white matter organization via magnetic resonance imaging (MRI)(Baseline to 28 days post-dose.)
- Spectral power in traditional frequency bands via Electroencephalography (EEG)(Pre-dose; 2, 4, and 6 hours post-dose)