Investigating the Interaction of Psilocybin and Context of Its Administration in Healthy Volunteers
a study on Psilocybin
Summary
- Eligibility
- for people ages 21-70 (full criteria)
- Healthy Volunteers
- healthy people welcome
- Location
- at San Francisco, California
- Dates
- study startedcompletion around
- Principal Investigator
- by Robin Carhart-Harris, PhDJennifer Mitchell, PhD
Description
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).
Official Title
2 X 2 Factorial, Double-blind, Randomized Trial of 'set and Setting': a Translational Study in Healthy Volunteers
Details
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.
Keywords
Healthy Participants with Lower-than-average Mental Well-being, well-being, psilocybin, psychedelic, neuroimaging, healthy volunteers, Context 1, Context 2, Psilocybin C1, Psilocybin C2
Eligibility
You can join if…
Open to people ages 21-70
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.
- Willing to provide contact details for a friend or family member, should there be an inability to make direct contact with the participant
You CAN'T join if...
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 current or previously diagnosed psychotic disorder or bipolar disorder
- Have a previously diagnosed psychiatric disorder that renders the person unsuitable for the study (e.g., personality disorder)
- Have one or more immediate family members with a current or previously diagnosed psychotic disorder (such as schizophrenia) or bipolar disorder
- Have a medically significant condition that renders the person unsuitable for the study (e.g., cardiovascular or cerebrovascular conditions for which an acute increase in blood pressure would be clinically concerning, hepatic or renal disease, etc.)
- Have a history of suicidal ideation or attempted suicide in the past year that, in the opinion of the study clinician or PI, may present a risk of suicidal or self-injurious behavior
- Have a wellbeing score on the WHO-5 higher than 65 points
- Have used a moderate-to-high dose of a psychedelic substance on more than 10 occasions in the past five years and/or have used a moderate-to-high dose of a psychedelic within the last 6 months.
- Give a positive alcohol breathalyzer test result on any study visit
- Have used cocaine, stimulants (other than nicotine and caffeine), amphetamines, cannabis, ecstasy, opiates, sedatives, pain pills, sleeping pills, or other psychoactive drugs within 7 days of an Experimental Session
- A positive urine drug screen to any of the above prior to an Experimental Session, which warrants exclusion based on concerns that it may compromise safety or confound outcomes
- Are currently taking any of the medications or substances listed in Appendix 1 or, in the opinion of the study clinician or PI, engage in excessive use of alcohol or drugs of abuse
- Are breastfeeding, or have a positive pregnancy test at screening or at any point during the course of the study
- Have a recent history of suicidal ideation or attempted suicide (ahead of dosing session), as assessed through the screening interview and specifically with the C-SSRS and/or PHQ-9
- 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.
- Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) as determined by an MRI contraindications questionnaire.
- Are using any dietary supplements or drugs with potentially concerning drug-drug interaction (e.g., SSRIs, MAO-Is, TCAs, lithium, serotonin-acting dietary supplements such as St. John's wort)
- Have any current problem which, in the opinion of the investigator or clinician, might interfere with participation.
Location
- UCSF Mission Bay
San Francisco California 94158 United States
Lead Scientists at UCSF
- Robin Carhart-Harris, PhD
Professor, Neurology, School of Medicine. Authored (or co-authored) 207 research publications - Jennifer Mitchell, PhD
Details
- Status
- not yet accepting patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Robin Carhart-Harris, PhD, MA
- ID
- NCT06626139
- Phase
- Phase 2 Psilocybin Research Study
- Study Type
- Interventional
- Participants
- Expecting 120 study participants
- Last Updated