Precision Functional Brain Mapping to Understand the Mechanisms of Psilocybin
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Functional Connectivity
研究概览
简要总结
This project will employ functional brain imaging to study the mechanism and immediate and long-term effects of psilocybin, a serotonin receptor 2A agonist, on cortical and cortico-subcortical brain networks in healthy adults.
详细描述
Psilocybin shows promise as a safe, transformational therapeutic across several psychiatric conditions. However, little is know about its mechanism of action. This study aims to establish a neuroimaging paradigm for use in future clinical research testing the effectiveness of psilocybin in various clinical applications.
In this study, we will assess both acute (during psilocybin exposure) and sustained (one week post-exposure) effects of 5-HT2A receptor agonism on brain circuits using resting state functional connectivity and precision functional mapping (PFM). Using a randomized, controlled crossover study design, a small number of healthy volunteers will receive either psilocybin or methylphenidate (MTP) and will undergo MRI (structural, task, blood flow, extended resting state). After two weeks, participants will return for a second exposure with the alternate of what they received in the first session. This study involves up to five separate imaging sessions.
Functional connectivity will be measured using the following PFM approach:
- Extended functional magnetic resonance imaging (fMRI) image acquisition
- Aggressive data cleaning
- Analysis designed to examine functional brain connectivity at the individual level
This will allow us to map the effects of 5-HT2A receptor agonism on cortical and cortico-subcortical brain networks at the individual level with precision that is unparalleled in the current literature. This is the first step in developing a precision neuroimaging approach for mechanistic understanding of psilocybin's therapeutic effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Participants will be aware that they are receiving either psilocybin or methylphenidate at each medication imaging session, but will not be told in what order they will receive study medication (psilocybin first versus methylphenidate first).
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •men and woman between 18 and 40 years of age;
- •Have used a psychedelic substance within the previous 5 years but not within the last 6 months
- •No active psychiatric conditions requiring treatment with psychotropic medications (may be included if psychiatric condition is stable and participant is willing to discontinue medication for 1 month prior to participation with permission from their treating provider);
- •Able to provide informed consent.
排除标准
- •Presence of medical conditions that may confound results of imaging study or that are contraindications to psilocybin exposure (e.g. neurological, renal, hypertension, metabolic or cardiovascular disease or pregnancy);
- •No prior exposure to classic psychedelics (psilocybin, LSD, ayahuasca, mescaline);
- •Presence of psychiatric conditions that may confound interpretation of results or that are contraindications to psilocybin exposure (e.g. major mood disorder, current substance use disorder, personal or immediate family history (parents, siblings) of any schizophrenia spectrum disorders);
- •Use of psychotropic medication during the study;
- •Presence of contraindications to MRI scanning (implantable devices, bone hardware, IUD).
- •Prior adverse reactions to psychedelics, based on the Challenging Experiences Questionnaire administered during initial screening
研究组 & 干预措施
Psilocybin first
Participants will receive 25 mg of psilocybin at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the control drug (methylphenidate) at their second drug exposure neuroimaging session.
干预措施: Psilocybin (Drug)
Psilocybin first
Participants will receive 25 mg of psilocybin at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the control drug (methylphenidate) at their second drug exposure neuroimaging session.
干预措施: Methylphenidate (Drug)
Methylphenidate first
Participants in this group will be randomized to receive 40 mg of methylphenidate at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the active comparator (psilocybin) at their second drug exposure neuroimaging session.
干预措施: Psilocybin (Drug)
Methylphenidate first
Participants in this group will be randomized to receive 40 mg of methylphenidate at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the active comparator (psilocybin) at their second drug exposure neuroimaging session.
干预措施: Methylphenidate (Drug)
结局指标
主要结局
Functional Connectivity
时间窗: 1 week
Our overall goal is to use a Functional Connectivity (very long scans to produce individual connectomes) to examine the effects of psilocybin on cortical and cortico- subcortical brain networks that could explain its rapid and sustained behavioral effects.
次要结局
- Mystical Experiences(1 week)
- Personality Change(1 week)
研究者
Ginger E Nicol
Professor of Psychiatry
Washington University School of Medicine