Safety and Psychological Effects of Psilocybin and D-Serine Formulation in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment-emergent adverse events (TEAEs) following administration of psilocybin and D-serine
研究概览
简要总结
The goal of this open-label, dose-escalation, prospective study is to evaluate the safety and psychological effects of a Psilocybin and D-Serine formulation in healthy volunteers.
The main objectives are:
- To assess the psychological and physiological effects of psilocybin administered with D-Serine in healthy adults.
- To determine whether D-Serine modulates or attenuates the psychedelic effects of psilocybin.
- To evaluate the safety and tolerability of psilocybin and D-Serine co-administration.
Study population includes: 10 healthy male or female volunteers aged 25-60 years with no history of psychiatric or major medical disorders and no current evidence of such disorders.
The study includes two cohorts. The first cohort of 5 participants will receive 15 mg of Psilocybin and 5 g of D-Serine. Safety data will be collected and submitted in an interim report to the Ethics Committee. If no safety concerns arise, the second cohort will receive an increased dose of 25 mg of Psilocybin and 7 g of D-Serine to help determine the optimal dose for a future Phase IIa clinical trial.
详细描述
This is a first-in-human, Phase I, exploratory clinical trial designed to evaluate the safety, tolerability, and initial psychological and physiological responses to a single administration of psilocybin in combination with D-Serine in healthy adult volunteers. The rationale for this combination stems from preclinical evidence indicating that D-Serine, a naturally occurring co-agonist at the NMDA receptor, may attenuate the acute psychedelic effects of psilocybin while preserving its neuroplastic and therapeutic properties.
Preclinical studies demonstrated that D-Serine reduced the psilocybin-induced head-twitch response (HTR) in rodent models and enhanced the expression of synaptic plasticity markers (e.g., GAP43, PSD95, SV2A, synaptophysin) across multiple brain regions, with effects sustained up to 12 days post-treatment. These findings suggest that the combination may improve the safety and tolerability of psilocybin, particularly for populations sensitive to its psychoactive effects.
The trial will consist of four sequential components:
Screening Phase - to assess eligibility.
Preparation Phase - to establish therapeutic rapport and baseline assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 25-60 years, male or female.
- •Medically healthy, as confirmed by a comprehensive clinical assessment.
- •Written informed consent provided.
排除标准
- •History of any Axis 1 psychiatric disorder requiring pharmacotherapy such as schizophrenia, schizoaffective disorder, any other psychotic disorder, bipolar disorder, as well as non-psychotic disorders such as generalized anxiety disorder, major depressive disorder, obsessive-compulsive disorder, posttraumatic stress disorder.
- •Family history (among first-degree relatives) of schizophrenia, bipolar disorder, or other psychotic disorder
- •History of cardiovascular disorders.
- •Pregnant or breastfeeding women or women of childbearing age not using effective contraception.
- •Use of psilocybin or other psychedelic compound in the 12 months preceding the study
- •Use of medications that interact with psilocybin or D-Serine.
- •Positive urinary drug screening.
研究组 & 干预措施
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Psilocybin and D-Serine (Drug)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Physical Examination (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Vital signs (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: ECG test (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Comprehensive Blood Panel (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Complete Blood Count (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Urinalysis (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Urine Toxicology Screen (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: A pregnancy Urine test (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Electroencephalogram (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Plasma Amino Acid Levels (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Plasma Inflammation Markers (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Plasma Brain-Derived Neurotrophic Facto (Diagnostic Test)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Mini International Neuropsychiatric Interview (Other)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Family Psychiatric History Assessment (Other)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Beck Depression Inventory (Other)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: State-Trait Anxiety Inventory (Other)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Profile of Mood States (Behavioral)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Subjective Units of Distress Scale (Behavioral)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Five-Dimensional Altered States of Consciousness questionnaire (Other)
15 mg of Psilocybin and 5 gr of D-Serine
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Integration (Behavioral)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Psilocybin and D-Serine (Drug)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Physical Examination (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Vital signs (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: ECG test (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Comprehensive Blood Panel (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Complete Blood Count (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Urinalysis (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Urine Toxicology Screen (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: A pregnancy Urine test (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Electroencephalogram (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Plasma Amino Acid Levels (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Plasma Inflammation Markers (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Plasma Brain-Derived Neurotrophic Facto (Diagnostic Test)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Mini International Neuropsychiatric Interview (Other)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Family Psychiatric History Assessment (Other)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Beck Depression Inventory (Other)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: State-Trait Anxiety Inventory (Other)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Profile of Mood States (Behavioral)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Subjective Units of Distress Scale (Behavioral)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Five-Dimensional Altered States of Consciousness questionnaire (Other)
25 mg of Psilocybin and 7 gr of D-Serine
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
干预措施: Integration (Behavioral)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (TEAEs) following administration of psilocybin and D-serine
时间窗: From time of dosing (Day 1) through Day 84 (final follow-up visit)
The number, type, severity, timing, and relatedness of treatment-emergent adverse events following administration of psilocybin and D-serine. Adverse events will be assessed through continuous clinical monitoring, spontaneous reports, and structured instruments including the UKU Side Effect Rating Scale. Safety will also be evaluated via changes in vital signs, ECG, and laboratory tests (SMAC-20, CBC, urinalysis). Events will be classified using standard regulatory definitions and graded for severity and relatedness to study treatment.
次要结局
- Change in subjective psychedelic experience measured by the 5D-ASC scale(6 hours post-dosing and Day 2 follow-up)
- Change in mood states assessed by the Profile of Mood States (POMS)(Baseline, 8 and 20 hours post-dosing, Day 2, Week 1, and Day 84)
- Change in anxiety and stress measured by the Subjective Units of Distress Scale (SUDS)(Baseline, 8 and 20 hours post-dosing, Day 2)
- Change in plasma D-serine concentration(Baseline and Week 1 (Day 7))
- Change in plasma inflammatory markers concentration.(Baseline and Week 1 (Day 7))
- Change in plasma BDNF concentration(Baseline and Week 1 (Day 7))
- Change in plasma glutamate concentration(Baseline and Week 1 (Day 7))
- Beck Depression Inventory-II (BDI-II) total score(Baseline (Day -1), Day 2, Day 7, and Day 84)
- State-Trait Anxiety Inventory (STAI) - State and Trait scores(Baseline (Day -1), Day 2, Day 7, and Day 84)