Safety and Psychological Effects of Psilocybin and D-Serine Formulation in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Incidence and severity of treatment-emergent adverse events (TEAEs) following administration of psilocybin and D-serine
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 25 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Aged 25-60 years, male or female.
- •Medically healthy, as confirmed by a comprehensive clinical assessment.
- •Written informed consent provided.
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: Integration (Behavioral)
Outcomes
Primary Outcomes
Incidence and severity of treatment-emergent adverse events (TEAEs) following administration of psilocybin and D-serine
Time Frame: 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.
Secondary Outcomes
- 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)