Safety and Psychological Effects of Psilocybin and D-Serine Formulation in Healthy Volunteers
1 other identifier
interventional
10
1 country
1
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:
- 1.To assess the psychological and physiological effects of psilocybin administered with D-Serine in healthy adults.
- 2.To determine whether D-Serine modulates or attenuates the psychedelic effects of psilocybin.
- 3.To evaluate the safety and tolerability of psilocybin and D-Serine co-administration.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 healthy-volunteers
Started Dec 2025
Longer than P75 for phase_1 healthy-volunteers
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 15, 2025
CompletedFirst Posted
Study publicly available on registry
July 23, 2025
CompletedStudy Start
First participant enrolled
December 11, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2027
February 5, 2026
July 1, 2025
11 months
July 15, 2025
February 3, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence and severity of treatment-emergent adverse events (TEAEs) following administration of psilocybin and D-serine
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.
From time of dosing (Day 1) through Day 84 (final follow-up visit)
Secondary Outcomes (9)
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)
- +4 more secondary outcomes
Study Arms (2)
15 mg of Psilocybin and 5 gr of D-Serine
EXPERIMENTALThe investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
25 mg of Psilocybin and 7 gr of D-Serine
EXPERIMENTALThe investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
Interventions
A single administration of the drug, with dosage divided as follows: Cohort 1: 15 mg of Psilocybin and 5 gr of D-Serine Cohort 2: 25 mg of Psilocybin and 7 gr of D-Serine
The physical examination will include diagnosis and documentation of any significant clinical abnormalities or diseases. It will be performed during the baseline rating visit (preparation phase).
Vital sign measurements (blood pressure, pulse, and oxygen saturation) will be taken at screening, preparation, baseline rating, administration day, day 2, day 28, and day 84. Vital signs will be assessed at the following time points on the administration day and on day 2: pre-administration, and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours post-administration.
A 12-lead ECG will be performed to rule out underlying cardiac abnormalities. An ECG will be conducted for each patient during the screening and Day 2 visits.
A comprehensive blood panel will be performed to assess kidney and liver function, electrolyte balance, and glucose levels. It will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.
Complete Blood Count will be performed to check for hematological abnormalities. It will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.
Urinalysis will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.
Urine Toxicology Screen will be performed to rule out illicit drug use. It will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.
The Profile of Mood States (POMS) will be administered to assess baseline mood and emotional state. It will be administered at the following visits: screening, baseline, administration day, day 2, day 7, day 28, and day 84. On the administration day and on day 2, it will be administered at the following time points: pre-administration, and 8 and 20 hours post-administration.
Subjective Units of Distress Scale (SUDS) will be administered to assess anxiety and stress levels. It will be administered at the following visits: screening, baseline, administration day, day 2, day 7, day 28, and day 84. On the administration day and on day 2, it will be administered at the following time points: pre-administration, and 8 and 20 hours post-administration.
The Five-Dimensional Altered States of Consciousness questionnaire (5D-ASC) will be used to assess the acute subjective psychedelic experience. It will be administered after the acute effects have subsided - at 6.0 hours post-administration on the administration day, and again on day 2 - to evaluate five key experiential dimensions: visual restructuralization, oceanic boundlessness, reduction of vigilance, anxious ego dissolution, and auditory alterations. Each item will be rated using a Visual Analogue Scale (VAS) ranging from "NO, not more than usually" (0 mm) to "YES, much more than usually" (100 mm).
The integration process is conducted to support participants in processing and incorporating their therapeutic experience into daily life, with the aim of enhancing emotional insight and psychological well-being. Integration will take place at the following visits: 8.0 hours post-treatment on the administration day, day 2, day 7, day 28, and day 84.
A urine pregnancy test will be performed for women of childbearing potential only. It will be conducted during the screening and baseline rating visits. If the urine test is positive, a serum β-hCG test will be performed for confirmation.
EEG will be performed during the baseline rating scale and Day 7 visits to evaluate brain activity
The following blood test parameters - D-Serine, L-Serine, and Glycine - will be assessed during the Screening and Day 28 visits.
The following blood test parameters - Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), and C-Reactive Protein (CRP) - will be assessed during the Screening and Day 28 visits.
Plasma BDNF (Brain-Derived Neurotrophic Factor) levels will be measured during the screening and Day 28 visits.
The Mini International Neuropsychiatric Interview (MINI) will be administered during the screening visit to rule out any current or past major psychiatric disorders.
The Family Psychiatric History Assessment (FPHA) will be administered during the screening visit to help rule out any current or past major psychiatric disorders.
The Beck Depression Inventory (BDI) will be administered at the following visits: screening, baseline, day 7, day 28, and day 84. It will be used to assess baseline mood and to rule out depressive symptoms.
State-Trait Anxiety Inventory (STAI) will be administered at the following visits: screening, baseline, day 7, day 28, and day 84. It will be used to screen for anxiety disorders.
Eligibility Criteria
You may qualify if:
- Aged 25-60 years, male or female.
- Medically healthy, as confirmed by a comprehensive clinical assessment.
- Written informed consent provided.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Hadassah Medical Organization, Jerusalem, Israel
Jerusalem, Israel
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 15, 2025
First Posted
July 23, 2025
Study Start
December 11, 2025
Primary Completion (Estimated)
November 1, 2026
Study Completion (Estimated)
February 1, 2027
Last Updated
February 5, 2026
Record last verified: 2025-07