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.
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.
Aged 25-60 years, male or female.
Medically healthy, as confirmed by a comprehensive clinical assessment.
Written informed consent provided.
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.
Sequential
Psilocybin and D-Serine
DrugA 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
Physical Examination
Diagnostic testThe 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 signs
Diagnostic testVital 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.
ECG test
Diagnostic testA 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.
Comprehensive Blood Panel
Diagnostic testA 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
Diagnostic testComplete 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
Diagnostic testUrinalysis will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.
Urine Toxicology Screen
Diagnostic testUrine 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.
A pregnancy Urine test
Diagnostic testA 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.
Electroencephalogram
Diagnostic testEEG will be performed during the baseline rating scale and Day 7 visits to evaluate brain activity
Plasma Amino Acid Levels
Diagnostic testThe following blood test parameters - D-Serine, L-Serine, and Glycine - will be assessed during the Screening and Day 28 visits.
Plasma Inflammation Markers
Diagnostic testThe 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 Brain-Derived Neurotrophic Facto
Diagnostic testPlasma BDNF (Brain-Derived Neurotrophic Factor) levels will be measured during the screening and Day 28 visits.
Mini International Neuropsychiatric Interview
Other interventionThe Mini International Neuropsychiatric Interview (MINI) will be administered during the screening visit to rule out any current or past major psychiatric disorders.
Family Psychiatric History Assessment
Other interventionThe Family Psychiatric History Assessment (FPHA) will be administered during the screening visit to help rule out any current or past major psychiatric disorders.
Beck Depression Inventory
Other interventionThe 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
Other interventionState-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.
Profile of Mood States
BehavioralThe 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
BehavioralSubjective 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.
Five-Dimensional Altered States of Consciousness questionnaire
Other interventionThe 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).
Integration
BehavioralThe 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.
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.
Change in subjective psychedelic experience measured by the 5D-ASC scale
Assessment of subjective altered states of consciousness using the 5-Dimensional Altered States of Consciousness scale. Full questionnaire consists of 94 items, each item reflects a subjective experience during the altered state. Each rated on a visual analog scale from 0 to 100, where: 0 = "not at all" 100 = "extremely" The items are grouped into 5 empirically derived dimensions, each representing a core aspect of altered consciousness: Oceanic Boundlessness- Positively experienced ego dissolution, unity, bliss High scores = mystical-type experiences Anxious Ego Dissolution- Anxiety, loss of ego control, cognitive impairment High scores = difficult or fearful experiences Visionary Restructuralization -Visual imagery, hallucinations, synesthesia High scores = complex visual phenomena Auditory Alterations - Changes in auditory perception, e.g., hearing sounds or voices Reduction of Vigilance- Reduced alertness or drowsiness (less relevant in classic psychedelic states)
Change in mood states assessed by the Profile of Mood States (POMS)
Change in emotional and mood states as measured by the POMS scale. Participants complete the questionnaire at multiple time points to evaluate transient mood fluctuations in response to treatment. The administered version of the POMS questionnaire consists of 28 adjectives describing various feelings and emotions, and participants rate the extent to which they have experienced each over a specified period (e.g., the past week), typically using a 5-point Likert scale ranging from 0 ("not at all") to 4 ("extremely").
Change in anxiety and stress measured by the Subjective Units of Distress Scale (SUDS)
Subjective assessment of distress and anxiety using the SUDS, a self-report scale ranging from 0 (no distress) to 100 (extreme distress). Assessed multiple times to track acute and residual anxiety responses.
Change in plasma D-serine concentration
Measurement of plasma D-serine (in micromoles per liter (µmol/L)) to explore potential neurobiological correlates of treatment. Blood collected at baseline and follow-up.
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