Safety and Psychological Effects of Psilocybin and D-Serine Formulation in Healthy Volunteers

Обзор

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.

Подробное описание

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.

Administration Phase - involving a single oral administration of the investigational combination (psilocybin + D-Serine).

Follow-up Phase - including in-person follow-up visits on Day 2, Day 7, Day 28, and Day 84 post-treatment to monitor safety outcomes, subjective responses, and potential delayed effects.

Вмешательства

• Препарат Psilocybin and D-Serine
  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
• Диагностический тест Physical Examination
  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).
• Диагностический тест Vital signs
  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.
• Диагностический тест ECG test
  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.
• Диагностический тест Comprehensive Blood Panel
  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.
• Диагностический тест Complete Blood Count
  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.
• Диагностический тест Urinalysis
  Urinalysis will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.
• Диагностический тест Urine Toxicology Screen
  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.
• Диагностический тест A pregnancy Urine test
  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.
• Диагностический тест Electroencephalogram
  EEG will be performed during the baseline rating scale and Day 7 visits to evaluate brain activity

Первичные конечные точки

• Incidence and severity of treatment-emergent adverse events (TEAEs) following administration of psilocybin and D-serine [Срок оценки: From time of dosing (Day 1) through Day 84 (final follow-up visit)]

Вторичные конечные точки (9)

• Change in subjective psychedelic experience measured by the 5D-ASC scale [Срок оценки: 6 hours post-dosing and Day 2 follow-up]
• Change in mood states assessed by the Profile of Mood States (POMS) [Срок оценки: 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) [Срок оценки: Baseline, 8 and 20 hours post-dosing, Day 2]
• Change in plasma D-serine concentration [Срок оценки: Baseline and Week 1 (Day 7)]
• Change in plasma inflammatory markers concentration. [Срок оценки: Baseline and Week 1 (Day 7)]
• Change in plasma BDNF concentration [Срок оценки: Baseline and Week 1 (Day 7)]
• Change in plasma glutamate concentration [Срок оценки: Baseline and Week 1 (Day 7)]
• Beck Depression Inventory-II (BDI-II) total score [Срок оценки: Baseline (Day -1), Day 2, Day 7, and Day 84]
• State-Trait Anxiety Inventory (STAI) - State and Trait scores [Срок оценки: Baseline (Day -1), Day 2, Day 7, and Day 84]

Критерии участия

Критерии включения

• Aged 25-60 years, male or female.
• Medically healthy, as confirmed by a comprehensive clinical assessment.
• Written informed consent provided.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Израиль · 1 центр

• Hadassah Medical Organization, Jerusalem, Israel — Jerusalem

Идентификаторы

NCT: NCT07079930 · Ps-PD-24-01-HMO-CTIL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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