NCT07079930

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Hadassah Medical Organization · Academic / Other
• Sex: All
• Age: 25 Years – 60 Years
• Healthy volunteers: Accepted

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. 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. 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.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
DRUG	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
DIAGNOSTIC_TEST	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).
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	Urinalysis	Urinalysis will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	Electroencephalogram	EEG will be performed during the baseline rating scale and Day 7 visits to evaluate brain activity
DIAGNOSTIC_TEST	Plasma Amino Acid Levels	The following blood test parameters - D-Serine, L-Serine, and Glycine - will be assessed during the Screening and Day 28 visits.
DIAGNOSTIC_TEST	Plasma Inflammation Markers	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.
DIAGNOSTIC_TEST	Plasma Brain-Derived Neurotrophic Facto	Plasma BDNF (Brain-Derived Neurotrophic Factor) levels will be measured during the screening and Day 28 visits.
OTHER	Mini International Neuropsychiatric Interview	The Mini International Neuropsychiatric Interview (MINI) will be administered during the screening visit to rule out any current or past major psychiatric disorders.
OTHER	Family Psychiatric History Assessment	The Family Psychiatric History Assessment (FPHA) will be administered during the screening visit to help rule out any current or past major psychiatric disorders.
OTHER	Beck Depression Inventory	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.
OTHER	State-Trait Anxiety Inventory	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.
BEHAVIORAL	Profile of Mood States	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.
BEHAVIORAL	Subjective Units of Distress Scale	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.
OTHER	Five-Dimensional Altered States of Consciousness questionnaire	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).
BEHAVIORAL	Integration	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.

Timeline

• Start date: 2025-12-11
• Primary completion: 2026-11-01
• Completion: 2027-02-01
• First posted: 2025-07-23
• Last updated: 2026-02-05

Locations

1 site across 1 country: Israel