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

NCT ID: NCT07079930

Last Updated: 2025-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-30

Study Completion Date

2027-02-28

Brief Summary

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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

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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

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Healthy Volunteers

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The study will include 2 cohorts:

First cohort of 5 participants will be recruited and administered a single dose of 15 mg of Psilocybin and 5 gr of D-Serine. Safety data will be collected, and an interim safety report will be submitted to the Ethics Committee (EC).

Following administration to the initial cohort, safety and tolerability will be evaluated, and if no significant concerns are identified, the second cohort will be enrolled to receive a higher dose in order to determine the optimal dosage

The second cohort of 5 participants will receive an increased one time dose of 25 mg of Psilocybin and 7 gr of D-Serine to determine the effective dose.

The following visits will be conducted for both cohorts: Screening, Preparation, Administration (Day 1), and follow-up visits on Day 2, Day 7, Day 28, and Day 84.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Psilocybin and D-Serine

Intervention Type DRUG

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

Physical Examination

Intervention Type DIAGNOSTIC_TEST

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 signs

Intervention Type DIAGNOSTIC_TEST

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.

ECG test

Intervention Type DIAGNOSTIC_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.

Comprehensive Blood Panel

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

Urinalysis will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.

Urine Toxicology Screen

Intervention Type DIAGNOSTIC_TEST

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.

A pregnancy Urine test

Intervention Type DIAGNOSTIC_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.

Electroencephalogram

Intervention Type DIAGNOSTIC_TEST

EEG will be performed during the baseline rating scale and Day 7 visits to evaluate brain activity

Plasma Amino Acid Levels

Intervention Type DIAGNOSTIC_TEST

The following blood test parameters - D-Serine, L-Serine, and Glycine - will be assessed during the Screening and Day 28 visits.

Plasma Inflammation Markers

Intervention Type DIAGNOSTIC_TEST

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 Brain-Derived Neurotrophic Facto

Intervention Type DIAGNOSTIC_TEST

Plasma BDNF (Brain-Derived Neurotrophic Factor) levels will be measured during the screening and Day 28 visits.

Mini International Neuropsychiatric Interview

Intervention Type OTHER

The 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

Intervention Type OTHER

The 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

Intervention Type OTHER

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

Intervention Type OTHER

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.

Profile of Mood States

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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.

Five-Dimensional Altered States of Consciousness questionnaire

Intervention Type OTHER

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).

Integration

Intervention Type BEHAVIORAL

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.

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.

Group Type EXPERIMENTAL

Psilocybin and D-Serine

Intervention Type DRUG

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

Physical Examination

Intervention Type DIAGNOSTIC_TEST

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 signs

Intervention Type DIAGNOSTIC_TEST

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.

ECG test

Intervention Type DIAGNOSTIC_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.

Comprehensive Blood Panel

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

Urinalysis will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.

Urine Toxicology Screen

Intervention Type DIAGNOSTIC_TEST

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.

A pregnancy Urine test

Intervention Type DIAGNOSTIC_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.

Electroencephalogram

Intervention Type DIAGNOSTIC_TEST

EEG will be performed during the baseline rating scale and Day 7 visits to evaluate brain activity

Plasma Amino Acid Levels

Intervention Type DIAGNOSTIC_TEST

The following blood test parameters - D-Serine, L-Serine, and Glycine - will be assessed during the Screening and Day 28 visits.

Plasma Inflammation Markers

Intervention Type DIAGNOSTIC_TEST

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 Brain-Derived Neurotrophic Facto

Intervention Type DIAGNOSTIC_TEST

Plasma BDNF (Brain-Derived Neurotrophic Factor) levels will be measured during the screening and Day 28 visits.

Mini International Neuropsychiatric Interview

Intervention Type OTHER

The 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

Intervention Type OTHER

The 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

Intervention Type OTHER

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

Intervention Type OTHER

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.

Profile of Mood States

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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.

Five-Dimensional Altered States of Consciousness questionnaire

Intervention Type OTHER

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).

Integration

Intervention Type BEHAVIORAL

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.

Interventions

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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

Intervention Type DRUG

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).

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Urinalysis

Urinalysis will be conducted during the Screening visit, and on Day 2, Day 28, and Day 84.

Intervention Type 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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Electroencephalogram

EEG will be performed during the baseline rating scale and Day 7 visits to evaluate brain activity

Intervention Type 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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Plasma Brain-Derived Neurotrophic Facto

Plasma BDNF (Brain-Derived Neurotrophic Factor) levels will be measured during the screening and Day 28 visits.

Intervention Type DIAGNOSTIC_TEST

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type OTHER

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.

Intervention Type 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.

Intervention Type BEHAVIORAL

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).

Intervention Type OTHER

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.

Intervention Type BEHAVIORAL

Other Intervention Names

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SMAC-20 CBC EEG Plasma BDNF MINI FPHA BDI STAI POMS SUDS 5D-ASC

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. 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.
2. Family history (among first-degree relatives) of schizophrenia, bipolar disorder, or other psychotic disorder
3. History of cardiovascular disorders.
4. Pregnant or breastfeeding women or women of childbearing age not using effective contraception.
5. Use of psilocybin or other psychedelic compound in the 12 months preceding the study
6. Use of medications that interact with psilocybin or D-Serine.
7. Positive urinary drug screening.
Minimum Eligible Age

25 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Hadassah Medical Organization

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hadassah Medical Organization, Jerusalem, Israel

Jerusalem, , Israel

Site Status

Countries

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Israel

Central Contacts

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Bernard Lerer, MD

Role: CONTACT

+972-50-7874575

Facility Contacts

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Hadas Lemberg, PhD

Role: primary

00 972 2 6777572

Other Identifiers

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Ps-PD-24-01-HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id

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