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

H

Hadassah Medical Center

Status and phase

Enrolling
Phase 1

Conditions

Healthy Volunteers

Treatments

Diagnostic Test: A pregnancy Urine test
Other: Beck Depression Inventory
Diagnostic Test: Urinalysis
Other: Mini International Neuropsychiatric Interview
Other: State-Trait Anxiety Inventory
Diagnostic Test: Plasma Amino Acid Levels
Diagnostic Test: Physical Examination
Diagnostic Test: Complete Blood Count
Drug: Psilocybin and D-Serine
Behavioral: Subjective Units of Distress Scale
Other: Family Psychiatric History Assessment
Diagnostic Test: Plasma Brain-Derived Neurotrophic Facto
Diagnostic Test: Urine Toxicology Screen
Diagnostic Test: Plasma Inflammation Markers
Diagnostic Test: Vital signs
Diagnostic Test: Electroencephalogram
Behavioral: Integration
Diagnostic Test: Comprehensive Blood Panel
Other: Five-Dimensional Altered States of Consciousness questionnaire
Behavioral: Profile of Mood States
Diagnostic Test: ECG test

Study type

Interventional

Funder types

Other

Identifiers

NCT07079930
Ps-PD-24-01-HMO-CTIL

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 estimated patients

Sex

All

Ages

25 to 60 years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

10 participants in 2 patient groups

15 mg of Psilocybin and 5 gr of D-Serine
Experimental group
Description:
The investigational drug, 15 mg of Psilocybin and 5 g of D-Serine, will be administered as a single oral dose in solution form.
Treatment:
Diagnostic Test: ECG test
Behavioral: Profile of Mood States
Other: Five-Dimensional Altered States of Consciousness questionnaire
Diagnostic Test: Comprehensive Blood Panel
Behavioral: Integration
Diagnostic Test: Electroencephalogram
Diagnostic Test: Plasma Inflammation Markers
Diagnostic Test: Vital signs
Diagnostic Test: Urine Toxicology Screen
Diagnostic Test: Plasma Brain-Derived Neurotrophic Facto
Other: Family Psychiatric History Assessment
Behavioral: Subjective Units of Distress Scale
Drug: Psilocybin and D-Serine
Diagnostic Test: Complete Blood Count
Diagnostic Test: Physical Examination
Diagnostic Test: Plasma Amino Acid Levels
Other: State-Trait Anxiety Inventory
Other: Mini International Neuropsychiatric Interview
Other: Beck Depression Inventory
Diagnostic Test: A pregnancy Urine test
Diagnostic Test: Urinalysis
25 mg of Psilocybin and 7 gr of D-Serine
Experimental group
Description:
The investigational drug, 25 mg of Psilocybin and 7 g of D-Serine, will be administered as a single oral dose in solution form.
Treatment:
Diagnostic Test: ECG test
Behavioral: Profile of Mood States
Other: Five-Dimensional Altered States of Consciousness questionnaire
Diagnostic Test: Comprehensive Blood Panel
Behavioral: Integration
Diagnostic Test: Electroencephalogram
Diagnostic Test: Plasma Inflammation Markers
Diagnostic Test: Vital signs
Diagnostic Test: Urine Toxicology Screen
Diagnostic Test: Plasma Brain-Derived Neurotrophic Facto
Other: Family Psychiatric History Assessment
Behavioral: Subjective Units of Distress Scale
Drug: Psilocybin and D-Serine
Diagnostic Test: Complete Blood Count
Diagnostic Test: Physical Examination
Diagnostic Test: Plasma Amino Acid Levels
Other: State-Trait Anxiety Inventory
Other: Mini International Neuropsychiatric Interview
Other: Beck Depression Inventory
Diagnostic Test: A pregnancy Urine test
Diagnostic Test: Urinalysis

Trial contacts and locations

1

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Central trial contact

Bernard Lerer, MD

Data sourced from clinicaltrials.gov

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