Psilocybin with D-Serine: safety and psychological effects in healthy adults

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

This study will test whether combining psilocybin with D-Serine is safe and how it changes psychological and physiological responses in healthy adults aged 25–60.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 25 Years to 60 Years
• Sex: All
• Sponsor: Hadassah Medical Organization (other)
• Locations: 1 site (Jerusalem)
• Trial ID: NCT07079930 on ClinicalTrials.gov

What this trial studies

This open-label, first-in-human Phase 1 study uses a dose-escalation design to characterize safety, tolerability, and initial psychological and physiological responses to a single oral administration of psilocybin co‑administered with D‑Serine in healthy volunteers. Ten participants are enrolled in two sequential cohorts: five will receive 15 mg psilocybin with 5 g D‑Serine and, if interim safety review is favorable, five will receive 25 mg psilocybin with D‑Serine. Participants undergo screening and preparatory sessions, in-person dosing, and structured follow-up visits on Days 2, 7, 28, and 84 to monitor adverse events, vital signs, ECG, lab tests, and subjective effects. The rationale is based on preclinical data suggesting D‑Serine can attenuate acute psychedelic responses while preserving synaptic plasticity markers observed after psilocybin exposure.

Who should consider this trial

Good fit: Healthy men and women aged 25–60 with no major medical or psychiatric disorders, not pregnant or breastfeeding, and not using interacting medications are ideal candidates.

Not a fit: People with current or past major psychiatric disorders, a family history of psychosis, cardiovascular disease, pregnancy/lactation, recent psychedelic use, positive drug screens, or those on interacting medications would not be eligible and are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could make psilocybin administration safer and better tolerated, potentially widening its future therapeutic use.

How similar studies have performed: This is a novel first-in-human combination: preclinical rodent studies showed D‑Serine reduced psilocybin-like behaviors and enhanced synaptic plasticity markers, but human data are not yet available.

Eligibility criteria

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.

Where this trial is running

Jerusalem

• Hadassah Medical Organization, Jerusalem, Israel — Jerusalem, Israel (RECRUITING)

Study contacts

• Study coordinator: Bernard Lerer, MD

Conditions: Healthy Volunteers, psilocybin D-Serine healthy volunteers