NCT07183748

Psilocybin Microdosing With Psychotherapy for Treatment-Resistant Depression

A Double-blind, Phase II Feasibility Study to Assess the Safety and Efficacy of Psilocybin Microdosing Combined With Psychotherapy in Treatment-resistant Depression

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Beersheva Mental Health Center · Other Government
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Objective: To assess the safety and efficacy of a six-week microdosing regimen of psilocybin combined with short-term, experience-based psychotherapy in patients with treatment-resistant depression who have not responded to previous pharmacological or long-term psychological interventions. Hypothesis: Compared to baseline, the group that begins with psilocybin will exhibit a more rapid reduction in depressive symptoms after six weeks, compared to the group that begins with placebo and receives only psychotherapy. Following the crossover between conditions, the placebo-first group will also show an accelerated reduction in these measures after the subsequent six weeks. Alternative hypothesis: No difference will be observed between groups in the rate of symptom reduction. Objective: To examine biological markers that may mediate potential improvements in depressive symptoms among participants receiving psilocybin microdosing compared to placebo. Hypothesis: Compared to baseline, six weeks of active psilocybin dosing will result in decreased levels of cortisol and inflammatory markers, and increased levels of oxytocin and BDNF in saliva. Objective: To assess psychological factors that may mediate potential improvements in depressive symptoms among participants receiving psilocybin microdosing compared to placebo. Hypothesis: Compared to baseline, six weeks of active psilocybin dosing will lead to increased cognitive flexibility, greater self-compassion, and enhanced present-moment awareness. Objective: To explore a subpopulation of women experiencing premenstrual symptom exacerbation (PMS) and the potential for improvement in depressive symptoms in the days preceding menstruation, if any. Hypothesis: Among women with worsened premenstrual symptoms, psilocybin will reduce premenstrual symptoms, specifically depressive symptoms, compared to baseline.

Conditions

• Treatment Resistant Depression

Interventions

Type	Name	Description
DRUG	Psilocybin (drug)	0.4 grams
OTHER	Placebo	Placebo

Timeline

• Start date: 2025-12-01
• Primary completion: 2027-06-01
• Completion: 2028-06-01
• First posted: 2025-09-19
• Last updated: 2025-11-19

Locations

1 site across 1 country: Israel