NCT07183748RecruitingPhase 2
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
Source: ClinicalTrials.gov · Last updated 19 Nov 2025
Brief summary (registry, in English)
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.
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 20 (estimated)
- First submitted
- 15 Jun 2025
- Start date
- 1 Dec 2025
- Primary completion date
- 1 Jun 2027
- Lead sponsor
- Beersheva Mental Health Center
- Diseases
- Depression
- NCT number
- NCT07183748
What you commit to
- Study type: Interventional · Phase 2
- Planned participants: 20
- From 1 Dec 2025 to the primary completion date, 1 Jun 2027
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Severe suicidal risk or aggressive behavior toward others, as assessed by the investigator and standardized depression/suicide assessment questionnaires.
- History of chronic benzodiazepine use (at least 4 mg lorazepam daily for over two years), or signs and symptoms of benzodiazepine use within two weeks prior to randomization.
Other illness
- Significant unstable physical illness (including cardiac, hepatic, renal, respiratory, endocrinological, neurological, or hematological conditions), based on the investigator's judgment.
- Psychotic spectrum disorders.
- Bipolar disorder.
- Post-traumatic disorder involving dissociative symptoms.
- Uncontrolled anxiety disorder.
- Chronic perceptual disorder (HPPD).
- Head injury or cognitive impairment (including intellectual disability or dementia).
- Any active addiction (substance use disorder).
- Current or past epilepsy.
- Individuals with focal or generalized encephalopathy (e.g., tumor, stroke, meningitis, encephalitis), or head trauma that may be epileptogenic.
Age
- Pregnant women, breastfeeding women, or women of childbearing age who are not using medically approved contraceptive methods (e.g., condoms).
- Men who are sexually active and may cause pregnancy but are unwilling to use contraception.
Other
- Investigators and their immediate family members are not permitted to participate in the study. Immediate family is defined as the investigator's spouse, parent, child, grandparent, or grandchild.
- Alcohol and/or substance abuse within the past 6 months, based on the clinical judgment of the investigator.
Who the study is looking for
- Age range between 18-65 years.
- Diagnosis of treatment-resistant major depression as defined by the DSM-IV criteria (309.81) (ASA 1994) and determined by the BDI (BDI-II, 1996).
- Willingness to discontinue psychiatric medication starting two weeks prior to the beginning of the study and throughout its duration, as well as to cease the use of drugs and licensed cannabis, and to suspend psychotherapy for the duration of the study. Participants also commit not to initiate psychiatric medication or psychotherapy during the study without consulting the research team. All under supervision within a day treatment framework.
- Abstinence from drugs and other psychiatric medications.
- Negative pregnancy test for women, and use of contraception by both men and women during the study period.
- Willingness to sign a confidentiality waiver allowing the research team to consult with the participant's treating physician.
- Willingness to provide the contact information of a close and relevant person in case suicidal ideation arises.
- Commitment to participate in all stages of the study, including follow-up assessments.
- Willingness not to participate in another study during the current study period.
Age in the registry: 18 years to 65 years · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Mental Health Center Beer Sheva Coordinator of this site? Confirm its status | Beersheba | Israel | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.