Anxiety, Depression, Psychological Stress
Conditions
Keywords
psilocybin, psilocybin-assisted therapy, intergenerational trauma, psychedelic, stress, genocide
Brief summary
This is an open-label psilocybin-assisted therapy study that will examine the safety and tolerability of psilocybin-assisted therapy in the offspring of genocide survivors with mood and anxiety disorders. The study will also investigate the efficacy of psilocybin-assisted therapy in reducing symptoms such as depression, anxiety and stress, as well as changes to the psychological effects of parental exposure to genocide, and changes to psychological resilience.
Detailed description
This study is investigating whether Psilocybin-assisted therapy improves depression, anxiety and stress symptoms in the offspring (biological children) of genocide survivors. Intergenerational trauma is the concept that the effects of experiencing extreme stress can be perpetuated to future generations. A genocide here is defined by the extinction or threat of extinction of a racial, religious or ethnic group, by an oppressive regime. A genocide survivor here is defined by an individual who survived or escaped a genocide in their country of origin. Currently, there are no evidence-based treatments developed specifically for the syndrome associated with Intergenerational trauma. This study aims to assess the safety and tolerability of psilocybin-assisted therapy, and assess the efficacy of psilocybin-assisted therapy in reducing symptoms such as depression, anxiety and stress, as well as changes to the psychological effects of parental exposure to genocide, and changes to psychological resilience. Participants will be asked to attend one or more screening visits to assess eligibility. If eligible, participants will be treated with two separate doses of the study medication, Psilocybin, 3-4 weeks apart. This is an open-label research study, meaning all participants will receive Psilocybin (25mg). Two trained clinical practitioners will work with participants across preparation, dosing, and integration processes. Participants will complete assessments throughout the study until their participation has ended. Safety measures are in place to check the overall health and well-being of participants Participation will consist of: * Screening Period (up to 4 weeks): Phone screen, informed consent, eligibility assessment. * Tapering & Enrollment Period (variable): Enrollment, supervised medical tapering where necessary as discussed with the study doctor, biomarker collection and psychometric baseline assessments. * Preparatory & Treatment Period (up to 14 weeks): Three preparatory sessions with study clinicians, assessments; two dosing days at least three weeks apart, three weekly integration sessions with study clinicians following each dose, a 72-hour check-in call after each dosing day, assessments. * Follow-Up Period (up to 5 weeks): Follow-up one month after final integration session, assessments, clinical evaluation, biomarker collection
Interventions
DRUGPsilocybin
Psilocybin 25mg, capsules taken orally under the supervision of two trained study therapists
BEHAVIORALIntegration sessions
weekly integration sessions (therapy) for 6 weeks
Sponsors
Rachel Yehuda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age at least 18 years old at time of signing the informed consent. * Biological child of at least one parent who directly survived/escaped a genocide. * Evidence of clinically significant intergenerational trauma-related symptoms, as determined by the modified Parental PTSD Questionnaire (mPPQ). * Meet diagnostic criteria for a depressive, anxiety, trauma-, or stressor-related disorder on the Structured Clinical Interview for DSM-5 (SCID-5). * BMI of ≥ 17. * Capable of providing written informed consent and complying with study procedures. * If of reproductive potential, willing to use a highly effective method of contraception throughout study participation. Participants who can father a child and have partners of reproductive potential must also agree to use effective contraception throughout study participation. * Willing and medically appropriate to discontinue serotonergic medications before study treatment and remain off such medications throughout study participation, as determined by the study physician in consultation with the participant's treating healthcare provider. * Fluent in speaking and reading English. * Able to swallow pills. * Agree to have all study visits (both in-person and remote) recorded with audio and video. * Able to provide a contact person who can be reached by investigators in the event of the participant becoming unwell or unreachable. * Must agree to inform the investigators within 48 hours of any medical conditions and procedures. * Agree to release relevant medical and psychiatric records for eligibility determination and safety monitoring. * Agree to comply with protocol-specified lifestyle restrictions and study requirements. Safety note (not incl./excl. criteria): Note to Potential Participants: Individuals interested in this study should not stop, taper, or otherwise change prescribed medications before speaking with the study team. Any medication changes required for study participation will be evaluated by qualified study clinicians and, when appropriate, coordinated with the participant's treating healthcare provider.
Exclusion criteria
* Individual was directly exposed to the genocide. * Current or recent illicit drug or prescription drug substance use disorder (excluding cannabis and tobacco use disorders), as determined by DSM-5 criteria and clinical assessment. * Current or recent alcohol or cannabis use disorder that, in the opinion of the investigator, may interfere with safe participation or study outcomes. * Current psychiatric hospitalization or psychiatric hospitalization within the last 6 months. * Recent use of psychedelic substances. * Recent non-medical or illicit use of ketamine. * Past or current psychotic disorder (including psychotic MDD), mania, or bipolar disorder. * Current serious suicide risk, recent suicidal behavior, or clinician concern that the participant poses a risk to self or others. * Acute, severe, or unstable medical illness, including clinical or laboratory evidence of severe renal and/or hepatic impairment. * Any physical or intellectual disability adversely affecting ability to complete assessments. * Current pregnancy or currently chest/breastfeeding. * Any clinically meaningful abnormal laboratory test result, as determined by the investigator. * Current treatment with medications contraindicated with study treatment that cannot be safely tapered, discontinued, or substituted in accordance with the protocol. * History of clinically significant QT prolongation or other clinically significant cardiac conduction abnormality. * Use of medications known to prolong the QT interval that cannot be safely discontinued. * Any congenital prolongation of the QT interval or a family history of long QT syndrome. * A family history in a first-degree relative of psychosis/schizophrenia or related disorders as assessed by clinical interview with Study MD. * A first-degree family history of bipolar disorder as assessed by clinical interview with Study MD. * Current anorexia nervosa or bulimia nervosa as determined by DSM-V criteria using the SCID-V. * A clinically meaningful history of cardiac arrhythmias or who require treatment with an antiarrhythmic medication. * Preexisting clinically meaningful cardiovascular conditions, including cardiac valvulopathy, pulmonary hypertension that may be worsened/exacerbated by elevated blood pressure or heart rate. * Neurological conditions including stroke, transient ischemic attack (TIA), epilepsy, neurodegenerative disease, brain tumor, or other neurological disorders that would impact participation in the trial. * Insulin-dependent diabetes. * Vital sign abnormalities at screening that exceed protocol-defined safety thresholds. * Hypersensitivity to psilocybin. * Psychiatric or other condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin. * Positive toxicology findings not adequately explained by prescribed medications or approved treatment regimens. * Clinically meaningful abnormalities on screening electrocardiogram (ECG). * Fall risk if not mitigated by assistance from study staff. * Can't identify a support person who will be able to accompany them home and stay the night with them post experimental session.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Columbia-Suicide Severity Rating Scale (C-SSRS) | up to 23 weeks | Suicide risk as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Full Scale: 0 - 6. Higher scores indicate increased risk of suicide. |
| Brief Psychiatric Rating Scale (BPRS-6) | up to 23 weeks | Brief Psychiatric Rating Scale (BPRS-6) - Full Scale: 0 - 36. Higher scores indicate the number and severity of psychiatric symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Depression, Anxiety, and Stress Symptoms Scale (DASS-21) | Baseline (V0), Weeks Week 4-10 (V7), Week 6-15 (V11), Week 23(V12) | Change in Depression, Anxiety, and Stress Symptoms Scale (DASS-21) score. Stress scale - Subscale: 0 - 42 Anxiety scale - Subscale: 0 - 42 Depression scale - Subscale: 0 - 42 Full scale: 0 - 126 Higher scores indicate higher severity of symptomology. |
| Change in Parental PTSD Questionnaire (PPQ) | Baseline (V0) and Week 23 (V12) | Change in Parental PTSD Questionnaire (PPQ) score. Full Scale: 11 - 55 Higher scores indicate more negatively affected by perception of parents' trauma |
| Change in Resilience Scale for Adults (RSA) | Baseline (V0) and at Week 23 (V12) | Change in Resilience Scale for Adults (RSA) score. Full Scale: 33- 231 Higher scores indicate higher resilience |
Countries
United States
Contacts
CONTACTLauren Lepow, MD, PhD
CONTACTEvelyn Alkin, MA
PRINCIPAL_INVESTIGATORRachel Yehuda, PhD
Icahn School of Medicine at Mount Sinai
Outcome results
None listed