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.