Inclusion & Exclusion Criteria

1. Is female aged 18 to 45 years, inclusive, at the time of signing the Informed Consent Form (ICF).Disease Characteristics
2. Is ≤15 months postpartum at Screening and meets DSM-5 criteria for PPD: experiencing a major depressive episode that began at any time during the period starting at the beginning of the second trimester (≥14 weeks) of pregnancy through 4 weeks following delivery, confirmed by the SCID-5-CT.
3. Has a HAMD-17 total score of ≥24 at Screening and Baseline (Day -1 prior to dosing).
4. Is not currently receiving and is willing to delay the use of any psychotropic pharmacotherapy regimens (including antidepressant or antianxiety medication), and/or psychotherapy (unless on already a stable, established regimen of SSRIs and/or psychotherapy for 30 days prior to Screening) until Day 7 study assessments have been completed. Patients should not discontinue current, adequate psychotropic treatment(s) for the sole purpose of enrollment into the study.Sex, Contraceptive/Barrier Requirements, and Breastfeeding
5. Has ceased breastfeeding at Screening (i.e., must have already fully and permanently weaned their infant[s] from breastfeeding).
6. Is using an effective and appropriate method of contraception (as described in Clinical Study Protocol Appendix 4) at Screening and agrees to continue to use such a method throughout the duration of the study. The method of contraception agreed to must be documented for each patient.
7. Has a negative pregnancy test at Screening and Day 0 prior to study drug administration.Informed Consent
8. Is capable of giving signed informed consent as described in the Clinical Study Protocol Section 10.3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.Other Inclusion Criteria
9. Is willing and able to nominate a trusted caregiver who:
   1. Can assist in providing support, care, and attention to the patient’s infant(s) for the entirety of the dosing day (Day 0) through a 24-hour post-dose (Day 1) visit.
10. Agrees to adhere to the study requirements.

Medical Conditions

1. History or active postpartum psychosis per Investigator assessment.
2. History of treatment-resistant depression within the current postpartum depressive episode as defined by having previously failed to respond to adequate courses (e.g., doses for ≥4 weeks) of pharmacotherapy from ≥2 different classes of antidepressants.
3. Has a significant risk of suicide according to the C-SSRS at Screening or Baseline (Day 1) or has attempted suicide within 12 months prior to the Screening Visit.
   1. Acute suicidality as evidenced by answering “yes” for Question 4 (“In the Past Year”) or Question 5 (“In the Past Year”) on the C-SSRS, indicating active suicidal ideation with any intent to act at Screening or Baseline (Day 0).
   2. History of suicidal behavior such that a determination of “yes” is made on the Suicidal Behavior section of the C-SSRS (“In the Past Year”) for “Actual Attempt,” “Interrupted Attempt,” “Aborted Attempt,” or “Preparatory Acts or Behavior.”
4. Active or medical history of bipolar disorder, schizophrenia, schizoaffective disorder, psychotic disorder and/or borderline personality disorder, as assessed by the SCID-5-CT and per Investigator’s judgment), or first-degree family history of psychosis or bipolar disorder.
5. Medically significant condition rendering unsuitability for the study (e.g., neurologic disorders, diabetes, epilepsy, severe cardiovascular disease including patients with preexisting valvulopathy or pulmonary hypertension, uncontrolled thyroid dysfunction, hepatic or renal failure [e.g., creatinine clearance <30 mL/min], or uncontrolled hypertension) in the opinion of the Investigator.
6. Active or medical history of seizures other than childhood febrile seizures.
7. A positive COVID-19 antigen test within 14 days of Treatment Day 0.
8. Has a QTc interval prolongation at Screening of >450 msec and/or additional risk factors for torsade de pointes (e.g., family history, electrolyte derangement, inherited long QT syndrome), and/or use of concomitant medications that prolong the QT/QTc interval (e.g., citalopram >40 mg/day).Prior/Concomitant Therapy
9. Exposure to another clinical study involving study treatment within 30 days prior to Screening.
10. Administration of electroconvulsive therapy (ECT) or transcranial magnetic stimulation within 90 days prior to Screening and/or plans to administer ECT before the Study Day 28 Visit.
11. Use of psychedelics such as psilocybin, ayahuasca, mescaline, or LSD (with the exception of cannabis) within 12 months prior to Screening.
12. Initiated new psychotherapy (cognitive behavioral therapy) within 30 days prior to Screening. No changes to stable psychotherapy, within 30 days prior to Screening.
13. Use of prohibited medications/agents as listed in the Clinical Study Protocol Section 6.9.3.
14. Known sensitivity or intolerance to hallucinogenic or psychedelic substances, or potential rescue medications (e.g., short-acting benzodiazepines or standard of care for nausea or vomiting) as reported by the patient and/or determined by the Investigator.
15. Current (within the last 12 months) alcohol or substance use disorder or positive urine drug screen for illicit drugs (including cannabis) or drugs of abuse at Screening or Day 0. A positive test for cannabinoids (e.g., marijuana) at Screening may not exclude a patient if, after discussion with and evaluation by the Investigator, the patient agrees not to use any marijuana or other cannabinoid products during the study, and if allowed to participate, the patient must test negative for cannabinoids on Day 0. Any positive urine drug test will be reviewed with patients to determine the pattern of use and eligibility will be determined at the Investigator’s discretion in conjunction with the Medical Monitor.Other Exclusion Criteria
16. Patient who, as determined by the Investigator, is not otherwise considered a suitable study patient (i.e., extreme or significant complicating co-morbidities, past or current trauma, social stressors/instability and/or personal circumstances and behavior that might be incompatible with the establishment of rapport or safe exposure to RE104).
17. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.