Inclusion Criteria:

• Age 21-65 years.

• Diagnosis of post-traumatic stress disorder (PTSD) according to DSM-5 criteria, as assessed by CAPS-5.

• At least 1 year since the traumatic event.

• Moderate or greater PTSD severity (CAPS-5 score ≥ 25).

• Ability to provide written informed consent.

• Ability to read, write, speak, and understand Hebrew.

• Prior trauma-focused psychotherapy.

• Medically healthy at screening, as determined by a study physician, including:

  • No exclusionary medical conditions.
  • Resting blood pressure between 90/60 and 150/90 mmHg and heart rate between 45-100 bpm.
  • Normal laboratory results (including liver function, renal function, and electrolytes).

Exclusion Criteria:

• Current or past diagnosis of psychotic disorders, bipolar disorder, schizoaffective disorder, dissociative identity disorder, or borderline personality disorder (as assessed by MINI or SCID-5-SPQ).
• Current psychotic features.
• First-degree relative with a history of a psychotic disorder.
• History of antidepressant-induced mania or hypomania.
• Significant suicidal risk as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS), including active suicidal ideation with intent or plan, or suicidal behavior within the past 6 months.
• Substance use disorder (excluding nicotine and caffeine); mild-to-moderate alcohol or cannabis use may be permitted under monitoring and PI approval.
• Use of psychedelic substances within 3 months before enrollment
• Participation in a clinical trial involving administration of a psychedelic substance within the past 12 months.
• History of adverse psychological reaction to psychedelics requiring hospitalization.
• Significant cardiovascular disease, including ischemic heart disease, uncontrolled hypertension, arrhythmia, or heart failure (NYHA class ≥3).
• Dementia or suspected cognitive impairment.
• Traumatic brain injury with loss of consciousness >24 hours or post-traumatic amnesia >7 days (unless cleared by neurological evaluation).
• Pregnancy, breastfeeding, or positive pregnancy/drug test (excluding cannabis) on the day of dosing.
• BMI <18 or >33
• Abnormal liver or renal function tests.
• Use of medications contraindicated with psilocybin.
• Changes in psychiatric medication (dose or type) within one month before enrollment.
• Needle phobia or inability to undergo blood testing.