Psilocybin and Methylenedioxymethamphetamine (MDMA) for Post-traumatic Stress Disorder (PTSD)

Inclusion Criteria: * \>=21 years old * Military Veteran * Have given written informed consent * Able to swallow pills * Have a confirmed DSM-5 diagnosis of Post-traumatic Stress Disorder with symptom duration \>= 6 months * Have a baseline CAPS-5 score of \>=28 * Be judged by study team clinicians to be at low acute risk for suicidality * Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study. * Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests * Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days. * Agree to refrain from using any psychoactive drugs, including alcoholic beverages within 24 hours of each drug administration. The exceptions are caffeine and nicotine. * Agree to refrain from using any caffeine or nicotine within 2 hours of dosing session start. * Agree not to take any as needed (PRN) medications on the mornings of drug sessions without approval of the treatment team. * Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration. * Agree to stop taking 5HT2A antagonist medications at least 5 half-lives before dosing. * Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals. * Have no lifetime use of serotonin 2A receptor (5-HT2A) agonist hallucinogens and/or MDMA at a greater dosage than a level typically defined as 'microdose.' * Have at least a high school level of education or equivalent (e.g. GED). * Weigh between 40kg- 120kg. * Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable * Agree to be released into the custody of a close friend or family member who has agreed to take charge of the study participant as a condition of leaving the testing facility, or agree to be accompanied home or to an accommodation by a member of the study team * May have a history of or current Diabetes Mellitus (Type 2) if additional screening measures rule out underlying cardiovascular disease, if the condition is judged to be stable on effective management, and with approval by the Medical Monitor * May have hypothyroidism if taking adequate and stable thyroid replacement medication * May have a history of, or current, glaucoma if approval for study participation is received from an ophthalmologist Exclusion Criteria: * Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder * Current or history within one year of meeting DSM-5 criteria for a moderate or severe alcohol, or other drug use disorder (excluding tobacco, caffeine, and cannabis) * Current or history within one year of meeting DSM-5 criteria for Borderline Personality Disorder. * Clinically significant suicidal ideation (e.g. with strong intent or means; C-SSRS \> 3) within past 6 months * Have a first degree relative with schizophrenia or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I disorder * Nicotine dependence that would be incompatible with an individual to be nicotine free for 8-10 hours on a dosing session day * Medical condition incompatible with MDMA or psilocybin administration (e.g., cardiovascular, drug-induced hyperthermia, hyponatremia). * Currently taking on a daily basis any medications (including herbal substances and supplements) with a Central Nervous System effect on serotonin (including serotonin-reuptake inhibitors (SRIs), monoamine oxidase inhibitors (MAOIs)), or any medications that affect liver enzyme (2D6) metabolism (e.g., Bupropion) * Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, uridine diphosphate glucuronosyltransferase enzyme (UGT1A9) inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag. * On unstable/changing dose of opioid, benzodiazepine or other psychoactive or pain medication within 4 weeks prior to enrollment and/or unable to abstain from medication on drug administration day * Current use/positive toxicology for illicit drugs; or positive breath alcohol test at screening and/or prior to each drug administration session * Lifetime use of any psychedelic drug (e.g., MDMA, psilocybin) at a dosage greater than a level typically defined as 'microdose.' * Clinically significant transaminitis (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than two times normal value). * Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; * Women who are of child-bearing potential and sexually active agree to use highly effective means of birth control (i.e. implants, injectables, combined oral contraceptives, progestin-containing intrauterine device (IUD) or vasectomised partner) for the duration of this study. * Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged corrected QT interval (QTc) (i.e., QTc \> 450 msec), heart valve, or transient ischemic attack (TIA) in the past year. * History of seizures and/or epilepsy with history of seizures. * Type 1 diabetes. * BMI \< 18 * Are likely, in the investigator's opinion and via observation during the Preparatory Period, to be re-exposed to the index trauma or other significant trauma in daily life, lack social support, or lack a stable living situation. * Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment * Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, or aneurysm. * Participants with other mild, stable chronic medical problems may be enrolled if the site physician and investigators agree the condition would not significantly increase the risk of MDMA administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the study drugs. Examples of stable medical conditions that could be allowed include, but are not limited to Diabetes Mellitus (Type 2), Human Immunodeficiency Virus (HIV) infection, Gastroesophageal Reflux Disease (GERD), etc. * Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism would require exclusion * Have symptomatic liver disease or significant liver enzyme elevations