• Are at least 18 years old.
• Are fluent in speaking and reading the predominantly used or recognized language of the study site.
• Are able to swallow pills.
• Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions.
• Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
• If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session.
• Must not participate in any other interventional clinical trials during the duration of the study.
• Must be willing to remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures.
• At baseline, have moderate PTSD diagnosis.
• Are not able to give adequate informed consent.
• Have uncontrolled hypertension.
• Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula).
• Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Have evidence or history of significant medical disorders.
• Have symptomatic liver disease.
• Have history of hyponatremia or hyperthermia.
• Weigh less than 48 kilograms (kg).
• Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control.
• Are abusing illegal drugs.

• 21 to 65 years old
• Able to swallow capsules
• If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study
• Have an identified support person and agree to be accompanied home by that person following dosing
• Have sustained moderate-severe depression symptoms at Screening and Baseline
• Meet DSM-5 criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 60-day duration at the time of screening
• Women who are pregnant or who intend to become pregnant during the study or who are currently nursing
• Have any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, tachycardia, artificial heart valve, a clinically significant screening ECG abnormality, or any other significant cardiovascular condition
• Have a history of stroke or Transient Ischemic Attack (TIA)
• Have moderate to severe hepatic impairment
• Have epilepsy
• Have insulin-dependent diabetes
• Have a positive urine drug test
• Nicotine dependence that would disallow an individual to be nicotine free for the 7-10 hours during the dosing period
• Meet DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features, or Bipolar I or Bipolar II Disorder
• Meet DSM-5 criteria for antisocial personality disorder
• Meet DSM-5 criteria for a moderate or severe alcohol or drug use disorder

• Age 21 to 60 years at screening
• Medically healthy (does not meet criteria for an exclusionary medical condition)
• No current DSM-5 psychiatric diagnosis
• No current use of psychotropic medications
• Ability/willingness to complete all study activities
• Use of acceptable contraceptive methods (sexually active males and women of childbearing potential)
• Speaks and reads English
• No use of psychedelic drugs within prior 3 months
• Able to swallow oral medications
• Pregnancy
• Current exclusionary medical illness
• Current DSM-5 psychiatric diagnosis and/or suicidal thoughts/behavior within prior 12 months
• Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)
• Clinically significant electrocardiogram (ECG)
• Hypertension or tachycardia
• First degree relative(s) with a history of schizophrenia, schizophreniform disorder, bipolar I disorder, bipolar II disorder, major depressive disorder with psychotic features