Table 2 Full exclusion criteria

Mental health diagnosis

Current or past history of schizophrenia or other psychotic disorders or bipolar I or II disorder as assessed by clinical interview. Patients with MDD with psychotic features will be excluded. Also excluded will be individuals with a known first-degree relative with these disorders.

Diagnosis of PTSD

Diagnosis of an eating disorder

Current risk

Stage II or higher treatment-resistant depression as defined by the Thase and Rush [33] staging criteria for the current depressive episode.

Risk of suicide as determined by The Columbia-Suicide Severity Rating Scale (C-SSRS). Specifically, patients answering “yes” to items 3–5 covering the last 3-month period will be excluded.

Drug use

Substance dependence in the previous 6 months use as assessed by clinical interview with a New Zealand modified version of the NM-ASSIST.

Problematic use of alcohol defined as a score on the AUDIT of 16 or greater.

Use of monoamine oxidase inhibitors, methylphenidate, or dexamphetamine.

Excessive ongoing medication burden as determined by a study physician.

Regular use of any medications/supplements deemed to be contraindicating as judged by a study physician.

Treatment with another investigational drug or other intervention within 2 months.

Any lifetime history of psychedelic microdosing.

Use of serotonergic psychedelic drugs (LSD, psilocybin, DMT, etc.) in the last year.

Lifetime history of self-medicating with psychedelics to treat their depression.

Physical health

BMI < 18 and > 35.

Planned or current pregnancy or lactation.

Vital signs

Cardiovascular conditions including abnormal heart rate or blood pressure to be checked at screening. A threshold of exceeding 160 mmHg (systolic) and 90 mmHg (diastolic), averaged across three assessments taken on the screening day will be used. Participants with well-managed hypertension will not be excluded.

Laboratory tests

Significant renal or hepatic impairment.

Abnormal 12-lead ECG as judged by a study physician.

Abnormal laboratory test findings (complete blood count, liver function test, renal function test, thyroid function test) as judged by a study physician.

Diagnoses

Any unstable medical or neurological condition.

Any other condition judged by the treating clinician as likely to impact on the ability of the participant to complete the trial.