Shortened LSD Intervention for Major Depressive Disorder

Inclusion Criteria: * Have given written informed consent * Meet DSM-5 criteria for MDD * MADRS \>= 28 at screening Can read, write, and speak English fluently * Be judged by study team clinicians to be at low risk for suicidality Exclusion Criteria: * Women who are pregnant, nursing, or not practicing an effective means of birth control * Cardiovascular conditions: hypertension with resting blood pressure systolic \>139 or diastolic \>89, angina, heart rate \> 99, a clinically significant ECG abnormality (e.g., atrial fibrillation, QTc \> 450), TIA in the last 6 months stroke, peripheral or pulmonary vascular disease, cardiac valvulopathy * Epilepsy * Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia * Currently taking antipsychotics, or MAO inhibitors * Patients taking antidepressant medications and unable to taper * Moderate or strong CYP2D6 inhibitor antidepressants must undergo a washout period of 4 weeks or five half-lives prior to treatment * Currently taking CYP2D6 inhibitor other than an antidepressant that will be tapered * Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or UGT1A9 inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag * Have a seizure disorder, multiple sclerosis, history of significant head trauma, CNS tumor, movement disorders or any neurodegenerative condition * Morbidly obese (\>100 lbs. above i…