Intervención Acortada con LSD para el Trastorno Depresivo Mayor (SLIM)

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 ideal body weight, or BMI >=40, or BMI >=35 with high blood pressure or diabetes)
• Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal
• Body weight < 45 kg
• Significant acute adverse reaction (e.g., dystonia) to an antipsychotic
• Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (including substance-induced), Bipolar I or II Disorder or Major
• Depression with psychotic features
• Have a first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or Bipolar I Disorder.