. 2022 Oct 26;13:954388. doi: 10.3389/fpsyt.2022.954388

Table 1.

Key inclusion and exclusion criteria.

Inclusion criteria [informed by (35)]
• At Screening, meet DSM-5 criteria for current MDD with a symptom duration of more than 12 weeks and less than 2 years • At Baseline, have at least moderate MDD per MADRS and symptoms in the last month constituting a MADRS Total Severity Score of 20 or greater • ≧18 years of age • Sufficient competency in the Norwegian language • Capacity to provide consent • Agreement to provide a support person who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable • Agreement to follow specific lifestyle modifications Exclusion criteria
• Electroconvulsive Therapy (ECT) or ketamine within 12 weeks of enrollment • Current or previously diagnosed psychotic disorder, significant history of mania, or evidence of a personality disorder • Current eating disorder with active purging • Current moderate or severe alcohol or cannabis use disorder within the 12 months prior to enrollment • Active illicit (other than cannabis) or prescription drug substance use disorder at any severity within 12 months prior to enrollment • Current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion • The use of any psychoactive medication not approved by the research team from Baseline through Study Termination (with the exception of gabapentin or certain opiates for pain control) • Positive pregnancy test or breastfeeding. Unable to agree to the use of highly effective contraception methods • 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. Mild, stable chronic medical problems (diabetes mellitus type 2, for example) are allowed in the study if the symptoms from that disease are not being confused with side effects from MDMA or interfering with study participation • Uncontrolled hypertension. Participants with well-controlled hypertension might be enrolled if acceptable cardiovascular risk (family history, smoking, lipid levels, body weight, level of physical activity) and no signs of ongoing cardiovascular or cerebrovascular disease from history, physical exam or ECG supplemented by echocardiography or nuclear imaging, and carotid ultrasound • History of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease • Have a marked Baseline prolongation of QT/QTc interval e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] in males and >460 ms in females (corrected by Fridericia's formula) • Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) • Symptomatic liver disease or significant liver enzyme elevation • History of clinically significant hyponatremia or hyperthermia • Weight < 48 kilograms (kg)

Inclusion criteria [informed by (35)]

• At Screening, meet DSM-5 criteria for current MDD with a symptom duration of more than 12 weeks and less than 2 years
• At Baseline, have at least moderate MDD per MADRS and symptoms in the last month constituting a MADRS Total Severity Score of 20 or greater
• ≧18 years of age
• Sufficient competency in the Norwegian language
• Capacity to provide consent
• Agreement to provide a support person who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable
• Agreement to follow specific lifestyle modifications
Exclusion criteria

• Electroconvulsive Therapy (ECT) or ketamine within 12 weeks of enrollment
• Current or previously diagnosed psychotic disorder, significant history of mania, or evidence of a personality disorder
• Current eating disorder with active purging
• Current moderate or severe alcohol or cannabis use disorder within the 12 months prior to enrollment
• Active illicit (other than cannabis) or prescription drug substance use disorder at any severity within 12 months prior to enrollment
• Current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion
• The use of any psychoactive medication not approved by the research team from Baseline through Study Termination (with the exception of gabapentin or certain opiates for pain control)
• Positive pregnancy test or breastfeeding. Unable to agree to the use of highly effective contraception methods
• 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. Mild, stable chronic medical problems (diabetes mellitus type 2, for example) are allowed in the study if the symptoms from that disease are not being confused with side effects from MDMA or interfering with study participation
• Uncontrolled hypertension. Participants with well-controlled hypertension might be enrolled if acceptable cardiovascular risk (family history, smoking, lipid levels, body weight, level of physical activity) and no signs of ongoing cardiovascular or cerebrovascular disease from history, physical exam or ECG supplemented by echocardiography or nuclear imaging, and carotid ultrasound
• History of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease
• Have a marked Baseline prolongation of QT/QTc interval e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] in males and >460 ms in females (corrected by Fridericia's formula)
• Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Symptomatic liver disease or significant liver enzyme elevation
• History of clinically significant hyponatremia or hyperthermia
• Weight < 48 kilograms (kg)