Danforth 2018.

Study characteristics
Methods	4‐week parallel trial of MDMA + psychotherapy versus placebo + psychotherapy
Participants	Inclusion criteria: aged ≥ 21 years have at least two years of college education or the equivalent complete the autism diagnostic observation schedule ‐ 2 Module 4 (adult) by a designated Independent Rater (IR) who was research reliability certified have moderate to severe symptoms of social anxiety with a combined Liebowitz Social Anxiety Scale score of at least 60 able to safely discontinue any current psychotropic medications that could interfere with action of the experimental drug. Exclusion criteria: psychiatric exclusion criteria included family history in first‐degree relatives of schizophrenia or bipolar I disorder, or participant diagnoses of active or past psychotic disorder, borderline personality disorder, dissociative identity disorder, eating disorder or active suicidal ideation. Setting: Los Angeles Biomedical Research Institute in Torrance, CA, USA Sample size: placebo (n = 4); MDMA (n = 8) Reason for dropouts/withdrawals: from MDMA group, 1 treatment discontinuation due to not meeting inclusion criteria Current or previous medications: previous medications MDMA: antidepressants (5), anxiolytics (1), antipsychotics (1), stimulant (3), other (3). Placebo: antidepressants (2), antipsychotics (1), stimulant (1) Mean age: placebo mean age 28.3 years, MDMA mean age 32.8 years Mean IQ: details not provided Gender: MDMA 25% female, placebo all male Baseline ABC‐Irritability scores: not an outcome Concomitant medications ‐ not reported Previous medications: previous medications: MDMA antidepressants (5), anxiolytics (1), antipsychotics (1), stimulant (3), other (3). Placebo antidepressants (2), antipsychotics (1), stimulant (1)
Interventions	Intervention (MDMA + psychotherapy): "after three 60‐ to 90‐min non‐drug preparatory psychotherapy sessions, participants received two blinded experimental sessions with MDMA or placebo, spaced approximately 1 month apart. Following each experimental session, three 60‐ to 90‐min non‐drug integrative psychotherapy sessions occurred over 3 weeks" Comparator (placebo + psychotherapy): "after three 60‐ to 90‐min non‐drug preparatory psychotherapy sessions, participants received two blinded experimental sessions with MDMA or placebo, spaced approximately 1 month apart. Following each experimental session, three 60‐ to 90‐min non‐drug integrative psychotherapy sessions occurred over 3 weeks"
Outcomes	Primary outcomes: adverse events Secondary outcomes: tolerability Timing of outcome assessments: baseline, post‐intervention, and 6 months
Notes	Study start date: February 2014 Study end date: April 2017 Funding: "The trial was sponsored and funded by the Multidisciplinary Association for Psychedelic Studies (MAPS), a 501(c)(3) nonprofit organization. MAPS Public Benefit Corporation (MPBC), wholly owned by MAPS, was the trial organizer." Conflicts of interest: in receipt of various grants and some authors were eployed by the funder of the study. Other: clinical trial registry ‐ NCT02008396
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Participants, therapists, and IR [Independent Rater] were blinded to drug assignment"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	An independent rater (IR) administered the Leibowitz Social Anxiety Scale (LSAS) at baseline, 1 day, 2 weeks, and 4 weeks after each experimental session and readministered it before the blind was broken at 6 months.
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT analysis, only one dropout
Selective reporting (reporting bias)	Low risk	Same primary outcomes on clinical trial registration
Other bias	High risk	The trial was sponsored and funded by the Multidisciplinary Association for Psychedelic Studies.