Social Anxiety MDMA-Assisted Therapy Investigation

NCT05138068 | Completed Phase 2 FDA Drug

• 1 other identifier: IUSA5
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label delayed treatment study to assess the safety and effect of MDMA-assisted therapy in treating 20 participants diagnosed with moderate-to-severe social anxiety disorder (SAD) of the generalized subtype. This study will obtain an estimate of effect size for two experimental sessions of MDMA-assisted therapy for the treatment of social anxiety disorder on measures of safety, social anxiety, functional outcomes, psychiatric symptoms, and putative mechanisms of action. The primary outcome for this study will be the Liebowitz Social Anxiety Scale (LSAS) administered by a blinded Independent Rater (IR). Other assessments, including physiological, self-report, and behavioral tasks will be used to assess other exploratory variables. An additional aim of the trial will be the development of a treatment manual for MDMA-AT for SAD for future research.

Conditions

Social Anxiety Disorder

Keywords

3,4-methylenedioxymethamphetamine; MDMA; Psychotherapy; Mental Disorders; Hallucinogens; Serotonin Agents; Neurotransmitter Agents; Adrenergic Uptake Inhibitors; Adrenergic Agents; Neurotransmitter Uptake Inhibitors; Psychotropic Drugs; Anxiety disorders; Phobia, Social

Outcome Measures

Primary Outcomes (1)

• Evaluate the effect of MDMA-assisted therapy on severity of social anxiety disorder symptoms, as measured by total score on the Liebowitz Social Anxiety Scale (L-SAS).

  Primary outcome analyses are intent-to-treat comparing mean scores on the Liebowitz Social Anxiety Scale (LSAS) at post-treatment assessment point in the immediate treatment condition compared to the 16 week assessment in the delayed treatment condition. A participant is considered eligible for the ITT analysis if they have completed at least one Experimental Session and at least one LSAS assessment beyond baseline. The LSAS (Heimberg et al., 1999) is a 24-item, semi-structured interview on the severity of social anxiety disorder, which assesses fear (0 to 3 = none, mild, moderate, severe) and avoidance (0 to 3 = never, occasionally, often, usually) of 24 social situations over the previous week, providing an overall social anxiety severity rating and subscale scores for performance fear, performance avoidance, social fear, and social avoidance. Scores range from a minimum of 0 to maximum of 144 with higher scores indicating a worse outcome.

  Baseline, Primary outcome (2 weeks after final integration session), follow up (26-weeks after primary outcome)

Secondary Outcomes (6)

• Evaluate the effectiveness of MDMA-assisted therapy for SAD in clinician-rated functional impairment, as measured by the mean change in item scores on the Sheehan Disability Scale (SDS).

  Baseline, Primary outcome (2 weeks after final integration session), follow up (26 weeks after primary outcome)

• Evaluate change in internalized shame as a potential process of change in MDMA-Assisted Therapy for SAD, as measured by mean change in Internalized Shame Scale (ISS) scores from pre- to post-treatment.

  Baseline, Primary outcome (2 weeks after final integration session)

• Evaluate change in acceptance of self-conscious emotions as a potential process of change in MDMA-Assisted Therapy for SAD, as measured by mean change in Acceptance of Shame and Embarrassment Scale (ASES) scores from pre- to post-treatment.

  Baseline, Primary outcome (2 weeks after final integration session)

• Evaluate change in subjective belonging as a potential process of change in MDMA-Assisted Therapy for SAD, as measured by mean change in Interpersonal Needs Questionnaire (INQ) - Thwarted Belongingness scores from pre- to post-treatment.

  Baseline, Primary outcome (2 weeks after final integration session)

• Evaluate change in self-concealment as a potential process of change in MDMA-Assisted Therapy for SAD, as measured by mean change in Hidden Self Scale (HSS) scores from pre- to post-treatment.

  Baseline, Primary outcome (2 weeks after final integration session)

Study Arms (2)

MDMA-assisted psychotherapy

EXPERIMENTAL

Two sessions of manualized MDMA-assisted psychotherapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose 1.5 to 2 hours later. MDMA sessions are preceded by 3 non-drug preparatory psychotherapy sessions and followed by 3 integrative non-drug psychotherapy sessions.

Drug: MDMA; Behavioral: Psychotherapy

Delayed treatment

OTHER

Participants randomly assigned to the delayed treatment control condition will wait 16 weeks and then receive MDMA-assisted therapy protocol described in the experimental arm of the study.

Drug: MDMA; Behavioral: Psychotherapy

Interventions

MDMA DRUG

Two 8-hour experimental sessions will occur within the 11-session intervention in which participants will take a dose of MDMA. In the first Experimental Session, the initial dose will be 80 mg MDMA, with a supplemental dose of 40 mg 1.5 to 2 hours later unless contraindicated. In the second Experimental Session, the initial dose may be increased to 120 mg MDMA unless contraindicated with an additional dose of 40 mg 1.5 to 2 hours after the initial dose is given unless contraindicated.

Also known as: 3,4-Methylenedioxymethamphetamine

Delayed treatment; MDMA-assisted psychotherapy

Psychotherapy BEHAVIORAL

Adjunctive, manualized psychotherapy will be provided by a team of two therapists during the MDMA-assisted therapy sessions

Delayed treatment; MDMA-assisted psychotherapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are between the ages of 18 and 65 years old.
• Live in the Portland, OR area.
• Are fluent in speaking and reading English.
• Are able to swallow pills.
• Agree to have study visits recorded, including Experimental Sessions, assessments, and non-drug psychotherapy sessions.
• Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
• If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session.
• Agree to the necessary lifestyle modifications.
• Able to identify support person who can stay with participant overnight after experimental sessions.
• Suitable home environments to allow completion of all study procedures, including sufficient privacy and access to computer or mobile device with internet access.
• At Screening, meet DSM-5 criteria for current SAD, generalized subtype.
• At Screening, may have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if they pass additional screening to rule out underlying cardiovascular disease.
• At Screening, may have asymptomatic hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.
• At Enrollment confirmation for those in delayed treatment group, continue to meet criteria for SAD, generalized subtype.

You may not qualify if:

• Are not able to give adequate informed consent.
• Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of SAD or any other psychiatric disorder.
• Are likely, in the investigator's opinion and via observation during the Preparatory Period, to lack social support or lack a stable living situation or supportive family/network.
• Have any current problem which, in the opinion of the investigator or Study Physician, might interfere with participation.
• Would present a serious risk to others as assessed by investigator, Study Physician, or study team.
• Require certain excluded medications.
• Have evidence or history of significant (controlled or uncontrolled) hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of MDMA administration (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded).
• Have uncontrolled hypertension using the standard criteria of the American Heart Association (values of 140/90 millimeters of Mercury \[mmHg\] or higher assessed on three separate occasions).
• Have a marked baseline prolongation of QT/QTc interval.
• Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions.
• Have symptomatic liver disease.
• Have history of hyponatremia or hyperthermia.
• Weigh less than 48 kilograms (kg).
• Are pregnant, nursing, or are able to become pregnant and are not practicing an effective means of birth control.

Sponsors & Collaborators

• Jason B Luoma: lead
• Oregon Research Institute Center for Evaluation Services: collaborator
• Multidisciplinary Association for Psychedelic Studies: collaborator
• Portland Psychotherapy Clinic, Research, and Training Center: collaborator

Study Sites (1)

Portland Psychotherapy Clinic, Research, & Training Center

Portland, Oregon, 97227, United States

Location

Related Publications (5)

• Danforth AL, Grob CS, Struble C, Feduccia AA, Walker N, Jerome L, Yazar-Klosinski B, Emerson A. Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology (Berl). 2018 Nov;235(11):3137-3148. doi: 10.1007/s00213-018-5010-9. Epub 2018 Sep 8.

  PMID: 30196397 BACKGROUND

• Luoma J, Lear MK. MDMA-Assisted Therapy as a Means to Alter Affective, Cognitive, Behavioral, and Neurological Systems Underlying Social Dysfunction in Social Anxiety Disorder. Front Psychiatry. 2021 Sep 27;12:733893. doi: 10.3389/fpsyt.2021.733893. eCollection 2021.

  PMID: 34646176 BACKGROUND

• Luoma JB, Shahar B, Kati Lear M, Pilecki B, Wagner A. Potential processes of change in MDMA-Assisted therapy for social anxiety disorder: Enhanced memory reconsolidation, self-transcendence, and therapeutic relationships. Hum Psychopharmacol. 2022 May;37(3):e2824. doi: 10.1002/hup.2824. Epub 2021 Nov 5.

  PMID: 34739165 BACKGROUND

• Danforth AL, Struble CM, Yazar-Klosinski B, Grob CS. MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:237-49. doi: 10.1016/j.pnpbp.2015.03.011. Epub 2015 Mar 25.

  PMID: 25818246 BACKGROUND

• Lear MK, Smith SM, Pilecki B, Stauffer CS, Luoma JB. Social anxiety and MDMA-assisted therapy investigation: a novel clinical trial protocol. Front Psychiatry. 2023 Jul 14;14:1083354. doi: 10.3389/fpsyt.2023.1083354. eCollection 2023.

  PMID: 37520237 DERIVED

MeSH Terms

Conditions

Phobia, Social; Mental Disorders; Anxiety Disorders

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy

Condition Hierarchy (Ancestors)

Phobic Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Behavioral Disciplines and Activities

Study Officials

• Jason B Luoma, Ph.D.

  Portland Psychotherapy Clinic, Research, and Training Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Primary outcome measures will be administered by blinded, independent raters.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: CEO

Model Details: This is a randomized, open-label delayed treatment study to assess the safety and effect of MDMA-assisted therapy in treating 20 participants diagnosed with moderate-to-severe social anxiety disorder (SAD) of the generalized subtype.

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: November 30, 2021
• Study Start: April 13, 2022
• Primary Completion: February 6, 2025
• Study Completion: August 12, 2025
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: At time of study publications
• Access Criteria: Contact the sponsor-investigator to access data that is not publicly shared. Some deidentified data sets with be publicly shared.

Locations

US (1)