Social Anxiety MDMA-Assisted Therapy Investigation
- Conditions
- Social Anxiety Disorder
- Interventions
- Behavioral: Psychotherapy
- Registration Number
- NCT05138068
- Lead Sponsor
- Jason B Luoma
- 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.
- Detailed Description
SAD is a prevalent and disabling disorder characterized by intense fear of being scrutinized or negatively evaluated by others in social situations. SAD is the fourth most commonly diagnosed psychological disorder in the United States with onset commonly occurring in adolescence and assuming a chronic course even when treated. Evidence-based treatments for SAD exist, including medications and therapy, but a significant proportion of patients fail to improve, indicating the need for novel effective treatments.
3,4-methylenedioxymethamphetamine (MDMA) is a monoamine releaser and re-uptake inhibitor with indirect effects on neurohormone release. The combined neurobiological effects appear to reduce defenses and fear of emotional injury, enhance communication and introspection, and can increase empathy and compassion. MDMA may also enhance fear extinction learning in humans. The subjective effects of MDMA appear to create a productive psychological state that enhances the therapeutic process. These subjective effects of MDMA create a productive psychological state that enhances the therapeutic process for the treatment of SAD and other anxiety disorders. A Phase 2 MDMA-assisted therapy (MDMA-AT) trial sponsored by MAPS has provided preliminary evidence that social anxiety among adults with autism is treatable with two MDMA-AT sessions and associated non-drug preparatory and integrative psychotherapy (Danforth et al., 2018).
In this open-label Phase 2 study intended to gather supportive data on the safety and effectiveness of MDMA-assisted therapy (MDMA-AT), each of the 20 subjects will participate in two experimental sessions, with half proceeding immediately into treatment once enrolled, and half receiving the experimental treatment after an initial 16 week wait. This study involves a dose of MDMA administered during the Treatment Period with manualized therapy in two monthly Experimental Sessions. This 8-week Treatment Period is preceded by three 90-minute non-drug Preparatory Sessions. Each experimental Session is followed by three 90-minute non-drug Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is assessed by a blinded Independent Rater at study enrollment, at the primary outcome assessment point (2-weeks after the final integration session), and follow up assessment 26 weeks later. Participants will also be offered the chance to sign up for a long-term follow up extension study at the follow up assessments (with long-term follow up conducted 24 months post-treatment).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 90
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MDMA-assisted psychotherapy MDMA 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. MDMA-assisted psychotherapy Psychotherapy 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. Delayed treatment Psychotherapy 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. Delayed treatment MDMA 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.
- Primary Outcome Measures
Name Time Method 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). Baseline, Primary outcome (2 weeks after final integration session), follow up (26-weeks after primary outcome) 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.
- Secondary Outcome Measures
Name Time Method 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) The SDS is a clinician-rated assessment of functional impairment (Sheehan, 1986). The items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely) and has been validated for use in clinical trials (K. H. Sheehan \& Sheehan, 2008). Higher scores indicate a higher degree of functional impairment.
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) The ASES is a 17 item self-report measure (Sedighimornani, Rimes, Verplanken, \& Gauntlett-Gilbert, 2019) intended to assess avoidance of shame and embarrassment, two emotions hypothesized to be central to the experience of SAD. The measure shows good internal reliability, factor structure, and correlation with theoretically meaningful constructs (Sedighimornani et al., 2019). Scores range from a minimum of 0 to maximum of 102 with higher scores indicating a better outcome.
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) The 9-item Thwarted Belongingness subscale from the INQ (Freedenthal, Lamis, Osman, Kahlo, \& Gutierrez, 2011) will be used to assess the degree to which participants feel a sense of belonging, connection, and closeness with others. Scores range from a minimum of 9 to maximum of 63 with higher scores indicating a worse 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) The ISS is a 24-item self-report questionnaire measuring internalized shame that has been used in numerous studies of trait shame and has been demonstrated to have good construct validity and reliability in both clinical and nonclinical populations (del Rosario \& White, 2006). Scores range from 0 - 96, with higher scores indicate higher levels of internalized shame.
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) The HSS (Levinson, Rodebaugh, Lim, \& Fernandez, 2015) is a 4-item subscale of the Core Extrusion Schema-Revised and is thought to measure attempts to hide ones "true self" from others so as to avoid potential ostracism and rejection. This measure was created for use in SAD populations. The measure has demonstrated good psychometrics and the HSS subscale predicts the intensity of social interaction anxiety. Scores range from a minimum of 0 to maximum of 36 with higher scores indicating a worse outcome.
Evaluate change in self-compassion as a potential process of change in MDMA-Assisted Therapy for SAD, as measured by mean change in Self-Compassion Scale scores from pre- to post-treatment. Baseline, Primary outcome (2 weeks after final integration session) The SCS short form (Raes, Pommier, Neff, \& Van Gucht, 2010) is a 12-item self-report measure of self-compassion, or responding to one's own failure, suffering or inadequacies with kindness and compassion and recognizing one's own flaws and suffering as part of common human experience. The measure was modified in this study to assess self-compassion in the past week. Scores range from a minimum of 12 to maximum of 60 with higher scores indicating a better outcome.
Trial Locations
- Locations (1)
Portland Psychotherapy Clinic, Research, & Training Center
🇺🇸Portland, Oregon, United States