MDMA-Assisted Psychotherapy for Social Anxiety Disorder

(SAMATI Trial)

No longer recruiting at 1 trial location

Overseen By Jason Luoma, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jason B Luoma

Must not be taking: QT prolonging drugs

Disqualifiers: Cardiovascular, Neurological, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether MDMA-assisted therapy can help individuals with social anxiety disorder (SAD) feel more at ease in social situations. Participants will undergo therapy sessions that include MDMA, a substance that may reduce anxiety, along with regular therapy before and after the MDMA sessions. The trial aims to assess the safety and effectiveness of this treatment and may develop a guide for using MDMA in therapy for SAD in the future. This trial could suit those living in Portland, OR, diagnosed with moderate-to-severe social anxiety disorder and willing to try a new treatment approach. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to innovative therapy development.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that certain medications are excluded. It's best to contact the research team for more details.

Is there any evidence suggesting that MDMA-assisted psychotherapy is likely to be safe for humans?

Research has shown that MDMA-assisted therapy can be safe for individuals with certain conditions. One study found that people with PTSD, a mental health condition caused by trauma, used MDMA along with therapy without experiencing harm. Another study examined MDMA therapy for social anxiety in adults with autism and found it could be both effective and safe.

However, some side effects occur. About 45% of people using MDMA in therapy reported side effects like anxiety, compared to 30% of those who did not take MDMA. These side effects were usually mild and manageable.

Overall, MDMA-assisted therapy shows promise as a safe treatment, especially when conducted in a controlled setting with professional guidance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

MDMA-assisted psychotherapy is unique because it uses MDMA, a compound known for its effects on mood and social behavior, to enhance the effectiveness of psychotherapy for social anxiety disorder. Unlike standard treatments like SSRIs and cognitive-behavioral therapy, which focus on altering brain chemistry or changing thought patterns over time, MDMA works by promoting feelings of openness and emotional connectedness during therapy sessions, potentially leading to faster and more profound breakthroughs. Researchers are excited about this treatment as it offers a new approach that could complement existing therapies, addressing the emotional barriers that often hinder progress in traditional treatments.

What evidence suggests that MDMA-assisted psychotherapy might be an effective treatment for social anxiety disorder?

Research has shown that therapy using MDMA might help reduce symptoms of social anxiety. In one study, autistic adults experienced quick and lasting improvements in social anxiety after this treatment. Another study found that MDMA-assisted therapy significantly lowered overall anxiety levels. This trial will evaluate MDMA-assisted psychotherapy, with participants receiving two sessions of manualized MDMA-assisted psychotherapy. These results suggest that MDMA could effectively treat social anxiety disorder. While more research is needed, current evidence is promising for this approach. ^{1 6 7 8 9}

Who Is on the Research Team?

Jason B Luoma, Ph.D.

Principal Investigator

Portland Psychotherapy Clinic, Research, and Training Center

Are You a Good Fit for This Trial?

Adults aged 18-65 with moderate-to-severe social anxiety disorder, living in Portland, OR. Participants must speak/read English, agree to recorded sessions and lifestyle changes, have a support person for post-session care, and use birth control if applicable. Stable hypertension or treated hepatitis C is okay; glaucoma patients need ophthalmologist approval.

Inclusion Criteria

Agree to have study visits recorded, including Experimental Sessions, assessments, and non-drug psychotherapy sessions

You give permission for your study visits to be recorded, including therapy sessions, tests, and experimental sessions.

If you are a woman who can become pregnant, you need to have a negative pregnancy test before and during the study. You also need to agree to use effective birth control for at least 10 days after the study.

Exclusion Criteria

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

Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of SAD or any other psychiatric disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Sessions

Three 90-minute non-drug preparatory psychotherapy sessions

3 weeks

3 visits (in-person)

Treatment

Participants receive two MDMA-assisted therapy sessions with manualized therapy

8 weeks

2 visits (in-person) for MDMA sessions, 6 visits (in-person) for integrative sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Follow-up assessments at 2 weeks and 26 weeks post-treatment

Long-term Follow-up Extension

Participants may opt into a long-term follow-up study conducted 24 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• MDMA

Trial Overview The trial tests MDMA-assisted therapy's safety and effectiveness on social anxiety disorder using two experimental sessions. It measures the impact on social anxiety through the Liebowitz Social Anxiety Scale and other assessments like physiological responses and self-reports.

How Is the Trial Designed?

Group I: MDMA-assisted psychotherapy Experimental Treatment 2 Interventions

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.

Group II: Delayed treatment Experimental Treatment 2 Interventions

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.

MDMA is already approved in United States for the following indications:

Approved in United States as MDMA for:

• Posttraumatic stress disorder (PTSD)

Who Is Running the Clinical Trial?

Jason B Luoma

Lead Sponsor

Trials

1

Recruited

90+

Lykos Therapeutics

Collaborator

Trials

12

Recruited

330+

Oregon Research Institute Center for Evaluation Services

Collaborator

Trials

1

Recruited

90+

Multidisciplinary Association for Psychedelic Studies

Collaborator

Trials

40

Recruited

1,200+

Portland Psychotherapy Clinic, Research, and Training Center

Collaborator

Trials

1

Recruited

90+

Published Research Related to This Trial

In a study involving 39 healthy adults, MDMA did not reduce physiological or subjective stress responses during a public speaking task, contrary to the hypothesis that it would dampen stress reactions.

While MDMA is known for its potential benefits in treating PTSD, this research indicates that a single dose does not moderate acute stress responses, suggesting that its therapeutic effects may depend on different conditions or contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDMA does not alter responses to the Trier Social Stress Test in humans. Bershad, AK., Miller, MA., de Wit, H.[2018]

A systematic review of 16 studies and a meta-analysis of 10 studies involving 168 patients suggest that MDMA, when used in conjunction with psychotherapy, shows promising efficacy in treating post-traumatic stress disorder (PTSD).

The analysis highlights both the potential benefits and adverse events associated with MDMA treatment, indicating that it may be particularly beneficial for treatment-resistant patients, thus paving the way for future drug development in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis. Tedesco, S., Gajaram, G., Chida, S., et al.[2021]

MDMA may enhance psychotherapy for social anxiety disorder by improving memory reconsolidation, which can help patients process and integrate their experiences more effectively.

The drug may also foster self-transcendent emotions like compassion and love, and strengthen the therapeutic relationship, both of which are crucial for successful treatment outcomes in disorders characterized by social disconnection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential processes of change in MDMA-Assisted therapy for social anxiety disorder: Enhanced memory reconsolidation, self-transcendence, and therapeutic relationships. Luoma, JB., Shahar, B., Kati Lear, M., et al.[2022]

An estimated 0.9% of individuals aged 12 and older in the U.S. reported using ecstasy/MDMA in the past year, indicating that while use is relatively rare, it is more common among younger age groups and certain racial minorities.

Factors such as past-year use of other drugs, prescription drug misuse, nicotine dependence, and alcohol use disorder were associated with increased odds of ecstasy/MDMA use, highlighting the need for targeted prevention and harm reduction strategies for at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Correlates of Past Year Ecstasy/MDMA Use in the United States. Yang, KH., Kepner, W., Nijum, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10379654/

Social anxiety and MDMA-assisted therapy investigation This paper presents a protocol for an open-label pilot study of MDMA-assisted therapy (MDMA-AT) for social anxiety disorder.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30196397/

Reduction in social anxiety after MDMA-assisted ... Conclusions: This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy.

3. nature.com nature.com/articles/s41598-020-75706-1

MDMA-assisted psychotherapy for treatment of anxiety and ... At the primary endpoint, the MDMA group had a greater mean (SD) reduction in STAI-Trait scores, − 23.5 (13.2), indicating less anxiety, compared ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05138068

Social Anxiety MDMA-Assisted Therapy Investigation 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 ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.733893/epub

MDMA-Assisted Therapy and Social Anxiety Results from this trial suggest promise for the treatment of SAD in the absence of autism. Although autism spectrum disorder appears to confer ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02008396

Phase 2 Pilot Safety Study of MDMA-assisted Therapy for ... The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective at reducing social anxiety in adults with autism.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3122379/

the first randomized controlled pilot study The hypothesis tested is that MDMA could be administered without harm to people with chronic, treatment-resistant PTSD and, in conjunction with psychotherapy, ...

8. nature.com nature.com/articles/s41386-024-01865-8

Side-effects of mdma-assisted psychotherapy: a systematic ... In total, 45% of MDMA-AP participants versus 30% of controls reported side effects during medication sessions. Odds of experiencing anxiety and ...

9. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20230681

MDMA and MDMA-Assisted Therapy | American Journal of ... A considerable body of preliminary evidence suggests that MDMA-AT delivered in a controlled clinical setting is a safe and efficacious treatment for PTSD.