Methylone for PTSD

(IMPACT-EXT Trial)

No longer recruiting at 8 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Transcend Therapeutics

Disqualifiers: Non-compliance, Physical or psychological findings

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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of Methylone for individuals with PTSD, a condition where past trauma causes distress and anxiety. Researchers will monitor participants' symptoms over a year to determine the treatment's safety and effectiveness. If PTSD symptoms return, participants may receive another round of treatment. This trial is open to those who successfully completed an earlier study with the same treatment and can commit to not joining other trials during this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that Methylone is likely to be safe for humans?

Research has shown that methylone, also known as TSND-201, is under investigation for its safety and effectiveness in treating PTSD. Participants in studies have reported side effects like headaches, but these were usually mild and manageable.

In another study, methylone reduced PTSD symptoms for many patients. Importantly, no serious side effects were commonly reported, suggesting it is generally well-tolerated.

Methylone has also been labeled a "Breakthrough Therapy" for PTSD, indicating it shows promise and could offer significant benefits over current treatments. While this is encouraging, ongoing research will continue to ensure its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Most treatments for PTSD involve psychotherapy and medications like SSRIs (Selective Serotonin Reuptake Inhibitors) that can take weeks to show results. Methylone is unique because it works differently, acting as a psychedelic with potential to rapidly alter brain pathways linked to trauma response. This rapid action could mean quicker relief of symptoms compared to traditional therapies. Researchers are excited about Methylone's potential to offer a new pathway for treatment, bringing hope for faster and possibly more effective management of PTSD.

What evidence suggests that Methylone might be an effective treatment for PTSD?

Research has shown that methylone, the investigational treatment in this trial, may help treat PTSD. Studies indicate that it supports brain cell growth and reduces PTSD symptoms by improving how the brain handles fear. In animal studies, methylone effectively reduced fear responses quickly, which is promising for humans. It also helps manage fear-related memories and activity in the amygdala, a part of the brain involved in processing emotions like fear. Additionally, several studies have shown that methylone is well-tolerated and has long-lasting positive effects on PTSD symptoms. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals who have completed a previous Transcend-sponsored clinical trial using Methylone for PTSD. Participants must not join other trials during this study and should be able to give informed consent.

Inclusion Criteria

I have successfully completed a previous clinical trial with methylone sponsored by Transcend.

I am willing and able to understand and provide my consent for the trial.

I agree not to join any other clinical trials while I am part of this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants may receive a course of TSND-201 treatment if criteria for relapse are met

Variable

As needed based on relapse criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Monthly visits

Open-label extension

Long-term evaluation of the efficacy and safety of Methylone for PTSD

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylone

Trial Overview The study observes the long-term effects of Methylone on PTSD over 52 weeks, with monthly assessments. If participants relapse, they may receive TSND-201 treatment again.

How Is the Trial Designed?

Group I: Treatment (Methylone) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Transcend Therapeutics

Lead Sponsor

Trials

4

Recruited

310+

Published Research Related to This Trial

SSRIs are the first-line treatment for PTSD, but they only help about 60% of patients, with less than 30% achieving full remission, highlighting the need for alternative treatments.

Risperidone has the strongest evidence as an effective add-on therapy for patients who do not respond well to SSRIs, while prazosin shows promise for treating PTSD symptoms like nightmares and insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review. Berger, W., Mendlowicz, MV., Marques-Portella, C., et al.[2022]

Methoxetamine (MXE), a ketamine analogue, has a high affinity for the NMDA receptor and may alleviate PTSD symptoms, as suggested by a case report of a US veteran who used it for its calming effects.

This case highlights the need for increased awareness of designer drugs like MXE, which are not detected by standard drug tests, to better address addiction treatment in both military and civilian populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Being with a Buddha": A Case Report of Methoxetamine Use in a United States Veteran with PTSD. Striebel, JM., Nelson, EE., Kalapatapu, RK.[2020]

Ketamine, an NMDA receptor antagonist, shows promising rapid antidepressant effects in PTSD, with evidence from various studies including case reports and randomized trials, indicating its potential as a treatment option for this challenging condition.

Despite the variability in clinical presentation and treatment approaches, ketamine demonstrates encouraging safety and efficacy signals, suggesting it could be a valuable off-label intervention for patients with chronic, refractory PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. Ragnhildstveit, A., Roscoe, J., Bass, LC., et al.[2023]

Post-traumatic nightmares (PTNs) are a significant issue for individuals with PTSD, leading to distress and decreased quality of life, and effective treatment of these nightmares can improve overall PTSD symptoms and health outcomes.

While traditional medications for PTSD have limited effects on nightmares, novel agents like ramelteon, cannabinoids, and ketamine show promise, but more large randomized controlled trials are needed to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. Geldenhuys, C., van den Heuvel, LL., Steyn, P., et al.[2022]

MDMA-assisted psychotherapy has received Breakthrough Therapy Designation from the FDA for treating PTSD, showing a large effect size in studies compared to the small to moderate effects of traditional medications like paroxetine and sertraline.

This treatment approach, which involves MDMA administration during psychotherapy sessions, demonstrated better safety profiles and lower dropout rates than conventional antidepressants, with minimal risk of overdose or withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Feduccia, AA., Jerome, L., Yazar-Klosinski, B., et al.[2020]

Methylone demonstrated rapid and significant antidepressant-like effects in preclinical tests, reducing immobility by nearly 95% in the Forced Swim Test, with effects lasting at least 72 hours after a single dose, which is much more effective than the SSRI fluoxetine.

In addition to its antidepressant effects, methylone also showed anxiolytic properties, suggesting it may be beneficial for treating both depression and anxiety, potentially offering a faster-acting alternative to traditional SSRIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity. Warner-Schmidt, J., Pittenger, C., Stogniew, M., et al.[2023]

MDMA-assisted psychotherapy has received Breakthrough Therapy Designation from the FDA for treating PTSD, showing a large effect size in pooled analyses, which suggests it may be significantly more effective than traditional medications like paroxetine and sertraline.

The treatment involves MDMA administered in a controlled setting with psychotherapy, resulting in lower dropout rates and minimal risks of overdose or withdrawal symptoms, indicating a safer profile compared to conventional pharmacotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Feduccia, AA., Jerome, L., Yazar-Klosinski, B., et al.[2023]

Selective serotonin reuptake inhibitors (SSRIs) like sertraline and paroxetine are the most effective first-line treatments for PTSD, showing significant efficacy in short-term trials (6-12 weeks) and reducing relapse rates with continued treatment for 6-12 months.

If SSRIs are not effective, alternative treatments such as serotonin-potentiating non-SSRIs and atypical antipsychotics can be considered, with the latter showing promise in managing symptoms like paranoia and flashbacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SSRIs versus non-SSRIs in post-traumatic stress disorder: an update with recommendations. Asnis, GM., Kohn, SR., Henderson, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05741710?intr=Methylone&rank=4

NCT05741710 | A Study to Assess the Use of Methylone in ... This study is evaluating the safety, tolerability, and efficacy of methylone in adults with PTSD. The study will be conducted in two parts. ... Eligible ...

2. transcendtherapeutics.com transcendtherapeutics.com/new-data-demonstrating-the-mechanism-of-action-of-tsnd-201-methylone-for-the-treatment-of-ptsd-published-in-neuropsychopharmacology/

New Data Demonstrating the Mechanism of Action ... The study, published in Neuropsychopharmacology, demonstrated that acute dosing of TSND-201 promotes rapid neuronal growth and long-lasting ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584624002690

Methylone regulates fear memory and amygdala activity Methylone regulates both recent and remote extinction memories. Methylone inhibits the renewal, spontaneous recover, and fear generalization.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10882719/

Methylone is a rapid-acting neuroplastogen with less off-target ... Methylone also showed a rapid and robust improvement in fear extinction in a mouse model of PTSD which was also not attributed to locomotor ...

5. nature.com nature.com/articles/s41386-025-02206-z

Methylone promotes neurite outgrowth and has long ... Methylone has been well-tolerated in multiple human studies [6,7,8,9,10] and demonstrated rapid, robust, and long-lasting beneficial effects in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06215261

Study Details | NCT06215261 | An Evaluation of the Safety ... The total score ranges from 0 to 80, with a higher score indicating more severe PTSD symptoms. 9 weeks (Part A) / 12 weeks (Part B). Change from Baseline in ...

7. empr.com empr.com/news/methylone-designated-breakthrough-therapy-for-ptsd/

Methylone Designated Breakthrough Therapy for PTSD Loss of PTSD diagnosis: 60.7% vs 30.8% (P =.014). Regarding safety, the most common adverse reactions reported with TSND-201 were headache, ...

8. anncaserep.com anncaserep.com/open-access/clinical-evidence-for-the-use-of-methylone-in-the-treatment-8922.pdf

Clinical Evidence for the Use of Methylone in the Treatment ... It has been used outside of medical settings to treat Posttraumatic Stress Disorder (PTSD) and depression with encouraging preliminary clinical ...