Methylone for PTSD

(IMPACT-2 Trial)

Recruiting at 1 trial location

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Transcend Therapeutics

Disqualifiers: Other DSM-5 disorders, Cardiovascular, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks (Part A) / 4 weeks (Part B)

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether methylone, a potential new drug, is safe and effective for treating PTSD, a mental health condition triggered by experiencing or witnessing a traumatic event. The trial consists of two parts: Part A administers methylone to all participants, while Part B randomly assigns different doses to compare effects. It targets individuals with severe PTSD symptoms persisting for at least six months who have not found success with other treatments. Participants will receive weekly doses of methylone and be monitored for changes in their symptoms. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial mentions that the use of certain medications is prohibited, but it doesn't specify which ones. It's best to discuss your current medications with the trial team to see if they are allowed.

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 generally safe for people. Studies have found that the most common side effects include headaches, reduced appetite, nausea, dizziness, and increased blood pressure. These side effects are usually mild and manageable.

The FDA has granted methylone a Breakthrough Therapy designation for treating PTSD, indicating promise and safety based on early research. Although new treatments can carry risks, current data suggests that methylone is relatively safe for people with PTSD. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for PTSD?

Unlike the standard treatments for PTSD, which often include therapies like SSRIs and psychotherapy, methylone acts differently by targeting the brain's serotonin and dopamine systems more directly. Researchers are excited about methylone because it has the potential to induce positive mood changes and emotional processing, possibly leading to quicker and more profound relief from PTSD symptoms. The study is testing different doses to optimize the balance between efficacy and safety, which could make it a more versatile option compared to existing treatments.

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

Research has shown that methylone, also known as TSND-201, might be a promising treatment for PTSD (post-traumatic stress disorder). This trial will evaluate different doses of TSND-201—low, mid, and high—to determine its effectiveness and safety. Earlier studies suggested that methylone can work quickly, with effects that may last, helping to reduce PTSD symptoms. It changes the brain's chemical signals, potentially providing relief with fewer side effects because it doesn't involve certain serotonin receptors. While more research is needed to confirm these findings, early results are encouraging for those seeking new PTSD treatments. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with severe PTSD who have tried at least one treatment without success. They must not have other significant illnesses, meet specific criteria for PTSD lasting 6+ months, and be able to read and write well enough to complete questionnaires.

Inclusion Criteria

Have you been experiencing PTSD symptoms for at least 6 months?

Have you tried at least 1 treatment for PTSD?

Exclusion Criteria

Are you currently taking any psychiatric medications?

Have you used psychedelics in the last year?

Have you been diagnosed with Borderline Personality Disorder?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive methylone once weekly during the Treatment Period

3 weeks (Part A) / 4 weeks (Part B)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks (Part A) / 8 weeks (Part B)

What Are the Treatments Tested in This Trial?

Interventions

• Methylone

Trial Overview The study tests Methylone's safety and effectiveness in treating PTSD. It has two parts: Part A where everyone gets Methylone, and Part B which is a blind test comparing Methylone with a placebo (a dummy pill), given once weekly over three weeks.

How Is the Trial Designed?

Group I: TSND-201 Mid Dose Experimental Treatment 1 Intervention

Part B only

Group II: TSND-201 Low Dose Experimental Treatment 1 Intervention

Part B only

Group III: TSND-201 High Dose Experimental Treatment 1 Intervention

Part B only

Methylone is already approved in United Kingdom, United States for the following indications:

Approved in United Kingdom as Methylone for:

• None (Controlled under the Misuse of Drugs Act 1971)

Approved in United States as Methylone for:

• Post-traumatic stress disorder (PTSD) - Under investigation, not approved

Who Is Running the Clinical Trial?

Transcend Therapeutics

Lead Sponsor

Trials

4

Recruited

310+

Published Research Related to This Trial

MDMA, once used as a therapeutic aid before being classified as a Schedule I drug in 1985, has shown promise in treating posttraumatic stress disorder (PTSD) when used in psychotherapy, despite limited research due to its scheduling.

The review highlights the brain regions affected by both PTSD and MDMA, such as the amygdala and hippocampus, suggesting that MDMA may work through specific neurochemical mechanisms to enhance therapeutic outcomes in PTSD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. Amoroso, T.[2015]

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]

Methylone shows linear pharmacokinetics in humans, meaning that as the dose increases (from 50 to 200 mg), the plasma concentration increases proportionally, which is different from the non-linear pharmacokinetics seen with MDMA.

The study established a validated LC-MS/MS method to accurately measure methylone and its metabolites in plasma, demonstrating that methylone reaches peak concentration (Cmax) within 1.5 to 2 hours after ingestion, with a half-life (T1/2) of about 5.8 to 6.9 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans. Poyatos, L., Lo Faro, AF., Berardinelli, D., et al.[2022]

MDMA-assisted therapy (MDMA-AT) has shown significant efficacy in treating treatment-resistant PTSD, with 54% of participants no longer meeting PTSD criteria after two sessions, and 67% after three sessions in the first phase-III trial.

The positive effects of MDMA-AT appear to be long-lasting, with 67% of participants still not diagnosable with PTSD after one year and 74% after nearly four years, indicating its potential as a durable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Therapy in Hawaii: A Brief Review. Inouye, A., Wolfgang, A.[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 is extensively metabolized in rats, producing several metabolites, with 3,4-methylenedioxycathinone (MDC) being the only metabolite that significantly affects the brain's dopamine and serotonin levels, indicating its potential role in the drug's psychoactive effects.

The pharmacokinetics of methylone show that it and MDC peak quickly after administration, while other metabolites like HHMC and HMMC take longer to peak and persist longer in the system, suggesting different roles in the drug's overall effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats. Elmore, JS., Dillon-Carter, O., Partilla, JS., et al.[2018]

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]

Methylone, a synthetic drug similar to ecstasy, was found to significantly increase locomotion and induce hyperthermia in adolescent male rats, with effects peaking around 30 minutes after administration, indicating potential risks for users.

The study revealed that methylone's toxicity may be higher than that of ecstasy (MDMA), posing serious health risks such as hyperthermia and serotonin syndrome, especially in crowded environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats. Štefková, K., Židková, M., Horsley, RR., 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]

In a phase 2 trial involving 26 veterans and first responders with chronic PTSD, MDMA doses of 75 mg and 125 mg combined with psychotherapy significantly reduced PTSD symptoms compared to a 30 mg dose, with large effect sizes indicating strong efficacy.

The treatment was well tolerated, with only 5% of reported adverse events being serious, suggesting that MDMA-assisted psychotherapy is a safe option for this population when administered in a controlled setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Mithoefer, MC., Mithoefer, AT., Feduccia, AA., et al.[2019]

The deuterium-substituted form of MDMA (d2-MDMA) shows similar effectiveness to MDMA in producing desired interoceptive effects, which are important for its therapeutic use in PTSD treatment.

d2-MDMA has a reduced potential for causing hyperthermia compared to MDMA, suggesting it may have a better safety profile while maintaining therapeutic benefits, warranting further research into its cardiovascular effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. Berquist, MD., Leth-Petersen, S., Kristensen, JL., et al.[2021]

Citations

1. transcendtherapeutics.com transcendtherapeutics.com/transcend-therapeutics-presents-positive-phase-2-results-of-the-placebo-controlled-impact-1-study-of-ptsd-at-american-society-of-clinical-psychopharmacology-ascp-annual-meeting-supporting-tsnd-201-a/

Transcend Therapeutics Presents Positive Phase 2 Results ... Transcend is developing TSND-201 as a rapid-acting and durable treatment for PTSD and other central nervous system (CNS) indications.

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6435835/

A Review of 3,4-methylenedioxymethamphetamine (MDMA) This paper provides a brief review of the history, proposed pharmacological mechanisms, safety issues, and clinical applications of the medicine 3,4- ...

4. 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 ... “This publication supports a mechanism of how acute treatment with no 5HT2A receptor activity can provide rapid and long-lasting effects,” said ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06237426

Study Details | NCT06237426 | An Evaluation of the Long- ... This is an extension study of participants who previously completed a Transcend-sponsored clinical trial evaluating TSND-201 as a treatment for PTSD.

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

Study Details | NCT06215261 | An Evaluation of the Safety ... Study Overview. Brief Summary. This study is evaluating the safety and efficacy of methylone in adults with PTSD. The study is conducted ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10660711/

MDMA-Based Psychotherapy in Treatment-Resistant Post ... Abstract. Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals.

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

Methylone Designated Breakthrough Therapy for PTSD Regarding safety, the most common adverse reactions reported with TSND-201 were headache, decreased appetite, nausea, dizziness, increased blood ...