Methylone for PTSD

(IMPACT-2 Trial)

Recruiting at 6 trial locations

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

1 Power Preferred Clinic 1 of this trial's clinic is considered top 20 on Power

Compensation: Varies

Number of Visits: 0

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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is evaluating the safety and efficacy of methylone in adults with PTSD. The study is conducted in two parts. * Part A is open-label and will enroll up to 15 participants with PTSD * Part B is randomized (1:1:1), single-blind and will enroll up to 45 participants with PTSD Eligible participants will enter a 3-week Treatment Period (Part A) or 4-week Treatment Period (Part B) where they will receive methylone once weekly. Following the Treatment Period, participants will enter a 6-week Follow-up Period (Part A) or 8-week Follow-up Period (Part B).

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.

What data supports the effectiveness of the drug Methylone for treating PTSD?

Methylone, a drug similar to MDMA, has shown rapid-acting benefits in PTSD patients and was well-tolerated in early studies. Additionally, MDMA, which is chemically related to Methylone, has demonstrated significant effectiveness in treating PTSD when used in combination with psychotherapy, suggesting potential for Methylone as well. ^{1 2 3 4 5}

Is Methylone safe for use in humans?

Methylone was well-tolerated in two Phase 1 studies with healthy volunteers, suggesting it may be generally safe for human use. ^{1 3 6 7 8}

How does the drug Methylone differ from other treatments for PTSD?

Methylone is unique because it acts rapidly compared to traditional treatments like SSRIs, which can take weeks to show effects. It is an entactogen, meaning it enhances feelings of emotional closeness, and has shown significant benefits in PTSD patients with fewer side effects in early studies. ^{1 6 9 10 11}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. [2020]

4. England 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. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

"Being with a Buddha": A Case Report of Methoxetamine Use in a United States Veteran with PTSD. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Therapy in Hawaii: A Brief Review. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans. [2022]