Methylone for PTSD
(IMPACT-2 Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Transcend Therapeutics
Disqualifiers: Other DSM-5 disorders, Cardiovascular, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
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.
12345Is 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.
13678How 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.
1691011Eligibility 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
I have tried at least one treatment for PTSD that didn't work.
You do not have any other important health problems.
I have been diagnosed with severe PTSD for at least 6 months.
+2 more
Trial 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)
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: TSND-201 Mid DoseExperimental Treatment1 Intervention
Part B only
Group II: TSND-201 Low DoseExperimental Treatment1 Intervention
Part B only
Group III: TSND-201 High DoseExperimental Treatment1 Intervention
Part B only
Methylone is already approved in Australia, United Kingdom, United States for the following indications:
🇦🇺 Approved in Australia as Methylone for:
- None (Scheduled as a controlled substance)
🇬🇧 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Segal TrialsLauderhill, FL
CNS HealthcareOrlando, FL
Uptown Clinical ResearchChicago, IL
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Who Is Running the Clinical Trial?
Transcend TherapeuticsLead Sponsor
References
Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity. [2023]Label="Introduction" NlmCategory="UNASSIGNED">Selective serotonin reuptake inhibitor (SSRI) antidepressants represent first-line pharmacological treatment for a variety of neuropsychiatric illnesses, including major depressive disorder (MDD), anxiety, and post-traumatic stress disorder (PTSD), which show high rates of comorbidity. SSRIs have a delayed onset of action. Most patients do not show significant effects until 4-8 weeks of continuous treatment, have impairing side effects and as many as 40% of patients do not respond. Methylone (3,4-methylenedioxy-N-methylcathinone; MDMC, βk-MDMA, M1) is a rapid-acting entactogen that showed significant benefit in a clinical case series of PTSD patients and was well-tolerated in two Phase 1 studies of healthy volunteers. Based on these early observations in humans, in the current study we tested the hypothesis that methylone has antidepressant-like and anxiolytic effects in preclinical tests.
The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. [2015]Prior to 1985, ±3,4-methylenedioxymethamphetamine (MDMA) was readily used as a psychotherapeutic adjunct. As MDMA became popular in treating various psychiatric illnesses by mental health professionals, the public started to abuse the MDMA-containing recreational drug "ecstasy." This alarmed the DEA, which led to emergency scheduling of MDMA as a Schedule I drug. Due to its scheduling in 1985, human research and clinical use has been limited. The majority of research on MDMA has been focused on the drug's potential harmful effects rather than its possible therapeutic effects. The limitations on retrospective human studies and preclinical animal models of MDMA neurotoxicity are examined in this analysis. New research has shown that MDMA, used as a catalyst in psychotherapy, is effective in treating posttraumatic stress disorder (PTSD). This review also examines the psychopharmacological basis for the efficacy of MDMA-assisted psychotherapy. Specifically, the brain regions involved with both PTSD and those activated by MDMA (i.e., amygdala, anterior cingulate cortex, and hippocampus) are examined. Also, the possible neurochemical mechanisms involved in MDMA's efficacy in treating PTSD are reviewed.
Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. [2020]Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for Psychedelic Studies (MAPS) obtained Breakthrough Therapy Designation (BTD) from the FDA for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD on the basis of pooled analyses showing a large effect size for this treatment. This review covers data supporting BTD. In this treatment, MDMA is administered with psychotherapy in up to three monthly 8-h sessions. Participants are prepared for these sessions beforehand, and process material arising from the sessions in follow-up integrative psychotherapy sessions. Comparing data used for the approval of paroxetine and sertraline and pooled data from Phase 2 studies, MAPS demonstrated that MDMA-assisted psychotherapy constitutes a substantial improvement over available pharmacotherapies in terms of safety and efficacy. Studies of MDMA-assisted psychotherapy had lower dropout rates compared to sertraline and paroxetine trials. As MDMA is only administered under direct observation during a limited number of sessions, there is little chance of diversion, accidental or intentional overdose, or withdrawal symptoms upon discontinuation. BTD status has expedited the development of MAPS phase 3 trials occurring worldwide, leading up to a planned submission seeking FDA approval in 2021. Clinical Trial Registration: www.ClinicalTrials.gov, identifiers NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.
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]Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population.
Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. [2023]Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for Psychedelic Studies (MAPS) obtained Breakthrough Therapy Designation (BTD) from the FDA for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD on the basis of pooled analyses showing a large effect size for this treatment. This review covers data supporting BTD. In this treatment, MDMA is administered with psychotherapy in up to three monthly 8-h sessions. Participants are prepared for these sessions beforehand, and process material arising from the sessions in follow-up integrative psychotherapy sessions. Comparing data used for the approval of paroxetine and sertraline and pooled data from Phase 2 studies, MAPS demonstrated that MDMA-assisted psychotherapy constitutes a substantial improvement over available pharmacotherapies in terms of safety and efficacy. Studies of MDMA-assisted psychotherapy had lower dropout rates compared to sertraline and paroxetine trials. As MDMA is only administered under direct observation during a limited number of sessions, there is little chance of diversion, accidental or intentional overdose, or withdrawal symptoms upon discontinuation. BTD status has expedited the development of MAPS phase 3 trials occurring worldwide, leading up to a planned submission seeking FDA approval in 2021. Appeared originally in Front Psychiatry 2019; 10:650.
"Being with a Buddha": A Case Report of Methoxetamine Use in a United States Veteran with PTSD. [2020]Methoxetamine (MXE) is a ketamine analogue with a high affinity for the N-methyl-D-aspartate (NMDA) receptor. MXE is a newly emerging designer drug of abuse and is widely available through on-line sources and is not detected by routine urine drug screens. In this report, we describe a United States (US) veteran with posttraumatic stress disorder (PTSD) and heavy polysubstance use, who injected high dose MXE for its calming effect. Given MXE's structural similarities to ketamine and recent work showing that ketamine reduces PTSD symptoms, we hypothesize that MXE alleviated this veteran's PTSD symptoms through action at the NMDA receptor and via influences on brain-derived neurotrophic factor (BDNF). To our knowledge, this is the first case report of self-reported use of MXE in the US veteran population. More awareness of designer drugs, such as MXE, is an important first step in engaging patients in the treatment of designer drug addiction in both military/veteran settings and civilian settings.
3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Therapy in Hawaii: A Brief Review. [2022]The Food and Drug Administration (FDA) granted breakthrough therapy status to 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) in 2017 due to preliminary evidence supporting its efficacy and safety in treating post-traumatic stress disorder (PTSD). A series of six phase-II clinical trials studying MDMA-AT for treatment-resistant PTSD found that 54% of MDMA-AT full-dose participants no longer met the diagnosis of PTSD after two MDMA sessions, compared to 23% in the control group. In the first phase-III clinical trial, 67% no longer met the criteria for PTSD after three sessions. The effects are durable, with 67% no longer diagnosable after one year and 74% at nearly four years. The MDMA-AT is being fast-tracked for potential FDA approval by 2023. In 2021, Hawaii's Senate Bill 738 unsuccessfully proposed that psilocybin be removed from the Schedule I controlled substances list due to its clinical efficacy for major depressive disorder. Methylenedioxymethamphetamine is also a Schedule I controlled substance and has proven to be a treatment option that could potentially benefit the people of Hawaii.
In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. [2021]Recent clinical studies support the use of 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct treatment for posttraumatic stress disorder (PTSD). Despite these promising findings, MDMA administration in controlled settings can increase blood pressure, heart rate, and body temperature. Previous studies indicate thatO-demethylated metabolites of MDMA contribute to its adverse effects. As such, limiting the conversion of MDMA to reactive metabolites may mitigate some of its adverse effects and potentially improve its safety profile for therapeutic use.
Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats. [2018]3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance and the β-keto analog of 3,4-methylenedioxy-N-methylamphetamine (MDMA). It is well established that MDMA metabolism produces bioactive metabolites. Here we tested the hypothesis that methylone metabolism in rats can form bioactive metabolites. First, we examined the pharmacokinetics (PKs) of methylone and its metabolites after subcutaneous (sc) methylone administration (3, 6, 12 mg/kg) to male rats fitted with intravenous (iv) catheters for repeated blood sampling. Plasma specimens were assayed by liquid chromatography tandem mass spectrometry to quantify methylone and its phase I metabolites: 3,4-methylenedioxycathinone (MDC), 3,4-dihydroxy-N-methylcathinone (HHMC), and 4-hydroxy-3-methoxy-N-methylcathinone (HMMC). The biological activity of methylone and its metabolites was then compared using in vitro transporter assays and in vivo microdialysis in rat nucleus accumbens. For the PK study, we found that methylone and MDC peaked early (Tmax=15-45 min) and were short lived (t1/2=60-90 min), while HHMC and HMMC peaked later (Tmax=60-120 min) and persisted (t1/2=120-180 min). Area-under-the-curve values for methylone and MDC were greater than dose-proportional, suggesting non-linear accumulation. Methylone produced significant locomotor activation, which was correlated with plasma methylone, MDC, and HHMC concentrations. Methylone, MDC, and HHMC were substrate-type releasers at monoamine transporters as determined in vitro, but only methylone and MDC (1, 3 mg/kg, iv) produced significant elevations in brain extracellular dopamine and 5-HT in vivo. Our findings demonstrate that methylone is extensively metabolized in rats, but MDC is the only centrally active metabolite that could contribute to overall effects of the drug in vivo.
Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats. [2020]Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused our research on pharmacokinetics, and on a detailed evaluation of temporal effects of methylone and its metabolite nor-methylone on behavior and body temperature in rats. Methylone [5, 10, 20, and 40 mg/kg subcutaneously (s.c.)] and nor-methylone (10 mg/kg s.c.) were used in adolescent male Wistar rats across three behavioral/physiological procedures and in two temporal windows from administration (15 and 60 min) in order to test: locomotor effects in the open field, sensorimotor gating in the test of prepulse inhibition (PPI), and effects on rectal temperature in individually and group-housed rats. Serum and brain pharmacokinetics after 10 mg/kg s.c. over 8 h were analyzed using liquid chromatography mass spectrometry. Serum and brain levels of methylone and nor-methylone peaked at 30 min after administration, both drugs readily penetrated the brain with serum: brain ratio 1:7.97. Methylone dose-dependently increased overall locomotion. It also decrease the amount of time spent in the center of open field arena in dose 20 mg/kg and additionally this dose induced stereotyped circling around the arena walls. The maximum of effects corresponded to the peak of its brain concentrations. Nor-methylone had approximately the same behavioral potency. Methylone also has weak potency to disturb PPI. Behavioral testing was not performed with 40 mg/kg, because it was surprisingly lethal to some animals. Methylone 10 and 20 mg/kg s.c. induced hyperthermic reaction which was more pronounced in group-housed condition relative to individually housed rats. To conclude, methylone increased exploration and/or decreased anxiety in the open field arena and with nor-methylone had short duration of action with effects typical for mixed indirect dopamine-serotonin agonists such as 3,4-metyhlenedioxymethamphetamine (MDMA) or amphetamine. Given the fact that the toxicity was even higher than the known for MDMA and that it can cause hyperthermia it possess a threat to users with the risk for serotonin syndrome especially when used in crowded conditions.
Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans. [2022]The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50-200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0-24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 h·ng/mL and T1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10-14-fold lower and an AUC0-24 value that was 21-29-fold lower. Methylone pharmacokinetics was linear across 50-200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50-200 mg.