This page shows what was measured, who it was measured in, and what that does not settle.
What MIDOMAFETAMINE, (R)- does in the body
Most drugs that raise serotonin block the pump that clears it away.
MDMA does something more forceful: it runs the pump backwards, so serotonin is pushed out of the nerve cell into the gap in bulk, along with noradrenaline and some dopamine. The result is a few hours of raised mood, sociability and reduced fear response, followed by depletion — the cell has emptied a store it takes days to refill. In the trials that state is used as a window in which someone can talk about a traumatic memory without the fear response that normally shuts the conversation down.
Why people take it. Nothing approved. Two completed phase 3 trials tested it, with therapy, for post-traumatic stress disorder; the FDA turned the application down and asked for another trial
What happened in people
Systolic blood pressure above 160 mmHg in 33%, heart rate above 100 in 29% and temperature above 38 °C in 19% of 166 healthy volunteers
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That the trials measured what MDMA does — both arms received the same twelve therapy sessions from therapists who could tell which arm they were in
Where it acts
Presynaptic monoamine terminals — serotonergic projections to amygdala and prefrontal cortex
Kind of result
A number that stands in for health
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
Its recorded molecular formula is C11H15NO2, weighing 193.24.
PubChem record · 1615 · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 150 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Biomarker
A biomarker is a number from a test that stands in for something about health.
A picture of it, and where the picture fails
A biomarker is like a fuel gauge.
Where that stops being true. A gauge is wired to the tank. Many biomarkers are only loosely tied to health.
What people get wrong. A better number is read as a better life. Several medicines improved a number and helped nobody.
A measurable indicator used as a substitute for a clinical outcome of interest.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 36 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Mood
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer1 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Mood
profile of mood states
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
… Waiting for a reviewer
1 registered symptom measure.
— Not recorded
Harms were not a registered measure for this goal.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
CAPS-5 total severity score change from baseline, 2 months after the last experimental session
✓ The study showed what it set out to show
Who was studied
NCT03537014 (MAPP1)
How many people
90
Study design
Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P < 0.0001, d = 0.91 (mean change -24.4 vs -13.9)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No adverse events of abuse potential, suicidality or QT prolongation reported. Participants and therapists could generally identify allocation from the acute drug effect.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule, three supervised eight-hour sessions inside a twelve-session therapy course
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
CAPS-5 total severity score change, blinded independent assessors
✓ The study showed what it set out to show
Who was studied
NCT04077437 (MAPP2)
How many people
104
Study design
Phase 3 confirmatory
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
LS mean change -23.7 (95% CI -26.94 to -20.44) vs -14.8 (95% CI -18.28 to -11.28), P < 0.001, d = 0.7
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Severe treatment-emergent adverse events in 5 of 53 on MDMA (9.4%) versus 2 of 51 on placebo (3.9%). Effect size fell from 0.91 in MAPP1 to 0.7 here.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule, three supervised eight-hour sessions inside a twelve-session therapy course
Interval reported. 95% CI -26
Written into the record, not signed off as a reviewed claim.
Cardiovascular, thermoregulatory and subjective safety parameters after single 75 mg or 125 mg doses
✓ The study showed what it set out to show
Who was studied
Pooled safety pharmacology, nine controlled crossover studies (Vizeli & Liechti)
How many people
166
Study design
Phase 1 pooled analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Systolic BP >160 mmHg in 33%, heart rate >100 bpm in 29%, temperature >38 °C in 19%; all significantly more frequent at 125 mg than 75 mg
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Adverse effects and bad subjective drug effects significantly more frequent in women. No cardiovascular or psychiatric patients were studied.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule, three supervised eight-hour sessions inside a twelve-session therapy course
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.3 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.2 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
□AnimalsNo evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
□Cells in a dishNo evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
MIDOMAFETAMINE, (R)-
What a person takes: Oral capsule, three supervised eight-hour sessions inside a twelve-session therapy course.
The measurement behind this step
In the phase 3 protocol the drug is given three times, each in an eight-hour session with two therapists present, surrounded by three preparatory and nine integrative 90-minute sessions. The product under review was explicitly a drug plus a psychological intervention, which is part of why the review was difficult: the agency was being asked to approve something it does not have a standard framework for evaluating.
Getting in
Swallowed as a capsule, with a top-up two hours later
A capsule by mouth, then usually a smaller second dose after about two hours to extend the session. Effects begin within about half an hour.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Oral 75 to 180 mg of the hydrochloride. Peak plasma concentration at roughly 2 hours. MDMA inhibits CYP2D6, the enzyme that clears it, so exposure rises more than proportionally with dose and a split regimen produces a different exposure profile from a single equivalent dose.
Carried into the nerve terminal by the transporter it targets
The molecule is not just blocking the serotonin pump — it is picked up by the pump and carried inside the cell.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
MDMA is a substrate at SERT, NET and DAT rather than a blocker, so it is translocated into the presynaptic terminal. Once inside it also disrupts the vesicular monoamine transporter, moving serotonin from vesicles into the cytoplasm.
The pump runs backwards. Instead of clearing serotonin from the gap it pours it out, along with noradrenaline and some dopamine.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Carrier-mediated efflux through SERT, NET and DAT, with relative potency serotonin > norepinephrine > dopamine. MDMA also releases oxytocin and vasopressin and is a weak 5-HT2A partial agonist. The superfusion release assay is what distinguishes this from reuptake blockade.
People report reduced defensiveness and less fear when recalling a traumatic memory, which is the state the therapy protocol is built around.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Reduced amygdala reactivity to threat cues and increased prefrontal engagement are the reported functional correlates. Whether this window is causally necessary for the clinical outcome has not been tested, because no trial has given MDMA without the therapy or the therapy without MDMA in the same design.
PTSD severity falls, and the store takes days to refill
PTSD scores measured two months later are lower than after placebo with the same therapy. In the days immediately after a session, mood is often worse — the cell has emptied a supply it has to rebuild.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Measured endpoints are CAPS-5 total severity and Sheehan Disability Scale, rated by blinded independent assessors. The subacute low-mood period reflects depletion of releasable serotonin, which recovers over days; it is dose-dependent and more frequent in women.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
profile of mood states
social network questionnaire
world health organization quality of life brief version
Measured
Things only a test, a scale or a device shows.
concentrations of mdma and metabolites
changes in blood pressure
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (31)
effect of duloxetine on the subjective response to mdma
effect of clonidine on the subjective response to mdma
subjective effect during 24 hours
effects on social cognition
emotional enhancement as determined by fmri
fmri brain activity
emg of right orbicularis oculi muscle
responses to affective touch
acute subjective effects i
acute subjective effects ii
acute subjective effects iii
multifaceted empathy test
moral inference task
zurich prosocial game
social gaze task
moral expansion task
pro social voting behavior
oxford utilitarianism scale
compassion scale
inclusion of others in the self
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
In the phase 3 trials: adults with moderate to severe PTSD, after psychiatric medication washout, receiving three preparatory and nine integrative therapy sessions around three eight-hour dosing sessions. There is no lawful medical route to it in the United States.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
NDA 215455 received a complete response letter in August 2024 with a request for an additional phase 3 trial
Ricaurte et al., Science 2002, retracted in September 2003 after the vials were found to contain methamphetamine
The MAPP2 effect size was smaller than MAPP1, the usual direction of travel on replication
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Not available
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral capsule, three supervised eight-hour sessions inside a twelve-session therapy course
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
In the phase 3 protocol the drug is given three times, each in an eight-hour session with two therapists present, surrounded by three preparatory and nine integrative 90-minute sessions.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The product under review was explicitly a drug plus a psychological intervention, which is part of why the review was difficult: the agency was being asked to approve something it does not have a standard framework for evaluating.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Acute effects last about four hours. In 166 healthy volunteers, systolic blood pressure exceeded 160 mmHg in a third, heart rate exceeded 100 in 29% and body temperature exceeded 38 °C in 19%, all dose-dependent, with adverse effects more frequent in women. The recognised acute emergencies outside a clinical setting are hyperthermia and dilutional hyponatraemia, the latter from drinking large volumes of water while vasopressin release impairs free-water excretion. A subacute low-mood period over the following days reflects depletion of releasable serotonin. Concurrent serotonergic drugs, especially MAO inhibitors, carry a serotonin-syndrome risk. Cardiovascular disease was an exclusion in every study cited here, so the risk in that group is uncharacterised.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear∅Nothing found in the sources checked
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral capsule, three supervised eight-hour sessions inside a twelve-session therapy course
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: The product under review was explicitly a drug plus a psychological intervention, which is part of why the review was difficult: the agency was being asked to approve something it does not have a standard framework for evaluating.
No source is stored against this line.
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of MIDOMAFETAMINE, (R)- studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the trials measured what MDMA does — both arms received the same twelve therapy sessions from therapists who could tell which arm they were in
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That severe dopaminergic neurotoxicity follows a recreational regimen in primates: the experiment behind that claim used methamphetamine and was retracted
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That reduced SERT binding in users establishes functional cognitive harm — the best-controlled field study found little cognitive difference
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That two positive phase 3 trials imply approvability; the FDA concluded otherwise on the application as filed
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of MIDOMAFETAMINE, (R)- are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
MAPP1: a 10.5-point CAPS-5 advantage over placebo with the same therapy
In plain words
In the first phase 3 trial, 90 people with severe PTSD got identical therapy; half also got MDMA. The MDMA group improved by about ten more points on the standard PTSD scale.
What was measured
CAPS-5 total severity change at 2 months after the last dosing session
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Randomised, double-blind, placebo-controlled, multi-site phase 3 (NCT03537014). After psychiatric medication washout, 90 participants with severe PTSD were randomised 1:1 to manualised therapy with MDMA or with placebo, each combined with three preparatory and nine integrative therapy sessions. Primary endpoint was CAPS-5 total severity at two months after the last experimental session, assessed by blinded independent assessors. Mean CAPS-5 change among completers was -24.4 (SD 11.6) with MDMA and -13.9 (SD 11.5) with placebo, P<0.0001, d=0.91. Sheehan Disability Scale change was significant at P=0.0116, d=0.43. The paper reports no adverse events of abuse potential, no suicidality signal and no QT prolongation. Comorbid dissociation, depression, alcohol and substance use history and childhood trauma were all admitted rather than excluded.
Written into the record, not signed off as a reviewed claim
MAPP2 replicated it in a more diverse sample, with a smaller effect
In plain words
The confirmatory trial found the same direction of result in 104 people, with an effect about a quarter smaller than the first trial.
What was measured
CAPS-5 total severity change, blinded independent assessors
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Multi-site, randomised, double-blind confirmatory phase 3 (NCT04077437): 53 to MDMA-assisted therapy, 51 to placebo with identical therapy. 26.9% had moderate and 73.1% severe PTSD; 26.9% identified as Hispanic or Latino and 33.7% as other than White. Least-squares mean CAPS-5 change was -23.7 (95% CI -26.94 to -20.44) with MDMA versus -14.8 (95% CI -18.28 to -11.28) with placebo, P<0.001, d=0.7 — against d=0.91 in MAPP1. Sheehan Disability Scale change was -3.3 (95% CI -4.03 to -2.60) versus -2.1 (95% CI -2.89 to -1.33), P=0.03, d=0.4. Seven participants had a severe treatment-emergent adverse event, five on MDMA (9.4%) and two on placebo (3.9%); no deaths and no serious treatment-emergent adverse events.
Written into the record, not signed off as a reviewed claim
The FDA rejected the application in August 2024 and asked for another phase 3
In plain words
Two positive phase 3 trials were not enough. The FDA issued a complete response letter, which means the application is not approvable as filed, and told the sponsor to run another trial.
What was measured
Regulatory outcome of NDA 215455
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
NDA 215455, midomafetamine (MDMA) capsules, was submitted by Lykos Therapeutics for the treatment of post-traumatic stress disorder. The Psychopharmacologic Drugs Advisory Committee met on 4 June 2024 at FDA White Oak to discuss the application and was asked to discuss the overall benefit-risk profile including potential public health impact (89 FR 38903, docket FDA-2024-N-1938). In August 2024 the FDA issued a complete response letter requiring more clinical evidence before approval and requesting an additional phase 3 trial to further explore efficacy and safety in adults with PTSD. A complete response letter is not a finding that the drug does not work; it is a finding that the application as submitted does not support approval. As of this audit no replacement phase 3 trial for the PTSD indication is registered on ClinicalTrials.gov.
Written into the record, not signed off as a reviewed claim
Ricaurte 2002 was retracted: the monkeys had been given methamphetamine
In plain words
A Science paper reported that recreational doses of MDMA destroyed dopamine neurons in primates. The lab later found the vials had been mislabelled and the animals had received methamphetamine instead. The paper was withdrawn a year later.
What was measured
That a common recreational MDMA regimen produces severe dopaminergic neurotoxicity in primates — the experiment that produced this claim was performed with a different drug
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Ricaurte et al. reported severe dopaminergic neurotoxicity in non-human primates after a dose regimen modelled on human recreational use, concluding that MDMA users might be putting themselves at risk of dopamine- or serotonin-related neuropsychiatric disorders. The paper was retracted in Science on 12 September 2003 after the authors determined that the vials used had contained methamphetamine rather than MDMA — Science's own news coverage titled the report "Paper on toxic party drug is pulled over vial mix-up". The retraction is a textbook case of a result that entered policy discussion before it entered replication: the paper appeared while MDMA scheduling legislation was under debate, and the dopaminergic finding it reported has never been reproduced with correctly labelled MDMA. It says nothing either way about the separate and much older serotonergic literature.
Written into the record, not signed off as a reviewed claim
Serotonergic neurotoxicity in humans: measured once by PET, then complicated
In plain words
A 1998 imaging study found fewer serotonin transporters in the brains of ecstasy users, in proportion to how much they had used. A carefully controlled 2011 study of users who took almost nothing else found little cognitive difference from non-users.
What was measured
Brain 5-HT transporter binding by PET, and neuropsychological performance in confound-minimised field study
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
McCann et al. imaged 14 abstinent MDMA users and 15 never-users with PET and the SERT-selective ligand [11C]McN-5652, and found decreased global and regional 5-HT transporter binding in users, correlating positively with extent of previous use. That is a real measurement in a small, self-selected, polydrug-exposed sample. Halpern et al. later compared 52 illicit ecstasy users with 59 non-users, excluding anyone with significant lifetime exposure to other illicit drugs or alcohol, restricting both groups to the same subculture, and verifying abstinence with breath, urine and hair testing; across 15 neuropsychological tests they found little evidence of decreased cognitive performance, save poorer strategic self-regulation which they noted might be pre-morbid. Their own conclusion was that the finding contrasted with many previous results including their own. Neither study settles the question; together they define its shape — reduced transporter binding is measured, functional consequence in humans is not established.
Written into the record, not signed off as a reviewed claim
Acute safety pharmacology in 166 healthy volunteers, with the numbers by dose
In plain words
Pooling nine controlled studies, a third of people given 125 mg had blood pressure over 160, and one in five ran a temperature above 38 degrees. Women had more adverse effects than men.
What was measured
Proportion of subjects exceeding blood pressure, heart rate and temperature thresholds by dose
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Vizeli and Liechti pooled nine double-blind, placebo-controlled crossover studies performed in one laboratory, 166 healthy subjects, single 75 mg or 125 mg doses. Subjective effects lasted 4.2 ± 1.3 hours (range 1.4 to 8.2). MDMA raised systolic blood pressure above 160 mmHg in 33%, heart rate above 100 beats per minute in 29% and body temperature above 38 °C in 19% of subjects, each significantly more often at 125 mg than at 75 mg. Acute and subacute adverse effects were dose-dependent and more frequent in women, as were bad subjective drug effects. No effect on liver or kidney function at end of study 29 ± 22 days later, and no serious adverse events. The authors state plainly that risk is likely higher in cardiovascular disease and remains uninvestigated in psychiatric patients.
Written into the record, not signed off as a reviewed claim
The trials measured a drug plus a therapy, and cannot say what the drug did alone
In plain words
Both arms of both phase 3 trials received the same twelve therapy sessions. That is good design for testing the package and no design at all for separating the pill from the talking.
What was measured
That the CAPS-5 separation measures the pharmacological effect of MDMA, when the trial measures a drug-and-therapy package against a therapy-and-placebo package delivered by unblinded therapists
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
MAPP1 and MAPP2 both compared manualised therapy with MDMA against manualised therapy with placebo — three preparatory sessions, three eight-hour experimental sessions and nine integrative sessions in each arm. The comparison is therefore MDMA-versus-placebo within a fixed therapy, which is the right question for a combination product and answers nothing about MDMA given without that therapy, or about the therapy given without MDMA. Because MDMA produces unmistakable acute effects, participants and therapists in the room could generally tell allocation, so the "identical therapy" was delivered by people who knew which arm they were in; the CAPS-5 was rated by independent assessors who were not, which mitigates but does not remove the problem. A JAMA Psychiatry viewpoint made the psychotherapy component itself the central question about the validity of these trials.
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What is not here
5 questions this page could not answer
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How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
How this medicine reached us — found nothing in the sources checked.
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The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
Two positive phase 3 trials, a rejected new drug application, and a retracted Science paper — the clearest example on this site of a drug whose pharmacology is settled and whose evidence base is not.
Recorded evidence blocks (9)
Q1
What did MIDOMAFETAMINE, (R)-'s largest trial (200 people) and its longest (11 years) measure?
200 people in MIDOMAFETAMINE, (R)-'s largest registered study, 11 years in its longest registered window, measuring MDMA effects on human brain function and relationship between plasma MDMA concentrations and human brain function. ClinicalTrials.gov · 2026-09-01
39 phase2, 29 phase1, 9 early phase1, 5 phase3, 4 na, 3 na or unstated; NCT01404754; 2022-08-05; no ageing endpoint recorded. Last human test completed 2025, NCT06081179.
Interpretation These counts include studies where MIDOMAFETAMINE, (R)- was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase2
39
phase1
29
early phase1
9
phase3
5
na
4
na or unstated
3
1 more recorded row
Last recorded human testNCT06081179
2025-09-22
recorded 2026-09-01 · last checked 2026-09-04
Q2
MIDOMAFETAMINE, (R)- was tested only in human — what did it show?
Interpretation MDMA effects on human brain function and relationship between plasma MDMA concentrations and human brain function. — the recorded outcome words.
Show the evidence
humanNCT01148342
biomarker; MDMA effects on human brain function and relationship between plasma MDMA concentrations and human brain function.; 86
recorded 2026-09-01 · last checked 2026-09-04
Q3
9 of MIDOMAFETAMINE, (R)-'s trials stopped: safety, accrual/recruitment, funding/business, other?
safety (1), accrual/recruitment (2), funding/business (2) and other (4): MIDOMAFETAMINE, (R)-'s stop wording, clustered. ClinicalTrials.gov · 2026-09-01
"This study was terminated after enrolling five subjects due to staff turnover and its effects on quality of data collection."; 9 of 86 registered studies
Show the evidence
Trial
NCT00402298
terminated; "This study was terminated after enrolling five subjects due to staff turnover and its effects on quality of data collection."
NCT01958593
terminated; "This pilot study was terminated early by sponsor due to insufficient rate of accrual."
NCT03752918
withdrawn; "Funding ended."
NCT04073433
withdrawn; "Funding"
NCT04454684
withdrawn; "No site was initiated."
NCT04784143
terminated; "The study was terminated early by the sponsor due to administrative, non-safety related reasons."
3 further recorded trials
NCT04968938
withdrawn; "Sponsor decided not to pursue the study. Study ended prior to study start."
NCT05173831
withdrawn; "Transfer of Sponsorship"
NCT06353282
withdrawn; "Under review with FDA"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of MIDOMAFETAMINE, (R)- used Active Placebo Dose MDMA-assisted therapy (25 mg) — over how long?
Human studies of MIDOMAFETAMINE, (R)- used "Active Placebo Dose MDMA-assisted therapy (25 mg)". ClinicalTrials.gov · 2026-09-01
8 recorded entries; human; also "Full Dose MDMA-assisted therapy (125 mg)", "Open-Label Full Dose MDMA-assisted therapy (125 mg)", "Comparator Dose (40mg) MDMA HCl"
Show the evidence
human
NCT01689740
Active Placebo Dose MDMA-assisted therapy (25 mg)
NCT01689740
Full Dose MDMA-assisted therapy (125 mg)
NCT01689740
Open-Label Full Dose MDMA-assisted therapy (125 mg)
NCT01793610
Comparator Dose (40mg) MDMA HCl
NCT01793610
Active Dose 2 (100 mg) MDMA HCl
NCT01793610
Active Dose 1 (125 mg) MDMA HCl
2 more recorded rows
humanNCT05770375
MDMA 120mg
humanNCT07494214
MDMA 125 mg
recorded 2026-09-01 · last checked 2026-09-04
Q5
Could one person measure MIDOMAFETAMINE, (R)-'s effect on effect of duloxetine on the subjective response to mdma?
Effect of duloxetine on the subjective response to mdma: measured in MIDOMAFETAMINE, (R)-'s trials.
Interpretation effect of duloxetine on the subjective response to mdma is the recorded endpoint.
Show the evidence
biomarkers
effect of duloxetine on the subjective response to mdma; 2026-09-01
effect of clonidine on the subjective response to mdma; 2026-09-01
profile of mood states; 2026-09-01
concentrations of mdma and metabolites; 2026-09-01
subjective effect during 24 hours; 2026-09-01
effects on social cognition; 2026-09-01
14 more recorded rows
biomarkers
changes in blood pressure; 2026-09-01
biomarkers
emotional enhancement as determined by fmri; 2026-09-01
biomarkers
fmri brain activity; 2026-09-01
biomarkers
emg of right orbicularis oculi muscle; 2026-09-01
biomarkers
responses to affective touch; 2026-09-01
biomarkers
acute subjective effects i; 2026-09-01
biomarkers
acute subjective effects ii; 2026-09-01
biomarkers
acute subjective effects iii; 2026-09-01
biomarkers
multifaceted empathy test; 2026-09-01
biomarkers
moral inference task; 2026-09-01
biomarkers
zurich prosocial game; 2026-09-01
biomarkers
social gaze task; 2026-09-01
biomarkers
moral expansion task; 2026-09-01
biomarkers
social network questionnaire; 2026-09-01
human trials at or under30
61
Not recorded for this substance
a recorded half-life
smallest human trial
0; NCT03752918; PHASE1; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN
Q6
Which of acute subjective effects i, acute subjective effects ii and acute subjective effects iii did MIDOMAFETAMINE, (R)-'s trials measure?
acute subjective effects i, acute subjective effects ii and acute subjective effects iii lead 36 outcome terms across MIDOMAFETAMINE, (R)-'s trials. ClinicalTrials.gov · 2026-09-01
concentrations of mdma and metabolites, subjective effect during 24 hours, effects on social cognition, changes in blood pressure, emotional enhancement as determined by fmri and fmri brain activity follow.
Show the evidence
effect of duloxetine on the subjective response to mdma
1
effect of clonidine on the subjective response to mdma
1
profile of mood states
1
concentrations of mdma and metabolites
1
subjective effect during 24 hours
1
effects on social cognition
1
14 more recorded rows
changes in blood pressure
1
emotional enhancement as determined by fmri
1
fmri brain activity
1
emg of right orbicularis oculi muscle
1
responses to affective touch
1
acute subjective effects i
1
acute subjective effects ii
1
acute subjective effects iii
1
multifaceted empathy test
1
moral inference task
1
zurich prosocial game
1
social gaze task
1
moral expansion task
1
social network questionnaire
1
recorded 2026-09-01 · last checked 2026-09-04
Q7
Which of MIDOMAFETAMINE, (R)-'s 23 ongoing trials reports first?
Area under curve from dosing time to last measurement (AUC(0-t)) - MDMA; Change from Baseline on symptoms of Post-Traumatic Stress based on the PTSD Checklist for DSM-5 (PCL-5) at Treatment Termination; latest 2030-01
Show the evidence
Trial
NCT03606538
"MDMA in Subjects With Moderate Hepatic Impairment and Subjects With Normal Hepatic Function"; n 16; "Area under curve from dosing time to last measurement (AUC(0-t)) - MDMA"; 2028-12
NCT05455996
"MDMA-Assisted Therapy for Stress Disorders in Healthcare Workers and First Responders"; n 30; "Change from Baseline on symptoms of Post-Traumatic Stress based on the PTSD Checklist for DSM-5 (PCL-5) at Treatment Termination"; 2028-06
NCT05584826
"MDMA-assisted Therapy for Adjustment Disorder (AD) in Dyads of Patients With Cancer and a Concerned Significant Other"; n 20; "To assess the effectiveness of the intervention on Adjustment Disorder and relationship functioning in patients with cancer and a CSO."; 2028-11
NCT05746572
"MDMA Plus Exposure Therapy for PTSD"; n 40; "Effect of MDMA-assisted massed exposure therapy on clinician-rated PTSD symptoms"; 2026-10-31
NCT05770375
"Tolerability of MDMA in Schizophrenia"; n 20; "Positive and Negative Syndrome Scale for Schizophrenia (PANSS): Disorganized speech."; 2028-03-01
NCT05783817
"MDMA-Assisted CBT for OCD (MDMA-CBT4OCD Study)"; n 40; "Chnage in the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS)"; 2026-12-01
14 further recorded trials
NCT05790239
"MDMA-Assisted Therapy for Veterans With Moderate to Severe Post Traumatic Stress Disorder"; n 40; "Compare changes in PTSD symptom severity in the MDMA vs active control group."; 2028-03-01
NCT05837845
"MDMA-assisted Cognitive Processing Therapy Versus Cognitive Processing Therapy for Veterans With Severe Posttraumatic Stress Disorder"; n 30; "Change in Clinician Administered PTSD Scale (CAPS-5) Total Severity Score"; 2027-12
NCT05943665
"MDMA for AUD/PTSD Comorbidity"; n 18; "Number of standard unit drinks form the TLFB"; 2026-01-30
NCT06066853
"MDMA-assisted Therapy for Fibromyalgia"; n 20; "Change in self-reported pain severity and pain interference (Brief Pain Inventory)"; 2026-12
NCT06117306
"MDMA-assisted Massed Prolonged Exposure for PTSD"; n 20; "Clinician-rated PTSD symptoms"; 2027-03
NCT06418178
"Dose Optimization of MDMA-Assisted Therapy for PTSD"; n 60; "PTSD Checklist for DSM-5 (PCL-5)"; 2029-10
NCT06683014
"MDMA in Borderline Personality Disorder"; n 10; "Change in Self-Reported Social Cognition After 1 Dose of MDMA."; 2026-09
NCT06789705
"Plasma Oxytocin Changes in Response to Low-dose MDMA vs. Placebo in Patients With Arginine Vasopressin Deficiency and Healthy Controls"; n 24; "Area under the concentration-time curve in plasma oxytocin level"; 2026-12
NCT06989957
"Psilocybin and Methylenedioxymethamphetamine (MDMA) for Post-traumatic Stress Disorder (PTSD)"; n 40; "Incidence of Adverse Events"; 2029-08
NCT07102576
"MDMA-Assisted Therapy for Mental Healthcare Providers"; n 30; "Mental Health Continuum-Short Form (MHC-SF)"; 2029-12-21
NCT07288151
"MDMA-Assisted Massed Exposure Therapy for PTSD"; n 200; "Changes in PTSD symptoms measured by CAPS-5-R"; 2030-01
NCT07301632
"Ecstasy to Alleviate SEvere Chronic Neuropathic Pain Trial"; n 50; "The primary outcome of this pilot trial is to determine feasibility of a large-scale, multi-center trial."; 2028-12-01
NCT07303907
"A Phase 2A Trial of DT402 for Autism Spectrum Disorder"; n 20; "Change from Baseline in 11-point Numerical Rating Scale (NRS) scores"; 2027-08
NCT07469098
"Group vs Individual MDMA-Assisted Therapy for PTSD After the October 7, 2023 Events"; n 168; "Change in PTSD symptoms as measured by CAPS-5"; 2029-03-31
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which 26 trials of MIDOMAFETAMINE, (R)- posted no result?
Posted no result
26 of 26 completed trials
Registrations
NCT00895804, NCT00886886, NCT00990067, NCT01136278, NCT01270672 and NCT01447472, and 20 more
Completion dates
oldest 2002-03; newest 2024-07-15
Show the evidence
Trial
NCT00895804
2002-03
NCT00886886
2010-03
NCT00990067
2010-05
NCT01136278
2010-12
NCT01270672
2011-05
NCT01447472
2011-05
14 further recorded trials
NCT01386177
2012-01
NCT01148342
2012-07-18
NCT01465685
2013-01
NCT01616407
2013-04
NCT01771874
2013-09
NCT01951508
2014-12
NCT02232789
2014-12
NCT02102802
2015-08-03
NCT03019822
2018-09-04
NCT03181763
2020-08-01
NCT03527316
2020-12-24
NCT05123716
2022-05-01
NCT01404754
2022-08-05
NCT04516902
2022-08-22
Q9
At the median, MIDOMAFETAMINE, (R)-'s trials enrolled 23 people — anything larger?
Median enrolment
23
Largest enrolment
200
Registered trials counted
85
Where it is registeredIdentifiers, relations and other names
ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · derived from this page's own recorded fields; no external licence
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 4 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.