Dose-Response Study of MDMA-assisted Psychotherapy in People With PTSD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose-Response Study of MDMA-assisted Psychotherapy in People With PTSD (NCT01793610), a randomized phase 2 study. The primary outcome is Change in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) Total Severity Score From Baseline to One Month Post 2nd Experimental Session.

2. Clinical Question

The CAPS-IV score measures PTSD symptom severity through a structured clinician-administered interview. Its scale ranges from 0 to 136, with higher scores indicating greater severity. The reported mean changes are negative in all three arms, indicating lower mean scores at the follow-up assessment than at baseline, according to the stated change endpoint. These within-arm summaries alone do not establish whether the active-dose groups differed from the 40 mg comparator, or whether any difference can be attributed to MDMA dose rather than other aspects of care or chance.

The trial also listed six secondary outcomes covering PTSD symptoms, depression, functioning, sleep, dissociation, and posttraumatic growth. Those outcomes broaden the questions the trial was designed to explore, but their presence does not substitute for a reported analysis of the primary dose comparison.

3. Trial Design

This was a randomized, parallel-group, phase 2 pilot study. The registry labels the masking as triple, but does not identify which participant, clinician, assessor, or other roles were masked. The three Stage 1 groups received 125 mg, 100 mg, or comparator-dose 40 mg MDMA with psychotherapy. Because the comparator also received MDMA and psychotherapy, the central contrast is between dose strategies within that care context.

The registry record gives enrollment of 29 and describes the primary endpoint population as the mITT set of Stage 1 participants. The displayed arm summaries have different group sizes: 12 for the 125 mg arm, 9 for the 100 mg arm, and 6 for the 40 mg arm. These are the group sizes attached to the reported endpoint summaries; the record does not explain the relationship between enrollment and the endpoint-specific group sizes in the information.

The trial summary describes three non-drug preparatory sessions, three MDMA-assisted therapy sessions, and three non-drug integrative sessions after each MDMA-assisted session. Separately, the arm descriptions say that participants received an initial dose during each of two therapy sessions. The registry record does not reconcile these descriptions, so the session details should be read as reported rather than treated as a single fully specified schedule.

The primary endpoint was assessed from baseline to one month after the second experimental session. The study is marked completed, with start and primary completion dates of 2013-05-13 and 2015-12-03. It is identified as a pilot study; details of the sample-size justification, allocation concealment, and the operational procedures for masking are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Stage 1 Randomized, Double-blind Period

Stage 2 Open-Label Crossover Period

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat set (mITT), Stage 1 participants

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Intent-to-Treat (ITT)

6. Primary Endpoint

The registry lists the primary outcome as Change in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) Total Severity Score From Baseline to One Month Post 2nd Experimental Session, measured over Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint).

The primary endpoint is change in the Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) total severity score from baseline to one month after the second experimental session. The scale is based on a structured clinician interview and combines symptom frequency and intensity across re-experiencing, avoidance, and hypervigilance. The total severity score ranges from 0 to 136; higher scores indicate greater PTSD symptom severity.

Change scores express how the measured score at follow-up differs from baseline. Here, the posted group summaries are means with standard deviations. A negative mean change therefore represents a decrease in the score on this severity scale over the specified interval. This describes the average observed change in each arm; it does not by itself answer whether the dose groups differ beyond the variation among participants.

A clinician-administered measure is used to quantify symptoms through a structured assessment rather than relying only on an unstructured impression. The CAPS-IV is the trial’s stated primary measure, so it defines the main registered outcome for judging the dose-response question. The primary assessment time is specific: one month after the second experimental session, not an unspecified long-term follow-up. The registry record does not report a threshold for what would count as a clinically important change, or an inferential comparison of the arm means.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change summarize?

A mean change is the arithmetic average of participants’ change scores over the endpoint interval. It condenses a group’s observations into one central summary. In this study, the interval runs from baseline to one month after the second experimental session. The reported mean values are negative, consistent with a decrease in CAPS-IV severity scores on average. A mean does not describe every participant’s experience: some individual changes can be smaller, larger, or in the opposite direction while the group average remains negative.

The registry labels the summary measure as a mean and the spread measure as a standard deviation. The standard deviation describes how dispersed individual values are around the group mean. It is not the uncertainty interval for the mean and does not directly provide the uncertainty around a contrast between two arms. The reported standard deviations are 29.52, 24.22, and 21.21 for the 125 mg, 100 mg, and 40 mg groups. Their size relative to the group means is a reminder that individual change scores vary; a mean alone cannot convey that distribution in full.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of a statistical method. For a treatment comparison, an interval around the difference in mean change would show both the direction and precision of the estimated contrast. A sufficiently wide interval would signal that the data are compatible with a broad range of possible contrasts. A narrow interval would indicate greater precision, though interpretation would still depend on the clinical context and the analysis plan. The registry record does not report confidence intervals for the primary endpoint summaries or the between-arm contrasts, so that assessment is unavailable.

Why is the randomized comparison important?

Random assignment is intended to make assigned groups comparable, on average, in factors that could affect outcomes. The principal estimate of a dose effect should therefore come from a direct comparison of randomized groups, not from judging whether change within one arm differs from zero. A between-group analysis estimates how much the average change differs between assigned dose strategies. It also needs an uncertainty estimate and a clearly described analysis population. The record gives group means, standard deviations, and group sizes, but does not report the inferential analysis for the primary endpoint. The available summaries consequently support description of the arms, not a formal claim of a dose difference.

The comparator was 40 mg MDMA-assisted psychotherapy. A contrast with this group estimates differences relative to that active-dose psychotherapy condition. It does not isolate the effect of psychotherapy from MDMA, or the combined program from no treatment. The specific treatment contrast determines what conclusions a randomized comparison can support.

What does the sample-size illustration represent?

In general, a planning sample size estimates how many participants might be needed for a future study to detect a chosen effect under specified assumptions. The registry’s sample-size material describes a planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; it considers effects defined as fractions of the observed effect. Such calculations are planning scenarios, not observed power, and they do not describe the probability that this completed trial detected an effect. They also do not establish the sample-size justification used when this trial was designed. That justification is not reported in the registry record.

For the primary continuous endpoint, the record indicates that values are missing or not estimable for a two-arm comparison. As a result, the planning illustration does not supply a usable sample-size estimate for that comparison in the record being summarized. No number of participants per arm should be inferred from the observed group means alone. Any planning result would depend on assumptions about the target contrast, variability, analysis method, and design. These assumptions are not interchangeable with the observed results.

What is not available about the analysis?

The primary result is presented as a continuous outcome summarized by means and standard deviations. The record does not report the statistical model, covariate adjustment, handling of repeated measurements, or a test statistic for comparing arms. It also does not report p-values or confidence intervals for the primary dose contrasts. The statistical interpretation therefore distinguishes the descriptive results from inferential conclusions, rather than recreating an analysis that the registry does not report.

In general, the choice between a simple comparison of change scores and a model adjusting for baseline can affect an estimate’s precision and sometimes its value. Repeated-measures models can use measurements over time, but their assumptions and missing-data handling need to be specified. The registry record does not provide enough information to determine which approach was used for the primary endpoint. No model should be attributed to the trial without that information.

Over-dispersion is a concept for outcomes whose variability exceeds what a chosen probability model expects. It matters when the model’s variance assumptions are too restrictive, because standard errors and tests can then be unreliable. The primary endpoint is continuous and summarized with standard deviations; the registry record does not identify an over-dispersion model or a need for one. This general concept should not be mistaken for a finding about this trial.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Active Dose 1 (125 mg) MDMA and Psychotherapy", "Active Dose 2 (100 mg) MDMA and Psychotherapy", "Comparator-dose (40 mg) MDMA and Psychotherapy")
n   <- c(12, 9, 6)
m   <- c(-26.3, -24.4, -11.5)
sp  <- c(29.52, 24.22, 21.21)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Active Dose 1 (125 mg) MDMA and Psychotherapy  12  -26.300  29.520  -45.056  -7.544
CARM  Active Dose 2 (100 mg) MDMA and Psychotherapy  9  -24.400  24.220  -43.017  -5.783
CARM  Comparator-dose (40 mg) MDMA and Psychotherapy  6  -11.500  21.210  -33.759  10.759

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcomes in addition to the primary CAPS-IV endpoint. They cover PTSD symptoms, depression, global functioning, sleep quality, dissociative experiences, and posttraumatic growth. Testing several outcomes can increase the chance of apparently notable findings arising by chance if each is examined independently. In general, multiplicity can be addressed through a prespecified hierarchy, adjusted significance thresholds, or other planned methods. The registry record does not report a multiplicity strategy, so it is not possible to tell whether or how the secondary outcomes were intended to be interpreted as a family of tests.

The record indicates that zero analyses were posted for this continuous endpoint. It does not provide inferential primary results or numerical results for the six secondary outcomes in the information. Their existence as registered outcomes should not be treated as evidence that an analysis was completed or that any outcome changed in a particular direction.

The primary population is described as the modified intent-to-treat set (mITT), Stage 1 participants. The record does not define the mITT inclusion rules, state how many participants in that population contributed endpoint data, or explain exclusions from the analysis. Although group sizes are attached to the endpoint summaries, the handling of participants without a measurement at the target time is not reported in the registry record.

Missing-data methods are also not reported. In general, missing outcomes can affect estimates if the likelihood or reason for missingness is related to participants’ outcomes or assigned groups. Methods such as imputation or likelihood-based analyses require assumptions that should be described. No such method or assumption can be inferred from the posted means and standard deviations. The record also does not report sensitivity analyses assessing the impact of missing measurements.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ruptured ovarian cyst (11.1%), breast cancer (11.1%), tibia fracture (11.1%).

For the Stage 1 groups, the registry reports serious adverse events affecting 0 of 13 participants in the 125 mg group, 1 of 9 in the 100 mg group, and 0 of 6 in the 40 mg comparator group. These are counts of participants affected, not a measure of the total number of events or an estimate of comparative risk. The registry also reports zero deaths in each of those Stage 1 groups.

The record lists serious-event terms including ruptured ovarian cyst, breast cancer, and tibia fracture, each with a reported frequency of 11.1%. Those entries are event-term listings; they should not be assigned to a particular randomized arm based on the information. The record does not provide enough detail to determine the event timing, clinical context, or relationship to study treatment from these summaries alone.

Other adverse events are reported separately from serious adverse events. The registry includes additional entries for open-label sessions, crossover open-label sessions, twelve-month follow-up, and SRRs. These are different reporting periods or group labels and should not be combined with Stage 1 counts. They may involve participants who also appear in other periods, and the record does not establish that these are independent groups. Serious adverse-event counts should be read as descriptive safety reporting, not as proof of safety or of a treatment-related cause.

13. What the Result Does, and Does Not, Mean

The posted primary endpoint summaries show average reductions in CAPS-IV severity scores in each of the three randomized dose groups over the specified baseline-to-follow-up interval. The mean changes are -26.3 for 125 mg, -24.4 for 100 mg, and -11.5 for 40 mg, with standard deviations of 29.52, 24.22, and 21.21. This is a descriptive account of the endpoint values recorded for the groups.

These results do not, on their own, establish that the doses differ. A formal conclusion about comparative change requires an analysis of the between-group contrast and its uncertainty. The registry record does not report a primary inferential comparison, confidence intervals, or p-values for the endpoint. It also does not provide enough detail to assess adjustment, missing-data handling, or other analysis choices. The pattern of means should therefore not be recast as proof that one dose is superior to another.

The record’s comparator is an active 40 mg MDMA-assisted psychotherapy condition. Therefore, the registered question concerns dose levels in a psychotherapy context, not MDMA versus placebo, psychotherapy versus no psychotherapy, or treatment versus no treatment. Changes within all arms can reflect the broader treatment context and other influences; the posted summaries cannot isolate those components.

The endpoint is measured one month after the second experimental session. It does not establish what happened at other times unless separate results are available. The listed secondary outcomes could address other aspects of participants’ health and functioning, but their numerical results are not reported in the record. Nor is a threshold for clinically important CAPS-IV change reported, so the magnitude of the mean changes cannot be mapped to such a threshold from this record alone.

The safety summaries describe reported serious adverse events and deaths in the listed groups and periods. They are not sufficient to determine causality or to compare safety reliably across doses. Taken together, the available record supports a description of the trial design, observed group summaries, and reported event counts. It does not support a definitive efficacy or safety conclusion.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a numerical pattern and an inferential result. The three posted CAPS-IV mean changes differ descriptively, but the registry record does not provide the direct statistical comparison needed to quantify uncertainty in those differences. Reporting group means without a contrast can invite readers to infer more than the data summary establishes.

The study also illustrates how the choice of comparator shapes interpretation. The 40 mg arm received MDMA-assisted psychotherapy, so the randomized design addresses differences among dose strategies in that setting. It does not directly answer what would happen without MDMA or without psychotherapy. Defining the estimand—the precise effect a study aims to estimate—is essential before interpreting a treatment comparison.

Unequal endpoint group sizes and sizeable standard deviations are relevant to precision. In general, variability and the amount of information in each arm influence how precisely a contrast can be estimated. Without confidence intervals or a reported analysis, the reader cannot determine whether the apparent separation in means is compatible with a range of between-group effects.

The record further shows why registered outcome lists and reported analyses should be distinguished. Six secondary outcomes are named, but numerical results and a multiplicity approach are not reported. Naming outcomes documents what the trial intended to assess; it does not demonstrate that results were analyzed or that a particular finding is robust.

Finally, the mITT label alone does not explain which observations entered the analysis or how missing outcomes were handled. Clear population definitions and missing-data methods are important for reproducibility. These reporting gaps limit the conclusions that can be drawn from a completed randomized pilot, even when its descriptive summaries are available.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to the information in this registry record. First, it gives arm-level mean changes and standard deviations but does not report an inferential analysis of the primary endpoint. There are no posted confidence intervals or p-values for the randomized dose comparisons. The descriptive differences therefore cannot be evaluated for statistical precision from this record alone.

Second, the endpoint group sizes are 12, 9, and 6, while overall enrollment is reported as 29. The registry information does not explain the difference between the enrollment figure and the endpoint group sizes, or identify how many participants were excluded or lacked endpoint data. The mITT population is named but not operationally defined.

Third, the registry record does not report the analysis model, baseline adjustment, multiplicity handling, or missing-data method. These omissions prevent assessment of whether the reported summaries correspond to the planned analysis and how sensitive conclusions might be to unobserved outcomes or analytic choices. The sample-size justification and any interim analyses are also not reported in the registry record.

Fourth, the trial is a phase 2 pilot and has limited endpoint group sizes, which constrains the amount of information available for precise dose comparisons. The record does not report a clinically important change threshold for CAPS-IV, so the clinical interpretation of the score changes cannot be anchored to such a criterion.

Finally, the registry’s summary and arm descriptions differ in how they describe the number of MDMA-assisted sessions. The record also contains safety entries from multiple periods, including open-label and follow-up periods. These should not be treated as a single set of independent groups or as directly comparable randomized Stage 1 observations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dose-Response Study of MDMA-assisted Psychotherapy in People With PTSD — NCT01793610.
• Registry record last updated 2025-06-05; status last verified 2025-05.
• Results first posted 2020-10-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01793610 is a completed randomized, triple-masked, parallel-group phase 2 pilot of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. It compares 100 mg and 125 mg MDMA-assisted psychotherapy with a 40 mg comparator condition. The primary endpoint is change in CAPS-IV total severity score from baseline to one month after the second experimental session in the Stage 1 mITT population.

Posted mean changes are -26.3, -24.4, and -11.5 for the 125 mg, 100 mg, and 40 mg groups, respectively. Standard deviations are 29.52, 24.22, and 21.21. The record does not report an inferential primary comparison, confidence intervals, or p-values. Six secondary outcomes are listed, but their numerical results are not reported in the available record. Stage 1 serious adverse events affected 0 of 13, 1 of 9, and 0 of 6 participants across the three dose groups; no deaths are reported in those groups.