Dopamine Enhancement of Fear Extinction Learning in PTSD (1R21MH108753): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dopamine Enhancement of Fear Extinction Learning in PTSD (1R21MH108753) (NCT02560389), a randomized phase 4 study. The primary outcome is Galvanic Skin Response.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, quadruple-masked, parallel-group phase 4 study sponsored by the University of Wisconsin, Madison. Its status is completed. The study began in 2016-03, and primary completion was recorded as 2018-05-01. Overall enrollment was 103. The registry lists placebo and levodopa as drug interventions, with arm descriptions specifying placebo, 100mg levodopa, or 200mg levodopa, each administered once by mouth.

The primary outcome was galvanic skin response, described as a unitless mean with standard deviation. Its timeframe was within 30 days of the MRI. The registry’s description specifies differential response to a conditioned stimulus versus a control stimulus, compared at an aggregate level among the three arms. The outcome-specific posted counts are 33 for placebo, 25 for 100mg L-DOPA, and 27 for 200mg L-DOPA. These are the counts attached to the primary outcome, not a replacement for the overall enrollment figure.

Two secondary outcomes are posted: percentage change in functional activation of the amygdala and functional activation of the anterior cingulate cortex. Both have the same stated timeframe, within 30 days of the MRI. For each of these outcomes, the posted counts are 29 for placebo, 22 for 100mg L-DOPA, and 24 for 200mg L-DOPA. The record does not explain why outcome-specific counts differ from one another or from the primary outcome counts. The trial’s original sample-size assumptions, detailed eligibility criteria, allocation procedures, masking procedures, and analysis populations 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.

Before assignment: 103 participants enrolled but only 91 started in the study. 12 participants did not start in the study (6 did not show up, 3 were claustrophobic, 1 was too large to fit in MRI scanner and 2 were tested positive for having used cannabis)

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Galvanic Skin Response, measured over Within 30 days of the MRI.

Galvanic skin response is a physiological measure of changes in skin conductance. In this study, the endpoint was not described as a response to the conditioned stimulus alone: it was the differential response to a conditioned stimulus compared with a control stimulus. This contrast is intended to capture how strongly the conditioned cue elicits a response relative to the control cue. The registry specifies that the investigators would compare aggregate group results for placebo, 100mg L-DOPA, and 200mg L-DOPA.

The endpoint is relevant to the study’s stated interest in fear-extinction learning because it records a physiological response connected to the conditioned stimulus. However, the posted mean does not itself show how participants’ responses changed across the extinction-learning task, and the registry does not give further details about the task or the timing of individual measurements. The outcome is unitless, so its numerical scale does not directly translate into a clinical unit. The timeframe was within 30 days of the MRI.

The posted group means were 0.37 for placebo, 0.29 for 100mg L-DOPA, and 0.36 for 200mg L-DOPA. The standard deviations were 0.05, 0.06, and 0.05, respectively. A lower differential response is a difference in the measured endpoint, but the registry record does not establish that a lower value is necessarily better, clinically important, or evidence of improved therapy outcomes.

7. Results Posted in the Registry

• 100mg L-DOPA: mean 0.29 versus 0.37 on control; difference -0.08 (95% CI -0.11 to -0.05), standardized effect d = -1.47; z-test p = <0.001.
• 200mg L-DOPA: mean 0.36 versus 0.37 on control; difference -0.01 (95% CI -0.04 to 0.02), standardized effect d = -0.20; z-test p = 0.441.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage Change in Functional Activation of Amygdala

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 100mg L-DOPA: mean -0.06 versus -0.10 on control; difference 0.04 (95% CI 0.02 to 0.06), standardized effect d = 0.87; z-test p = 0.002.
  • 200mg L-DOPA: mean -0.05 versus -0.10 on control; difference 0.05 (95% CI 0.03 to 0.07), standardized effect d = 1.09; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 100mg L-DOPA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 200mg L-DOPA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Functional Activation of Anterior Cingulate Cortex

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 100mg L-DOPA: mean 0.09 versus 0.08 on control; difference 0.01 (95% CI -0.15 to 0.17), standardized effect d = 0.03; z-test p = 0.901.
  • 200mg L-DOPA: mean 0.07 versus 0.08 on control; difference -0.01 (95% CI -0.18 to 0.16), standardized effect d = -0.03; z-test p = 0.907.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 100mg L-DOPA and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 200mg L-DOPA and the control. The interval gives the range of effects that remain compatible with the data.

The secondary measures provide a mixed pattern across brain regions. The recalculated amygdala activation comparisons are positive relative to placebo for both levodopa groups, and both unadjusted intervals exclude zero. The anterior cingulate comparisons are close to zero, with intervals that include zero. These outcomes differ from the primary galvanic skin response measure, so their direction and uncertainty should be considered as related but not interchangeable evidence.

The amygdala results do not establish that the primary endpoint’s group difference reflects improved fear extinction, nor do they establish a clinical effect. The anterior cingulate findings do not resolve whether the primary contrast is meaningful either. The endpoints represent distinct physiological measurements, and the registry does not report a model connecting activation changes with galvanic skin response or clinical outcomes. The brief summary says that improving outcomes for people undergoing certain PTSD therapies was beyond the scope of the project.

Unadjusted secondary results carry less weight as confirmatory evidence when multiple endpoints and comparisons are examined. Without a reported multiplicity strategy, the chance of encountering apparently notable results across a collection of tests is not accounted for in the individual unadjusted p-values. The registry record lists no reported analyses for these secondary outcomes and does not report whether they were designated as confirmatory or exploratory. The results are therefore best read as descriptive and hypothesis-generating rather than as independent proof of a treatment effect.

Across the secondary measures, the more consistent pattern is in the amygdala comparisons, while the anterior cingulate estimates remain uncertain. That contrast is a description of the posted summaries, not evidence that one brain region is more clinically relevant. The record does not give thresholds for meaningful percentage changes or explain how these activation outcomes should be interpreted alongside the primary endpoint.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage Change in Functional Activation of Amygdala
• Functional Activation of Anterior Cingulate Cortex

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: the registry reports a mean and standard deviation for each arm. A mean describes the group’s average observed value. A standard deviation describes the spread of individual observations around that average. It is not the same as a standard error, which describes uncertainty in an estimated mean. The primary outcome uses standard deviations, as do the posted amygdala summaries; the anterior cingulate summaries are reported with standard errors.

What does a mean difference represent?

A mean difference compares the average outcome in one group with the average in the reference group. For the primary comparisons, placebo is the reference. The recalculated mean difference for 100mg L-DOPA is -0.08, so the posted mean is lower in that group by the direction represented by the subtraction. The corresponding difference for 200mg L-DOPA is -0.01. A difference describes the scale of the observed contrast; it does not by itself say whether that contrast matters clinically.

These comparisons are labelled recalculated because they are simple, unadjusted calculations from posted summary statistics. They are not described as the trial investigators’ fitted models. The registry record does not report a model specification, covariate adjustment, handling of repeated observations, or an overall test across the three groups. The displayed comparison estimates should therefore be read as summary-statistic comparisons, not as a reconstruction of an undocumented analysis plan.

What does a confidence interval add?

A confidence interval gives a range of values reasonably compatible with the data and the calculation method. In general, an interval that excludes zero is inconsistent with a zero mean difference at the corresponding confidence level, whereas an interval that includes zero leaves zero among the plausible differences. This is a general statistical interpretation, not a statement about clinical importance. The interval’s width also matters: narrower intervals indicate greater precision than wider intervals, all else equal.

For the primary 100mg comparison, the interval lies below zero. For the 200mg comparison, it includes zero. These interval patterns align with the reported unadjusted p-values. A p-value measures how unusual data at least as discrepant as those observed would be under a specified null model; it is not the probability that the null hypothesis is true, and it does not measure the magnitude or clinical value of an effect. The record does not state a multiplicity adjustment for these comparisons.

Why does the choice of dispersion measure matter?

Standard deviation and standard error answer different questions. The standard deviation describes variability among individual measurements. The standard error describes uncertainty in the estimated mean and depends on both variability and the amount of information contributing to that mean. Treating one as the other can misrepresent uncertainty. In particular, the anterior cingulate outcome is posted with standard errors, so its dispersion values should not be interpreted as individual-level standard deviations.

Normal-approximation planning illustrations can become especially sensitive when the observed effect is small relative to variation. A small signal relative to noise is harder to distinguish from random variation, which generally implies a need for more participants to achieve a specified power under the same assumptions. This is a general statistical principle. The unusually large planning estimates for the anterior cingulate comparisons reflect the small recalculated mean differences relative to the dispersion used for those calculations; they are hypothetical planning results, not an account of the trial’s actual design.

How should the p-values be read?

The p-values listed for comparisons are unadjusted. The primary comparison against placebo has p < 0.001 for 100mg L-DOPA and 0.441 for 200mg L-DOPA. For the secondary outcomes, the amygdala comparisons have p = 0.002 and p < 0.001, while the anterior cingulate comparisons have p = 0.901 and p = 0.907. These values do not account for the family of multiple outcomes and comparisons unless an adjustment is specified; no such adjustment is reported in the registry record.

The registry lists no reported analyses for the secondary endpoints. That absence does not establish that no analysis was conducted outside the registry; it means the record does not report one. Nor does an unadjusted comparison alone reveal whether the analysis followed a prespecified plan. The protocol’s statistical methods, handling of missing data, analysis population definitions, and treatment of multiple testing are not reported in the registry record.

What does the estimate of effect size mean?

The comparisons also include standardized effect-size values. A standardized effect expresses a mean difference relative to a measure of pooled variability, making the contrast less dependent on the original measurement scale. It is a statistical description, not a clinical threshold. A larger standardized effect does not automatically imply an important clinical outcome, and its stability depends on the estimates of both the group difference and variability. The registry does not report a clinically meaningful threshold for galvanic skin response.

In this analysis, statistical interpretation should keep the raw mean difference, uncertainty interval, p-value, and measurement context together. The primary outcome is unitless and physiological; the trial’s stated longer-term interest in therapy outcomes was beyond the scope described in the brief summary. Consequently, even a clearly nonzero group contrast cannot be translated directly into a claim about symptoms or clinical benefit.

11. Confidence Intervals and Precision

Precision is reflected in the width of a confidence interval: a narrow interval indicates that the estimate is more tightly constrained, while a wide interval allows a broader range of differences. For the primary comparison with 100mg L-DOPA, the interval excludes zero and supports a negative difference in the posted mean relative to placebo. For the 200mg comparison, the interval includes zero, so the estimated difference is less clearly distinguished from no mean difference. Neither interval alone determines clinical importance.

The primary estimates are based on outcome-specific counts of 33 for placebo, 25 for 100mg L-DOPA, and 27 for 200mg L-DOPA. The record does not explain why the endpoint counts differ from the overall enrollment or from the counts for secondary outcomes. It also does not report whether missing measurements were imputed, excluded, or handled through another method. That information matters because precision and potential bias depend on which observations enter an analysis and why others may be absent.

For the secondary outcomes, the amygdala comparison intervals are on the positive side of zero for both levodopa groups. The anterior cingulate intervals include zero for both comparisons and are wide relative to the small estimated mean differences. The posted anterior cingulate dispersion is a standard error, not a standard deviation, which is important when interpreting its uncertainty. No confidence interval can establish that the effect is clinically meaningful, and the registry record does not report clinical thresholds for these measures.

These intervals come from simple recalculations using posted summary statistics, not a reported adjusted trial model. They describe uncertainty under that calculation and do not incorporate possible uncertainty from unreported analysis choices, missing data, or multiple comparisons.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning estimates are participants per arm, not total enrollment or total events. They use the observed comparison effect as a starting point and show illustrations for planning around 100%, 75%, and 50% of that observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The trial’s own original design assumptions are not reported in the registry record; these planning assumptions are separate illustrations, not necessarily the assumptions used to design the trial.

The 80% power column gives the illustrative number of participants per arm for an analysis to have an 80% chance of detecting the assumed effect under those planning assumptions, if the effect is real and the assumptions hold. The 90% power column gives the corresponding target for a 90% chance. These are prospective planning concepts. They do not state the probability that this completed trial detected an effect, and they are not observed power.

Smaller target effects require more participants because a modest difference is harder to distinguish from random variation. For the primary comparison of 100mg L-DOPA with placebo, planning for 100% of the observed effect gives 8 participants per arm for 80% power and 10 for 90% power; planning for 50% of the observed effect gives 30 and 40. For the 200mg comparison, the corresponding values are much larger: 393 and 526 for the full observed effect, and 1,570 and 2,102 for half the observed effect. These estimates are sensitive to the observed effect and variability, so they should not be treated as fixed requirements for a future study. The planning display does not report total event targets because these are continuous outcomes.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.080; pooled standard deviation σ = 0.055.
2. n = 2 × (1.96 + 0.842)² × 0.055² / -0.080² = 7.3, rounded up to 8 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.08                      # observed difference in means
sigma <- 0.0545108115095398                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2560389)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 8 (80% power), 10 (90% power)
 75% of observed effect: n per arm = 13 (80% power), 18 (90% power)
 50% of observed effect: n per arm = 30 (80% power), 40 (90% power)
power.t.test: 8.4 
Simulated power at n = 8 per arm: 0.778 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry posts a primary outcome with comparisons of each levodopa group against placebo, as well as two secondary outcomes with comparisons against placebo. This creates multiple opportunities to observe nominally notable results. The listed p-values are unadjusted, and the record does not report a multiplicity correction, a hierarchy among tests, or a rule for selecting which result would be treated as confirmatory. Accordingly, the p-values should not be read as if they necessarily control the error rate across all outcomes and contrasts.

The registry record does not report the full statistical analysis plan, prespecification status of the comparisons, covariates, or whether an omnibus test across all arms was performed. It also does not report a direct test comparing 100mg L-DOPA with 200mg L-DOPA. The posted pairwise comparisons against placebo cannot answer that direct dose comparison by themselves.

Outcome-specific counts are not the same across measures. The reason for these differences, the amount and pattern of missing outcome data, and how missingness was handled are not reported in the registry record. No analysis-population definitions are reported, such as whether the posted summaries correspond to all randomized participants or another set. The count attached to a result should therefore be interpreted as the posted count for that outcome, not assumed to represent every randomized participant.

The record does not report whether results were adjusted for baseline values or other participant characteristics, whether repeated measurements were modeled, or whether sensitivity analyses were conducted. Without these details, it is not possible to determine how closely the simple unadjusted recalculations match the investigators’ intended inferential analysis. The recalculated estimates are useful summaries of the posted group means, but they do not fill the gaps in the registry’s reporting.

15. 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 0% reporting threshold.

The posted safety counts list zero serious adverse events, zero other adverse events, and zero deaths in the placebo group, the 100mg L-DOPA group, and the 200mg L-DOPA group. The numbers at risk for these counts are 33, 25, and 27, respectively. These figures describe the events recorded for the listed groups in the registry record.

A zero count means that no event of that category is recorded in the posted results for that group; it does not prove that the underlying risk is zero. The record does not provide event terms for non-serious events, since none are listed, and does not give further details about ascertainment, follow-up completeness, or how events were collected. These counts should not be treated as precise estimates of safety, especially without broader information on monitoring and the duration of observation. They also do not establish that the groups have equivalent safety profiles.

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

The posted primary results distinguish the 100mg L-DOPA group from placebo on the simple unadjusted mean comparison: the estimated mean difference is -0.08, its interval excludes zero, and the unadjusted p-value is p < 0.001. The 200mg L-DOPA mean is close to the placebo mean, with a difference of -0.01, an interval including zero, and an unadjusted p-value of 0.441. This is a result about the measured differential galvanic skin response, not a direct measure of PTSD symptoms or treatment success.

The registry describes a study of fear-extinction learning and cognitive effects, including an interest in whether genetic profile affects how well levodopa enhances cognitive abilities. It does not post genetic findings in the results summarized in this record. Nor does the record establish that any observed physiological difference leads to improved outcomes for people receiving PTSD therapy; the brief summary explicitly places that aim beyond the scope of the project.

A statistically distinguishable mean is not automatically clinically important. The primary measure is unitless, and no clinically meaningful threshold is reported. The direction of a difference also needs substantive interpretation: a lower differential response cannot be assumed to be beneficial based only on the registry’s outcome definition. The posted data therefore support a limited conclusion about group means, with different evidence for the two dose comparisons, rather than a broad conclusion about the treatment’s effect.

The study’s randomized and masked design is relevant to interpreting group contrasts, but details of implementation and analysis are not reported in the registry record. The simple recalculations do not adjust for multiple comparisons or establish that the posted contrasts were prespecified. The secondary outcomes provide additional physiological observations, but they do not independently establish clinical benefit. The safety counts record no events in the listed categories, yet they cannot prove that risk is absent or precisely characterize uncommon events.

17. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should start with the endpoint and its scale. A contrast in differential galvanic skin response is not equivalent to a contrast in symptoms or therapeutic outcomes. Even when an unadjusted result is statistically distinguishable from zero, its clinical interpretation depends on whether the measure has a meaningful direction and threshold. Neither is established in the registry record.

The results also show why dose groups should be considered separately rather than assuming a simple dose-response pattern. The 100mg comparison has a clear negative mean contrast with placebo in the posted summaries, while the 200mg contrast is close to zero and its interval includes zero. The registry does not report a direct comparison of the two levodopa doses, so the separate placebo comparisons do not demonstrate that the doses differ from each other.

Finally, the trial highlights the value of reporting analysis plans, missing-data handling, analysis populations, and multiplicity procedures. Those details would help readers judge how the posted estimates relate to prespecified questions and how much weight to give unadjusted secondary findings. The planning illustrations also demonstrate that sample-size projections depend strongly on the assumed effect: a smaller target effect requires more participants. These projections are not evidence about the probability that this completed trial detected an effect.

18. 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.

The registry record leaves important interpretive details unreported. It does not provide the original sample-size justification, a statistical analysis plan, the analysis populations, missing-data methods, or a multiplicity strategy. It also does not give enough detail to determine why outcome-specific counts differ or whether all randomized participants contributed to each measure. Those gaps limit assessment of how the posted summaries relate to the original protocol and intended analyses.

The primary outcome is a unitless physiological measure, and the registry does not state a clinically meaningful threshold or establish whether a lower value is favorable. The trial’s stated interest in fear-extinction learning should not be conflated with evidence about symptoms or therapy outcomes. The brief summary says that evaluating improved outcomes for people undergoing certain PTSD therapies was beyond the project’s scope.

The reported comparisons are unadjusted recalculations from summary statistics rather than reported investigator analyses. Their intervals and p-values do not account for unreported model choices or multiple testing. The secondary measures use differing dispersion descriptions, including standard deviations for amygdala activation and standard errors for anterior cingulate activation; these are not interchangeable. No genetic-profile results are posted in the record.

Safety reporting is also limited to the posted event counts. Zero recorded events in the listed categories cannot establish absence of risk, and the record does not describe event ascertainment or completeness of follow-up. These limitations do not negate the posted summaries, but they narrow the conclusions that can reasonably be drawn from them.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Dopamine Enhancement of Fear Extinction Learning in PTSD (1R21MH108753) — NCT02560389.
• Registry record last updated 2019-06-25; status last verified 2019-06.
• Results first posted 2019-06-25.
• 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.

22. Record Summary

The registry record describes a completed randomized, quadruple-masked, parallel-group phase 4 study sponsored by the University of Wisconsin, Madison, with overall enrollment of 103. The study compared placebo with single oral doses of 100mg L-DOPA and 200mg L-DOPA. Its primary endpoint was differential galvanic skin response to conditioned versus control stimuli within 30 days of the MRI.

The posted primary summary shows a lower mean for 100mg L-DOPA than placebo, with a recalculated unadjusted difference of -0.08 and p < 0.001. The 200mg comparison is -0.01, with an interval including zero and p = 0.441. Secondary brain-activation summaries show differing patterns across the amygdala and anterior cingulate cortex. Safety counts list no serious adverse events, other adverse events, or deaths in the groups. The registry does not report key analysis details, missing-data handling, multiplicity procedures, or clinical thresholds for interpreting these physiological outcomes.