Visual Surround Suppression and Perceptual Expectation Under Psilocybin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Visual Surround Suppression and Perceptual Expectation Under Psilocybin (NCT04424225), a randomized phase 1 study. The primary outcome is Psychophysical Descrimination Threshold - No Surround Suppression (NS) Dose 1.

2. Clinical Question

This question concerns a narrowly defined perceptual task rather than a broad assessment of vision or psychedelic experience. A participant judged which of two visual stimuli appeared to have higher contrast; an adaptive staircase procedure was used to derive a discrimination threshold. The record also lists visual suppression and psychedelic experiences among the conditions of interest, but those labels do not establish what was measured in each outcome or how each was analyzed. The central statistical issue is therefore how much can be learned from the posted threshold summaries, given the small number of endpoint observations and the crossover design.

3. Trial Design

The registry identifies this as a Phase 1, randomized, triple-masked, crossover study sponsored by the University of Minnesota. It lists an enrollment of 10 and gives the trial status as terminated. The recorded start date is 2021-08-30, and the primary completion date is 2023-09-01. These administrative details describe the registered trial; they do not by themselves explain why the study was terminated or whether the planned study procedures were completed.

The crossover structure is reflected in two treatment sequences. One sequence began with psilocybin and then used niacin; the other began with niacin and then used psilocybin. In a crossover design, participants may contribute observations under more than one treatment condition, so results can depend on how periods, sequences, and within-participant measurements are handled. The registry does not report the washout interval, treatment doses, period structure beyond the sequence descriptions, or whether any period or carryover terms were included in the analysis.

Randomization and triple masking are recorded design features. The record does not identify which groups of people were masked or describe the randomization procedure, concealment, or how masking was maintained. It also does not report the protocol’s statistical analysis plan, a sample-size justification, or planned interim analyses. Those elements should not be inferred from the design labels.

The primary outcome record describes a mean psychophysical discrimination threshold in the no-surround-suppression condition, measured three hours after dose 1. The posted result lists three observations for each treatment label. The registry’s total enrollment and the endpoint-specific group counts are different types of information: enrollment describes the registered trial, while the result counts describe observations reported for this endpoint. The record does not explain the relationship between those figures, including whether all enrolled participants contributed usable endpoint data.

The registry lists six outcome measures and zero posted analyses. It reports no secondary outcomes in the results record. The status, limited endpoint counts, and absence of a posted statistical comparison mean that the record offers descriptive information but little documentation about the intended or completed inferential analysis.

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.

Overall Study

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 Psychophysical Descrimination Threshold - No Surround Suppression (NS) Dose 1, measured over 3 hours after dose 1.

The primary endpoint is the psychophysical discrimination threshold in the no-surround-suppression condition. Participants made perceptual judgments about which of two visual stimuli appeared to have higher contrast. An adaptive staircase technique used those responses to estimate the threshold at which contrast differences could be discriminated. The endpoint is reported in percent contrast, with the registry specifying the mean and standard deviation as its summary measures.

A threshold provides a quantitative way to describe performance on a particular perceptual task. It differs from a simple report of whether a participant noticed a stimulus: it is derived from repeated judgments and reflects the contrast level associated with discrimination under the task conditions. The no-surround-suppression label identifies the visual condition in which the task was conducted; it should not be treated as a general measure of visual function or as a direct measure of every visual effect associated with psilocybin.

Using the same task after different treatment conditions can support a comparison of measured thresholds. In a crossover study, however, interpretation also depends on the sequence and timing of measurements, and on how observations from the same participant are modeled. The registry specifies a measurement three hours after dose 1, but does not report the analytic handling of the crossover structure. It also does not report a clinical interpretation threshold for the endpoint or explain what size of threshold change would be considered important. The result therefore describes task performance in the stated units; the record alone does not establish the practical significance of any difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous endpoint summarized by its mean and standard deviation. Those summaries describe the central value and the spread of the recorded threshold observations. They are useful for understanding the measured data, but they are not by themselves a treatment-effect analysis. A comparison requires an estimate of the contrast between conditions and a measure of uncertainty that reflects the design and the observed data.

What does a confidence interval add?

In general, a confidence interval is a range of values calculated from a sample using a specified statistical method. It communicates uncertainty about an estimated quantity, such as a treatment contrast. A narrower interval indicates greater precision under the assumptions of that method; a wider interval indicates less precision. An interval does not guarantee that the true effect lies within its bounds, and its interpretation depends on the study design and analysis being appropriate.

No confidence interval for the primary treatment comparison is reported in the registry record. Therefore, the precision of that comparison cannot be assessed from an interval. The standard deviations in the result describe observed spread within the treatment-labelled groups; they are not confidence intervals and should not be read as limits on the treatment effect.

Why does the crossover design matter?

In general, a crossover design allows a participant to receive treatments in different periods, making within-participant comparisons possible. Measurements from the same person are often related. An analysis that treats every measurement as independent can misrepresent uncertainty when the data include repeated observations from the same participant. A suitable analysis ordinarily needs to reflect the pairing or repeated-measures structure, as well as relevant period and sequence features.

The registry describes randomized treatment sequences but does not report how the endpoint results were analyzed in relation to those sequences. It does not state whether the treatment comparison used first-period data only, paired measurements across periods, or a model of repeated observations. The record also does not report whether period, sequence, or carryover effects were considered. It is not possible to determine from the posted summaries whether the crossover structure was incorporated into an analysis.

How should the mean and standard deviation be read?

In general, the mean is the arithmetic average of the recorded measurements, while the standard deviation describes how dispersed those measurements are around the mean. The standard deviation is not the standard error of a treatment contrast. Nor can it be used alone to decide whether two treatment conditions differ statistically. A direct comparison needs to account for the number of observations, the relationship between observations when the design is repeated-measures, and the analysis assumptions.

The registry reports three endpoint observations under each treatment label. At such small group counts, estimates of the mean and spread can be sensitive to individual observations. The standard deviations are therefore descriptive summaries of the observed data, not stable guarantees about the variability that would be seen in a larger study. The record does not provide participant-level data or an inferential comparison with which to evaluate this uncertainty.

What would a treatment-effect estimate mean?

In general, a treatment-effect estimate expresses the contrast between conditions on the endpoint scale. For this outcome, that scale is percent contrast. An estimate would need to be accompanied by uncertainty information and interpreted according to the crossover design. The registry record does not report an estimated treatment contrast, its confidence interval, or a p-value. No recalculated treatment estimate is presented because the record does not provide the analysis details needed to reflect the crossover structure.

A p-value, when reported, describes how incompatible the observed data are with a specified null model under the assumptions of a statistical test. It does not measure the probability that a treatment works, nor does it establish the size or importance of an effect. Since no p-value or test is posted, no significance claim can be made from the registry results.

Why might variability need special treatment?

In general, over-dispersion means that observed variability is greater than a chosen statistical model expects. It matters when the model’s uncertainty estimates rely on a variance assumption that does not fit the data: standard errors and tests can then be misleading. The current endpoint is continuous and is summarized with means and standard deviations; the registry does not report a model that would permit an assessment of over-dispersion. This concept is general statistical context, not a reported finding about this trial.

Likewise, assumptions about normally distributed errors, outliers, or the shape of the measurement distribution are not described in the registry record. With few observations, such assumptions are difficult to assess from group summaries alone. The posted summaries do not reveal the individual measurements or their distribution.

What can planning calculations tell readers?

In general, sample-size calculations are planning illustrations: they estimate the number of participants needed under specified assumptions about the effect to detect, variability, allocation, significance level, and analysis method. Such calculations are not observed power and do not show that a completed trial had a particular probability of detecting an effect. The registry’s stated assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The record does not report that this illustration was the trial’s original design calculation.

Any planning estimate based on an observed effect is especially dependent on the effect estimate used and the assumptions behind the calculation. It cannot compensate for a missing treatment-effect analysis, establish the precision of the observed result, or explain the trial’s enrollment. The registry does not report a sample-size justification for the trial itself. The planning assumptions should therefore be read as illustrative rather than as evidence that the study was designed with a particular target effect or power.

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("Psilocybin", "Niacin")
n   <- c(3, 3)
m   <- c(0.4849, 0.499)
sp  <- c(0.11731, 0.04398)
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  Psilocybin  3  0.485  0.117  0.193  0.776
CARM  Niacin  3  0.499  0.044  0.390  0.608

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, but the results record reports zero secondary outcomes and zero analyses. The primary endpoint is one of the registered outcome measures; the record does not supply a statistical comparison for it. The list of outcomes alone does not indicate which measures were analyzed, which were intended as primary or secondary in the final analysis, or whether any outcomes were changed.

Multiplicity arises when several outcomes, time points, subgroups, or treatment contrasts are tested. In general, testing multiple hypotheses can increase the chance of obtaining a nominally notable result by chance, so a statistical plan may specify how that issue is handled. The registry does not report a multiplicity strategy. Because no analyses are posted, it is not possible to assess whether multiplicity was relevant to a completed analysis or how it was handled.

Missing-data methods and analysis populations are also not reported in the registry record. The result gives three observations for each treatment label, whereas overall enrollment is recorded as 10. The record does not explain whether endpoint measurements were missing, excluded, unavailable, or not part of the reported analysis, and it does not identify an intention-to-treat, per-protocol, or other analysis population. The reason the endpoint counts differ from enrollment is not reported in the registry record.

The registry does not describe how incomplete crossover periods, participant withdrawals, or unusable task measurements were handled. It also does not state whether imputation or a sensitivity analysis was used. These omissions limit assessment of possible bias: readers cannot determine whether the reported observations represent all participants who began the study or a selected subset with available measurements. The absence of this information is not evidence that missing data occurred; it means the record does not explain the analysis population or missing-data handling.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for the psilocybin group among 9 participants at risk and for the niacin group among 8 participants at risk. No serious adverse events are reported in either group. Deaths are reported as zero in both groups. The registry does not list serious adverse-event terms.

For other adverse events, the record reports that 6 participants in the psilocybin group and 5 participants in the niacin group were affected. These figures refer to participants affected, as represented in the registry, and should not be read as the total number of individual event occurrences. The number at risk for these other events is 9 for psilocybin and 8 for niacin.

These are descriptive safety counts. The at-risk denominators differ, and the record does not explain the reason. Because the design is crossover, the figures should not automatically be interpreted as independent parallel-group counts; the registry does not report how adverse events were attributed across treatment periods or participants. It also does not provide event severity details for the non-serious events, exposure timing, or a statistical comparison. The absence of reported serious events in these groups does not establish that serious events cannot occur, and the counts alone do not support a comparative safety conclusion.

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

The registry result documents a measured threshold for a visual discrimination task under a condition without surround suppression. It reports means and standard deviations under the psilocybin and niacin labels, with three observations in each group. The psilocybin mean is lower than the niacin mean, and the posted standard deviation is larger for psilocybin. This is a description of the reported sample summaries, not a conclusion that the treatments produce different effects.

The record does not report a treatment contrast, confidence interval, p-value, or model-based analysis. It therefore does not show how precise the contrast is or whether the observed difference is distinguishable from random variation. With few endpoint observations and a crossover design whose analysis is not described, the summaries are particularly limited as a basis for inference.

The endpoint measures performance on one psychophysical task at a specified time after dose 1. It does not, by itself, characterize all visual experiences, all effects of psilocybin, or outcomes outside the task. The registry’s condition labels include perception disturbance, visual suppression, and psychedelic experiences, but they do not substitute for detailed results on those concepts. No clinical importance threshold for the discrimination measure is reported.

The result also does not establish equivalence between psilocybin and niacin. A lack of a posted test or confidence interval is not evidence that there is no difference. Similarly, a difference between reported means is not proof of a treatment effect. The information supports a narrow descriptive account of recorded task measurements and leaves the statistical uncertainty and design-adjusted comparison unresolved.

Finally, the record does not explain the terminated status, the endpoint-specific counts relative to enrollment, or the handling of missing measurements. Those limits matter when considering how representative the posted observations are of the trial experience. The registry results should be interpreted as incomplete descriptive evidence rather than a definitive estimate of the treatment effect.

14. Why This Trial Matters Statistically

This study raises statistical issues that are common in early clinical research: small endpoint samples, repeated measurements, and outcomes that are specific to a task. A pilot study can be useful for documenting feasibility and generating estimates, but descriptive summaries from a small sample are imprecise. Here, the registry reports three observations under each treatment label for the primary endpoint. That makes it important to distinguish the observed group summaries from a well-supported estimate of a treatment effect.

The crossover design is central to that distinction. Because treatment sequences are registered, a comparison may need to account for repeated observations within participants, and for period and sequence structure. Yet the registry does not describe the analytic method. The same mean-and-standard-deviation display can be compatible with different underlying data structures, and the correct uncertainty calculation depends on how participants contributed measurements.

The record also illustrates why complete results reporting matters. A total enrollment figure does not explain the endpoint-specific observations, and the absence of a posted inferential analysis leaves readers without an estimate of precision. Reporting the analysis population, handling of missing data, crossover model, and treatment contrast would make the results more interpretable. Without those details, even the direction of the observed means should remain a descriptive observation rather than a substantive claim.

Statistically, the trial matters as an example of the boundary between measurement and inference. A clearly specified psychophysical threshold can quantify a particular response, but meaningful comparison requires transparent methods and uncertainty estimates that match the design. The registry record identifies the endpoint and the treatment sequence structure, while leaving these analytic questions unresolved.

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.

The endpoint-specific group counts are small, and the registry does not report participant-level observations. This prevents assessment of the distribution of thresholds, the influence of individual measurements, or whether there were outliers. The reported standard deviations provide only a limited description of spread in these small groups.

The record does not report a treatment-effect estimate, confidence interval, p-value, or analysis model. It therefore does not permit assessment of inferential precision. Although the design is described as crossover, the registry does not say whether results used paired observations, first-period data, or another approach, or whether period, sequence, or carryover effects were considered.

The endpoint is tied to a specific no-surround-suppression task and a measurement three hours after dose 1. The record does not provide a clinical interpretation threshold or explain what magnitude of threshold change would be meaningful. The results cannot be generalized from this task alone to all visual effects or experiences.

The registry reports enrollment of 10 but gives three endpoint observations for each treatment label. It does not explain the relationship between these figures, identify the analysis population, or describe missing-data handling. The reason for the terminated status is not reported in the registry record. Dose details, washout information, and details of masking and randomization are also not reported in the registry record. These trial-specific reporting gaps constrain interpretation of both the endpoint summaries and the adverse-event figures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Visual Surround Suppression and Perceptual Expectation Under Psilocybin — NCT04424225.
• Registry record last updated 2025-06-27; status last verified 2025-06.
• Results first posted 2025-06-27.
• 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

The University of Minnesota registered a Phase 1 randomized, triple-masked crossover study of psilocybin and niacin. The trial enrolled 10, began on 2021-08-30, reached primary completion on 2023-09-01, and is listed as terminated. Participants were assigned to a sequence beginning with either psilocybin or niacin.

The primary endpoint was the mean psychophysical discrimination threshold in a visual task without surround suppression, measured three hours after dose 1 and expressed in percent contrast. The posted result gives three observations per treatment label, with a mean and standard deviation for each. No inferential analysis, treatment comparison, or confidence interval is reported. The registry lists six outcome measures, zero posted analyses, and zero secondary outcomes in the results record.

Safety results report no serious adverse events or deaths in either group. Other adverse events affected 6 participants in the psilocybin group and 5 in the niacin group. The record does not explain the endpoint counts relative to enrollment, the analysis population, missing-data handling, or the reason for termination.