Mechanisms of CBD for Chronic Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mechanisms of CBD for Chronic Pain (NCT04044729), a randomized early/phase 1 study. The primary outcome is Neurochemical Brain Changes.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, parallel-group early-phase study sponsored by the University of Utah. The registry record marks the study as completed and reports enrollment of 11 participants. The listed start date is 2020-03-16, and the primary completion date is 2024-12-01. These dates describe the study record; they do not by themselves indicate when outcomes were analyzed or reported.

Participants were assigned to cannabidiol or placebo. The arm descriptions specify an oral dose once a day for five days, with pain ratings before and after dosing each day. The primary outcome description focuses on magnetic resonance spectroscopy (MRS) measures from the ACC, comparing baseline visit (day 1) with visit five (day 5). The record also lists Pain Improvement as a secondary outcome.

Of four participants assigned to cannabidiol, one did not complete the dosing visits, leaving three for analysis. Of seven assigned to placebo, one did not complete the dosing visits and one was excluded because of motion artifacts, leaving five for analysis. These details show that the numbers analyzed for the primary endpoint were smaller than the numbers assigned to the groups. The record does not state whether the analysis used an intention-to-treat, per-protocol, or other named population.

Although randomization and masking are listed, the method used to generate the allocation sequence, conceal allocation, or maintain masking is not reported in the registry record. The protocol’s sample-size justification, planned interim analyses, and detailed statistical analysis plan are also not reported in the registry record. The available description therefore supports a summary of the registered design, but not a reconstruction of all procedures used in conducting or analyzing the study.

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

Analysis population for the primary outcome, as defined in the registry: Of the four participants assigned to the Cannabidiol group, one did not complete the dosing visits, leaving three for analysis. Of the seven participants in the placebo group, one did not complete the dosing visits and one was excluded due to motion artifacts, leaving five for analysis.

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 Neurochemical Brain Changes, measured over 5 Days.

The primary endpoint is described as neurochemical brain changes measured with proton magnetic resonance spectroscopy (1H-MRS). The stated target region is the anterior cingulate cortex (ACC), and the metabolites named are glutamate and GABA. The outcome is the change in metabolite measures from Visit 1 to Visit 5, corresponding to Day 1 and Day 5. Positive values are defined as increases from Day 1 to Day 5; negative values are defined as decreases.

The registry reports concentrations in institutional units (IU), rather than absolute concentrations. Its explanation is that MRI scanner properties can vary across sessions, making absolute signal intensities difficult to convert consistently into absolute concentrations. Normalized relative signal intensities are used so that measurements can be compared across MRI sessions. This makes the outcome a relative, instrument-dependent measure rather than a direct absolute concentration.

In general, measuring change over time can describe whether a participant’s recorded signal differs between two visits. A comparison between randomized groups could then address whether the observed changes differ by assigned group, subject to the study’s analysis methods and uncertainty. The registry record does not report the numerical group means, standard deviations, confidence intervals, or a statistical test for the primary endpoint. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Consequently, the record does not offer a single numerical estimate that can be interpreted as the primary between-group effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is identified as a continuous measure summarized by a mean and standard deviation. In general, a mean describes the arithmetic center of a set of measurements. A standard deviation describes how dispersed individual measurements are around that center. The mean alone does not show how variable the measurements are, and the standard deviation alone does not describe the group’s direction of change. Both are useful for characterizing observed data, but neither supplies a between-group comparison by itself.

The registry specifies that positive values represent an increase in metabolite concentrations from Day 1 to Day 5 and negative values represent a decrease. That sign convention clarifies the direction of a reported change. It does not indicate which group had an increase or decrease, because numerical results are not reported in the registry record. A comparison of group means would be needed to describe the difference between assigned groups, and an uncertainty measure would be needed to show how precisely that difference was estimated.

What would a confidence interval add?

In general, a confidence interval gives a range of values that are compatible with the data and the method used to calculate the interval. Its width conveys precision: wider intervals generally indicate less precise estimates, while narrower intervals indicate greater precision. A confidence interval does not make an estimate certain, and it does not by itself establish a clinical interpretation. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from this record.

What does the MRS measurement represent?

The endpoint uses proton magnetic resonance spectroscopy to quantify glutamate and GABA in a voxel localized to the ACC. The record states that results are expressed in institutional units because scanner properties can vary across sessions and absolute signal intensities may not translate into absolute concentrations. In general, normalization can support comparisons of relative signals across sessions, but the resulting units should not be read as absolute biochemical concentrations. The record’s stated interpretation is relative signal change between visits.

Measurements made on different days can also vary for reasons beyond a change in the biological quantity of interest. General sources of variability can include measurement conditions and data quality. In this study, motion artifacts were specifically recorded as the reason one placebo participant was excluded from primary analysis. The registry does not describe a broader quality-control protocol or how other potential measurement issues were handled.

Why does the analysis population matter?

The numbers assigned and the numbers analyzed differ. The record states that one participant in the cannabidiol group did not complete dosing visits. In the placebo group, one participant did not complete dosing visits and one was excluded due to motion artifacts. The resulting primary analysis groups were three and five participants, respectively. In general, analyzing only participants with available measurements can yield a different estimate from an analysis that retains everyone as randomized, especially when missingness or exclusions relate to participant characteristics or outcomes. The registry does not report an imputation method, a sensitivity analysis, or an assessment of why the missing or excluded measurements occurred beyond the stated reasons.

The statistical analysis population is also not given a formal label. The registry does not say whether the primary analysis was intention-to-treat, per-protocol, or another approach. It does not report an adjusted model, covariates, assumptions, or a method for comparing groups. These details are important because they define how the recorded measurements are converted into an estimate and how uncertainty is calculated.

What does the absence of a single comparison mean?

The registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This means the record does not identify one numerical result as the complete primary comparison. In general, multiple outcomes, metabolites, or time points can create multiplicity: when many statistical comparisons are made, the chance of at least one apparently unusual result can increase. Statistical plans sometimes address this through a prespecified hierarchy or an adjustment, but the registry does not report whether any such approach was planned or used. No particular multiplicity method should be assumed.

The record reports zero analyses. It therefore does not provide the estimated effects, uncertainty measures, or test results needed to reproduce or evaluate the primary statistical analysis. The registry’s design description is informative about what the study set out to measure, but it is not a substitute for an outcome analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and names Pain Improvement as a secondary outcome. The primary outcome description covers neurochemical changes, including glutamate and GABA measures and multiple visits. The record explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It does not identify a single reported primary contrast or provide numerical results for the outcome categories.

In general, multiplicity refers to the interpretive challenge created when several outcomes, time points, or statistical comparisons are considered. The more comparisons made, the greater the possibility of finding an apparently notable result by chance if no plan accounts for the number of comparisons. A protocol may specify a primary contrast, an outcome hierarchy, or an adjustment procedure. Whether this study had such procedures is not reported in the registry record, so no multiplicity correction or testing strategy can be attributed to it.

The record gives some reasons why participants were not included in the primary analysis: one participant in each group did not complete the dosing visits, and one additional placebo participant was excluded because of motion artifacts. It does not report how missing outcome data were otherwise handled, whether any values were imputed, or whether sensitivity analyses examined the effect of missingness or exclusion. The analysis population is not identified by a formal label such as intention-to-treat.

These omissions limit the interpretation of any comparison, even if numerical values were available, because the target population and handling of unavailable measurements affect what an estimate represents. Here, the registry reports zero analyses and no numerical primary outcome results. The analysis approach, missing-data assumptions, and multiplicity procedures are not reported in the registry record.

11. 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 records zero serious adverse events among the four participants at risk in the cannabidiol group and among the seven participants at risk in the placebo group. It also records zero deaths in both groups. For other adverse events, the record lists three affected participants among four at risk in the cannabidiol group and four affected participants among seven at risk in the placebo group.

These are descriptive counts from a small study. They do not establish whether an adverse event was caused by the assigned intervention, and the counts alone do not characterize event type, timing, severity, or duration. The registry record does not list serious adverse-event terms. It does not provide a detailed breakdown of the other adverse events in the information.

In general, absence of a recorded serious event in a small study does not demonstrate that the risk is absent. Likewise, counts of other adverse events are not a formal comparative safety analysis unless the definitions, follow-up, and statistical methods are considered. These figures describe what the registry records for the groups at risk; they do not resolve the separate primary question about neurochemical changes.

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

The record establishes that a small randomized, double-masked, parallel early-phase study was conducted to examine CBD versus placebo in chronic non-cancer pain. It describes a five-day dosing schedule and an MRS-based primary outcome focused on changes in glutamate and GABA measures in the ACC between Day 1 and Day 5. It also reports that three participants assigned to cannabidiol and five assigned to placebo were included in the primary analysis.

What the record does not establish is the observed direction or size of the primary outcome changes, whether the groups differed, or how precisely any difference was estimated. Numerical endpoint results and statistical comparisons are not reported in the registry record. The listed secondary outcome, Pain Improvement, also has no numerical results in the record. A completed study designation is not evidence that a particular result was obtained.

In general, a mechanistic measurement can be useful for describing changes in a biological signal, but a change in a relative MRS measure is not automatically equivalent to a change in symptoms or a clinical benefit. The record’s institutional units are normalized relative signal intensities, not absolute concentrations. The registry description alone does not establish how a neurochemical measure relates to pain ratings or to broader clinical outcomes.

The small analysis groups and the exclusions described in the record are important context for interpreting any future estimates. With few observations, estimates can be sensitive to individual measurements, and missing or excluded data can affect what population an analysis represents. The record does not report enough analysis detail to assess those issues empirically.

Accordingly, the defensible conclusion is limited: the registry documents the study question, design, endpoint definition, participant flow, and selected safety counts. It does not report the primary or secondary outcome findings needed to judge the observed neurochemical or pain-rating patterns.

13. Why This Trial Matters Statistically

This study raises statistical questions common to early mechanistic trials. Its primary endpoint is a relative MRS measure expressed in institutional units, and the registry explicitly distinguishes those normalized signals from absolute concentrations. That distinction matters because an analysis must be interpreted according to what the instrument actually measures. A relative signal can support comparisons across sessions while still not representing an absolute biochemical quantity.

The study also illustrates why the analysis population needs to be clear. Eleven participants enrolled, while the primary outcome description reports three analyzed in the cannabidiol group and five in the placebo group. The reasons given include dosing-visit noncompletion in both groups and motion-artifact exclusion in the placebo group. Reporting both assignment and analysis numbers helps readers see that the endpoint analysis involved fewer participants than enrollment alone suggests. The record does not, however, describe a named analysis population or missing-data strategy.

Another important issue is that the primary endpoint involves multiple metabolites and visits, while the record does not reduce it to a single comparison. In general, prespecifying which contrast is primary and explaining how multiple comparisons are handled can make results easier to interpret. Those details are not reported in the registry record, and no outcome analyses are posted.

Finally, this record shows the difference between a completed study and a complete account of statistical results. Study design and safety counts are documented, but the numerical primary outcome estimates and their uncertainty are absent. For researchers, that distinction is essential: transparent endpoint definitions and participant flow are useful, but they cannot replace estimates, uncertainty intervals, and an account of the analysis used.

14. 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 most consequential limitation of the registry record is the absence of numerical primary outcome results. It describes the endpoint and the direction convention for changes, but does not report group means, standard deviations, effect estimates, confidence intervals, or p-values. The direction and precision of any comparison therefore remain unknown. The record also lists Pain Improvement as a secondary outcome without reporting its results.

The primary outcome is described across multiple categories or time points and is not reduced to one comparison. The record does not state which contrast, if any, was treated as the principal statistical test. Multiplicity procedures, model choice, covariate adjustment, and assumptions are not reported in the registry record. Nor is a detailed analysis plan available in the record.

There is also a difference between enrollment and the primary analysis population. The registry reports three analyzed participants assigned to cannabidiol and five assigned to placebo, following dosing noncompletion in both groups and a motion-artifact exclusion in the placebo group. It does not report an imputation method, sensitivity analyses, or a formal analysis-population designation. These omissions make it difficult to assess how missing measurements and exclusions shaped the analysis.

The endpoint is a relative MRS measure in institutional units, not an absolute concentration. This is explained in the record, but no further information is reported about measurement reliability, quality-control procedures beyond the stated motion-artifact exclusion, or how measurement variability was handled analytically. The small numbers analyzed also mean that any estimate, if reported, would need to be read with its uncertainty and sensitivity to individual observations in mind.

Finally, safety information is limited to counts of participants with serious and other adverse events and deaths. Detailed event descriptions are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mechanisms of CBD for Chronic Pain — NCT04044729.
• Registry record last updated 2026-10-29; status last verified 2026-10.
• Results first posted 2026-10-29.
• 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.

18. Record Summary

NCT04044729, titled “Mechanisms of CBD for Chronic Pain,” is a completed, randomized, double-masked, parallel early-phase study sponsored by the University of Utah. It enrolled 11 participants and compared oral cannabidiol with oral placebo over a five-day dosing schedule for chronic non-cancer pain.

The primary outcome was change in glutamate and GABA measures in the anterior cingulate cortex, assessed by proton magnetic resonance spectroscopy from Day 1 to Day 5 and reported in institutional units. The registry reports three cannabidiol-group participants and five placebo-group participants in the primary analysis. It lists Pain Improvement as a secondary outcome.

The record reports no numerical primary or secondary outcome analyses. It records zero serious adverse events and zero deaths in each group, with other adverse events recorded for three participants in the cannabidiol group and four in the placebo group.