Characterization of the Analgesic Effect of CBD in Healthy, Normal Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Characterization of the Analgesic Effect of CBD in Healthy, Normal Volunteers (NCT02751359), a randomized phase 1, phase 2 study. The primary outcome is Analgesia: Change From Baseline in Pain Tolerance and Threshold as Measured by the Cold Pressor Test.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled study in healthy, normal volunteers. It lists the study as Phase 1 and Phase 2, with a single-group model and enrollment of 18. The study status is completed. The listed start was 2016-07, and primary completion was 2017-07. The sponsor was the University of California, Los Angeles.

The arm descriptions indicate a repeated-dose schedule: each participant was to receive each active CBD dose, 200, 400, and 800 mg, on three of four study days, and placebo cannabidiol (0 mg) on one of four days. This schedule means the record describes measurements under multiple dose conditions within participants. However, the listed single-group model does not explain how the study was analyzed or how the randomized schedule was organized. The order of doses, allocation sequence, and any washout interval are not reported in the registry record.

Randomization can help prevent systematic differences in treatment assignment, while double blinding can reduce the influence of treatment expectations on participants’ reports and study procedures. Those are general design considerations; the record does not give details on the randomization or masking procedures. It also does not report a protocol-level statistical plan, the planned sample-size justification, or interim analyses. Although the record lists two outcome measures and one secondary outcome, it lists no analyses. The registry record therefore describes the planned study structure more fully than it documents the statistical comparison or the numerical primary findings.

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

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.

Population: Demographics were collected for study completers

6. Primary Endpoint

The registry lists the primary outcome as Analgesia: Change From Baseline in Pain Tolerance and Threshold as Measured by the Cold Pressor Test, measured over Baseline, 60 minutes, 120 minutes 180 minutes, 240 minutes, 300 minutes and 360 minutes after each dose.

The primary outcome was titled as change from baseline in pain tolerance and threshold measured with the Cold-Pressor Test, with results expressed in seconds. Pain threshold was defined as the time until a participant first felt pain while the hand was in cold water. Pain tolerance was defined as the time until the participant withdrew the hand. These measures capture different responses: the first concerns the onset of reported pain, while the second concerns the point at which the participant stops the test.

The Cold-Pressor Test is a laboratory model of pain. The registry summary states that it was selected because it has predictive validity for the clinical use of analgesics. That rationale describes why the test was used in this study; it does not establish that a change in the test measure predicts a particular clinical outcome for an individual.

Measurements were scheduled at baseline and 60, 120, 180, 240, 300, and 360 minutes after each dose. The description says that changes in threshold from baseline were averaged across study sessions for each CBD dose. The record does not report the resulting means, standard errors, or a numerical estimate of change for either threshold or tolerance. It also does not specify a single time point as the primary comparison in the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the study as randomized and double-blind, with CBD and placebo conditions. Randomization is a general method for assigning study conditions in a way intended to limit systematic allocation differences. Blinding is a general method for reducing the influence of knowledge about treatment assignment on expectations, measurement, or reporting. The record does not describe the randomization procedure, the people who were masked, or whether masking was maintained.

What do the repeated measurements imply?

The outcome schedule includes baseline and six post-dose assessments: 60, 120, 180, 240, 300, and 360 minutes after each dose. In general, measurements from the same participant are correlated rather than independent, because they come from the same person. A statistical analysis of repeated measurements should account for that dependence. Treating every measurement as if it came from a separate participant can make uncertainty estimates misleading. The registry record does not report the model used for repeated measurements, or whether the analyses used all scheduled times or selected summaries.

The arm descriptions also indicate repeated conditions within participants: the active doses and placebo were assigned across four study days. For such a design, general analysis considerations include the ordering of conditions, possible period effects, and whether responses to an earlier dose could affect a later measurement. These are considerations rather than claims about what occurred in this study. The order of conditions, any washout period, and the methods used to address order or period effects are not reported in the registry record.

What does a mean and standard error describe?

The primary outcome specifies a mean and standard error for a continuous measure reported in seconds. A mean summarizes the central value of the measurements. The standard error describes the estimated variability of the mean across repeated samples under the assumed statistical model; it is not the same as the spread of individual measurements. A confidence interval, when reported, can communicate a range of plausible values for an estimate under the model. No primary endpoint means or standard errors are reported in the registry record, and no confidence interval is listed for the primary outcome.

Changes from baseline are often used to describe how a measure differs from its starting value. The registry description says threshold changes were averaged across study sessions for each CBD dose. General interpretation depends on how the baseline and post-dose values were paired, how the session averages were constructed, and how missing observations were handled. Those analysis details are not reported in the registry record. The record does not provide a corresponding numerical estimate for changes in tolerance.

Why can over-dispersion matter?

Over-dispersion is a general issue for count outcomes when the observed variability is greater than a statistical model assumes. It matters because a model that understates variability can give uncertainty intervals that are too narrow or tests that are too optimistic. The primary outcome in this study is continuous, measured in seconds, so over-dispersion is not the central concern for that measure. The posted adverse-event information consists of counts, but the registry record does not report a statistical model for those counts. No conclusion about over-dispersion or its handling can be drawn from the record.

How should planning calculations be read?

In general, sample-size calculations describe how many participants might be required under stated assumptions to detect a particular effect with a chosen statistical power and significance level. They are planning illustrations, not observed power and not evidence that a study did or did not detect an effect. The assumptions recorded for planning illustrations include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. The record does not report numerical planning estimates or the fractions used. Because the primary outcome effect is not reported, no numerical planning result can be interpreted from the registry record.

The record lists no analyses. It therefore does not establish which statistical test or model was used, whether results were adjusted, or whether the assumptions of an analysis were checked. These methodological details are not reported in the registry record. The descriptive methods above explain general statistical concepts; they do not fill in missing study-specific methods.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description includes two related measures, pain threshold and pain tolerance, and assessments at baseline and 60, 120, 180, 240, 300, and 360 minutes after each dose. The study also includes three active CBD doses and placebo, as well as a secondary outcome concerning subjective drug effects related to abuse liability, measured with Visual Analog Scales. These multiple measures and comparisons raise a general multiplicity question: when many statistical tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that issue.

The registry record does not report a multiplicity strategy, a hierarchy of outcomes or time points, or which contrasts were intended to be confirmatory. It also lists zero analyses and does not report primary outcome results. It is therefore not possible to tell whether any adjustment was made or how findings across doses, measures, and times were interpreted.

Missing-data handling is also not reported in the registry record. The record gives no counts of missing primary outcome measurements, reasons for missingness, or methods for including participants with incomplete measurements. In general, missing observations can affect both the estimated treatment comparison and its uncertainty, particularly when the reason data are unavailable is related to participant response or treatment condition.

The analysis populations are not reported in the registry record. It does not state which participants or observations were included in an efficacy analysis, or whether all randomized participants were analyzed according to assigned condition. The record also does not report exclusions from analysis. Without these details, the posted registration information cannot establish how the study handled multiplicity, missing measurements, or analysis-population definitions.

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 lists serious adverse-event counts and other adverse-event counts separately for each condition. For Active CBD 200 mg, 18 were listed as at risk, 0 had a serious adverse event, and 5 had another adverse event. For Active CBD 400 mg, the corresponding counts were 18, 0, and 10. For Active CBD 800 mg, they were 17, 0, and 7. For placebo, they were 18, 0, and 7. The registry lists 0 deaths in each group.

These are registry counts, not a comparison adjusted for repeated exposure or other study features. The record does not explain how adverse events were defined, whether counts represent participants or events, or how events were collected and attributed to a condition. The group-specific counts should therefore be read descriptively. Zero listed serious adverse events does not mean that no other adverse events occurred; the registry records other adverse events in each group. The serious adverse-event terms are not reported in the registry record.

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

This record describes a completed study of oral CBD and placebo in healthy, normal volunteers, using the Cold-Pressor Test to measure pain threshold and pain tolerance. It specifies active CBD doses of 200, 400, and 800 mg, and placebo cannabidiol (0 mg), across a schedule of four study days. It also describes repeated assessments after dosing and a secondary outcome concerning subjective drug effects related to abuse liability.

The record does not report the numerical primary outcome results. It therefore does not show the size or direction of changes in pain threshold or tolerance, or the precision of any CBD-versus-placebo comparison. No confidence intervals or p-values for the primary outcome are listed, and the registry lists no analyses. The data presented in the registry record cannot establish whether the outcome measures differed between study conditions.

The Cold-Pressor Test is described in the study summary as a laboratory pain model with predictive validity for clinical use of analgesics. A laboratory measure is not itself a report of a participant’s experience outside the test setting, and the record does not report clinical pain outcomes. The study population is described as healthy, normal volunteers; the record does not establish how findings would apply to other populations or settings.

The safety counts provide descriptive information about events recorded under each condition, but do not provide a formal comparison or explain event collection and attribution. The registry information is thus useful for understanding the design, outcome definitions, assessment schedule, and recorded event counts. It is not enough to determine the magnitude, uncertainty, or statistical significance of the primary outcome findings. These results and analysis details are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for its repeated-condition structure and repeated outcome assessments. The arm descriptions say that participants received each active dose on one of three of the four study days and placebo on one day. The primary outcome was assessed at several times after dosing. Such designs can produce rich within-participant data, but their analysis needs to account for repeated observations from the same participant and for the schedule of study conditions. The registry record does not report how those features were handled analytically.

The outcome also distinguishes pain threshold from pain tolerance. Threshold is the time until pain is first felt; tolerance is the time until the hand is withdrawn. These are related but not interchangeable measures. Considering both across multiple times and dose conditions creates an interpretive challenge: a clear statistical plan is needed to identify which comparisons are central and how other comparisons should be understood. That plan is not reported in the registry record.

The record illustrates why design information and results information need to be read separately. It provides details about dosing conditions, timing, and the laboratory measure, but it lists no analyses and does not report numerical primary results. Without estimates and measures of uncertainty, readers cannot assess the magnitude or precision of any observed contrast. The listed adverse-event counts add descriptive safety information, but they do not resolve the missing efficacy results or statistical methods.

These are general statistical considerations applied to the features recorded for this study. They do not imply that a particular analytic approach was used or that any particular finding occurred. The relevant results and methods are not reported in the registry record.

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 main limitation for statistical interpretation is that the registry record does not report numerical results for the primary outcome. There are no listed estimates of changes in pain threshold or tolerance, standard errors, confidence intervals, or p-values. The record lists zero analyses, so a formal statistical comparison cannot be reconstructed from the information recorded.

The design description leaves important implementation details unspecified. Although randomization and double blinding are listed, the allocation procedure and masking procedures are not reported. The dose order, any washout interval, and the handling of possible period or carryover effects are also not reported in the registry record. The single-group model designation appears alongside a repeated-dose schedule, but the record does not explain that model designation or its relationship to the analysis.

For the primary outcome, the record gives a schedule with several post-dose assessment times and says threshold changes were averaged across study sessions for each dose. It does not specify a single primary time-point comparison in the results, detail how tolerance was summarized, or explain how repeated measurements were modeled. The statistical plan, analysis populations, missing-data handling, multiplicity strategy, and sample-size justification are not reported in the registry record.

Finally, the study is described as involving healthy, normal volunteers and a laboratory pain model. The registry record does not report clinical pain outcomes or participant characteristics beyond that description. The safety entries are counts without details on event definitions or collection methods. These limits restrict what can be concluded from the registry information; they do not establish what the unreported analyses or outcomes would have shown.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Characterization of the Analgesic Effect of CBD in Healthy, Normal Volunteers — NCT02751359.
• Registry record last updated 2021-05-12; status last verified 2021-04.
• Results first posted 2021-05-12.
• 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

NCT02751359 is a completed randomized, double-blind, placebo-controlled study sponsored by the University of California, Los Angeles. It was listed as Phase 1 and Phase 2, with a single-group model and enrollment of 18. The registry lists a start of 2016-07 and primary completion of 2017-07.

The study assessed oral CBD at 200, 400, and 800 mg and placebo cannabidiol (0 mg) using the Cold-Pressor Test. The primary outcome concerned changes in pain threshold and tolerance from baseline, with repeated post-dose assessments. A secondary outcome concerned subjective drug effects related to abuse liability. Numerical primary results, statistical analyses, analysis methods, and missing-data methods are not reported in the registry record.