Acute and Short-term Effects of CBD on Cue-induced Craving in Drug-abstinent Heroin-dependent Humans: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acute and Short-term Effects of CBD on Cue-induced Craving in Drug-abstinent Heroin-dependent Humans (NCT02539823), a randomized phase 2 study. The primary outcome is Changes in Cue-Induced In-Clinic Craving (From Baseline to Post-cue (30 Minutes), and From Test Day 1 Through Test Day 4 (1 Week)) - Via the Visual Analog Scale for Craving (VASC).

2. Clinical Question

The study title and outcome description place the question in a controlled, in-clinic setting: after study drug administration, participants encountered cue sessions and reported craving. This is a question about measured subjective craving under those study conditions. The record does not report whether findings generalize beyond the trial setting or population.

3. Trial Design

This was a phase 2, randomized, triple-masked, parallel trial, with a recorded enrollment of 45. The three listed arms were control (placebo), CBD 400 mg, and CBD 800 mg. The record identifies randomization and triple masking but does not identify who was masked or describe the randomization procedure, allocation concealment, or how masking was maintained. Those details are not reported in the registry record.

The study concerns opiate addiction and is titled as a study of CBD and cue-induced craving in drug-abstinent people with heroin dependence. Its stated purpose was to characterize acute and short-term effects of CBD administration on cue-induced craving. The primary outcome was a continuous measure: the mean VASC score, with dispersion described as standard error. The VASC ranges from 0 for “Not Craving at All” to 10 for “Extremely Craving.” The record lists vital signs as a secondary outcome and reports 9 outcome measures overall.

The study start is recorded as 2015-09, primary completion as 2017-05-24, and status as completed. The sponsor is listed as Hurd,Yasmin, Ph.D. The registry record does not report the recruitment setting, eligibility criteria, participant characteristics, actual treatment duration, or details of the study visits beyond the primary outcome schedule.

Enrollment is not the same as a report of how many participants contributed data to each outcome analysis. The adverse-event group counts show 15 at risk in control, 14 in CBD 400mg, and 13 in CBD 800mg. Reasons for any difference between the recorded enrollment and these adverse-event counts are not reported in the registry record. Arm-level counts for the primary outcome are also not reported.

The trial's randomized, parallel structure is relevant because the arms were intended as distinct treatment groups. However, without outcome estimates, participant flow, and analysis details, the record cannot support a quantitative account of how the groups compared on craving.

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 Changes in Cue-Induced In-Clinic Craving (From Baseline to Post-cue (30 Minutes), and From Test Day 1 Through Test Day 4 (1 Week)) - Via the Visual Analog Scale for Craving (VASC), measured over VASC: test day I, II and IV - at arrival, baseline for cue 1 and 2, post-cue 1 and 2, before discharge (approximately 2.5 hours from session start on average); test day III: at arrival and discharge (approx. 2.5 hours from session start on average).

The primary endpoint is change in cue-induced in-clinic craving, assessed with the Visual Analog Scale for Craving (VASC). The instrument asks participants to rate subjective craving on a scale from 0 for “Not Craving at All” to 10 for “Extremely Craving.” The recorded outcome summary is a mean, and its stated dispersion is standard error.

The endpoint description has two related time dimensions. One is the change from baseline before a cue to the post-cue measurement, with the title specifying post-cue at 30 minutes. The other is change in cue-induced craving over the short term, from test day 1 through test day 4 a week later. Cue sessions occur consecutively within a test day, and the description says changes before and after the cues, as well as changes over the test days, were to be monitored.

The stated measurement schedule is VASC on test day I, II and IV at arrival, baseline for cue 1 and 2, post-cue 1 and 2, and before discharge, approximately 2.5 hours from session start on average. On test day III, assessments were at arrival and discharge, also approximately 2.5 hours from session start on average. The registry record does not report numerical VASC results or specify which time-point contrast was used as the definitive arm comparison.

As a subjective rating, the VASC records a participant's reported craving rather than an objective measure of drug-seeking behavior. It is used in this study to quantify the response associated with the cue sessions and to track how that response changes across the recorded assessments. That rationale describes the measurement purpose, not evidence that the measure changed in any particular direction.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: A continuous outcome such as a scale score can be summarized by its mean, which describes the center of the observed scores. The registry record identifies the primary endpoint summary as a mean. A mean alone does not describe how variable individual scores are, and it does not quantify how precisely the mean or an arm contrast has been estimated.

The endpoint lists standard error as its dispersion measure. General statistical context: Standard error describes the sampling uncertainty of an estimate, rather than the spread of individual participant measurements. It is commonly used to express how precisely a mean is estimated. The registry record does not provide the standard errors or the means for the primary outcome, so neither the observed variation nor the precision of the VASC estimates can be evaluated.

General statistical context: A confidence interval gives a range of values compatible with an estimate under a specified statistical procedure. For a treatment contrast, it can convey both the estimated direction and the uncertainty around the contrast. A p-value addresses compatibility between data and a specified null hypothesis under the analysis assumptions; it does not measure the size or clinical importance of an effect. No primary outcome confidence intervals or p-values are reported in the registry record.

Random assignment is intended to create groups that can be compared without assigning treatment according to participant characteristics. This is a general rationale for randomized designs, not a claim about the success of randomization in this trial. The record says allocation was randomized, but does not describe the sequence-generation method, allocation concealment, or baseline characteristics. Consequently, it is not possible to assess from these details whether the groups were similar on measured or unmeasured characteristics.

The design is described as triple-masked. General statistical context: Masking can reduce the risk that knowledge of assigned treatment influences care, assessment, or reporting, depending on which people are masked and how the procedures are implemented. The registry record does not identify the masked parties or describe masking procedures. The label alone does not establish how masking operated in practice.

The parallel model means the registry describes separate arms rather than a crossover sequence. General statistical context: In a parallel comparison, each participant is assigned to an arm and outcomes are compared between arms. Repeated outcome measurements within participants still require attention to the relationship among measurements from the same person. The registry record's primary outcome schedule includes multiple assessments within days and across days, but does not report the model or method used to account for those repeated measurements.

General statistical context: Over-dispersion occurs when observed variability is greater than a statistical model assumes. If present and ignored, uncertainty estimates may be too small, which can make intervals too narrow or significance tests too optimistic. This is a general issue for models of variable outcomes; the registry record does not report a model, an over-dispersion assessment, or any related adjustment. No claim can be made that over-dispersion was relevant or occurred in this trial.

The primary outcome describes several related contrasts: pre-cue to post-cue change, and change over the short-term test-day schedule. General statistical context: When an analysis considers multiple outcomes, time points, or pairwise comparisons, the chance of at least one apparently unusual result can increase if each is tested separately without adjustment. Multiplicity methods can address this, but the suitable method depends on the planned scientific question and analysis. The registry record does not report a multiplicity strategy or identify a single primary contrast within the repeated schedule.

General statistical context: Missing outcome values can reduce precision and can bias an estimate if the reasons for missingness are related to the outcome or treatment. Analysis approaches may use assumptions about why data are missing, and sensitivity analyses can examine how conclusions change under alternative assumptions. The record does not report missing-data counts, reasons for missingness, imputation, or sensitivity analyses. The number enrolled and the adverse-event at-risk counts do not establish how many participants contributed VASC measurements.

The sample-size description is explicitly a planning illustration, not the trial's original design justification. It names a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. It says non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations give total events. Numerical sample-size illustrations are not reported in the registry record. The record also does not report the original sample-size justification or the effect used in the illustration. These planning concepts should not be confused with observed power, which is not a substitute for an effect estimate and its confidence interval.

The record reports 0 analyses. Accordingly, it does not supply the primary analysis model, covariate adjustment, treatment contrast, standard error estimates, confidence intervals, p-values, or analysis population. These omissions prevent independent assessment of the statistical methods used for the primary outcome.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is described across multiple assessments: pre-cue baseline and post-cue measurements, cue sessions within test days, and changes from test day 1 through test day 4 a week later. There are also 9 outcome measures overall, with vital signs listed as a secondary outcome. Multiple measurements and outcomes can create choices about which contrasts to emphasize and whether to adjust for multiple testing. The registry record does not report a multiplicity procedure, a hierarchy of outcomes, or a specific contrast designated for confirmatory inference.

The registry record reports 0 analyses. It does not give the primary outcome analysis model, the analysis population, or details such as whether analyses followed randomized assignment. It also does not report the number of VASC observations available at each assessment or by arm. The record's enrollment figure and adverse-event at-risk counts cannot be used to infer the number included in each primary outcome analysis.

Missing-data information is not reported in the registry record. In particular, the reasons for missing VASC measurements, the handling of incomplete repeated assessments, any imputation, and any sensitivity analysis are not described. General statistical context: In repeated-measure studies, incomplete observations may affect both precision and interpretation, especially if missingness is associated with participant characteristics, treatment, or measured outcomes. Appropriate handling depends on the missingness pattern and the assumptions used, none of which are stated.

The record also does not report whether there was a prespecified statistical analysis plan, interim analyses, or stopping rules. No such procedures should be inferred from the trial's phase or design labels.

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 serious adverse-event entries show 0 affected among 15 at risk in control, 0 among 14 at risk in CBD 400mg, and 0 among 13 at risk in CBD 800mg. Deaths are recorded as 0 in each of the three groups. The registry record lists no serious adverse-event terms.

Other adverse events are recorded separately: 3 affected among 15 at risk in control, 4 among 14 at risk in CBD 400mg, and 5 among 13 at risk in CBD 800mg. These are counts, not descriptions of the events. The registry record does not report the event terms, severity breakdown beyond the serious/non-serious distinction, timing, relatedness to study treatment, or whether participants had more than one event.

General statistical context: Observing no serious events in a group does not establish that the underlying risk is zero. Rare events may not occur in a study even when a nonzero risk exists, and a small observed count leaves substantial uncertainty. Comparing safety between groups requires attention to the number at risk, follow-up, event definitions, and the precision of the estimates. The registry record does not report comparative risk estimates or confidence intervals.

These figures should therefore be read as the reported event counts for the listed groups, not as proof of an absence of risk or as a complete safety profile.

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

The registry record establishes that a randomized, triple-masked, parallel phase 2 trial was conducted with control, CBD 400 mg, and CBD 800 mg arms and recorded enrollment of 45. It identifies cue-induced in-clinic craving on the VASC as the primary outcome and describes repeated assessments across cue sessions and test days. It also reports adverse-event counts and no deaths.

What the record does not establish is the observed effect of either CBD dose on VASC scores relative to control. No arm-level primary outcome estimates, between-arm contrasts, confidence intervals, or p-values are reported. Without those quantities, the direction, magnitude, and precision of any treatment difference cannot be determined. The absence of a reported estimate is not evidence that there was no effect, nor is it evidence of an effect.

The outcome is a subjective rating collected in an in-clinic cue-session context. It concerns reported craving under the study's measurement conditions. The registry record does not provide evidence about outcomes beyond this measure, nor does it report the information needed to evaluate whether findings apply outside the enrolled population and study setting.

The safety entries report zero serious adverse events and zero deaths in each listed group, alongside non-serious event counts. These are descriptive entries. Without detailed event descriptions, follow-up information, or uncertainty estimates, they do not demonstrate that an intervention is free of harm or permit precise safety comparisons.

General statistical context: Statistical significance, if it had been reported, would not by itself establish clinical importance; interpretation would also depend on the estimated effect, its uncertainty, and the relevance of the measure. In this record, those primary outcome estimates are absent. The appropriate conclusion is limited to what the record describes about the design, outcomes, and recorded event counts, without making a treatment-effect claim.

13. Why This Trial Matters Statistically

This trial raises a statistically distinctive measurement question because craving was assessed repeatedly around cue sessions and over a short-term schedule. The endpoint is not simply a single score at one visit: the description includes pre-cue and post-cue ratings, two cue sessions within test days, and changes across test days. Such a schedule can capture several aspects of the response, but it also requires a clear analysis plan to define the main contrast and account for repeated observations.

The registry record identifies the outcome as a mean VASC score with standard error, but does not report the estimates or the analysis. This makes the distinction between a measurement plan and an inferential result especially important. A detailed schedule tells readers what investigators intended to measure; it does not tell them what the data showed, how uncertain an estimate was, or whether a particular comparison was statistically compatible with a null hypothesis.

The trial has three arms, including two CBD doses and a placebo control, and the outcome covers multiple time points. General statistical context: Multiple arms and repeated measurements can generate numerous possible comparisons. Clear prespecification and transparent reporting help readers distinguish the primary scientific question from secondary or exploratory comparisons and understand how multiplicity was addressed. Those details are not reported in the registry record.

The sample-size information also illustrates a key interpretive distinction. The record describes planning illustrations based on the observed effect, but identifies them as illustrations rather than the trial's own design. Such planning calculations concern hypothetical detection targets. They are not observed power and cannot fill the gap left by missing outcome estimates.

Statistically, the central limitation is therefore not the choice of an unfamiliar method; it is the absence of reported primary analysis results and supporting analysis details. Transparent reporting of the arm-level estimates, contrasts, uncertainty, analysis population, and handling of repeated and missing measurements would be needed for readers to evaluate the findings.

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 trial-specific limitation of the registry information is that it does not report the primary outcome results. VASC means, standard errors, arm contrasts, confidence intervals, and p-values are not reported. The number of analyses is recorded as 0. As a result, the effects and their precision cannot be assessed.

The outcome schedule includes multiple time points and cue assessments, but the registry record does not identify a single analysis contrast or report how repeated measurements were modeled. It also does not report whether multiple comparisons were adjusted. The endpoint title and detailed timeframe describe related but not identical summaries, and the registry record does not explain how these were reconciled in an analysis.

Participant characteristics, eligibility criteria, primary outcome analysis counts, and participant flow are not reported in the information available for this analysis. The total enrollment is 45, while the adverse-event group counts at risk are 15, 14, and 13. The record does not explain the relationship between those counts or indicate how many participants posted outcome data at each time point.

Details of randomization and masking are limited to the labels randomized and triple-masked. The masked parties, sequence-generation process, allocation concealment, and procedures for maintaining masking are not reported in the registry record. The record also does not report the original sample-size justification, interim analyses, or the statistical analysis plan.

Safety reporting is likewise limited: serious adverse-event counts and deaths are recorded, and other adverse-event counts are listed, but event terms and follow-up details are not reported. These gaps limit interpretation of both efficacy and safety and preclude a complete assessment of the trial's statistical conduct.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Acute and Short-term Effects of CBD on Cue-induced Craving in Drug-abstinent Heroin-dependent Humans — NCT02539823.
• Registry record last updated 2022-09-01; status last verified 2022-08.
• Results first posted 2022-09-01.
• 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

The registry record describes a completed phase 2, randomized, triple-masked, parallel trial of CBD for cue-induced craving in drug-abstinent people with heroin dependence. Recorded enrollment was 45. The arms were control (placebo), CBD 400 mg, and CBD 800 mg.

The primary outcome was mean change in in-clinic cue-induced craving measured with the VASC, a scale ranging from 0 for “Not Craving at All” to 10 for “Extremely Craving.” Assessments covered pre-cue and post-cue ratings and changes across test days. Vital signs were listed as a secondary outcome, and 9 outcome measures were recorded overall.

The registry record reports 0 analyses and does not report primary outcome estimates or their uncertainty. Serious adverse events and deaths were recorded as 0 in each listed arm; other adverse-event counts were 3, 4, and 5 for control, CBD 400mg, and CBD 800mg, respectively. Numerical primary outcome findings and further analysis details are not reported in the registry record.