Craving self-reports as outcome measures in drug addiction trials: A systematic review of ClinicalTrials.gov

Abstract

Background and aims: The subjective experience of drug craving is characterized by an overwhelming urge to consume substances. Due to strong validity and ease of use, self-report measures are widely employed to assess substance-related motivational dynamics. Multi-item questionnaires are increasingly favored for capturing the multidimensional nature of craving, providing valuable insights for clinical care and relapse prediction. This review aimed to summarize craving self-report measurement tools registered in clinical trials and examine their methodological parameters.

Methods: A search was conducted in November 2022 and updated in November 2024 using the same methodology on ClinicalTrials.gov for trials reporting drug craving as an outcome measure. Trials using craving measurement tools were screened and included.

Results: From 5383 initial trials, 1255 met eligibility criteria. Craving was reported as the only primary outcome measure in 14.6%, one of the primary outcomes in 21.3% and as secondary or exploratory in 64.1% of the studies. The most studied substances were nicotine (32.5% of studies) and alcohol (27.5%), followed by opioids (14.2%). Multi-item questionnaires were the most frequently used approach (55.4%), followed by single-item questionnaires (27.3%) to measure craving. Among 107 identified multi-item questionnaires, only 38 were used three or more times. The most common multi-item questionnaires were the Questionnaire on Smoking Urges (20%), Penn Alcohol Craving Scale (12.1%) and Alcohol Urge Questionnaire (9.8%). Most trials focused on evaluating phasic (now) craving (51.6%) over tonic (in a certain time-interval) craving (38%).

Conclusion: Craving, measured through self-reports, is increasingly targeted as a primary outcome measure in drug addiction trials registered on ClinicalTrials.gov. Craving self-reports are highly variable, underscoring the need for standardized tools to enhance comparability across studies.

Keywords: alcohol; clinical trial; craving; measurement tools; nicotine; self‐report questionnaire; substance use disorders; urge.

FIGURE 1

PRISMA flowchart for craving assessment tools as outcome measures in drug addiction trials registered in the ClinicalTrials.Gov. The PRISMA flow chart illustrates the search strategy and screening process used to identify relevant trials entries from ClinicalTrials.gov database, specifically focusing on trials where craving assessment tools were used as an outcome measure in drug addiction trials. The flowchart displays the number of trials identified at each stage of the process: identification: total number of trials identified through database searching; screening: number of trials screened for eligibility based on predefined inclusion/exclusion criteria; eligibility: number of trials assessed for eligibility after screening; and included: number of trials ultimately included in the systematic review and analysis. In addition to standard PRISMA stages, the final included trials were further catgorized by substance. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐Analyses.

FIGURE 2

Trials with craving as an outcome measure by start date and substance of use. The annotated heat map illustrates the absolute number of clinical trials registered in each year according to their actual start date and substance of use since for which craving was measured as outcome. The map spans from the first identified entry in 1987 to 5 November 2024. X‐axis (year): the map displays trial entries from 1987 through 2022, with the first column representing all trials registered between 1987 and 2004, followed by subsequent annual entries from 2005 to 2022. Y‐axis (substance indication): each row corresponds to a different substance category (e.g. nicotine, alcohol opioids, stimulants, marijuana, multi‐substance and not specified). Color intensity: the heat map uses color intensity to show the absolute number of trials registered for each substance and year. Darker colors represent a higher number of trials, while lighter colors indicate fewer trials.

FIGURE 3

Trials by assessment title and types of interventions. The annotated heat map illustrates the relationship between craving assessment tools (n ≥ 3) (questionnaires) and the types of interventions used in clinical trials. Each cell in the heat map represents the use of a specific assessment title in trials using particular interventions. Abbreviations sorted by frequency in each category of substances. Multi‐item Questionnaires of Nicotine: QSU, Questionnaire on Smoking Urges; MNWS, Minnesota Nicotine Withdrawal Scale; CEQ, Craving Evaluation Questionnaire; TCQ, Tobacco Craving Questionnaire; MPSS, Mood And Physical Symptoms Scale; WSWS, Wisconsin Smoking Withdrawal Scale; FTND, Fagerström Test For Nicotine Dependence; SJWS, Shiffman Jarvik Withdrawal Scale; NCA, Nicotine Craving Assessment; QVC, Questionnaire Of Vaping Craving; WISDM, Wisconsin Inventory of Smoking Dependence Motives; HWQ, Hughes‐Hatsukami Withdrawal Questionnaire. Multi‐item Questionnaires of Alcohol: PACS, Penn Alcohol Craving Scale; AUQ, Alcohol Urge Questionnaire; OCDS, Obsessive Compulsive Drinking Scale; ACQ, Alcohol Craving Questionnaire; CrEQ, Craving Experience Questionnaire; AASS, Alcohol Abstinence Self‐Efficacy Scale; AUDIT, Alcohol Use Disorders Identification Test; SitCQ, Situational Confidence Questionnaire; DAQ, Desire for Alcohol Questionnaire; ADS, Alcohol Dependence Scale; YCS, Yale Craving Scale. Multi‐item Questionnaires of Opioid: OCS, Opioid Craving Scale, DDQ, Desire for Drug Questionnaire, SCS, Substance Craving Scale, HCQ, Heroin Craving Questionnaire, OCDUS, Obsessive Compulsive Drug Use Scale, PACSAD, Penn Alcohol Craving Scale adapted for opioids, SOWS, Subjective Opioid Withdrawal Scale. Multi‐item Questionnaires of Stimulant: CCQ, Cocaine Craving Questionnaire; SCS, Substance Craving Scale; SCQ, Stimulant Craving Questionnaire; MCCS, Minnesota Cocaine Craving Scale; CSSA, Cocaine Selective Severity Assessment; CCS, Cocaine Craving Scale; ACSA, Amphetamine Cessation Symptom Assessment. Multi‐item Questionnaires of Marijuana: MCQ, Marijuana Craving Questionnaire; MWCh, Marijuana Withdrawal Checklist. SIQ: Single‐Item Questionnaire.

FIGURE 4

Parameter space of multi‐item craving self‐reports used as outcome measures in trials registered in the ClinicalTrials.Gov. This sunburst chart illustrates the breakdown of multi‐item self‐report questionnaires used to assess craving, categorized by substance, theoretical framework, questionnaire title and version. Each layer provides progressively detailed information (the numbers in parentheses indicate the frequency of use in the reviewed studies). Substance category (innermost layer): represents the substances targeted by the questionnaires. Categories include by frequency, nicotine, alcohol, opioids, stimulants, marijuana. Underlying theoretical model (second layer): indicates the theoretical basis of the questionnaires, grouped into single‐dimensional and multi‐dimensional frameworks. Single dimension: IFD, intensity‐frequency‐duration. Multiple dimensions: CT, cognitive theory; OC, obsessive‐compulsive; AE, abstinence effects (craving and withdrawal symptoms); and NS, not specified. Questionnaire title (third layer): lists the specific titles of craving questionnaires categorized by substance. Nicotine: QSU, Questionnaire Of Smoking Urges; MNWS, Minnesota Nicotine Withdrawal Scale; CEQ, Cigarette Evaluation Questionnaire; TCQ, Tobacco Craving Questionnaire; MPSS, Mood and Physical Symptoms Scale; FTND, Fagerström test for Nicotine Dependence; WSWS, Wisconsin Smoking Withdrawal Scale; NCA, Nicotine Craving Assessment. Alcohol: PACS, Penn Alcohol Craving Scale; AUQ, Alcohol Urge Questionnaire; OCDS, Obsessive Compulsive Drinking Scale; ACQ, Alcohol Craving Questionnaire. Opioids: OCS, Opioid Craving Scale; PACSAD, Penn Alcohol Craving Scale adapted for opioids; DDQ, Desire for Drug Questionnaire; HCQ, Heroin Craving Questionnaire; SCS, Substance Craving Scale. Stimulants: CCQ, cocaine craving questionnaire; SCQ, Stimulant Craving Questionnaire; SCS, Substance Craving Scale; MCCS, Minnesota Cocaine Craving Scale. Marijuana: MCQ, Marijuana Craving Questionnaire. Questionnaire version (outermost layer): specifies the format or item count for each questionnaire. B, brief; O, original; AD, adapted; M, modified; RB, revised brief (using only few items of the questionnaires' brief version). Small circles (linked to outermost layer): represent the number of times each specific version was identified in the results. Background color of circles: reflects the craving time frame assessed: phasic, immediate craving; tonic, craving in a given moment; phasic‐tonic, combination of both; not specified, no clear indication.