{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T23:30:41Z","timestamp":1778974241731,"version":"3.51.4"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIDA","award":["R01DA059234"],"award-info":[{"award-number":["R01DA059234"]}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["F31AA029632"],"award-info":[{"award-number":["F31AA029632"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nBackground<\/jats:title>\nAs cannabis legalization continues to spread across the United States, average \u03949<\/jats:sup>-tetrahydrocannabinol concentrations in recreational products have significantly increased, and no prior study has evaluated effective treatments to reduce cannabis use among high potency cannabis users. Some research has found that the non-intoxicating cannabinoid cannabidiol reduces cannabis use and cannabis use disorder-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising but limited to synthetic or isolated forms of cannabidiol.<\/jats:p>\n<\/jats:sec>\n\nObjective<\/jats:title>\nConduct a placebo-controlled randomized control trial comparing the effects of hemp-derived cannabidiol on reducing \u03949<\/jats:sup>-tetrahydrocannabinol use in concentrate users with cannabis use disorder.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nDesign.<\/jats:bold> Double-blind, three-arm randomized placebo-controlled trial.<\/jats:p>\nSetting.<\/jats:bold> University in the Denver-Boulder, CO, USA area.<\/jats:p>\nStudy population.<\/jats:bold> Community members who are heavy, stable cannabis concentrate users that meet criteria for at least moderate cannabis use disorder and are seeking to decrease or stop cannabis use.<\/jats:p>\nData.<\/jats:bold> Self-report demographics, substance use, and mental health characteristics, blood and urine based biomarkers and anthropometrics.<\/jats:p>\nOutcomes.<\/jats:bold> Affective, physiological, and physical withdrawal symptoms, \u03949<\/jats:sup>-tetrahydrocannabinol use.<\/jats:p>\nAnalysis.<\/jats:bold> Three-group ANOVAs and \u03c72<\/jats:sup> tests will be used to compare baseline variables between groups. Characteristics that differ between groups will be evaluated as potential covariates in subsequent analyses. A multilevel modeling framework will be used for primary outcome analysis to account for the repeated observations nested within participants over time. Pairwise post-hoc simple effects tests will be conducted to confirm patterns of differences.<\/jats:p>\n<\/jats:sec>\n\nTrial registration<\/jats:title>\nClinicalTrials.gov NCT06107062<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0308262","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T17:30:04Z","timestamp":1727717404000},"page":"e0308262","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["LOTUS: Protocol for a double-blind placebo controlled randomized trial of hemp-derived cannabidiol for the treatment of cannabis use disorder"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-7586","authenticated-orcid":true,"given":"L. 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Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances","volume":"29","author":"Y Ren","year":"2009","journal-title":"Journal of Neuroscience"},{"key":"pone.0308262.ref022","article-title":"Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: A double-blind randomized placebo-controlled trial","author":"YL Hurd","year":"2019","journal-title":"American Journal of Psychiatry"},{"issue":"8","key":"pone.0308262.ref023","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1038\/npp.2013.54","article-title":"Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse","volume":"38","author":"M Haney","year":"2013","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"pone.0308262.ref024","article-title":"Acute objective and subjective intoxication effects of legal-market high potency THC-dominant versus CBD-dominant cannabis concentrates.","author":"ML Drennan","year":"2021","journal-title":"Scientific Reports 2021 11:1"},{"key":"pone.0308262.ref025","author":"SH Lovibond","year":"1996","journal-title":"Manual for the depression anxiety stress scales"},{"key":"pone.0308262.ref026","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1176\/appi.ajp.2011.10111704","article-title":"The Columbia\u2013Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings From Three Multisite Studies With Adolescents and Adults.","author":"K Posner","year":"2011","journal-title":"Am J Psychiatry"},{"issue":"5","key":"pone.0308262.ref027","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1037\/0022-006X.68.5.898","article-title":"Comparison of extended versus brief treatments for marijuana use.","volume":"68","author":"RS Stephens","year":"2000","journal-title":"J Consult Clin Psychol"},{"issue":"1\u20132","key":"pone.0308262.ref028","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.drugalcdep.2010.02.017","article-title":"An improved brief measure of cannabis misuse: the Cannabis Use Disorders Identification Test-Revised (CUDIT-R).","volume":"110","author":"SJ Adamson","year":"2010","journal-title":"Drug Alcohol Depend"},{"issue":"3","key":"pone.0308262.ref029","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1037\/0021-843X.112.3.393","article-title":"The time course and significance of cannabis withdrawal.","volume":"112","author":"AJ Budney","year":"2003","journal-title":"J Abnorm Psychol. 2003\/08\/29."},{"key":"pone.0308262.ref030","article-title":"Development and Initial Validation of a Momentary Cannabis Craving Scale Within a Homogeneous Sample of U.S. Emerging Adults.","author":"CN Davis","year":"2024","journal-title":"Assessment"},{"issue":"4","key":"pone.0308262.ref031","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1037\/0022-006X.59.4.558","article-title":"Marijuana and Cocaine Effect Expectancies and Drug Use Patterns.","volume":"59","author":"J Schafer","year":"1991","journal-title":"J Consult Clin Psychol."},{"key":"pone.0308262.ref032","article-title":"The Cannabis Effects Expectancy Questionnaire\u2013Medical (CEEQ-M): Preliminary psychometric properties and longitudinal validation within a clinical trial.","author":"JH Weiss","year":"2023","journal-title":"Psychol Assess"},{"issue":"12","key":"pone.0308262.ref033","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/ijo.2013.36","article-title":"The Stanford Leisure-Time Activity Categorical Item (L-Cat): a single categorical item sensitive to physical activity changes in overweight\/obese women.","volume":"37","author":"M Kiernan","year":"2013","journal-title":"Int J Obes (Lond)"},{"issue":"3","key":"pone.0308262.ref034","first-page":"141","article-title":"A Simple Method to Assess Exercise Behavior in the Community.","volume":"10","author":"G Godin","year":"1985","journal-title":"Canadian Journal of Applied Sports Sciences"},{"issue":"1","key":"pone.0308262.ref035","doi-asserted-by":"crossref","DOI":"10.13063\/2327-9214.1015","article-title":"Advances in patient-reported outcomes: the NIH PROMIS\u00ae measures.","volume":"1","author":"JE Broderick","year":"2013","journal-title":"Egems."},{"issue":"20","key":"pone.0308262.ref036","first-page":"22","article-title":"The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.","volume":"59","author":"V. Sheehan D","year":"1998","journal-title":"Journal of Clinical Psychiatry."},{"issue":"5","key":"pone.0308262.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0178194","article-title":"Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU).","volume":"12","author":"C Cuttler","year":"2017","journal-title":"PLoS One."},{"key":"pone.0308262.ref038","first-page":"1","article-title":"The Alcohol Use Disorders Identification Test Guidelines for Use in Primary Care.","author":"TF Babor","year":"2001","journal-title":"World Health Organization"},{"key":"pone.0308262.ref039","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4612-0357-5_3","article-title":"Timeline Follow-Back.","author":"LC Sobell","year":"1992","journal-title":"Measuring Alcohol Consumption"},{"issue":"1","key":"pone.0308262.ref040","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1037\/0022-006X.47.1.204","article-title":"Relationship between clinical judgment, self-report, and breath-analysis measures of intoxication in alcoholics.","volume":"47","author":"MB Sobell","year":"1979","journal-title":"J Consult Clin Psychol"},{"key":"pone.0308262.ref041","doi-asserted-by":"crossref","first-page":"103186","DOI":"10.1016\/j.jbi.2019.103186","article-title":"The transformation of a gold standard in-person substance use assessment to a web-based, REDCap integrated data capture tool.","volume":"94","author":"R Martin-Willett","year":"2019","journal-title":"J Biomed Inform"},{"issue":"6","key":"pone.0308262.ref042","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1093\/sleep\/33.6.781","article-title":"Development and Validation of Patient-Reported Outcome Measures for Sleep Disturbance and Sleep-Related Impairments.","volume":"33","author":"DJ Buysse","year":"2010","journal-title":"Sleep"},{"issue":"5","key":"pone.0308262.ref043","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/FTD.0000000000000427","article-title":"An Atmospheric Pressure Chemical Ionization MS\/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine.","volume":"39","author":"J Klawitter","year":"2017","journal-title":"Ther Drug Monit"},{"issue":"2","key":"pone.0308262.ref044","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1037\/1082-989X.7.2.147","article-title":"Missing data: our view of the state of the art.","volume":"7","author":"JL Schafer","year":"2002","journal-title":"Psychol Methods"},{"issue":"4","key":"pone.0308262.ref045","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1037\/1082-989X.7.4.422","article-title":"Mediation in experimental and nonexperimental studies: New procedures and recommendations.","volume":"7","author":"PE Shrout","year":"2002","journal-title":"Psychol Methods"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T17:30:17Z","timestamp":1727717417000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308262"}},"subtitle":[],"editor":[{"given":"Vanessa","family":"Carels","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,30]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0308262","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,30]]}}}