{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:51:45Z","timestamp":1780591905709,"version":"3.54.1"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015070","name":"Department of Psychiatry, University of Toronto","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015070","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CAMH Academic Health Science Centre Alternative Funding Plan"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Severe behavioral problems (SBPs) are common contributors to morbidity and reduced quality of life for adults with intellectual and developmental disabilities (IDD) and their families. Current medications for SBPs show equivocal effectiveness and are associated with a high risk of side effects. New and safe treatments are urgently needed. While preliminary studies suggest that medical cannabinoids, particularly the synthetic cannabinoid nabilone, are plausible treatment options for SBPs in adults with IDD, data on the tolerability, safety and efficacy of nabilone in this population has never been investigated. Thus, we propose this first-ever Phase I pre-pilot open-label clinical trial to obtain preliminary data on the adherence, tolerability and safety profiles of nabilone in adults with IDD, and explore changes in SBPs pre- to post-treatment. We hypothesize that nabilone has favorable tolerability and safety profile for adults with IDD. The preliminary results will inform the next-stage pilot randomized controlled trials, followed by fully powered clinical trials eventually. This research helps fill the evidence gap in the use of cannabinoids in individuals with IDD to meet the needs of patients, families, and service providers.<\/jats:p>","DOI":"10.1371\/journal.pone.0282114","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T17:36:21Z","timestamp":1681320981000},"page":"e0282114","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nabilone treatment for severe behavioral problems in adults with intellectual and developmental disabilities: Protocol for a phase I open-label clinical trial"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-209X","authenticated-orcid":true,"given":"Hsiang-Yuan","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elia","family":"Abi-Jaoude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpal","family":"Desarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie H.","family":"Ameis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9593-5508","authenticated-orcid":true,"given":"Meng-Chuan","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-9728","authenticated-orcid":true,"given":"Yona","family":"Lunsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-2560","authenticated-orcid":true,"given":"Tarek K.","family":"Rajji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"pone.0282114.ref001","author":"SP Morris","year":"2018","journal-title":"A demographic, employment and income profile of Canadians with disabilities aged 15 years and over, 2017: Statistics Canada = Statistque Canada"},{"issue":"1","key":"pone.0282114.ref002","doi-asserted-by":"crossref","DOI":"10.23889\/ijpds.v6i1.1342","article-title":"Prevalence estimation of intellectual disability using national administrative and household survey data: The importance of survey question specificity","volume":"6","author":"O McBride","year":"2021","journal-title":"International Journal of Population Data Science"},{"issue":"5","key":"pone.0282114.ref003","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/YCO.0b013e32832e2a1e","article-title":"Epidemiology of mental ill health in adults with intellectual disabilities.","volume":"22","author":"SA Cooper","year":"2009","journal-title":"Curr Opin Psychiatry"},{"issue":"1","key":"pone.0282114.ref004","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/bjc.12118","article-title":"Challenging behaviours in adults with an intellectual disability: A total population study and exploration of risk indices","volume":"56","author":"DL Bowring","year":"2017","journal-title":"The British journal of clinical psychology"},{"issue":"7","key":"pone.0282114.ref005","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1365-2788.2011.01390.x","article-title":"Physical conditions and challenging behaviour in people with intellectual disability: a systematic review","volume":"55","author":"CF de Winter","year":"2011","journal-title":"J Intellect Disabil Res"},{"issue":"6","key":"pone.0282114.ref006","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/jir.12269","article-title":"The impact of caring for an adult with intellectual disability and psychiatric comorbidity on carer stress and psychological distress.","volume":"60","author":"F Dawson","year":"2016","journal-title":"J Intellect Disabil Res"},{"key":"pone.0282114.ref007","volume-title":"Challenging Behaviour and Learning Disabilities: Prevention and Interventions for People with Learning Disabilities Whose Behaviour Challenges.","author":"National Collaborating Centre for Mental H","year":"2015"},{"issue":"4","key":"pone.0282114.ref008","first-page":"254","article-title":"Primary care of adults with intellectual and developmental disabilities: 2018 Canadian consensus guidelines.","volume":"64","author":"WF Sullivan","year":"2018","journal-title":"Canadian family physician Medecin de famille canadien."},{"issue":"6","key":"pone.0282114.ref009","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1177\/0706743717727240","article-title":"Antipsychotic Use With and Without Comorbid Psychiatric Diagnosis Among Adults with Intellectual and Developmental Disabilities","volume":"63","author":"Y Lunsky","year":"2018","journal-title":"Canadian journal of psychiatry Revue canadienne de psychiatrie"},{"issue":"2","key":"pone.0282114.ref010","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1176\/appi.ps.201700032","article-title":"Predictors of Psychotropic Polypharmacy Among Outpatients With Psychiatric Disorders and Intellectual Disability.","volume":"69","author":"Y Lunsky","year":"2018","journal-title":"Psychiatric services (Washington, DC)."},{"key":"pone.0282114.ref011","doi-asserted-by":"crossref","first-page":"110017","DOI":"10.1016\/j.pnpbp.2020.110017","article-title":"Psychotropic medication use for adults and older adults with intellectual disability; selective review, recommendations and future directions","volume":"104","author":"SI Deutsch","year":"2021","journal-title":"Progress in neuro-psychopharmacology & biological psychiatry"},{"issue":"6","key":"pone.0282114.ref012","doi-asserted-by":"crossref","first-page":"e021911","DOI":"10.1136\/bmjopen-2018-021911","article-title":"Interventions for mental health problems in children and adults with severe intellectual disabilities: a systematic review","volume":"8","author":"L Vereenooghe","year":"2018","journal-title":"BMJ Open"},{"issue":"8","key":"pone.0282114.ref013","doi-asserted-by":"crossref","first-page":"e017406","DOI":"10.1136\/bmjopen-2017-017406","article-title":"Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study","volume":"7","author":"R Sheehan","year":"2017","journal-title":"BMJ Open"},{"issue":"10","key":"pone.0282114.ref014","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/jir.12772","article-title":"Metabolic syndrome and its components in people with intellectual disability: a meta-analysis.","volume":"64","author":"D Vancampfort","year":"2020","journal-title":"J Intellect Disabil Res"},{"key":"pone.0282114.ref015","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fnbeh.2018.00041","article-title":"The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders","volume":"12","author":"NJ Kolla","year":"2018","journal-title":"Frontiers in behavioral neuroscience"},{"issue":"4","key":"pone.0282114.ref016","doi-asserted-by":"crossref","first-page":"370","DOI":"10.2174\/1871527316666170223161908","article-title":"The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents.","volume":"16","author":"E Murillo-Rodriguez","year":"2017","journal-title":"CNS & neurological disorders drug targets."},{"key":"pone.0282114.ref017","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/7854_2016_14","article-title":"Role of Inflammation in the Development of Neuropsychiatric Symptom Domains: Evidence and Mechanisms","volume":"31","author":"L Capuron","year":"2017","journal-title":"Current topics in behavioral neurosciences"},{"issue":"6","key":"pone.0282114.ref018","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Current evidence and future directions.","volume":"12","author":"V Calsolaro","year":"2016","journal-title":"Alzheimers Dement."},{"key":"pone.0282114.ref019","article-title":"A pro-inflammatory phenotype is associated with behavioural traits in children with Prader-Willi syndrome.","author":"M Krefft","year":"2020","journal-title":"European child & adolescent psychiatry."},{"issue":"5","key":"pone.0282114.ref020","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.bbi.2007.11.008","article-title":"Antagonistic characteristics are positively associated with inflammatory markers independently of trait negative emotionality","volume":"22","author":"AL Marsland","year":"2008","journal-title":"Brain Behav Immun"},{"issue":"2","key":"pone.0282114.ref021","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1001\/jamapsychiatry.2013.3297","article-title":"Elevated plasma inflammatory markers in individuals with intermittent explosive disorder and correlation with aggression in humans","volume":"71","author":"EF Coccaro","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"pone.0282114.ref022","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3389\/fncel.2018.00234","article-title":"Altered Amygdala Excitation and CB1 Receptor Modulation of Aggressive Behavior in the Neuroligin-3(R451C) Mouse Model of Autism.","volume":"12","author":"S Hosie","year":"2018","journal-title":"Frontiers in cellular neuroscience."},{"issue":"4","key":"pone.0282114.ref023","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00213-001-0946-5","article-title":"Involvement of CB1 cannabinoid receptors in emotional behaviour","volume":"159","author":"M Martin","year":"2002","journal-title":"Psychopharmacology (Berl)."},{"issue":"16","key":"pone.0282114.ref024","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1007\/s00213-015-3939-5","article-title":"Role of CB2 receptors in social and aggressive behavior in male mice","volume":"232","author":"M Rodr\u00edguez-Arias","year":"2015","journal-title":"Psychopharmacology (Berl)."},{"issue":"4","key":"pone.0282114.ref025","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1097\/ACO.0000000000000616","article-title":"An overview of the cannabinoid type 2 receptor system and its therapeutic potential","volume":"31","author":"B Bie","year":"2018","journal-title":"Curr Opin Anaesthesiol"},{"key":"pone.0282114.ref026","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.neuropharm.2013.07.013","article-title":"CB1 cannabinoid receptor-mediated aggressive behavior","volume":"75","author":"M Rodriguez-Arias","year":"2013","journal-title":"Neuropharmacology"},{"key":"pone.0282114.ref027","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.neubiorev.2014.11.007","article-title":"The role of endogenous opioids in non-suicidal self-injurious behavior: methodological challenges.","volume":"48","author":"O Kirtley OJ","year":"2015","journal-title":"Neuroscience and biobehavioral reviews"},{"key":"pone.0282114.ref028","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.pharmthera.2018.10.006","article-title":"The neuropsychopharmacology of cannabis: A review of human imaging studies","volume":"195","author":"MAP Bloomfield","year":"2019","journal-title":"Pharmacol Ther"},{"issue":"1","key":"pone.0282114.ref029","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41398-019-0500-z","article-title":"Association between prefrontal glutamine levels and neuroticism determined using proton magnetic resonance spectroscopy","volume":"9","author":"G Hasler","year":"2019","journal-title":"Translational psychiatry"},{"key":"pone.0282114.ref030","author":"Hess P. Cannabis","year":"2020","journal-title":"and autism, explained"},{"issue":"3","key":"pone.0282114.ref031","doi-asserted-by":"crossref","first-page":"e034362","DOI":"10.1136\/bmjopen-2019-034362","article-title":"Does cannabidiol reduce severe behavioural problems in children with intellectual disability? Study protocol for a pilot single-site phase I\/II randomised placebo controlled trial","volume":"10","author":"D Efron","year":"2020","journal-title":"BMJ Open"},{"issue":"7","key":"pone.0282114.ref032","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/jpc.13902","article-title":"Medical cannabis for paediatric developmental-behavioural and psychiatric disorders.","volume":"54","author":"D Efron","year":"2018","journal-title":"J Paediatr Child Health"},{"key":"pone.0282114.ref033","volume-title":"Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids","author":"H. Abramovici","year":"2018"},{"key":"pone.0282114.ref034","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/bs.pmbts.2019.06.005","article-title":"Effects of cannabidiol (CBD) in neuropsychiatric disorders: A review of pre-clinical and clinical findings.","volume":"167","author":"S Elsaid","year":"2019","journal-title":"Progress in molecular biology and translational science"},{"issue":"6","key":"pone.0282114.ref035","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1177\/2045125312457586","article-title":"a complex plant: different compounds and different effects on individuals","volume":"2","author":"Atakan Z. Cannabis","year":"2012","journal-title":"Ther Adv Psychopharmacol"},{"key":"pone.0282114.ref036","volume-title":"Long-term Nabilone Use: A Review of the Clinical Effectiveness and Safety","author":"CADTH Rapid Response Reports","year":"2015"},{"issue":"11","key":"pone.0282114.ref037","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.jagp.2019.05.002","article-title":"Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer\u2019s Disease","volume":"27","author":"N Herrmann","year":"2019","journal-title":"The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry"},{"key":"pone.0282114.ref038","doi-asserted-by":"crossref","first-page":"2042098619846993","DOI":"10.1177\/2042098619846993","article-title":"Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review.","volume":"10","author":"JB Hillen","year":"2019","journal-title":"Therapeutic advances in drug safety."},{"issue":"12","key":"pone.0282114.ref039","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S2215-0366(19)30401-8","article-title":"Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis","volume":"6","author":"N Black","year":"2019","journal-title":"The lancet Psychiatry"},{"key":"pone.0282114.ref040","article-title":"Non-Motor Symptoms in Parkinson\u2019s Disease are Reduced by Nabilone","author":"M Peball","year":"2020","journal-title":"Annals of neurology"},{"issue":"5","key":"pone.0282114.ref041","first-page":"433","article-title":"An open label study of the use of dronabinol (Marinol) in the management of treatment-resistant self-injurious behavior in 10 retarded adolescent patients.","volume":"27","author":"T Kruger","year":"2006","journal-title":"Cannabinoids."},{"issue":"4","key":"pone.0282114.ref042","first-page":"4","article-title":"Use of dronabinol (delta-9-THC) in autism: a prospective single-case-study with an early infantile autistic child.","volume":"5","author":"R Kurz","year":"2010","journal-title":"J Dev Behav Pediatr"},{"issue":"5","key":"pone.0282114.ref043","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/j.1369-1600.2011.00427.x","article-title":"Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.","volume":"18","author":"G Bedi","year":"2013","journal-title":"Addict Biol"},{"issue":"1","key":"pone.0282114.ref044","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.lfs.2013.12.212","article-title":"Synthetic cannabinoids: analysis and metabolites","volume":"97","author":"MA Elsohly","year":"2014","journal-title":"Life Sci"},{"issue":"3","key":"pone.0282114.ref045","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1177\/0269881114565142","article-title":"The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects","volume":"29","author":"J van Amsterdam","year":"2015","journal-title":"Journal of psychopharmacology (Oxford, England)."},{"key":"pone.0282114.ref046","volume-title":"Nabilone for the Treatment of Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness and Guidelines","author":"T Cowling","year":"2019"},{"key":"pone.0282114.ref047","volume-title":"TEVA-NABILONE (Product Monograph).","author":"Teva Canada Limited"},{"issue":"21","key":"pone.0282114.ref048","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","article-title":"Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome","volume":"376","author":"O Devinsky","year":"2017","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0282114.ref049","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1352\/0047-6765(2001)039<0259:DBPCTO>2.0.CO;2","article-title":"Double-blind, placebo-controlled trial of clonidine in hyperactive children with mental retardation.","volume":"39","author":"V Agarwal","year":"2001","journal-title":"Mental retardation."},{"issue":"3","key":"pone.0282114.ref050","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1360-0443.2009.02776.x","article-title":"The abuse potential of the synthetic cannabinoid nabilone.","volume":"105","author":"MA Ware","year":"2010","journal-title":"Addiction (Abingdon, England)."},{"issue":"8","key":"pone.0282114.ref051","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: official publication of the American College of Neuropsychopharmacology"},{"key":"pone.0282114.ref052","author":"PS Appelbaum","year":"2001","journal-title":"MacArthur competence assessment tool for clinical research (MacCAT-CR): professional resource press\/professional resource exchange"},{"issue":"7","key":"pone.0282114.ref053","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1176\/appi.ajp.159.7.1201","article-title":"Capacity to provide informed consent for participation in schizophrenia and HIV research","volume":"159","author":"DJ Moser","year":"2002","journal-title":"The American journal of psychiatry"},{"issue":"12","key":"pone.0282114.ref054","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1001\/jamapediatrics.2014.1694","article-title":"Accuracy of the MacArthur competence assessment tool for clinical research (MacCAT-CR) for measuring children\u2019s competence to consent to clinical research.","volume":"168","author":"IM Hein","year":"2014","journal-title":"JAMA pediatrics."},{"issue":"1","key":"pone.0282114.ref055","first-page":"40","article-title":"Evaluating Medical Decision-Making Capacity in Practice","volume":"98","author":"C Barstow","year":"2018","journal-title":"American family physician"},{"issue":"6","key":"pone.0282114.ref056","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/BF00805440","article-title":"Validity of the PAS-ADD for detecting psychiatric symptoms in adults with learning disability (mental retardation).","volume":"32","author":"S Moss","year":"1997","journal-title":"Social psychiatry and psychiatric epidemiology."},{"issue":"4","key":"pone.0282114.ref057","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s10803-009-0911-4","article-title":"Adaptive behavior ratings correlate with symptomatology and IQ among individuals with high-functioning autism spectrum disorders.","volume":"40","author":"L Kenworthy","year":"2010","journal-title":"J Autism Dev Disord"},{"issue":"7","key":"pone.0282114.ref058","first-page":"28","article-title":"The clinical global impressions scale: applying a research tool in clinical practice.","volume":"4","author":"J Busner","year":"2007","journal-title":"Psychiatry (Edgmont (Pa: Township))."},{"issue":"12","key":"pone.0282114.ref059","doi-asserted-by":"crossref","first-page":"e1229","DOI":"10.1212\/WNL.0000000000009131","article-title":"Validation of the NIH Toolbox Cognitive Battery in intellectual disability","volume":"94","author":"RH Shields","year":"2020","journal-title":"Neurology"},{"issue":"5","key":"pone.0282114.ref060","first-page":"492","article-title":"Psychometric characteristics of the aberrant behavior checklist.","volume":"89","author":"MG Aman","year":"1985","journal-title":"Am J Ment Defic"},{"issue":"12","key":"pone.0282114.ref061","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1097\/CHI.0b013e3181bfd669","article-title":"Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial.","volume":"48","author":"MG Aman","year":"2009","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"4","key":"pone.0282114.ref062","first-page":"368","volume":"20","author":"P Oliver","year":"2007","journal-title":"Modified Overt Aggression Scale (MOAS) for people with intellectual disability and aggressive challenging behaviour: a reliability study."},{"issue":"6","key":"pone.0282114.ref063","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1023\/B:JADD.0000005999.27178.55","article-title":"Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation.","volume":"33","author":"AJ Esbensen","year":"2003","journal-title":"J Autism Dev Disord"},{"issue":"2","key":"pone.0282114.ref064","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1348\/014466505X29657","article-title":"The short-form version of the Depression Anxiety Stress Scales (DASS-21): construct validity and normative data in a large non-clinical sample.","volume":"44","author":"JD Henry","year":"2005","journal-title":"The British journal of clinical psychology"},{"issue":"4","key":"pone.0282114.ref065","first-page":"521","volume":"20","author":"JA Weiss","year":"2011","journal-title":"The brief family distress scale: A measure of crisis in caregivers of individuals with autism spectrum disorders."},{"issue":"9","key":"pone.0282114.ref066","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1002\/aur.1795","article-title":"The Social Communication Questionnaire for adults with intellectual disability: SCQ-AID.","volume":"10","author":"O Derks","year":"2017","journal-title":"Autism Res."},{"issue":"10","key":"pone.0282114.ref067","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/jcpp.12425","article-title":"Practitioner Review: Self-injurious behaviour in children with developmental delay","volume":"56","author":"C Oliver","year":"2015","journal-title":"J Child Psychol Psychiatry"},{"key":"pone.0282114.ref068","article-title":"R\u00f8ssberg JIJAiMH, Disabilities I. Adjustment of the UKU Side Effect Rating Scale for adults with intellectual disabilities","author":"AL Tveter","year":"2014","journal-title":"A pilot study"},{"key":"pone.0282114.ref069","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.pbb.2019.03.006","article-title":"Cannabinoids, interoception, and anxiety","volume":"180","author":"AK Andrade","year":"2019","journal-title":"Pharmacol Biochem Behav"},{"key":"pone.0282114.ref070","article-title":"Facilitating individuals and families affected by fragile X syndrome to participate in medication trials.","author":"SEA Eley","year":"2020","journal-title":"J Intellect Disabil Res."},{"key":"pone.0282114.ref071","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neuroimage.2013.05.041","article-title":"The WU-Minn Human Connectome Project: an overview.","volume":"80","author":"DC Van Essen","year":"2013","journal-title":"Neuroimage."},{"issue":"1","key":"pone.0282114.ref072","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13229-022-00499-1","article-title":"White matter microstructural and morphometric alterations in autism: implications for intellectual capabilities.","volume":"13","author":"CH Yeh","year":"2022","journal-title":"Mol Autism"},{"key":"pone.0282114.ref073","volume-title":"Canadian ADHD Practice Guidelines","author":"Canadian ADHD Resource Alliance (CADDRA)","year":"2018"},{"issue":"7","key":"pone.0282114.ref074","doi-asserted-by":"crossref","DOI":"10.1093\/jnci\/dju163","article-title":"Evaluation of statistical designs in phase I expansion cohorts: the Dana-Farber\/Harvard Cancer Center experience","volume":"106","author":"SE Dahlberg","year":"2014","journal-title":"J Natl Cancer Inst"},{"key":"pone.0282114.ref075","doi-asserted-by":"crossref","first-page":"102158","DOI":"10.1016\/j.cpr.2022.102158","article-title":"A systematic review of risk for the development and persistence of self-injurious behavior in intellectual and developmental disabilities","volume":"94","author":"AF Dimian","year":"2022","journal-title":"Clin Psychol Rev"},{"issue":"5","key":"pone.0282114.ref076","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nrn3475","article-title":"Power failure: why small sample size undermines the reliability of neuroscience","volume":"14","author":"KS Button","year":"2013","journal-title":"Nat Rev Neurosci"},{"issue":"5","key":"pone.0282114.ref077","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1097\/YCO.0b013e32832cd9b8","article-title":"Persistent challenging behaviour in people with an intellectual disability","volume":"22","author":"V Totsika","year":"2009","journal-title":"Curr Opin Psychiatry"},{"issue":"5","key":"pone.0282114.ref078","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1365-2788.2008.01046.x","article-title":"Persistence of challenging behaviours in adults with intellectual disability over a period of 11 years.","volume":"52","author":"V Totsika","year":"2008","journal-title":"J Intellect Disabil Res."},{"issue":"1","key":"pone.0282114.ref079","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1186\/s13063-020-04406-y","article-title":"An under-represented and underserved population in trials: methodological, structural, and systemic barriers to the inclusion of adults lacking capacity to consent","volume":"21","author":"V. Shepherd","year":"2020","journal-title":"Trials."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T17:37:05Z","timestamp":1681321025000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282114"}},"subtitle":[],"editor":[{"given":"Robert","family":"Didden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,4,12]]},"references-count":79,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0282114","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,12]]}}}