{ "abstract": "Background: Cocaine use disorder (CUD) is associated with high rates of relapse, with craving and cue reactivity playing important roles in ongoing use. Cue Exposure Therapy (CET) aims to reduce conditioned responses to drug-related cues through extinction learning, but traditional approaches may be limited by poor ecological validity. Virtual reality-enhanced Cue Exposure Therapy (VR-CET) offers a potentially more immersive and realistic method of delivering cue exposure. Concurrently, advances in wearable physiological monitoring and just-in-time adaptive ecological momentary assessment (JITA-EMA) enable the real-time assessment of craving in everyday life. Objective: To assess the feasibility of recruitment, consent, randomisation, blinding, intervention delivery and retention over 8 weeks post-randomisation. Method: This is a two-arm, parallel-group, randomised feasibility trial conducted in UK community drug treatment services. Sixty adults receiving treatment will be randomised (1:1) to either VR-CET or an active VR-Relaxation control condition. Both arms will receive six VR sessions over four weeks, alongside continuous physiological monitoring using a wearable device and smartphone-based JITA-EMA for eight weeks. Feasibility outcomes will include recruitment, retention, intervention adherence, wearable wear time, EMA completion, acceptability, and safety. Clinical outcomes will include cocaine use measured by Timeline Follow-Back, cue reactivity assessed through subjective and physiological measures, and participant-confirmed craving episodes captured via wearable-triggered JITA-EMA. Qualitative interviews with participants and service providers will explore intervention acceptability and implementation facilitators, barriers and suggestions. Results: Planned start date is July 2026, and enrolment is due to end in April 2027. Data analysis is estimated to be completed by the end of spring 2027. Conclusions: To our knowledge, this is the first feasibility RCT of VR-CET for CUD within UK drug treatment services. Results from this trial will help assess the feasibility of integrating VR-CET, continuous physiological monitoring, and real-time craving JITA within CUD treatment. This can be used to inform the design of a future definitive trial and contribute to the development of personalised, technology-enabled approaches to relapse prevention and substance treatment.", "abstract_shown": true, "affiliations": [ "National Addiction Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.", "Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.", "School of Psychology, University of Birmingham, Birmingham, United Kingdom.", "Centre for Health Service Studies, University of Kent, Canterbury, United Kingdom.", "Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.", "Department of Psychology, University of Southampton, Southampton, United Kingdom.", "Department of Psychology, University of Southern Denmark, Odense, Denmark.", "Centre for Addiction and Mental Health Research (CAMHR), Faculty of Health Science, University of Hull, Hull, United Kingdom.", "Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.", "Digital XR Innovation Lab, Orygen, Parkville, Australia." ], "article_type": "Study Protocol", "arxiv": null, "author_total": 20, "authors": [ { "affs": [ 0 ], "name": "Eileen Brobbin", "orcid": "0000-0001-8464-4847" }, { "affs": [ 1 ], "name": "Matteo Cella" }, { "affs": [ 2 ], "name": "Alexandre Copello" }, { "affs": [ 3 ], "name": "Simon Coulton" }, { "affs": [ 0 ], "name": "Hannah Darvell", "orcid": "0009-0007-0470-1356" }, { "affs": [ 1 ], "name": "Jerome Di Pietro" }, { "affs": [ 0 ], "name": "Colin Drummond" }, { "affs": [ 0 ], "name": "Joe Duffy" }, { "affs": [ 4 ], "name": "Amos Folarin" }, { "affs": [ 5 ], "name": "Steven Glautier", "orcid": "0000-0001-8852-3268" }, { "affs": [ 0 ], "name": "Tayler Holborn", "orcid": "0000-0002-8980-9281" }, { "affs": [ 6 ], "name": "Ceyda Kiyak", "orcid": "0000-0002-9218-2248" }, { "affs": [ 0 ], "name": "Jazmin Molai", "orcid": "0009-0002-3500-1196" }, { "affs": [ 7 ], "name": "Thomas Phillips" }, { "affs": [ 2 ], "name": "Heet Sankesara" }, { "affs": [ 2 ], "name": "Daniel Stahl" }, { "affs": [ 2 ], "name": "Callum Stewart" }, { "affs": [ 1, 8, 9 ], "name": "Lucia Valmaggia", "orcid": "0000-0001-6099-8464" }, { "affs": [ 0 ], "name": "Colin Williams" }, { "affs": [ 0 ], "name": "Paolo Deluca" } ], "bibtex": "https://research.draconitic.com/paper/4z2wdwvqvbagv.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0358193", "fulltext_url": "https://europepmc.org/articles/PMC13722318", "id": "4z2wdwvqvbagv", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0358193", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Adverse Events" ], [ "heading", "Alkaloids" ], [ "heading", "Behavior" ], [ "heading", "Behavioral Pharmacology" ], [ "heading", "Biology and Life Sciences" ], [ "heading", "Chemical Compounds" ], [ "heading", "Chemistry" ], [ "heading", "Clinical Medicine" ], [ "heading", "Clinical Research Design" ], [ "heading", "Clinical Trials" ], [ "heading", "Cocaine" ], [ "heading", "Conditioned Response" ], [ "heading", "Drug Research and Development" ], [ "heading", "Drug Therapy" ], [ "heading", "Medicine and Health Sciences" ], [ "heading", "Pharmaceutics" ], [ "heading", "Pharmacology" ], [ "heading", "Physical Sciences" ], [ "heading", "Physiological Adaptation" ], [ "heading", "Physiological Processes" ], [ "heading", "Physiology" ], [ "heading", "Psychology" ], [ "heading", "Questionnaires" ], [ "heading", "Randomized Controlled Trials" ], [ "heading", "Recreational Drug Use" ], [ "heading", "Research Assessment" ], [ "heading", "Research Design" ], [ "heading", "Research and Analysis Methods" ], [ "heading", "Social Sciences" ], [ "heading", "Study Protocol" ], [ "heading", "Survey Research" ], [ "plos", "/Biology and life sciences/Physiology/Physiological processes/Physiological adaptation" ], [ "plos", "/Biology and life sciences/Psychology/Behavior/Conditioned response" ], [ "plos", "/Medicine and health sciences/Clinical medicine/Clinical trials/Randomized controlled trials" ], [ "plos", "/Medicine and health sciences/Pharmaceutics/Drug therapy" ], [ "plos", "/Medicine and health sciences/Pharmacology/Behavioral pharmacology/Recreational drug use/Cocaine" ], [ "plos", "/Medicine and health sciences/Pharmacology/Drug research and development/Clinical trials/Randomized controlled trials" ], [ "plos", "/Physical sciences/Chemistry/Chemical compounds/Alkaloids/Cocaine" ], [ "plos", "/Research and analysis methods/Clinical trials/Randomized controlled trials" ], [ "plos", "/Research and analysis methods/Research assessment" ], [ "plos", "/Research and analysis methods/Research design/Clinical research design/Adverse events" ], [ "plos", "/Research and analysis methods/Research design/Survey research/Questionnaires" ], [ "plos", "/Social sciences/Psychology/Behavior/Conditioned response" ] ], "openalex": null, "pdf_url": "https://europepmc.org/articles/PMC13722318?pdf=render", "pmcid": "PMC13722318", "pmid": "42962044", "published": "2026-10-30", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/4z2wdwvqvbagv.ris", "sources": [ { "first_seen": "2026-10-31T12:20:55Z", "native_id": "10.1371/journal.pone.0358193", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0358193" }, { "first_seen": "2026-11-02T03:21:21Z", "native_id": "MED:42962044", "source": "europepmc", "url": "https://europepmc.org/article/MED/42962044" }, { "first_seen": "2026-11-03T12:22:51Z", "native_id": "PMC13722318", "source": "pmc", "url": "https://doi.org/10.1371/journal.pone.0358193" } ], "subjects": [ { "field": "biology", "origin": "heading:Biology and Life Sciences", "subfield": "general" }, { "field": "chemistry", "origin": "heading:Chemistry", "subfield": "general" }, { "field": "medicine", "origin": "plos:clinical trials", "subfield": "clinical-trials" }, { "field": "medicine", "origin": "heading:Pharmacology", "subfield": "pharmacology-toxicology" }, { "field": "medicine", "origin": "heading:Physiology", "subfield": "physiology" } ], "title": "A randomised feasibility trial of VR-enhanced cue exposure therapy versus neutral VR exposure for cocaine use disorder, with wearable monitoring and JITA-EMA: Feasibility randomised controlled trial protocol", "title_text": "A randomised feasibility trial of VR-enhanced cue exposure therapy versus neutral VR exposure for cocaine use disorder, with wearable monitoring and JITA-EMA: Feasibility randomised controlled trial protocol", "type": "peer-reviewed", "updated_at": "2026-11-03T12:22:51Z", "url": "https://research.draconitic.com/paper/4z2wdwvqvbagv", "venue": "PLOS One", "versions": [] }