{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:38:27Z","timestamp":1772217507245,"version":"3.50.1"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospital for Sick Children Foundation and the Canadian Institutes of Health Research","award":["N120-1028"],"award-info":[{"award-number":["N120-1028"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cannabis products have been used in the management of headaches in adults and may play a role in pediatric chronic pain. Canadian pediatricians report increasing use of cannabis for the management of chronic headaches, despite no well-controlled studies to inform its dosing, safety, and effectiveness. The aim of our clinical trial is to determine the dosing and safety of a Cannabidiol (CBD)-enriched Cannabis Herbal Extract (CHE) for the treatment of chronic headaches in adolescents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Youth, parents, and an expert steering committee co-designed this tolerability study. Twenty adolescents (aged 14 to 17 years), with a chronic migraine diagnosis for more than 6 months that has not responded to other therapies will be enrolled into an open label, dose escalation study across three Canadian sites. Study participants will receive escalating doses of a CBD-enriched CHE (MPL-001 with a THC:CBD of 1:25), starting at 0.2\u20130.4 mg\/kg of CBD per day and escalating monthly up to 0.8\u20131.0 mg\/kg of CBD per day. The primary objective of this study is to determine the safety and tolerability of CBD-enriched CHE in adolescents with chronic migraine. Secondary objectives of this study will inform the development of subsequent randomized controlled trials and include investigating the relationship between the dose escalation and change in the frequency of headache, impact and intensity of pain, changes in sleep, mood, function, and quality of life. Exploratory outcomes include investigating steady-state trough plasma levels of bioactive cannabinoids and investigating how pharmacogenetic profiles affect cannabinoid metabolism among adolescents receiving CBD-enriched CHE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This protocol was co-designed with youth and describes a tolerability clinical trial of CBD-enriched CHE in adolescents with chronic headaches that have not responded to conventional therapies. This study is the first clinical trial on cannabis products in adolescents with chronic headaches and will inform the development of future comparative effectiveness clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      CAN-CHA trial is registered with ClinicalTrials.gov with a number of register\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05337033\" xlink:type=\"simple\">NCT05337033<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0290185","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T13:36:19Z","timestamp":1726839379000},"page":"e0290185","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A multi-centre, tolerability study of a cannabidiol-enriched Cannabis Herbal Extract for chronic headaches in adolescents: The CAN-CHA protocol"],"prefix":"10.1371","volume":"19","author":[{"given":"Manik","family":"Chhabra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9024-150X","authenticated-orcid":true,"given":"Evan C.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Balshaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Breanne","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zina","family":"Zaslawski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trinity","family":"Lowthian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Alidina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melila","family":"Chesick-Gordis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenli","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britt I.","family":"Dr\u00f6gem\u00f6ller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galen E. 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