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Participants (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12\u00a0weeks to further assess tolerability.\n                    <\/jats:p>\n                    <jats:p>Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200945) versus 21% on placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200947;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200934) versus 3.6 points after placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200936);\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200995); 23% and 21% on pure-cannabinoids (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200993), and 8% and 15% on placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200994).\n                    <\/jats:p>\n                    <jats:p>Limitations<\/jats:p>\n                    <jats:p>Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3\u00a0months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      ClinicalTrials.gov: NCT02956226. Registered 06 November 2016,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02956226\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02956226<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13229-021-00420-2","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T08:04:25Z","timestamp":1612339465000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":171,"title":["Cannabinoid treatment for autism: a proof-of-concept randomized trial"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-4689","authenticated-orcid":false,"given":"Adi","family":"Aran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moria","family":"Harel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanoch","family":"Cassuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola","family":"Polyansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviad","family":"Schnapp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Wattad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Shmueli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphna","family":"Golan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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