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Current pharmacologic treatments offer limited efficacy and carry substantial risks, warranting the development of safe and effective alternatives. This multicenter, randomized, placebo-controlled phase 3 trial evaluated the efficacy and safety of VER-01 in CLBP. It enrolled 820 adults with CLBP (VER-01,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009394; placebo,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009426) and included a double-blind 12-week treatment phase (phase A), a 6-month open-label extension (phase B), followed by either a 6-month continuation (phase C) or randomized withdrawal (phase D). The primary endpoint of phase A was a change in mean numeric rating scale (NRS) pain intensity, with a change in total neuropathic pain symptom inventory (NPSI) score as a key secondary endpoint in participants with a neuropathic pain component (PainDETECT\u2009&gt;\u200918). The primary endpoint for phase D was time to treatment failure. The study met its primary endpoint in phase A, with a mean pain reduction of \u22121.9 NRS points in the VER-01 group (mean difference (MD) versus placebo\u2009=\u2009\u22120.6, 95% confidence interval (CI)\u2009=\u2009\u22120.9 to \u22120.3;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Pain further decreased to \u22122.9 NRS points in phase B, with effects sustained through phase C. The study also met its key secondary endpoint of phase A, with a mean NPSI decrease of \u221214.4 (standard error, 3.3) points from baseline in the VER-01 arm (MD versus placebo\u2009=\u2009\u22127.3, 95% CI\u2009=\u2009\u221213.2 to \u22121.3;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.017). Although phase D did not meet its primary endpoint (hazard ratio\u2009=\u20090.75, 95% CI\u2009=\u20090.44\u20131.27;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.288), pain increased significantly more with placebo upon withdrawal (MD\u2009=\u20090.5, 95% CI\u2009=\u20090.0\u20131.0;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.034). In phase A, the incidence of adverse events\u2014mostly mild to moderate and transient\u2014was higher with VER-01 than with placebo (83.3% versus 67.3%;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). VER-01 was well-tolerated, with no signs of dependence or withdrawal. VER-01 shows potential as a new, safe and effective treatment for CLBP. ClinicalTrials.gov registration:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04940741\" ext-link-type=\"uri\">NCT04940741<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-025-03977-0","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T15:03:10Z","timestamp":1759158190000},"page":"4189-4196","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Full-spectrum extract from Cannabis sativa DKJ127 for chronic low back pain: a phase 3 randomized placebo-controlled trial"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3502-0023","authenticated-orcid":false,"given":"Matthias","family":"Karst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-7696","authenticated-orcid":false,"given":"Winfried","family":"Meissner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Sator","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-5237","authenticated-orcid":false,"given":"Jens","family":"Ke\u00dfler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Schoder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-729X","authenticated-orcid":false,"given":"Winfried","family":"H\u00e4user","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"3977_CR1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.21037\/atm.2020.02.175","volume":"8","author":"A Wu","year":"2020","unstructured":"Wu, A. et al. 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Neurol."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03977-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03977-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03977-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T16:00:43Z","timestamp":1765814443000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03977-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":53,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["3977"],"URL":"https:\/\/doi.org\/10.1038\/s41591-025-03977-0","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,29]]},"assertion":[{"value":"2 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.K. has received speaker honoraria from the Federal Association of Pharmaceutical Cannabinoid Companies (BPC), Cannabis Social Club Bolzano, Cannamedical, Demecan, Grunenthal, Hormosan, Meet Your Master, Medical Service of the Health Insurance Funds, Novartis, Stadapharm and Tilray. He has received consultancy fees from Tetra Pharm and Vertanical. He has received expert opinion fees from several local and social courts. His institution has received research support from Friedrich and Alida Gehrke Foundation, German Pension Insurance Braunschweig-Hannover, Lower Saxony Ministry for Science and Culture and Vayamed. W.M. received payments for advisory boards and talks from Sanofi, MSD, Tafalgie, Kyowa, Mundipharma, Gr\u00fcnenthal and Ethypharm. His institution received research support from the European Commission, Gemeinsamer Bundesausschu\u00df (GBA), Medtronic, Pfizer, Mundipharma, Gr\u00fcnenthal and Vertanical. W.H. has received consulting fees\/honoraria from VIDAL, Biotechnology Value Fund, GH Research, Global Life Science, Science Direct, UCB and University of Duisburg (Germany) and support for travel to meetings from Bioevents and the European Pain Federation. S.S. has received payments for speaker honoraria, advisory boards and consensus from Gr\u00fcnenthal Austria, Medtronic, Ratiopharm Austria and Novartis Austria. J.K. has received speaker honoraria from Aurora, Esteve, Experten Schulungsakademie, Gr\u00fcnenthal, Hexal, Lilly and Teva. His institution has received research support from Bundesministerium f\u00fcr Bildung und Forschung, Deutsche Forschungsgemeinschaft, Dres. Majic\/Majic-Schlez-Foundation, GBA and Landesbank Baden-W\u00fcrttemberg-Foundation. V.S. is employed by Metronomia, which was contracted to perform data collation and statistical analysis.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}