{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:37:59Z","timestamp":1783633079482,"version":"3.55.0"},"reference-count":86,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["314061271\u2014TRR 205"],"award-info":[{"award-number":["314061271\u2014TRR 205"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031029","name":"University Medicine Zurich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031029","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (PPGLs) are still limited. In recent years, antitumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Investigation of the effects of cannabidiol (CBD) on patient-derived human NET\/PPGL primary cultures and on NET\/PPGL cell lines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We established primary cultures derived from 46 different patients with PPGLs (n = 35) or NETs (n = 11) who underwent tumor resection at 2 centers. Treatment of patient primary cultures with clinically relevant doses (5\u2005\u00b5M) and slightly higher doses (10\u2005\u00b5M) of CBD was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found opposing effects of 5\u2005\u00b5M CBD: significant antitumor effects in 5\/35 (14%) and significant tumor-promoting effects in 6\/35 (17%) of PPGL primary cultures. In terms of antitumor effects, cluster 2-related PPGLs showed significantly stronger responsivity to CBD compared to cluster 1-related PPGLs (P = .042). Of the cluster 2-related tumors, NF1 PPGLs showed the strongest responsivity (4\/5 PPGL primary cultures with a significant decrease in cell viability were NF1-mutated). We also found opposing effects of 10\u2005\u00b5M CBD in PPGLs and NETs: significant antitumor effects in 9\/33 of PPGL (27%) and 3\/11 of NET (27%) primary cultures and significant tumor-promoting effects in 6\/33 of PPGL (18%) and 2\/11 of NET (18%) primary cultures.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We suggest a potential novel treatment option for some NETs\/PPGLs but also provide evidence for caution when applying cannabinoids as supportive therapy for pain or appetite management to cancer patients and possibly as health supplements.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae241","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T03:23:47Z","timestamp":1712892227000},"page":"2892-2904","source":"Crossref","is-referenced-by-count":11,"title":["Opposing Effects of Cannabidiol in Patient-derived Neuroendocrine Tumor, Pheochromocytoma\/Paraganglioma Primary Cultures"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-1395","authenticated-orcid":false,"given":"Katharina","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Schober","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4555-8334","authenticated-orcid":false,"given":"Alessa","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich , CH-8091 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universita\u0308t Dresden , 01307, Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Peischer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Reul","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich , CH-8091 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich , CH-8091 Zurich ,","place":["Switzerland"]},{"name":"Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden , 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-9875","authenticated-orcid":false,"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-3984","authenticated-orcid":false,"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]},{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich , CH-8091 Zurich ,","place":["Switzerland"]},{"name":"The LOOP Zurich\u2014Medical Research Center , 8044 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6256-5902","authenticated-orcid":false,"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center , 28029 Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermine","family":"Mohr","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer, Helmholtz Center Munich , 85764 Neuherberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia S","family":"Pellegata","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer, Helmholtz Center Munich , 85764 Neuherberg ,","place":["Germany"]},{"name":"Department of Biology and Biotechnology, University of Pavia , 27100 Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-0296","authenticated-orcid":false,"given":"Katharina","family":"Schilbach","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kn\u00f6sel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, LMU Munich , 80337 Munich ,","place":["Germany"]},{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS-certified Center of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ilmer","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS-certified Center of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]},{"name":"Department of General, Visceral, and Transplantation Surgery, LMU University Hospital, LMU Munich , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Angele","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS-certified Center of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]},{"name":"Department of General, Visceral, and Transplantation Surgery, LMU University Hospital, LMU Munich , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kroiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]},{"name":"Department of Medicine I, Division of Endocrinology and Diabetes, University Hospital W\u00fcrzburg , 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Maccio","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Zurich , CH-8091 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Broglie-D\u00e4ppen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich , CH-8091 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Vetter","sequence":"additional","affiliation":[{"name":"Department of Visceral and Transplantation Surgery, University Hospital Zurich , CH-8091 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-9543","authenticated-orcid":false,"given":"Kuno","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Visceral and Transplantation Surgery, University Hospital Zurich , CH-8091 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3541-3767","authenticated-orcid":false,"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley B","family":"Grossman","sequence":"additional","affiliation":[{"name":"Green Templeton College, University of Oxford , Oxford OX2 6HG ,","place":["UK"]},{"name":"NET Unit, ENETS Centre of 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