%0 Journal Article
%T Opposing effects of cannabidiol in patient-derived neuroendocrine tumor, pheochromocytoma/paraganglioma primary cultures.
%A Wang K
%A Schober L
%A Fischer A
%A Bechmann N
%A Maurer J
%A Peischer L
%A Reul A
%A Hantel C
%A Reincke M
%A Beuschlein F
%A Robledo M
%A Mohr H
%A Pellegata NS
%A Schilbach K
%A Knösel T
%A Ilmer M
%A Angele M
%A Kroiss M
%A Maccio U
%A Broglie-Däppen M
%A Vetter D
%A Lehmann K
%A Pacak K
%A Grossman AB
%A Auernhammer CJ
%A Zitzmann K
%A Nölting S
%J J Clin Endocrinol Metab
%V 0
%N 0
%D 2024 Apr 12
%M 38605427
%F 6.134
%R 10.1210/clinem/dgae241
%X <B>BACKGROUND: </B>Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (together PPGLs) are still limited. In recent years, anti-tumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs.<BR><B>OBJECTIVE: </B>Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines.<BR><B>METHODS: </B>We established primary cultures derived from 46 different patients with PPGLs (n = 35) or NETs (n = 11) who underwent tumor resection at two centers. Treatment of patient primary cultures with clinically relevant doses (5 µM) and slightly higher doses (10 µM) of CBD was performed.<BR><B>RESULTS: </B>We found opposing effects of 5 µM CBD: significant anti-tumor effects in 5/35 (14%) and significant tumor-promoting effects in 6/35 (17%) of PPGL primary cultures. In terms of anti-tumor effects, cluster 2-related PPGLs showed significantly stronger responsivity to CBD compared to cluster 1-related PPGLs (p = 0.042). Of the cluster 2-related tumors, NF1 PPGLs showed strongest responsivity (4/5 PPGL primary cultures with a significant decrease in cell viability were NF1-mutated). We also found opposing effects of 10 µM CBD in PPGLs and NETs: significant anti-tumor effects in 9/33 of PPGL (27%) and 3/11 of NET (27%) primary cultures, significant tumor-promoting effects in 6/33 of PPGL (18%) and 2/11 of NET (18%) primary cultures.<BR><B>CONCLUSIONS: </B>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.