Cell viability of different human PPGL primary cultures (n = 35, n = 2 from the same patient) after incubation with 5 μM CBD for 72 hours (A) listed in numerical order and (B) listed in order of responsivity to CBD (significant decrease of cell viability, significant increase in cell viability, no significant decrease or increase of cell viability). Primary cultures 13.1 and 13.2 are from the same patient. Cluster 1-related PVs in red: SDHB (tumors 1, 32), SDHB and VUS in EPAS (tumor 2), SDHC (tumor 24), SDHD (tumors 11, 15), VUS in VHL (tumor 12). Cluster 2-related PVs in blue: NF1 (tumors 3, 4, 6, 7, 21; patterned blue), RET (tumors 13.1, 13.2, 17), HRAS (tumor 18), MAX (tumor 30). Other PVs in gold: BRCA (tumor 34), ATRX (tumor 35). Metastatic tumors 2, 35 framed in green. Germline and somatic testing was negative in tumors 8, 9, 19 (light grey). Tumors with negative germline testing and not available somatic status in black. Tumors without available germline and somatic status (unknown status) in dark grey. The detailed listing of the germline/somatic status of the individual PPGL patients can be found in Supplementary Table S3 (50). Each cell viability experiment comprised 3 to 8 samples per drug concentration and patient. The mean values ± SD are shown. Green asterisk: significant decrease of cell viability P < .05. Red asterisk: significant increase of cell viability P < .05.

Abbreviations: CBD, cannabidiol; PPGL, pheochromocytoma and paraganglioma; PV, pathogenic variant; VUS, variant of unknown significance.