ASAH1 and neuroblastoma: While gallein inhibited D,L-methadone-induced ER Ca2+ release in SK-N-MC neuroblastoma cells (Figure 1A), it did not do so in SEM (Figure 1B) and POETIC2 (Supplementary Figure S1B) leukemic cells, indicating that D,L-methadone-induced ER Ca2+ release in leukemic cells is independent of Gβγ. Previous studies have shown that stimulation of opioid receptors by D,L-methadone activates Gαi, which blocks adenylyl cyclase (AC) activity that in turn reduces [cAMP]i (Friesen et al., 2013; Kang et al., 2017).