Caffeine and MDMA (ecstasy) exacerbate ER stress triggered by hyperthermia
bioRxiv (Cold Spring Harbor Laboratory) Kathleen A. Trychta, Brandon K. Harvey 1 citation preprint
Hyperthermia—elevated body temperature—triggers the abnormal secretion of proteins normally retained inside the endoplasmic reticulum (ER), a process called ER exodosis. The club drugs MDMA (ecstasy) and caffeine, alone or combined, worsen this protein leakage in a cellular model. Hyperthermia also activates the unfolded protein response (UPR), a cellular stress pathway, but the drugs do not alter most UPR-related gene expression despite increasing ER exodosis of UPR proteins. One exception: MDMA raised BiP/Grp78 mRNA levels under hyperthermia. These results suggest that using club drugs in hot environments disrupts ER protein balance, potentially increasing cell toxicity.