N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer's disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk.
Alzheimer's research & therapy May 1, 2024 Dan Cheng, Zhuo-Gui Lei, Kin Chu et al. 41 citations
Chronic treatment with the psychedelic N,N-dimethyltryptamine (DMT) alleviated cognitive impairment and reduced amyloid-beta accumulation in the hippocampus and prefrontal cortex of 3×TG-AD transgenic mice, a model of Alzheimer's disease. DMT restored decreased sigma-1 receptor levels, reinstated multiple mitochondria-associated membrane proteins, and prevented abnormal physical contact and calcium dynamics between the endoplasmic reticulum and mitochondria in both in vitro and in vivo pathological conditions. DMT also modulated oxidative phosphorylation and ATP synthase in an in vitro Alzheimer's model. The protective effects are linked to DMT's activation of the sigma-1 receptor and preservation of ER-mitochondria crosstalk, suggesting potential as a preventive and therapeutic agent against Alzheimer's disease.