Investigating the Synergistic Neuroprotective Effects of Plant-Derived Antioxidants and the Psychedelic N,N-Dimethyltryptamine in Alzheimer's Disease Therapy.

Combining the psychedelic molecule N,N-Dimethyltryptamine (NN-DMT) with five plant-derived bioactive compounds—Withanone, Apigenin, Bacoside A, Baicalin, and Thymoquinone—reduces age-related mobility problems, decreases amyloid-β plaque buildup, and improves survival under oxidative stress more effectively than any single compound alone. This synergistic effect was observed in a transgenic Caenorhabditis elegans model of Alzheimer's disease. The findings suggest that multi-target therapies addressing both protein aggregation and oxidative damage may offer a more promising direction for Alzheimer's treatment than single-drug approaches.

Study at a glance

Abstract

Alzheimer's disease (AD) is a chronic and complex neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and irreversible impairment of brain functions. The etiology of AD is multifactorial, involving a complex interplay of genetic, environmental, and physiological factors, including the aggregation of amyloid-β (Aβ) and oxidative stress (OS). The role of OS in AD pathogenesis is of particular significance, given that an imbalance between oxidants and antioxidants promotes cellular damage, exacerbates Aβ deposition, and leads to cognitive deterioration. Despite extensive research, current therapeutic strategies have largely failed, likely due to the use of single-target drugs unable to halt the multifactorial progression of the disease. In this study, we investigated the synergistic therapeutic effect of plant-derived bioactive compounds Withanone, Apigenin, Bacoside A, Baicalin, and Thymoquinone in combination with N,N-Dimethyltryptamine (NN-DMT), a psychedelic molecule. We used a transgenic Caenorhabditis elegans model to assess the behavioral and molecular outcomes following compound exposure. Motility assays, thioflavin S staining, and survival assays under oxidative stress were employed to evaluate the treatment efficacy. The results of the behavioral and molecular analyses indicated that the combination therapy exhibited a higher efficacy than the monotherapies, leading to a significant reduction in age-related motility defects in the AD model. Furthermore, the combination treatment substantially reduced Aβ plaque burden, enhanced survival following OS insult, and demonstrated a synergistic effect in mitigating AD-related hallmarks. Taken together, these findings support the potential of combining NN-DMT with specific bioactive compounds as a promising multi-target therapeutic approach for AD.