Proliferative Effects of the Psychedelic N,N-Dimethyltryptamine (DMT) in Human Neural Stem Cells

Area of Science:

• Neuroscience
• Cell Biology
• Psychopharmacology

Background:

• Serotonergic psychedelics, like N,N-dimethyltryptamine (DMT), show promise for rapid antidepressant effects.
• Therapeutic benefits are potentially linked to neuroplasticity, including adult neurogenesis.
• The impact of brief DMT exposure on human neural stem cell (NSC) proliferation is not well understood.

Purpose of the Study:

• To investigate the effects of DMT on the proliferation and neurotrophin expression of human neural stem cells (NSCs).
• To determine if short-term DMT treatment can induce proliferative responses in human NSCs.

Main Methods:

• Human induced pluripotent stem cell-derived neural stem cells (iPSC-NSCs) were treated with varying concentrations of DMT.
• Cell proliferation was assessed, along with the expression of cell-cycle regulators and neurotrophin genes/proteins.
• Post-treatment, neurosphere formation and cell marker composition were analyzed after washout.

Main Results:

• DMT treatment increased NSC proliferation in a concentration-dependent manner, with a half-maximal effect at 59.7 nM.
• DMT upregulated G1 cell-cycle regulators and altered trophic gene expression, decreasing neurotrophin-3 while increasing nerve growth factor and BDNF.
• DMT-primed NSCs formed larger neurospheres, maintaining progenitor and early neuronal markers after washout.

Conclusions:

• Brief DMT exposure is sufficient to stimulate proliferative and neurotrophin-associated responses in human NSCs.
• The observed effects occur at concentrations consistent with those linked to DMT-induced neural plasticity.
• These findings support DMT's potential role in promoting neurogenesis and neural plasticity for therapeutic applications.