The brain's ability to rewire itself declines with age, but why remains unclear. This paper examines whether the compound N,N-dimethyltryptamine (DMT) helps maintain neuroplasticity, and whether its decline contributes to age-related loss of cognitive flexibility. DMT promotes synaptic growth and neurogenesis in animals, and levels are reportedly highest during development. However, evidence is mixed: one study finds DMT concentrations comparable to serotonin, while another finds it undetectable in rat brain. DMT's affinity for the sigma-1 receptor is three orders of magnitude higher than physiological concentrations, and a key finding about intracellular 5-HT2A receptor binding has not been replicated. The paper does not claim the hypothesis is established, but proposes a research program to test whether DMT depletion causes lost plasticity or is incidental.
The human body has enzymes that both make and rapidly break down DMT, a molecule structurally nearly identical to serotonin that binds to the same serotonin receptors. This raises the question of whether DMT serves an endogenous physiological function or is merely a metabolic byproduct. Evidence is mixed: one report finds DMT concentrations in the nanomolar range comparable to serotonin and dopamine, while another finds DMT undetectable in rat brain. DMT's affinity for the sigma-1 receptor is far weaker than its likely physiological concentrations, and a key finding about intracellular 5-HT2A receptor binding has not been replicated.