Inducing BDNF and mTOR-Mediated Synaptogenesis via Oral Agents: A Hypothetical Prophylaxis for Alzheimer’s Disease

Ketamine’s ability to lift mood and spur new synapse growth has put glutamate biology at the center of modern neurotherapeutics. Yet the drug’s intravenous route, monitoring requirements, and dissociative effects make it a poor candidate for long-term prevention of Alzheimer’s disease (AD).Here we advance a testable hypothesis: an all-oral “synaptogenic stack” could mimic ketamine’s downstream benefits—namely, the rise in brain-derived neurotrophic factor (BDNF) and the activation of mTOR—while avoiding its toxicities.The stack combines three inexpensive agents that have decades of human use. First, dextromethorphan, kept in circulation with a small dose of a CYP2D6 inhibitor, provides gentle NMDA antagonism. Second, piracetam acts as a positive modulator of AMPA receptors, boosting fast excitatory transmission. Third, oral L-glutamine replenishes presynaptic glutamate stores and buffers against excitotoxic spill-over. Working in concert, these drugs should reduce extrasynaptic NMDA stress, enhance AMPA throughput, and preserve dendritic spine density in the ageing brain.If this mechanism proves sound, the regimen offers a low-cost, scalable way to delay the clinical onset of AD, particularly in people who already show prodromal biomarkers or genetic risk. Prospective trials are needed to evaluate safety, target engagement, and long-term cognitive outcomes.