Timing Is Everything: Why the Cheung Glutamatergic Regimen Is Contraindicated in Young Children with Autism but Promising After Puberty

Autism spectrum disorder (ASD) follows an unusual two-stage course of synaptic change. Infancy and early childhood are marked by an exuberant rise in dendritic spines coupled with weak pruning, a profile driven in large part by overactive mTOR signalling. By adolescence and early adulthood, the pendulum appears to swing in the opposite direction, with evidence of compensatory over-pruning and a net loss of functional connections.Against this neurodevelopmental backdrop, we reviewed longitudinal MRI findings, post-mortem histology and mechanistic pharmacology to assess a putative "Cheung glutamatergic regimen." The protocol combines dextromethorphan (an NMDA-channel blocker), a CYP2D6-inhibiting antidepressant, piracetam and the amino-acid precursor l-glutamine.Available data suggest sharply divergent risk–benefit profiles across the lifespan. In children between two and ten years of age—when synaptic numbers can exceed neurotypical levels by as much as 50 per cent—any strategy that further amplifies glutamatergic drive may heighten excitotoxic risk and worsen core autistic features; the regimen is therefore contraindicated in this window. In contrast, once puberty ushers in accelerated pruning and the possibility of synaptic depletion, carefully titrated glutamate enhancement could prove restorative. By pairing transient NMDA blockade with boosted AMPA throughput and substrate support from glutamine, the combination may help re-establish γ-band synchrony and strengthen long-range cortico-cortical connectivity often weakened in older autistic individuals.Taken together, the Cheung glutamatergic regimen may emerge as a low-cost, easily deployed option with genuine promise for post-pubertal autistic patients. Its use in younger children, however, cannot be justified on current evidence and should be strictly avoided until the early surplus of synapses has resolved.