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Declarations Competing Interests The authors declare no competing interests
2023 Nov 17;15(22):4809
The three compounds, in a rigorous research approach, require: strict analytical control (MS + HPLC 98%), adapted administration route (intranasal for BBB crossing), standardised behavioural model with positive control, and exhaustive documentation for publication
Prior to the analyses shown here, the BMD 50 was estimated in addition to the BMD 100 to compare different critical effect sizes for ranking of NAs (data not shown)
These effects accumulate in brain tissue and persist longer than the compound remains in the bloodstream: A single dose's effects on synaptic density, VEGF signalling, and neuroprotective cascades may last for hours or days after blood levels have dropped to zero Repeated dosing likely leads to cumulative effectseach dose "adds to" the previous dose's neurobiological changes Anecdotal reports of sustained effects after discontinuation (weeks to months in some cases) are consistent with persistent brain changes rather than active drug presence Implications for Dosing This is a crucial point: the observation that effects outlast blood concentrations explains why some community members report benefits from periodic (not daily) dosing and why cycling protocols exist
