Analytical Approaches to the Quantitative Evaluation of Endocannabinoids and Glucocorticoids as Stress Markers: Growing Evidence for Hair Testing

Space is a stressful environment, and any analytical evaluation of biochemical stress markers needs to account for numerous confounding factors which may significantly affect its interpretation. Appropriate biochemical markers need to be defined to reflect the relevant stress kinetics, e.g. acute vs. chronic mechanisms to cope external influences. These markers—or corresponding diagnostic biotransformation products—need to be sufficiently stable in the relevant timeframe of stress adaptation and differ significantly from basal values. Another critical parameter is the selection of suitable biological matrices which reflects stress-related variations of its markers in a diagnostic way and permits retrospective diagnostics. This includes systemic challenges, because collection of matrix from the biochemically most insightful target location—which is mainly the brain—is only conceivable in animal experiments. Blood represents the most suitable and logical compromise between diagnostic value and practical feasibility (i.e. low-invasiveness) of sample collection. However, hair samples start to serve for certain parameters as very reliable biospecimens. Because of the growth rate they may not allow high time resolution of days or hours, but permit an integration of stress responses over several weeks and months, as a retrospective calendar of stress. Any other common specimen is affected by additional biotransformation reactions (in particular urine) and by substance-specific incorporation or excretion mechanisms and lacks specificity and sensitivity.