4. Discussion
depression, anxiety
The current study is the first double-blind, randomized, crossover study that explored the effect of a single dose of a proprietary saffron extract (Safr’InsideIrrespective of the treatment, the participants found the MAST to indeed be stressful, as suggested by the increase in perceived anxiety and stress 15 min after completing the stressor and to a lesser extent in the salivary cortisol and cortisone 30 min post-stressor. As expected, the HPA axis stress response related to cortisol secretion was in line with previous studies using the MAST in healthy young men [To our knowledge, no clinical study has investigated the efficacy of an acute saffron extract or safranal neither using oral nor sublingual administration in an acute experimental stress setting on psychological and biological markers, including salivary cortisol and its metabolite, cortisone. Salivary cortisol is commonly used as a surrogate marker of serum free cortisol in psychophysiological stress research with its tremendous advantage of non-invasive sample collection. Recently, salivary cortisone has been identified as a promising stress marker that showed a high discriminatory power and significant associations with subjective stress measures [Interestingly, the saffron extract and safranal increased the peaking time to reach the maximum concentration of salivary cortisol and cortisone after acute stress in comparison to the placebo, suggesting a delayed glucocorticoid secretion. However, the multiple pairwise comparison revealed a significant difference between the saffron extract and placebo groups. The anxiolytic effect of saffron was previously demonstrated in patients with mild to moderate depression [It is well known that stress activates the HPA axis, leading to the plasma corticosterone increase as a response in mice [Participants receiving Safr’InsideThe primary strength of this study includes the use of both objective and subjective outcomes measures to assess the anti-stress effect of a saffron extract and its main volatile compound, safranal, in healthy non-stressed men experiencing a validated laboratory stress procedure (MAST). Secondly, as the anti-stress effect should be collected quickly after product intake, we administered the tested product via the sublingual route to provide the immediate onset of pharmacological effect [However, despite several positive findings from this study, some limitations should be acknowledged, suggesting directions for future research. Firstly, as greater acute HPA responses have been found in adult men as compared to adult women [