Saffron as Medicine The crocins are hydrophilic carotenoids that can act as antioxidants, are an effective antidepressant/anxiolytic, improve learning and memory, can be used for treatment of brain injury, mood disorders, OCD, joint pain and muscle dysfunction in osteoarthritis, metabolic syndrome and neurodegenerative damage, and utilised for neuroprotective effects. While most of the data supports antidepressant effects, there is preliminary research indicating efficacy in ADHD and dementias and preclinical data suggesting possible use in a range of CNS conditions. Safranal is an effective anticonvulsant in animal models, shown to act as an agonist at GABAA receptors. Saffron extracts and crocetin had a clear binding capacity at the PCP binding side of the NMDA receptor and at the sigma-1 receptor while crocins attenuated schizophrenia-like behavioural deficits. Crocin has been shown to be an antioxidant and neural protective agent Aside from the NMDA affinity and sigma-1 binding, there is evidence that crocins act as reuptake inhibitors of dopamine and norepinephrine, while aside from it's GABAA affinity, safranal acts primarily on serotonin reuptake. "The antioxidant properties of saffron derivatives may also be relevant. Mood disorders are associated with elevated oxidative stress and a deficit of exogenous antioxidants, affecting immune and inflammatory responses in a way, which may promote neurodegeneration (Leonard and Maes, 2012). There is good evidence that the antioxidants in saffron extracts protect against oxidative stress in the central nervous system (Mehri et al. 2015; Oruc et al. 2016), constituting a second potential mechanism of therapeutic action." In an analysis of 63 saffrons, the crocin I content range was 6.6–23.7 %. Saffron has a good safety margin, while 30mg may prove effective “to a daily maximum dose of 1.5 grams there has not been any risk documented. Lethal dose is 20 g and the abortive dose, 10 g, because as such it was employed in the past due to its stimulating 1 action on the smooth muscle of the uterus. 5 g daily dose can already cause intoxication accompanied by vomiting, bloody diarrhea, hematuria, skin hemorrhages in nose, lips and eyelids, vertigo and dulling. The skin and mucous membranes take a yellowish colour similar to jaundice”. Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. It reputedly has acute effects. Saffron is a potential efficacious and tolerable treatment for major depressive disorder with anxious distress. [1] It increased mood, reduced anxiety and managed stress without side effects, offering a natural alternative to standard treatments [2] Saffron is as effective as fluvoxamine in the treatment of patients with mild to moderate OCD [3] Research for ADHD in children [4, 5] is promising and as an augmentation option with methylphenidate in adults [6] and it appears to potentially rival conventional therapeutic options in dementia [7] [1] https://www.ncbi.nlm.nih.gov/pubmed/27701683 [2] https://www.ncbi.nlm.nih.gov/pubmed/28735826 [3] https://www.ncbi.nlm.nih.gov/pubmed/29062366 [4] https://doi.org/10.1089/cap.2018.0146 [5] https://doi.org/10.3390/nu14194046 [6] https://doi.org/10.1016/j.aimed.2022.01.002 [7] https://doi.org/10.1186/s12906-020-03102-3 2