Saffron

Saffron was a mood-lifting herb. In his encyclopaedia Al-Hawi, Razi (Rhazes) wrote that it brings a strong feeling of pleasure, and he described it as a sedative and a heart-enlivening agent ^{46Reference 46Mollazadeh et al. · 2015ReviewRazi’s Al-Hawi and saffron (Crocus sativus): a review — historical/traditional-use reviewView study →}. It is still used for depression in Persian traditional medicine ^{7,42Reference 7Akhondzadeh et al. · 2005RCTCrocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomised and placebo-controlled trialView study →Reference 42Noorbala et al. · 2005RCTHydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomised pilot trialView study →}.

It was also a digestive. Razi wrote that it cleanses the stomach, aids digestion and strengthens the liver and stomach, and Persian practice counts it good for stomach complaints and as an antispasmodic ^{7,46Reference 7Akhondzadeh et al. · 2005RCTCrocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomised and placebo-controlled trialView study →Reference 46Mollazadeh et al. · 2015ReviewRazi’s Al-Hawi and saffron (Crocus sativus): a review — historical/traditional-use reviewView study →}.

Razi called saffron a diuretic and a stimulant of sexual desire, and Iranian medicine used it as an aphrodisiac and an emmenagogue ^{46Reference 46Mollazadeh et al. · 2015ReviewRazi’s Al-Hawi and saffron (Crocus sativus): a review — historical/traditional-use reviewView study →}.

It was given to ease difficult labour and uterine pain and to regulate the menstrual cycle. Razi wrote that 6–7 g of saffron brings on delivery, and he warned that about 13.5 g brings an excess of joy that may be fatal ^{46Reference 46Mollazadeh et al. · 2015ReviewRazi’s Al-Hawi and saffron (Crocus sativus): a review — historical/traditional-use reviewView study →}.

In Chinese medicine saffron is Zang Hong Hua (藏红花), and the drug is the dried stigma ^{39,49Reference 39CHANG PY et al. · 1964Studies on the pharmacological action of Crocus sativus L.: effects on the uterus and estrus cycle — animal study. https://pubmed.ncbi.nlm.nih.gov/14141441/View study →Reference 49Xing B et al. · 2021ReviewPhytochemistry, pharmacology, and potential clinical applications of saffron: A review — reviewView study →}.

It is classed as a herb that promotes blood circulation and resolves blood stasis. It also cools the blood and relieves toxicity, and it relieves depression ^{49Reference 49Xing B et al. · 2021ReviewPhytochemistry, pharmacology, and potential clinical applications of saffron: A review — reviewView study →}.

Its indications follow from that classification: depression, irregular menstruation, postpartum blood stasis (described in modern reviews as postpartum thrombosis), and bruises ^{49Reference 49Xing B et al. · 2021ReviewPhytochemistry, pharmacology, and potential clinical applications of saffron: A review — reviewView study →}.

Its use for low mood agrees with Persian practice, and its blood-moving action matches the emmenagogue use recorded by Razi ^{46,49Reference 46Mollazadeh et al. · 2015ReviewRazi’s Al-Hawi and saffron (Crocus sativus): a review — historical/traditional-use reviewView study →Reference 49Xing B et al. · 2021ReviewPhytochemistry, pharmacology, and potential clinical applications of saffron: A review — reviewView study →}.

Grieve’s early 20th-century herbal lists saffron as a carminative, diaphoretic and emmenagogue. It was given to children to bring on sweating, and to adults for chronic bleeding from the uterus ^{45Reference 45A Modern Herbal | SaffronA Modern Herbal | Saffron. (n.d.). Grieve, M. Retrieved from https://www.botanical.com/botanical/mgmh/s/saffro03.htmlView study →}.

In London, saffron “tea” flavoured with brandy was a household remedy for measles ^{45Reference 45A Modern Herbal | SaffronA Modern Herbal | Saffron. (n.d.). Grieve, M. Retrieved from https://www.botanical.com/botanical/mgmh/s/saffro03.htmlView study →}.

In a double-blind trial in 40 outpatients with mild to moderate depression, dried stigma at 30 mg/day beat placebo on the Hamilton Depression Rating Scale over six weeks ^{7Reference 7Akhondzadeh et al. · 2005RCTCrocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomised and placebo-controlled trialView study →}.

A companion trial reported the same for 30 mg/day of the petal ^{8Reference 8Moshiri et al. · 2006RCTCrocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomised and placebo-controlled trialView study →}, a different plant part from the stigma.

In active-comparator trials, saffron 30 mg/day performed like imipramine 100 mg/day in 30 patients ^{41Reference 41Akhondzadeh et al. · 2004RCTComparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomised trialView study →}, and a hydroalcoholic stigma extract at 30 mg/day performed like fluoxetine 20 mg/day in 40 patients ^{42Reference 42Noorbala et al. · 2005RCTHydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomised pilot trialView study →}.

A 2019 meta-analysis pooled nine trials and found saffron more effective than placebo (g = 0.89) and non-inferior to antidepressants ^{2Reference 2Tóth et al. · 2019Meta-analysisThe efficacy of saffron in the treatment of mild to moderate depression: a meta-analysisView study →}. A 2020 meta-analysis of 12 studies reached the same result, with no difference in adverse effects ^{3Reference 3Dai et al. · 2020Meta-analysisSafety and efficacy of saffron (Crocus sativus L.) for treating mild to moderate depression: a systematic review and meta-analysisView study →}. A 2025 meta-analysis of eight head-to-head trials found no difference from SSRIs for depression, with fewer adverse events on saffron ^{40Reference 40Shafiee A et al. · 2025Meta-analysisEffect of saffron versus selective serotonin reuptake inhibitors (SSRIs) in treatment of depression and anxiety: a systematic review and meta-analysis. https://pubmed.ncbi.nlm.nih.gov/38913392/View study →}.

An umbrella analysis of seven meta-analyses found a fall in Beck Depression Inventory scores, but no significant change in Hamilton scores ^{5Reference 5Musazadeh et al. · 2022Meta-analysisSaffron, as an adjunct therapy, contributes to relieve depression symptoms: an umbrella meta-analysisView study →}. A 2026 GRADE-assessed review of 34 trials (1,769 participants) found the same pattern: self-rated depression scores fell, while the clinician-rated Hamilton scale did not change significantly. It rated the certainty of the evidence as moderate ^{6Reference 6Mahmoudi R et al. · 2026Meta-analysisEffect of saffron on depression, anxiety and mood disorder: a GRADE-assessed systematic review and meta-analysis of 34 randomised controlled trialsView study →}.

In 128 adults with self-reported low mood, a standardised extract (affron® 28 mg/day) improved mood over four weeks, while 22 mg/day did not ^{9Reference 9Kell et al. · 2017RCTaffron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomised, placebo-controlled clinical trialView study →}. A 2025 trial in 51 adults with subclinical symptoms found no effect on its combined depression, anxiety and fatigue score ^{10Reference 10Amadieu C et al. · 2025RCTEffect of saffron extract supplementation on mood in healthy adults with subclinical symptoms of depression: a randomised, double-blind placebo-controlled studyView study →}.

Gap: the benefit is consistent on self-rated scales but not on clinician-rated ones, and the trials are short, mostly six to eight weeks, and modest in size. Long-term efficacy, relapse prevention and severe depression are untested.

Anxiety is usually measured as a secondary outcome in saffron’s mood trials.

In a network meta-analysis of herbs for anxiety, saffron did not significantly lower Hamilton anxiety scores in the main network (mean difference −2.71; 95% credible interval −6.06 to 0.57), although separate networks supported further study ^{4Reference 4Zhang et al. · 2022Meta-analysisMedicinal herbs for the treatment of anxiety: a systematic review and network meta-analysisView study →}. The 2026 review found a fall in self-rated anxiety (Beck Anxiety Inventory) but not in the clinician-rated Hamilton scale ^{6Reference 6Mahmoudi R et al. · 2026Meta-analysisEffect of saffron on depression, anxiety and mood disorder: a GRADE-assessed systematic review and meta-analysis of 34 randomised controlled trialsView study →}.

A 2025 meta-analysis of four trials found no difference between saffron and SSRIs for anxiety, with fewer adverse events on saffron ^{40Reference 40Shafiee A et al. · 2025Meta-analysisEffect of saffron versus selective serotonin reuptake inhibitors (SSRIs) in treatment of depression and anxiety: a systematic review and meta-analysis. https://pubmed.ncbi.nlm.nih.gov/38913392/View study →}. The affron® trial in healthy adults reported less stress and anxiety at 28 mg/day ^{9Reference 9Kell et al. · 2017RCTaffron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomised, placebo-controlled clinical trialView study →}, and the 2025 trial in adults with subclinical symptoms found no change in anxiety ^{10Reference 10Amadieu C et al. · 2025RCTEffect of saffron extract supplementation on mood in healthy adults with subclinical symptoms of depression: a randomised, double-blind placebo-controlled studyView study →}.

Few trials use anxiety as the primary endpoint or enrol people with a diagnosed anxiety disorder.

A 2022 meta-analysis of randomised trials found saffron improved several validated sleep scores against placebo. In its subgroup analysis, 100 mg/day gave the most stable effect ^{12Reference 12Lian J et al. · 2022Meta-analysisEffects of saffron supplementation on improving sleep quality: a meta-analysis of randomised controlled trialsView study →}.

In 66 adults with mild to moderate sleep problems linked to anxiety, 15.5 mg/day of an extract for six weeks increased time in bed on actigraphy and improved questionnaire sleep scores ^{13Reference 13Pachikian BD et al. · 2021RCTEffects of saffron extract on sleep quality: a randomised double-blind controlled clinical trialView study →}.

In 120 adults with poor sleep, 14 or 28 mg of affron® taken an hour before bed for 28 days improved sleep-quality ratings and raised evening melatonin, without changing cortisol ^{11Reference 11Lopresti et al. · 2021RCTAn investigation into an evening intake of a saffron extract (affron®) on sleep quality, cortisol, and melatonin concentrations in adults with poor sleep: a randomised, double-blind, placebo-controlled, multi-dose studyView study →}.

In a crossover trial in 30 adults, the constituent crocetin at 7.5 mg/day increased EEG delta power during sleep and improved feeling refreshed on waking ^{14Reference 14Umigai N et al. · 2018RCTEffect of crocetin on quality of sleep: a randomised, double-blind, placebo-controlled, crossover studyView study →}.

Most endpoints are questionnaires, and the objective measures come from small samples.

In a double-blind placebo-controlled trial, women aged 20–45 took saffron 30 mg/day (15 mg twice daily) for two menstrual cycles. Total premenstrual symptoms and Hamilton depression scores improved against placebo ^{15Reference 15Agha-Hosseini et al. · 2008RCTCrocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trialView study →}.

A 2026 meta-analysis of the randomised trials found a benefit for premenstrual symptoms (SMD −0.64; 95% CI −0.84 to −0.44) and a smaller effect on period pain (SMD −0.51; 95% CI −1.01 to −0.01) ^{16Reference 16Mohammadi MM · 2026Meta-analysisEffect of saffron on premenstrual syndrome and dysmenorrhea: a systematic review and meta-analysisView study →}.

The trial base is small, and the confidence interval for period pain comes close to zero.

Saffron and its constituents act as free-radical scavengers and raise antioxidant capacity in cell and animal studies ^{34Reference 34Boskabady et al. · 2016ReviewAnti-inflammatory, antioxidant, and immunomodulatory effects of Crocus sativus L. and its main constituents — reviewView study →}.

In people, the evidence is a biomarker. In a trial in 75 overweight or obese adults with prediabetes, 15 mg/day for eight weeks raised DPPH radical-scavenging activity within the saffron group, but the difference from placebo was only a trend ^{32Reference 32Karimi-Nazari E et al. · 2019RCTEffect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: a double-blinded, randomised controlled trialView study →}.

The antioxidant activity is a mechanism behind other findings rather than a clinical outcome in itself.

Gap: the one human measure is a within-group biomarker change that was only a trend against placebo.

The strongest data concern sexual dysfunction caused by fluoxetine. In a placebo-controlled trial, 36 men on stable fluoxetine took saffron 15 mg twice daily for four weeks, and erectile function and intercourse satisfaction improved ^{18Reference 18Modabbernia et al. · 2012RCTEffect of saffron on fluoxetine-induced sexual impairment in men: randomised double-blind placebo-controlled trialView study →}.

In 38 women on fluoxetine, 30 mg/day for four weeks improved the Female Sexual Function Index total, arousal, lubrication and pain scores, though not desire, satisfaction or orgasm ^{17Reference 17Kashani et al. · 2013RCTSaffron for treatment of fluoxetine-induced sexual dysfunction in women: randomised double-blind placebo-controlled studyView study →}.

A three-centre trial in 74 women with sexual dysfunction found 15 mg twice daily for six weeks improved desire, lubrication and satisfaction ^{19Reference 19Kashani L et al. · 2022RCTCrocus sativus (saffron) in the treatment of female sexual dysfunction: a three-center, double-blind, randomised, and placebo-controlled clinical trialView study →}. A topical saffron gel improved erectile function in 50 men with diabetes ^{20Reference 20Mohammadzadeh-Moghadam et al. · 2015RCTEffects of a topical saffron (Crocus sativus L.) gel on erectile dysfunction in diabetics: a randomised, parallel-group, double-blind, placebo-controlled trialView study →}.

The trials are short and small, and most concern dysfunction caused by antidepressants.

In 46 patients with mild to moderate Alzheimer’s disease, saffron 30 mg/day for 16 weeks improved cognitive scores (ADAS-cog) against placebo ^{21Reference 21Akhondzadeh et al. · 2010RCTSaffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16-week, randomised and placebo-controlled trialView study →}.

In 68 patients with moderate to severe Alzheimer’s disease, saffron extract 30 mg/day for 12 months performed like memantine 20 mg/day on cognitive decline ^{22Reference 22Farokhnia et al. · 2014RCTComparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer’s disease: a double-blind randomised clinical trialView study →}.

A 2020 meta-analysis of four randomised trials found saffron improved cognitive scores against placebo and did not differ from conventional drugs ^{23Reference 23Ayati Z et al. · 2020Meta-analysisSaffron for mild cognitive impairment and dementia: a systematic review and meta-analysis of randomised clinical trialsView study →}. A systematic review of five trials (325 people) found the same, with no difference from donepezil or memantine, and noted a potentially high risk of bias ^{24Reference 24Avgerinos et al. · 2020Systematic reviewEffects of saffron (Crocus sativus L.) on cognitive function: a systematic review of RCTsView study →}.

The trials are small and short relative to the course of dementia, and whether saffron slows the disease is unknown.

In a crossover trial in 100 adults with mild or moderate AMD, oral saffron 20 mg/day for three months improved visual acuity by 0.69 letters and shortened the retina’s electrical response time (mfERG latency). Among those already taking AREDS supplements, mfERG response density also improved ^{27Reference 27Broadhead et al. · 2019RCTSaffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trialView study →}.

In a 12-month open-label extension in 93 of these adults, mfERG response density was higher in the central rings. Visual acuity was 1.6 letters worse, possibly because of cataract progression ^{28Reference 28Broadhead GK et al. · 2024Saffron therapy for the ongoing treatment of age-related macular degenerationView study →}.

In 25 patients with early AMD, 20 mg/day for three months improved retinal flicker sensitivity ^{29Reference 29Falsini et al. · 2010Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degenerationView study →}.

In 60 patients with diabetic macular oedema that had not responded to standard treatment, crocin 15 mg/day for three months reduced central macular thickness and HbA1c and improved visual acuity against placebo ^{30Reference 30Sepahi et al. · 2018RCTEffects of crocin on diabetic maculopathy: a placebo-controlled randomised clinical trialView study →}.

The endpoints are mostly retinal function rather than long-term vision, the samples are small, and progression to advanced AMD is untested.

Most of the anti-inflammatory evidence is preclinical: saffron and its constituents crocin, crocetin and safranal modulate inflammatory mediators in cell and animal models ^{34Reference 34Boskabady et al. · 2016ReviewAnti-inflammatory, antioxidant, and immunomodulatory effects of Crocus sativus L. and its main constituents — reviewView study →}.

The clearest human signal is a placebo-controlled trial in 57 people with COPD. Crocin 15 mg twice daily for 12 weeks lowered serum TNF-α and improved lung function and six-minute walking distance ^{33Reference 33Aslani MR et al. · 2023RCTEffect of crocin of Crocus sativus L. on serum inflammatory markers (IL-6 and TNF-α) in chronic obstructive pulmonary disease patients: a randomised, double-blind, placebo-controlled trialView study →}.

Gap: the one controlled human trial used isolated crocin, not the whole stigma; the rest is cell and animal work.

In a six-week pilot trial, 54 children aged 6–17 with ADHD took saffron or methylphenidate at 20–30 mg/day by body weight. Teacher and parent rating scores did not differ between the two groups ^{25Reference 25Baziar et al. · 2019RCTCrocus sativus L. versus methylphenidate in treatment of children with attention-deficit/hyperactivity disorder: a randomised, double-blind pilot studyView study →}.

A 2024 review of four studies (118 patients in total), including trials of saffron alongside methylphenidate, found saffron helped ADHD symptoms with an acceptable safety profile ^{26Reference 26Seyedi-Sahebari S et al. · 2024Systematic reviewThe effects of Crocus sativus (saffron) on ADHD: a systematic reviewView study →}.

Gap: the studies are small and short, and the head-to-head trial had no placebo arm.

A 2024 meta-analysis pooled 15 trials in type 2 diabetes. Saffron extract lowered HbA1c by 0.35% (95% CI −0.65 to −0.06) and fasting glucose, and crocin lowered HbA1c, fasting glucose and systolic blood pressure. Powdered saffron raised BMI slightly, and crocin raised serum creatinine by 0.24 mg/dL ^{31Reference 31Amatto PPG et al. · 2024Meta-analysisEffect of Crocus sativus L. (saffron) and crocin in the treatment of patients with type-2 diabetes mellitus: a systematic review and meta-analysisView study →}.

In 75 overweight or obese adults with prediabetes, 15 mg/day for eight weeks lowered fasting glucose by 7.97 mg/dL and HbA1c by 0.15% against placebo, with no change in blood lipids ^{32Reference 32Karimi-Nazari E et al. · 2019RCTEffect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: a double-blinded, randomised controlled trialView study →}.

The effects are small and vary between trials.

Anticancer activity is entirely preclinical. A 2025 systematic review of 44 preclinical breast-cancer studies found saffron’s constituents, especially crocin and crocetin, act through apoptosis and cell-cycle effects ^{35Reference 35Hasheminasab FS · 2025Systematic reviewEfficacy of saffron (Crocus sativus L.) and its constituents on breast cancer: a systematic review of preclinical studies. https://pubmed.ncbi.nlm.nih.gov/40819247/View study →}. A review of crocin describes antitumour activity in experimental models ^{36Reference 36Alavizadeh et al. · 2014ReviewBioactivity assessment and toxicity of crocin: a comprehensive review. https://pubmed.ncbi.nlm.nih.gov/24275090/View study →}.

Gap: no human efficacy trials exist.

Trial doses. In the depression trials, saffron at about 30 mg/day caused adverse effects no more often than placebo or antidepressants ^{3Reference 3Dai et al. · 2020Meta-analysisSafety and efficacy of saffron (Crocus sativus L.) for treating mild to moderate depression: a systematic review and meta-analysisView study →}. Compared with SSRIs, it caused fewer ^{40Reference 40Shafiee A et al. · 2025Meta-analysisEffect of saffron versus selective serotonin reuptake inhibitors (SSRIs) in treatment of depression and anxiety: a systematic review and meta-analysis. https://pubmed.ncbi.nlm.nih.gov/38913392/View study →}.

Toxic doses. Toxic effects are reported from 5 g a day, and about 20 g can be lethal ^{23Reference 23Ayati Z et al. · 2020Meta-analysisSaffron for mild cognitive impairment and dementia: a systematic review and meta-analysis of randomised clinical trialsView study →}. Razi warned that 13.5 g brings an excess of joy that may be fatal ^{46Reference 46Mollazadeh et al. · 2015ReviewRazi’s Al-Hawi and saffron (Crocus sativus): a review — historical/traditional-use reviewView study →}.

Antidepressant and serotonergic drugs. Crocin and safranal have been proposed to inhibit serotonin reuptake ^{48Reference 48Siddiqui et al. · 2018ReviewSaffron (Crocus sativus L.): as an antidepressant — reviewView study →}, which suggests care alongside SSRIs and other serotonergic drugs. No interaction has been reported, and saffron has been trialled alongside fluoxetine to treat its sexual side effects ^{17,18Reference 17Kashani et al. · 2013RCTSaffron for treatment of fluoxetine-induced sexual dysfunction in women: randomised double-blind placebo-controlled studyView study →Reference 18Modabbernia et al. · 2012RCTEffect of saffron on fluoxetine-induced sexual impairment in men: randomised double-blind placebo-controlled trialView study →}.

Sedatives. Saffron extracts improved sleep in trials ^{11,12Reference 11Lopresti et al. · 2021RCTAn investigation into an evening intake of a saffron extract (affron®) on sleep quality, cortisol, and melatonin concentrations in adults with poor sleep: a randomised, double-blind, placebo-controlled, multi-dose studyView study →Reference 12Lian J et al. · 2022Meta-analysisEffects of saffron supplementation on improving sleep quality: a meta-analysis of randomised controlled trialsView study →}, so an additive effect with sedative drugs is possible. This has not been tested as an interaction.

Diabetes medicines. In people with type 2 diabetes, saffron extract and crocin lowered HbA1c and fasting glucose ^{31Reference 31Amatto PPG et al. · 2024Meta-analysisEffect of Crocus sativus L. (saffron) and crocin in the treatment of patients with type-2 diabetes mellitus: a systematic review and meta-analysisView study →}, so they may add to the effect of glucose-lowering drugs. Monitor blood sugar.

Anticoagulant and antiplatelet drugs. Saffron has affected platelet aggregation and coagulation in laboratory and animal studies ^{54Reference 54Ayatollahi H et al. · 2014RCTEffect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers — randomised controlled trialView study →}. In a double-blind trial in 60 healthy volunteers, 200 or 400 mg a day for seven days did not change PT, PTT, fibrinogen, factor VII or proteins C and S ^{54Reference 54Ayatollahi H et al. · 2014RCTEffect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers — randomised controlled trialView study →}. A bleeding interaction at normal doses is therefore theoretical, though care is reasonable with anticoagulants or a bleeding disorder.

Drug metabolism. In 34 healthy volunteers, a saffron stigma infusion for six days lowered CYP1A2 activity, measured by caffeine metabolism, by about 14% in saliva. The fall was significant in men but not in women, and CYP2A6, xanthine oxidase and NAT2 were unchanged ^{52Reference 52Begas E et al. · 2019Clinical trialEffects of short-term saffron (Crocus sativus L.) intake on the in vivo activities of xenobiotic metabolizing enzymes in healthy volunteers — human studyView study →}. The authors judged a CYP1A2 interaction possible in men and others unlikely ^{52Reference 52Begas E et al. · 2019Clinical trialEffects of short-term saffron (Crocus sativus L.) intake on the in vivo activities of xenobiotic metabolizing enzymes in healthy volunteers — human studyView study →}. A 2025 review of laboratory and animal work found that saffron, crocin and safranal affect CYP1A1/2, CYP2E1 and CYP3A4, with CYP3A4 inhibition the most important for drug interactions; none of this has been tested in people ^{53Reference 53Bathaei P et al. · 2025ReviewEffects of Crocus sativus and its active constituents on cytochrome P450: a review — reviewView study →}.

Kidney function. In the diabetes meta-analysis, crocin raised serum creatinine (by 0.24 mg/dL on average), so care is reasonable in people with kidney disease ^{31Reference 31Amatto PPG et al. · 2024Meta-analysisEffect of Crocus sativus L. (saffron) and crocin in the treatment of patients with type-2 diabetes mellitus: a systematic review and meta-analysisView study →}.

Children. A six-week pilot trial gave children aged 6–17 20–30 mg a day by body weight ^{25Reference 25Baziar et al. · 2019RCTCrocus sativus L. versus methylphenidate in treatment of children with attention-deficit/hyperactivity disorder: a randomised, double-blind pilot studyView study →}, and a review of four ADHD studies found an acceptable safety profile ^{26Reference 26Seyedi-Sahebari S et al. · 2024Systematic reviewThe effects of Crocus sativus (saffron) on ADHD: a systematic reviewView study →}. Paediatric data come only from these small, short studies.