tuneTypical Dose
15 mg twice daily
Chemical Compound
Crocin
Crocus sativus L. active carotenoid
Evidence TierCWADA NOT PROHIBITED
watchEffect Window
short-to-moderate, typically 4 to 12 weeks
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Crocin is a carotenoid glycoside from saffron with antioxidant and neuroactive properties. It is used for mood support and oxidative stress modulation, often within saffron extracts.
Randomized trials of saffron extracts rich in crocin show improvements in mild-to-moderate depressive symptoms and some PMS-related mood measures. Antioxidant and anti-inflammatory mechanisms are plausible contributors. Minority studies suggest appetite effects, erectile function improvements, and cognitive benefits, with variable strength of evidence. Effects depend on verified saffron authenticity and standardized extraction.
Potential mood and distress benefit aligns with anti-inflammatory and antioxidant patterns reported in trials, with incomplete evidence for direct nootropic performance effects.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Reduce BDI/BAI/GHQ symptom burden in selected adult clinical populations.
Secondary Outcomes
- Reduce neuropathic pain/sensory scores in selected trials. Improve sleep and withdrawal distress in specific opioid-treatment samples.
Safety
Contraindications and Interactions
Contraindications
- Pregnancy
- Lactation
- Unstable psychiatric disease
- Active severe liver or kidney disease
Side effects
- Dry mouth
- Anxiety
- Drowsiness
- Nausea at high doses
Interactions
- SSRIs, MAOIs, anticoagulants, multiple herbal mood agents with overlapping effects
Avoid if
- Active malignancy
- Unstable cardiovascular or psychiatric disease
Evidence
Study-level References
crocin-SRC-001Randomized, double-blind, placebo-controlled pilot clinical trial
Sourceopen_in_newPMID: 25484177, DOI: 10.1016/j.jad.2014.11.035
Population: Adults with major depressive disorder on SSRI treatment
Dose protocol: Crocin 15 mg twice daily (30 mg/day) for 4 weeks, adjunctive to SSRI
Key findings: Favorable. Depression/anxiety scale scores improved versus placebo. Significant BDI/BAI/GHQ improvements in treatment arm. Small sample and short follow-up.
Paper content
favorable; depression/anxiety scale scores improved versus placebo Significant BDI/BAI/GHQ improvements in treatment arm; small sample and short follow-up.
crocin-SRC-002Randomized, double-blind, placebo-controlled trial
Sourceopen_in_newPMID: 27101556, DOI: 10.1515/jcim-2015-0043
Population: Adults with anxiety and depression
Dose protocol: Saffron extract 50 mg twice daily for 12 weeks (indirect evidence on crocin-rich matrix)
Key findings: Favorable for BDI and BAI scores. Not pure crocin preparation. Significant mood-scale improvements at 12 weeks with lower internal validity for isolated crocin attribution.
Paper content
favorable for BDI and BAI scores; not pure crocin preparation Significant mood-scale improvements at 12 weeks with lower internal validity for isolated crocin attribution.
crocin-SRC-003Randomized clinical trial
Sourceopen_in_newPMID: 30795785, DOI: 10.1186/s13011-019-0198-1
Population: Patients under methadone maintenance treatment
Dose protocol: Crocin 15 mg twice daily for 8 weeks
Key findings: Favorable for depression/anxiety/sleep and some sexual-health metrics. Improved psychological scores and sleep compared with placebo. No severe safety signal reported.
Paper content
favorable for depression/anxiety/sleep and some sexual-health metrics Improved psychological scores and sleep compared with placebo; no severe safety signal reported.
crocin-SRC-004Randomized clinical trial
Sourceopen_in_newPMID: 33078480, DOI: 10.1002/ptr.6913
Population: Opioid patients under methadone maintenance
Dose protocol: Crocin 30 mg/day for 12 weeks
Key findings: Favorable for craving/withdrawal. Null for measured cognition. Craving and withdrawal scores improved. Cognitive tests did not show significant benefit.
Paper content
favorable for craving/withdrawal; null for measured cognition Craving and withdrawal scores improved; cognitive tests did not show significant benefit.
crocin-SRC-005Randomized, double-blind, placebo-controlled trial (crossover design)
Sourceopen_in_newPMID: 34390797, DOI: 10.1016/j.jep.2021.114511
Population: Adults with chemotherapy-induced peripheral neuropathy
Dose protocol: Crocin 15 mg twice daily (30 mg/day), 8-week crossover
Key findings: Favorable for neuropathic pain/sensory endpoints, moderate-to-small effect. Sensory, motor, and neuropathic pain scores improved versus placebo. Toxicities were mild.
Paper content
favorable for neuropathic pain/sensory endpoints; moderate-to-small effect Sensory, motor, and neuropathic pain scores improved versus placebo; toxicities were mild.
crocin-SRC-006Preliminary randomized triple-blind, placebo-controlled trial
Sourceopen_in_newPMID: 40813999, DOI: 10.1186/s40780-025-00484-9
Population: Adults with diabetic neuropathy
Dose protocol: Crocin 15 mg/day for 12 weeks
Key findings: Promising but preliminary. Pain/symptom scores improved vs placebo. Lower TSS, VAS, and MNSI trends at later visits. Trial size was small.
Paper content
promising but preliminary; pain/symptom scores improved vs placebo Lower TSS, VAS, and MNSI trends at later visits; trial size was small.
crocin-SRC-007Systematic review and meta-analysis of RCTs
Sourceopen_in_newPMID: 39632602, DOI: 10.1002/ptr.8380
Population: Adults in multiple disease contexts
Dose protocol: Crocin and saffron preparations. Most crocin studies 15-30 mg/day in the pooled set.
Key findings: favorable for CRP, TNF-α, IL-6 and TAC, but clinical endpoint linkage is limited Anti-inflammatory and antioxidant biomarker effects were observed with better signal in longer-duration regimens.
Paper content
favorable for CRP, TNF-α, IL-6 and TAC, but clinical endpoint linkage is limited Anti-inflammatory and antioxidant biomarker effects were observed with better signal in longer-duration regimens.
crocin-SRC-008Double-blind randomized controlled trial.
Sourceopen_in_newRezaiee R, Ghazizadeh H, Darroudi S, et al. The impacts of crocin on serum cytokines concentrations in participants with metabolic syndrome: a double-blind randomized clinical trial study. Sci Rep. 2025;15(1):29975. doi:10.1038/s41598-025-15953-2. PMID:40817397.
Population: Adults with metabolic syndrome.
Dose protocol: Crocin 15 mg/day for 8 weeks in adults with metabolic syndrome.
Key findings: Significant reductions in IL-2, IL-10, VEGF, and IFN-gamma versus baseline. Lipid profile and fasting glucose were not significantly changed.
Notes: Small sample (n=28) but extends the crocin cytokine-reduction signal into metabolic syndrome, a chronic low-grade inflammation population.
Paper content
This double-blind RCT tested crocin 15 mg/day for 8 weeks in 28 adults with metabolic syndrome. The crocin group showed significant reductions in IL-2, IL-10, VEGF, and IFN-gamma compared with baseline. Lipid profile and fasting glucose did not change meaningfully. The study extends the crocin inflammatory biomarker evidence into metabolic syndrome, a population with chronic low-grade inflammation. Sample size is small, limiting generalizability, but the direction aligns with prior saffron/crocin anti-inflammatory meta-analyses.