Benefits
Better mood scores in adults with low mood
In placebo-controlled trials of adults recruited for low mood rather than a diagnosis of depression, 28 mg/day of affron for 4 to 12 weeks improved mood or depression-symptom questionnaire scores more than placebo, including in a trial of women aged 50 to 70. In the largest trial the difference was modest, placebo responses were large, and other wellbeing measures did not differ. Most of these trials were funded by the manufacturer.
Mood scores as an add-on in adults taking antidepressants
In one 8-week trial of 139 adults with persistent depressive symptoms despite antidepressant treatment, adding affron 14 mg twice daily lowered clinician-rated scores more than placebo (41% vs 21%), but self-rated scores improved equally and the authors called the results conflicting. This single trial does not show equivalence to medication, affron is not a substitute for it, and medication changes belong with a prescriber.
Self-rated mood in teens aged 12 to 16 with mild to moderate symptoms
In an 8-week trial of 80 teens aged 12 to 16 with mild to moderate anxiety or low-mood symptoms, affron 14 mg twice daily improved the teens' own ratings more than placebo (total score down 33% vs 17%). Parent ratings agreed only partly: average parent-rated improvement favored affron (40% vs 26%), while other parent measures did not differ. Use in teens only with a healthcare professional's guidance.
Mood and psychological wellbeing during perimenopause
In a 12-week trial of 86 perimenopausal women, affron 14 mg twice daily reduced the psychological symptom score of a menopause questionnaire and negative mood ratings more than placebo. It did not improve hot flushes, physical symptoms or other quality-of-life measures compared with placebo. This is a single manufacturer-funded trial.
Sleep quality ratings in adults with poor sleep
Two 28-day placebo-controlled trials in adults with self-reported poor sleep found affron (14 mg twice daily, or 14 or 28 mg an hour before bed) improved questionnaire and sleep-diary ratings of sleep quality more than placebo, though several other sleep measures did not differ. Results rest on self-reported measures in people without a diagnosed insomnia disorder.
Mechanism of action
Bioactive compounds: crocins and safranal
Affron is standardized to more than 3.5% Lepticrosalides®, Pharmactive's measure of crocins plus safranal. EFSA's evaluation notes the combined content typically runs 3.5% to 3.9% and is mostly crocins, and a 2026 trial batch contained 3.48% crocins and 0.03% safranal, so any effects are likely driven mainly by crocins. Crocins are water-soluble carotenoids that give saffron its color; safranal gives its aroma.
Proposed serotonergic and neuroendocrine actions
A review of laboratory and animal studies proposed that saffron may act through serotonergic, antioxidant, anti-inflammatory, neuroendocrine and neuroprotective pathways. These are hypotheses drawn largely from preclinical work on saffron and its constituents; they have not been confirmed in people taking affron, and EFSA found the mechanism evidence submitted for affron insufficient.
Melatonin, stress-hormone and inflammation findings
In rats, affron raised blood melatonin and lowered kynurenine and inflammatory gene expression, and in a chronic stress model it lowered ACTH and corticosterone, though some changes were only near significance. In people, one sleep trial found higher evening melatonin with affron but no change in evening cortisol, and a trial in active adults found no between-group change in blood BDNF. Human mechanism data remain limited.
Clinical trials
Two-arm, 12-week randomized, double-blind, placebo-controlled trial of 28 mg/day affron versus placebo. Primary outcome: DASS-21 depression score; secondary outcomes included sleep scales, WHO-5 wellbeing and daily depression, stress and anxiety ratings. Sponsored by Pharmactive, and two authors are company employees (Lopresti et al. 2025, J Nutr)
202 adults aged 18 to 70 with subclinical depressive symptoms (low mood); not a diagnosed-depression sample.
Affron improved the DASS-21 depression score more than placebo (difference 2.92 points; Cohen's d 0.39), and 72.3% vs 54.3% reached a clinically significant change of 7 points or more. No other secondary outcome, including the daily ratings, differed between groups. An exploratory analysis found better sleep-disturbance scores only in people with more severe baseline sleep problems. Placebo responses were large, and no serious adverse reactions were reported.
Eight-week randomized, double-blind, placebo-controlled trial of affron 14 mg twice daily or placebo added to existing antidepressant medication. Co-primary outcomes: clinician-rated and self-rated MADRS. Funded by Pharmactive per the publisher's funding record (Lopresti et al. 2019, J Psychopharmacol)
160 adults with persistent depressive symptoms despite antidepressant medication were enrolled; 139 provided usable data.
Clinician-rated MADRS scores fell 41% with affron vs 21% with placebo (p = 0.001), but self-rated MADRS scores fell 27% vs 26% (p = 0.831). Antidepressant side-effect scores did not differ after adjusting for baseline values, and quality of life did not differ between groups. The authors called the results conflicting and asked for more research. This was research in a diagnosed population and does not show that affron can replace or match medication.
Eight-week randomized, double-blind, placebo-controlled trial of affron 14 mg twice daily or placebo. Outcomes were the youth and parent versions of the Revised Child Anxiety and Depression Scale. One author was affiliated with Pharmactive, and the publisher's funding record lists Pharmactive (Lopresti et al. 2018, J Affect Disord)
80 youth aged 12 to 16 with mild to moderate anxiety or depressive symptoms enrolled; 68 completed.
On the teens' own reports, affron improved overall internalising symptoms, separation anxiety, social phobia and depression scores more than placebo (total down 33% vs 17%). On parent reports, mean improvement in RCADS scores was greater with affron (40% vs 26%, p = 0.026), but no other parent measure differed, so the authors describe the parent results as inconsistent. Affron was well tolerated.
Three-arm, 4-week randomized, double-blind, placebo-controlled trial of affron 28 mg/day, 22 mg/day or placebo. Primary outcome: Profile of Mood States (POMS); PANAS, DASS-21 and PSQI sleep scores were also measured. One author was affiliated with Pharmactive, and the publisher's funding record lists Pharmactive (Kell et al. 2017, Complement Ther Med)
128 adults self-reporting low mood but not diagnosed with depression.
At 28 mg/day, affron reduced POMS total mood disturbance more than placebo (p < 0.001, d = -1.10), with lower stress and anxiety-related scores; 22 mg/day had no treatment effect. Screening and outcomes were all self-reported, which the authors list as the main weakness. In 2021 EFSA accepted that this study showed a mood effect but noted it had not been replicated at that time.
Twelve-week randomized, double-blind, placebo-controlled trial of affron 14 mg twice daily or placebo. Outcomes: Greene Climacteric Scale, PANAS and SF-36. Funded by Pharmactive (Lopresti and Smith 2021, J Menopausal Med)
86 perimenopausal women with menopausal complaints; 82 analysed.
Affron reduced the Greene psychological score more than placebo (P = 0.032), with anxiety and depression subscores down 33% and 32% from baseline, and reduced PANAS negative affect (P = 0.043). It did not improve hot flushes, physical symptoms or other quality-of-life measures compared with placebo. No major adverse events were reported; digestive complaints were somewhat more common with affron.
Six-week randomized, double-blind, placebo-controlled trial of affron 28 mg/day or placebo. Outcomes: exercise enjoyment, POMS mood, PROMIS-29, wearable sleep and heart rate variability, and blood BDNF, oxytocin and neuropeptide Y. Funded by Pharmactive (Lopresti and Smith 2022, J Int Soc Sports Nutr)
62 healthy adults who exercise regularly.
Across all participants there were no statistically significant between-group differences on any outcome, including mood. In a by-sex analysis, men taking affron reported greater exercise enjoyment and had higher heart rate variability than men on placebo, while women showed no differences; these subgroup results need confirmation.
Twelve-week randomized, double-blind, placebo-controlled trial of affron 28 mg/day (14 mg twice daily) or placebo. Primary outcome: DASS-21 depression score. Funded by Pharmactive, which supplied the product and helped design the study (Lopresti and Smith 2026, Front Nutr)
86 women aged 50 to 70 with low mood and self-reported poor sleep.
Affron reduced DASS-21 depression scores more than placebo (adjusted difference 2.37 points; d = 0.48), and 48.8% vs 25.6% reached a 7-point improvement. Self-esteem and sleep-related impairment also improved more with affron, which the authors call exploratory. Sleep disturbance, self-rated appearance and AI-estimated facial skin age did not differ. No serious adverse events were reported.
Twenty-eight-day randomized, double-blind, placebo-controlled trial of affron 14 mg twice daily or placebo. Primary outcome: Insomnia Severity Index. Funded by Pharmactive (Lopresti et al. 2020, J Clin Sleep Med)
63 healthy adults aged 18 to 70 with self-reported sleep problems; 55 analysed.
Affron improved Insomnia Severity Index (P = .017), Restorative Sleep Questionnaire (P = .029) and sleep-diary quality ratings (P = .014) more than placebo. All outcomes were self-reported. No adverse effects were reported.
Twenty-eight-day, three-arm randomized, double-blind, placebo-controlled trial of 14 mg or 28 mg affron or placebo taken 1 hour before bed. Primary outcome: sleep-diary sleep quality ratings (Lopresti et al. 2021, Sleep Med)
120 adults with unsatisfactory sleep.
Compared with placebo, affron improved sleep quality ratings, mood on waking, the Insomnia Symptom Questionnaire score and insomnia classification, and sleep improvements were similar for 14 mg and 28 mg. Other questionnaire and diary measures did not differ. Evening melatonin rose with affron; evening cortisol did not change. No significant adverse effects were reported.