Saffron gains in larger trials, independent replication, and a standardized product
STUDY: Lopresti AL et al, Psychiatry Research 2025
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Pharmactive Biotech Products SLU (manufacturer of the study product)
Background
Saffron has outperformed placebo and matched SSRIs in prior meta-analyses, but most trials recruited small samples of clinically depressed patients for 4–8 weeks. This is the largest trial to date, targeting a population psychiatrists see constantly: adults with subclinical depressive symptoms who don’t meet full criteria for major depressive disorder.
The Study
202 adults with subclinical depression were randomized to 28 mg daily of a standardized saffron extract (affron®) or placebo for 12 weeks. The primary outcome was the depression subscale of the Depression, Anxiety, and Stress Scale (DASS-21).
Saffron produced a 53% reduction in DASS-21 depression scores versus 39% with placebo (Cohen’s d=0.39). Clinically meaningful improvement — defined as a reduction of 7 or more points — occurred in 72% of the saffron group versus 54% on placebo. No differences emerged on anxiety, stress, sleep, or wellbeing. In participants with more severe sleep disturbance at baseline, an exploratory analysis found a modest sleep benefit (Cohen’s d=0.44), but this was post-hoc. No serious adverse events were reported.
Though the effect size is small-to-medium, the placebo response was large, as is common in milder populations.
Practice Implications
- Saffron at 28 mg/day is low-risk, reasonably supported, and now tested in a well-designed trial.
- Other studies find saffron deepens sleep quality, causes mild weight loss, and improves sexual function and cognition, making it a good alternative when antidepressants are not tolerated. It also has data in full, clinical depression.
- Affron is a standardized extract licensed through other brands, and is affordable at around $15/month
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
