The supermarket ‘antidepressant' in your spice rack

Sydney Morning Herald

15-07-2025

Probiotics and vitamin D were more likely than a placebo to reduce depressive symptoms, while most studies found no effects for Omega-3, according to lead author Rachael Frost, a senior lecturer at Liverpool John Moores University.
'However, St John's Wort and saffron more often showed effects compared to placebo, and similar results to prescription antidepressants,' Frost wrote in an accompanying editorial in Frontiers of Pharmacology.
Frost, we should note, is a herbal medicine practitioner herself; the first of many caveats we'll cover on this study.
It's not surprising St John's Wort showed a strong effect. A Cochrane review, the gold-standard for scientific evidence, found the flower extract could treat symptoms of depression as effectively as antidepressants back in 2008.
Ian Hickie, professor of psychiatry and co-director of health and policy at the University of Sydney's Brain and Mind Centre, said St John's Wort is known to be pharmacologically similar to a weak SSRI (selective serotonin reuptake inhibitor) antidepressant medication. 'It should be seen as a 'medicine' and not simply a natural product,' he says.
Hickie noted that many of the other natural interventions weighed up in the review were tested on subclinical depression, not the severe illness conventional antidepressants are aimed at, which is important to consider when interpreting the results.
The review also didn't analyse the statistical power of each trial's results, which most modern meta-analyses do, and instead simply collated the number of positive and negative experiments on each substance.
That doesn't take us far, particularly because most of the trials included in the review had small sample sizes.
So where does that leave us with the claim that saffron, alongside St John's Wort, could be as potent as a prescription antidepressant?
A narrow evidence base
Eighteen studies on saffron were included in the review. Most found the substance improved people's mood and alleviated depression at least as well as conventional medication.
But, reading the studies one by one, something caught my eye: at least half were co-authored by the same researcher.
Further, all but one of the studies emerged from a small group of research organisations in Iran. That's not surprising; Iran produces 90 per cent of the world's saffron, so naturally the country's scientists would lead experiments on its therapeutic potential.
What it does show, however, is that the experimental landscape for saffron is very concentrated. To be confident that a certain new drug or intervention works, ideally, you want labs across many countries running experiments with a range of settings and participants of different ethnicities.
It's safe to say the evidence base, as it stands, is narrow.
The one study referenced in the paper completed outside of Iran was an Australian one led by Dr Adrian Lopresti, which found saffron extract could help reduce depressive symptoms in people already taking a pharmaceutical antidepressant.
Lopresti, who's the managing director of Clinical Trials Australia, also just published a new paper that marks the largest study to date on saffron and mood, with 202 participants.
The trial found 72.3 per cent of participants with depressive symptoms (not clinical depression) taking saffron extract significantly improved compared to 54.3 per cent of people on a placebo.
Scientists believe saffron could address chemical issues associated with depression, which include problems with neurotransmitters, high inflammatory blood markers, and low levels of antioxidants.
'Saffron is an anti-inflammatory, it's an antioxidant, and it impacts on neurotransmitters too, so it probably works through those different mechanisms,' Lopresti says.
Fine print and industry funding
But these Australian studies, too, come with a crucial caveat: they were funded by a biotech company that sells saffron supplements.
'I think what you've got to really do is not hedge your bets on just one single study,' Lopresti says when I ask how people should interpret studies funded by industry. 'Has it been replicated across the world with different research organisations?'
Loading
Jerome Sarris, professor of integrative mental health at the NICM medical research institute, said it's important to note potential conflicts of interest. But they can be managed in placebo-controlled, double-blind studies – where participants and experimenters don't know who's on the placebo – as long as data is analysed independently of industry.
'Of course, read the fine print, look at the conflict of interest and weigh that up in your own mind. But I would also say universities are pretty good in terms of having safeguards around conflict of interest management,' he says.
People considering supplements for mood or mental illness should seek professional health advice. Herbs and other supplements can interact with other medications. St John's Wort, for example, can lead to a potentially life-threatening increase in serotonin when combined with some antidepressants.