on October 09, 2026
Mild depression and the problem of anhedonia
Depression is not a uniform phenomenon. Alongside more severe forms, there are conditions characterized by less intense but potentially persistent symptoms, in which fatigue, reduced initiative, sleep disturbances, difficulty concentrating, loss of interest, and above all anhedonia may predominate—that is, a diminished ability to experience pleasure or to perceive activities normally associated with a reward as gratifying.
Anhedonia represents one of the most complex domains of depression because it does not simply coincide with sadness. A person may not necessarily feel deeply sad, but instead experience a loss of motivation, interest, and positive emotional response toward what was previously pleasant.
From a neurobiological perspective, this phenomenon particularly involves the brain's reward circuits, in which dopaminergic transmission plays a central role. Pharmacological and neurobiological research also considers the interactions between serotonin, noradrenaline, glutamate, neurotrophic factors, the stress axis, and inflammatory processes to be important.
It is precisely in this area that the growing interest in saffron is situated.
Saffron and its bioactive molecules
Saffron is obtained from the dried stigmas of Crocus sativus L. and contains numerous bioactive compounds. Among the most studied are crocin, crocetin, picrocrocin, and safranal.
Crocins are water-soluble carotenoids derived from crocetin and represent one of the main phytochemical components used to characterize extracts intended for research. Safranal, on the other hand, is a volatile molecule largely responsible for saffron's characteristic aroma.
Their biological activity appears to be complex and multimodal. Experimental studies have described possible interactions with the serotonergic, dopaminergic, and noradrenergic systems, as well as effects on the GABAergic system, NMDA receptors, and neurotrophic pathways.
This is important because depression cannot be explained by a simple deficiency of a single neurotransmitter. Mood regulation depends on the dynamic interaction between neuronal circuits, synaptic plasticity, stress response, cellular metabolism, and neuroimmune signals.
The possible role of dopamine in motivation
One of the most interesting aspects of recent research concerns dopamine.
Dopamine is involved in the processes of motivation, associative learning, reward anticipation, and goal-directed behavior. An impairment of dopaminergic circuits can therefore contribute to the motivational component of anhedonia.
Some experimental studies suggest that saffron components may modulate the availability of dopamine and noradrenaline, also through changes in their reuptake. Experimental activity on monoamine oxidase has also been observed, although these data cannot automatically be transferred to the human clinical situation.
The most interesting perspective, therefore, is not to consider saffron as a simple “dopamine stimulant,” but as a substance potentially capable of intervening at multiple levels of neurochemical regulation.
The study of anhedonia, saffron, and the reward system
A study published in 2025 explored precisely this aspect through an experimental model of stress-induced anhedonia and a pilot clinical study.
In the animal model, sucrose self-administration protocols were used to assess motivation toward a reward. Animals subjected to stress showed a reduced motivational response, while repeated administration of a standardized saffron extract produced a recovery of motivation and responsiveness to reward-associated stimuli.
The molecular investigation also highlighted changes in dopaminergic signaling and the BDNF-TrkB pathway, especially at the level of the nucleus accumbens and the medial prefrontal cortex.
This finding is particularly interesting because the nucleus accumbens is a fundamental structure of the reward circuit, while the prefrontal cortex participates in decision-making, motivational, and emotional processes.
The result therefore suggests a possible effect of saffron not only on the “affective” component of depression, but also on the motivation to act.
From animal experimentation to humans
The clinical part of the same study was conducted through a randomized, double-blind, placebo-controlled protocol lasting eight weeks.
40 people with unipolar or bipolar depression characterized by mild to moderate symptoms were involved. Participants received antidepressant therapy combined with 30 mg daily of saffron extract or placebo.
After eight weeks, the group receiving saffron as an add-on treatment showed an overall improvement in depressive symptoms and a significant reduction in anhedonia. The result was interpreted as a possible pro-motivational effect of the extract.
However, it is essential to emphasize one point: the study evaluated saffron as an add-on therapy and not as a substitute for antidepressant therapy. Furthermore, the sample was small and the duration limited to eight weeks. The same authors therefore consider larger and longer studies necessary before definitive conclusions can be drawn.
Clinical evidence preceding the most recent study
Interest in saffron for depression did not arise with this study.
Previous randomized studies had already compared Crocus sativus extracts with placebo in people suffering from mild-to-moderate depression. In a six-week study conducted on 40 adults, 30 mg daily of saffron was associated with a significantly greater reduction in Hamilton scale scores compared to placebo. No significant differences in side effects were observed between the two groups.
Another small randomized trial compared 30 mg daily of saffron with imipramine in 30 adults with mild-to-moderate depression, highlighting a reduction in depressive symptoms in both groups without statistically significant differences in the primary outcome. The small sample size, however, requires caution in interpretation.
These initial results contributed to developing the hypothesis that standardized saffron extracts may play a role in treating mild or moderate depressive symptoms.
What meta-analyses say
The overall evidence was subsequently evaluated through systematic reviews and meta-analyses.
A meta-analysis of randomized studies included eight studies and found a difference favorable to saffron compared to placebo, while in comparison with fluoxetine, no significant difference in antidepressant efficacy emerged.
A subsequent systematic review and meta-analysis, including 23 studies, observed a favorable effect of saffron on depressive symptoms compared to placebo, both when used as a single treatment and as an add-on therapy to antidepressants. The authors, however, highlighted the presence of possible publication bias and limited geographical diversity of the studies, elements that reduce the strength of the conclusions.
Another meta-analysis specifically focused on mild-to-moderate depression reported greater efficacy of saffron compared to placebo and overall results comparable to synthetic antidepressants, without significant differences in the incidence of adverse events in the analyzed comparisons. However, in this case too, the heterogeneity of the preparations and methodologies represents a major limitation.
Overall, clinical literature therefore suggests a signal of efficacy, but it cannot yet be considered equivalent to that available for established antidepressant treatments.
A new study on mild depressive symptoms
The most recent evidence has further expanded this picture.
In 2026, a randomized, double-blind, placebo-controlled study was published, conducted on 56 adults with low mood and subclinical to mild depressive symptoms. A standardized formulation of saffron extract at a dose of 15 mg daily for 56 days was used.
Compared to placebo, the treated group showed significant improvements in several parameters related to mood, positive and negative affect, symptoms of depression, anxiety, and stress, and sleep quality. A reduction in serum cortisol levels was also observed. No serious adverse events were reported.
This study is particularly interesting because it focuses precisely on the population characterized by low mood and mild depressive symptoms, that is, the one in which interest in early and complementary interventions is greater.
However, in this case too, the number of participants remains limited and the duration relatively short.
BDNF, TrkB, and neuronal plasticity
One of the most interesting mechanisms emerging from recent research concerns the BDNF-TrkB system.
Brain-derived neurotrophic factor, or BDNF, is a neurotrophic factor essential for neuronal survival, synaptic plasticity, learning, and the adaptation of neuronal networks.
Depression has been associated with alterations in neurotrophic systems and brain plasticity. The TrkB receptor represents one of the main mediators of the biological effects of BDNF.
In the animal model of the most recent study, chronic administration of saffron increased BDNF levels and TrkB receptor phosphorylation in the nucleus accumbens and medial prefrontal cortex of anhedonic animals. These data suggest a possible activation of neurotrophic signaling associated with the reward response.
However, this is preclinical evidence: it does not mean that an increase in BDNF induced by saffron has already been demonstrated in humans as a direct cause of clinical improvement.
Serotonin, noradrenaline, and glutamate
Saffron activity also appears to involve other neurochemical systems.
Experimental research indicates that some components, especially crocin and safranal, can interfere with monoamine reuptake and modulate the serotonergic and noradrenergic systems. Interactions with GABA and NMDA receptors have also been described.
This multiple activity could be biologically relevant because depression involves a network of interconnected systems, in which mood regulation depends on communication between serotonergic, dopaminergic, noradrenergic, and glutamatergic circuits.
It is therefore not correct to reduce the action of saffron to a single mechanism.
Oxidative stress, inflammation, and the stress axis
Another level of interest concerns cellular stress and neuroinflammation.
Experimental studies have shown that crocins and crocetin can modulate some markers associated with oxidative stress and inflammation, while other models have shown effects on the regulation of the hypothalamus-pituitary-adrenal axis.
Experimental research has also linked the action of crocin to the modulation of intracellular pathways involved in neuronal plasticity and the stress response, including the CREB-BDNF and MAPK/ERK pathways.
These data contribute to building a model in which saffron could simultaneously act on neurotransmission, synaptic plasticity, biological stress, and oxidative balance.
However, in this case too, most of the mechanistic information comes from cellular or animal models and cannot be interpreted as evidence of a similar therapeutic effect in humans.
Why anhedonia may represent a particular target
The perhaps most innovative finding of recent research is precisely the focus on anhedonia.
The evaluation of depression through a single overall score can indeed hide important differences between patients. Two people may have a similar depressive score, but one may be characterized above all by sadness and sleep disturbances, while the other may present a marked loss of motivation, pleasure, and ability to respond to reward.
In the second case, saffron's interaction with the dopaminergic reward circuits and BDNF-TrkB signaling becomes particularly interesting from a research perspective.
The 2025 study therefore represents an important step because it did not limit itself to observing a generic reduction in the depressive score, but sought to characterize a specific domain of depression: the loss of motivation and response to reward.
Standardized extract: a fundamental aspect
When discussing saffron, not every preparation derived from the plant should be considered equivalent.
Clinical studies have used extracts that differ in botanical origin, extraction method, component ratio, and standardization. Consequently, the results obtained with a particular extract cannot automatically be attributed to any supplement containing saffron powder or to a generic amount of the spice used in food.
This is particularly important in phytotherapeutic research: the dose of the plant does not necessarily correspond to the dose of the clinically studied extract.
Standardization of the characteristic active principles is therefore essential to reproduce results and correctly compare studies.
Saffron and safety
Available clinical studies have generally reported good tolerability at the doses used in the trials, which frequently ranged around 15–30 mg per day of standardized extract. Meta-analyses have not shown significant differences in the incidence of adverse events compared with placebo or antidepressants in the studies examined.
However, this does not mean that saffron is free from pharmacological effects or that it can be used indiscriminately.
Particular caution is required in people taking medications that act on the central nervous system or blood coagulation, during pregnancy, and in the presence of complex clinical conditions. In individuals with bipolar disorder, any intervention that may potentially affect mood should also be assessed by a doctor, especially when combined with prescribed therapy.
In fact, the most recent clinical research on bipolar disorder has used saffron as an addition to antidepressant therapy rather than as a replacement for specialist treatment.
A promising, but yet to be confirmed, perspective
The available evidence allows for a scientifically interesting picture to emerge.
Randomized clinical trials suggest that saffron extracts may help reduce depressive symptoms, especially in mild or moderate cases. Meta-analyses have generally confirmed a favorable signal compared with placebo, while comparative studies with antidepressants have yielded results consistent with possible efficacy, but not sufficient to consider saffron equivalent to standard pharmacological treatments.
The most recent research adds a particularly interesting element: the possible action on motivational anhedonia, through the modulation of reward and BDNF-TrkB signaling dopaminergic circuits.
However, numerous aspects remain to be clarified: which components are most responsible for the effect, what is the optimal dose, which formulations are most reproducible, how long the benefits last after discontinuation, and which patient subgroups may respond best.
What is needed above all are multicenter studies with larger sample sizes, longer durations, and precise characterization of the preparations used.
Saffron is therefore one of the most interesting plant substances in research on mild and moderate depression, but its role must be considered within an overall therapeutic strategy. In cases of clinically significant depression, professional assessment remains essential, and the possible use of a saffron extract should be discussed with a doctor, especially when pharmacological therapies are already in place.
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Scientific references
- Therapeutic Potential of Saffron Extract in Mild Depression: A Study of Its Role on Anhedonia in Rats and Humans. Phytotherapy Research, 2025;39(3):1277-1291. DOI: 10.1002/ptr.8424.
- Standardized Saffron Extract Formulation for Low Mood and Subclinical Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial. 2026.
- Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Human Psychopharmacology: Clinical and Experimental, 2014. DOI: 10.1002/hup.2434.
- Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. Journal of Integrative Medicine, 2014.
- Effect of saffron supplementation on symptoms of depression and anxiety: a systematic review and meta-analysis. Nutrition Reviews, 2019;77(8):557-571. DOI: 10.1093/nutrit/nuz023.
- Safety and Efficacy of Saffron (Crocus sativus L.) for Treating Mild to Moderate Depression: A Systematic Review and Meta-analysis. 2020.
- Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. 2005.
- Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial. BMC Complementary and Alternative Medicine, 2004.
- Anti-Depressant Properties of Crocin Molecules in Saffron. Molecules, 2022;27(7):2076.
- Current Knowledge of the Antidepressant Activity of Chemical Compounds from Crocus sativus L. Pharmaceuticals, 2022;16(1):58.
