The intervention involved 84 women aged 18 to 26, with a mean age of 21.93, who were born between 1997 and 2006 and described themselves as feeling stressed or anxious. They were not diagnosed with a psychiatric condition, so the study did not evaluate a treatment for diagnosed anxiety disorder. Each morning for 28 days, participants took three capsules containing either 1.8 g of powdered Lion’s mane, 1.8 g of a blend containing 60% Lion’s mane and 40% Reishi, or placebo made from microcrystalline cellulose. The blend was standardized to 20% beta-glucans. Participants and the research team were kept unaware of treatment assignments during the study, while a separate research-centre director labelled the treatments and held the emergency code-break envelopes. A treatment-guess analysis found that participants were not significantly better at correctly identifying their assigned group than chance, including when active groups were combined and compared with placebo. Average compliance, calculated from returned capsules, was 96.7%.

The trial was preceded by a separate sort-and-rank study involving 38 women from the same target population. Participants ranked 54 statements derived from diagnostic criteria for acute stress disorder, generalized anxiety disorder, depressive disorders and attention-deficit hyperactivity disorder. Excessive anxiety and worry ranked highest, with 59.5% assigning the statement a score above +2 on the study’s 13-point scale, which represented placing an item among the 16 statements considered most important. Mental exhaustion, physical exhaustion, panic, overwhelming stress, worthlessness and low self-esteem also featured prominently. This formative phase was used to select outcome measures considered most relevant to participants, rather than leaving the trial’s targets entirely to investigators. It was a separate cohort, and its results informed measurement rather than contributing participants to the intervention comparison.

Anxiety measured by the GAD-7 was the prespecified primary outcome. Secondary measures included the anxiety subscale of the Hospital Anxiety and Depression Scale, the Perceived Stress Scale, a visual analogue scale for stress, the Chalder Fatigue Scale and Rosenberg’s Self-Esteem Scale. Participants completed full assessments at baseline and Day 28, shorter weekly questionnaires during treatment and an exploratory home assessment on Day 42, two weeks after supplementation ended. The statistical analysis used mixed models that included treatment, time, their interaction and baseline scores for the relevant outcome, with additional adjustment for baseline fruit and vegetable consumption, waist-to-hip ratio and visual analogue stress score. False-discovery-rate correction was applied across families of secondary outcomes to limit the chance of false positives. The main analysis followed the intention-to-treat population, which included participants according to their randomized assignments.

For the primary GAD-7 outcome, the researchers identified a main effect of treatment, meaning average anxiety scores differed among the three groups over the study as a whole. The mushroom blend averaged 6.49, lower than 7.76 for Lion’s mane alone, with p = 0.018 and a standardized effect size of 0.51. There was also a treatment-by-time interaction, for which p = 0.034. That interaction was most evident at the end of treatment: on Day 28, the blend group’s mean GAD-7 score was 4.16 versus 6.50 in the Lion’s mane group, with p = 0.003 and a standardized effect size of 0.94. These comparisons establish better performance than Lion’s mane alone for the primary outcome in this trial; they do not demonstrate superiority over placebo for that outcome at Day 28. The study therefore supports a treatment difference between the two active products without showing that every active product outperformed an inactive control on the primary endpoint.

Secondary results were less definitive. The treatment-by-time interaction for HADS anxiety initially met the conventional statistical threshold, at p = 0.023, but it did not remain significant after correction for multiple testing, which produced an adjusted q value of 0.072. Uncorrected post hoc comparisons favored the blend over Lion’s mane on Day 28 and over placebo on Day 42, the latter occurring two weeks after supplementation stopped. The PSS treatment interaction also fell from nominal significance, p = 0.036, to trend level after correction, again with q = 0.072. At Day 28, the blend group had a lower mean PSS score of 16.86 than both placebo, at 19.79, and Lion’s mane, at 19.35. These exploratory comparisons should not be treated as confirmatory evidence. No significant treatment effects were found for stress measured by the visual analogue scale, fatigue or self-esteem, and the trial therefore did not establish a broad pattern of supplement-specific benefits across every psychological measure.

All three groups improved over time, including the placebo group. Mean GAD-7 scores fell from 10.08 at baseline to 5.42 on Day 28 across all participants and were 6.12 on Day 42. Anxiety measured by HADS, stress measured by the PSS and visual analogue scale, and fatigue all declined, while self-esteem increased from a mean of 15.59 to 18.56 by Day 28. The broad pattern means that improvements seen within an active-treatment group cannot automatically be attributed to that supplement. The investigators identified expectancy, increased attention to wellbeing during repeated assessments, the structure of taking part in a trial and self-monitoring as possible contributors. The study measured no cortisol, inflammatory markers or other biological indicators that could help explain either supplement-specific or participatory effects. It therefore could not establish a biological pathway for the observed differences or determine whether the two mushrooms interacted in a way that produced the primary result.

Qualitative responses broadly paralleled the quantitative pattern. Participants in the Lion’s mane group more frequently reported “no change” in an analysis of their reasons for identifying their treatment, while the blend group more often reported mood improvement in exploratory comparisons. These observations were based on open-ended responses, coded independently by two researchers, and were not substitutes for the controlled questionnaire endpoints. The qualitative pattern adds context to the main result, but it came from multiple exploratory tests, and its interpretation should remain cautious. Notably, the study cannot determine whether Reishi enhanced Lion’s mane, acted independently or merely accompanied a different quantity of Lion’s mane. The Lion’s mane-only arm received 1.8 g of that mushroom, whereas the blend provided approximately 1.08 g of Lion’s mane plus 0.72 g of Reishi, and there was no Reishi-only arm. A dose-matched design would be needed to separate the contributions of the ingredients.

Safety findings were broadly reassuring but do not establish long-term safety. Participants reported 50 adverse events, involving 31 individuals. One participant discontinued because of a headache, but that person had received placebo. Statistical comparisons found no significant difference in adverse-event frequency among the three groups, including after false-discovery-rate correction. The overall pattern was consistent with good short-term tolerability in this sample, although the trial was not designed to detect rare events. Its four-week intervention also cannot address longer-term safety, optimal dose, supplement composition, bioavailability or the durability of any benefit. The intended sample of 135 was not reached because of recruitment challenges, leaving 84 participants and reducing confidence that subtler effects would have been detected. A post-hoc power calculation suggested high power for the observed primary interaction, but such retrospective calculations do not remove the uncertainty associated with an undersized trial.

The trial tested a specific Lion’s mane and Reishi blend rather than establishing that either mushroom was responsible for the primary result. Lion’s mane contains compounds such as hericenones and erinacines, while Reishi contains triterpenoids, including ganoderic acids, and polysaccharides such as beta-glucans. Preclinical research has proposed effects on nerve growth factor, brain-derived neurotrophic factor, neuroinflammation and inflammatory signaling, but the mechanisms underlying human mood effects remain unsettled, and results from earlier human studies have been inconsistent. The present trial also does not show that functional mushrooms broadly treat anxiety. Instead, it identifies a comparatively strong primary-outcome signal for one commercial blend in stressed or anxious young women without psychiatric diagnoses, while finding widespread improvement across all groups and weaker, multiplicity-adjusted evidence for other measures. Confirmatory trials would need dose-matched single-ingredient and combination arms, larger and more diverse populations, longer follow-up, biological measurements and assessment of whether the observed differences are large enough to matter outside a research setting.

Subject of Research: Four-week Lion’s mane and Reishi supplementation trial assessing anxiety, stress and wellbeing in young women.

Article Title: The effects of four-week supplementation of Lion’s mane and a Lion’s mane and Reishi blend on prioritised mood and wellbeing measures in young women

Article References: Smith, E. F., & Docherty, S. (2026). The effects of four-week supplementation of Lion’s mane and a Lion’s mane and Reishi blend on prioritised mood and wellbeing measures in young women. Frontiers in Nutrition, 13, Article 1887408. https://doi.org/10.3389/fnut.2026.1887408

Image Credits: AI Generated

DOI: 10.3389/fnut.2026.1887408

Keywords: Lion’s mane, Reishi, anxiety, young women, randomized trial, supplementation, mood, stress, placebo, wellbeing, effects, four-week