What randomized, placebo‑controlled clinical trials exist for Lion’s Mane (Hericium erinaceus) and what were their cognitive outcomes?
Executive summary
Three small randomized, placebo‑controlled trials and a handful of pilot RCTs have tested Lion’s Mane (Hericium erinaceus) for cognitive outcomes; results are mixed—some trials report modest benefits on specific measures or activities of daily living, others report no benefit or worse performance on memory tests—and all are limited by small samples, short durations, and variable dosing and extract standardization [1] [2] [3].
1. Which randomized, placebo‑controlled trials have been done
The most frequently cited double‑blind RCT enrolled 30 Japanese adults aged 50–80 with mild cognitive impairment (MCI) and administered lion’s mane extract for 16 weeks versus placebo, a trial commonly attributed to Mori et al. and summarized across reviews and clinical summaries [2] [4] [5]. Smaller randomized placebo‑controlled studies in healthy adults include trials of younger cohorts: one trial of 41 healthy adults (18–45) over four weeks and trials in college‑age or otherwise healthy young adults (sample sizes ~24) that tested daily supplementation for several weeks; these are described in the Alzheimer’s Drug Discovery Foundation summary and related reviews [1] [2]. More recent randomized, double‑blind, placebo‑controlled, parallel‑group pilot trials include a 2023 study in young adults (Nutrients/PubMed) and a 2025 Frontiers trial using a standardized 3 g extract with acute and chronic assessments; both used placebo controls and formal cognitive testing [6] [7] [8].
2. What cognitive outcomes those trials reported
In the 30‑person MCI RCT, investigators reported significant between‑group differences on a cognitive function scale at weeks 8, 12 and 16, and improvements in some functional measures of daily living, though formal cognitive domain improvements were limited and the trial size was small [5] [2]. Conversely, a randomized trial of 41 healthy adults found worse performance (fewer words recalled) on a delayed word recall task after four weeks of supplementation compared to placebo, indicating possible null or negative effects on episodic memory in that population [1]. Trials in college‑age or young adults generally failed to show consistent cognitive improvements: a 24‑participant single‑blind placebo‑controlled study reported no improvement on cognitive tests, while the 2023 double‑blind pilot found tentative improvements in speed (Stroop reaction time) and reductions in subjective stress but also null and some negative findings across other cognitive measures [2] [9] [6] [7]. The 2025 Frontiers study reported some acute cognitive improvements using a higher 3 g extract dose, but it remains a single relatively small trial and calls for replication [8].
3. Safety signals and tolerability reported in trials
Across trials lion’s mane supplements were generally well tolerated but not without adverse events: the MCI trial noted mild gastrointestinal symptoms and one withdrawal for stomach discomfort, and other small trials report nausea, abdominal discomfort or skin rash in some participants; a single severe case report of acute respiratory failure has been mentioned in the literature as possibly related to ingestion, underscoring limited safety data for supplements versus culinary use [2] [1] [5].
4. Quality, consistency, and mechanistic context
The evidence base is heterogeneous: studies vary in population (MCI, healthy young or middle‑aged adults), extract type and dose (powder, standardized extracts, fresh equivalent grams), duration (single dose to 49 weeks in some reports), and outcome measures, and systematic reviews conclude only two human trials showed positive results on at least one cognitive test, while others show null or negative effects; reviewers repeatedly call for larger, longer, standardized RCTs to clarify efficacy and mechanisms such as nerve growth factor modulation suggested in preclinical work [3] [1] [10].
5. Bottom line for cognition
Randomized, placebo‑controlled trials exist but are few and small; they deliver mixed signals—possible domain‑specific benefits (speed, some functional ADL gains in one MCI study) but also null or worse memory outcomes in healthy adults—so current RCT evidence is insufficient to conclude that Lion’s Mane reliably improves cognitive function in humans and warrants larger, standardized trials with careful safety monitoring [2] [1] [3] [6].