Lion's mane mushroom (Hericium erinaceus) has gained attention for its possible neuroprotective and nootropic effects, including support for acetylcholine-related pathways. Several animal studies and limited human research suggest that compounds in lion's mane, such as hericenones and erinacines, may stimulate nerve growth factor (NGF) synthesis, which plays a role in the survival and function of cholinergic neurons—the neurons that use acetylcholine as a neurotransmitter. In rodent models, lion's mane supplementation has been shown to improve memory and learning, possibly by enhancing acetylcholine signaling in the brain.

A few small human trials have reported cognitive benefits in older adults with mild cognitive impairment, with some improvements in memory and mental function. However, the mechanisms are not fully elucidated, and direct increases in acetylcholine levels have not been conclusively demonstrated in humans. The bulk of evidence is currently preclinical, with only preliminary clinical data available. Historically, lion's mane has been used in East Asian traditional medicine for general cognitive health, but its specific use for supporting acetylcholine systems is a product of recent scientific exploration rather than traditional applications.

In summary, while there is growing scientific interest and some preliminary support for lion's mane's effect on the acetylcholine system, the evidence remains limited, especially in humans, and further research is needed to confirm these effects.