Quick Comparison

AshwagandhaLion's Mane
Half-Life6-12 hours (withanolides)Bioactive compounds (hericenones, erinacines) accumulate with daily use; effects are cumulative
Typical DosageKSM-66 extract: 300-600 mg daily. Sensoril extract: 125-250 mg daily. Root powder: 3-6 g daily. Best taken with food. Can be taken morning or evening (does not cause drowsiness in most people).Standard: 500-3000 mg daily of fruiting body extract. For NGF stimulation: look for extracts containing both hericenones (from fruiting body) and erinacines (from mycelium). Dual-extract products provide both. Take consistently for 4+ weeks for noticeable effects.
AdministrationOral (capsules, powder). Standardized extracts (KSM-66 or Sensoril) are preferred over raw root powder for consistent dosing.Oral (capsules, powder, tincture, whole mushroom). Extracts standardized for beta-glucans and/or hericenones are preferred.
Research Papers9 papers9 papers
Categories

Mechanism of Action

Ashwagandha

Ashwagandha's withanolide compounds (withaferin A, withanolide A, withanone) modulate the hypothalamic-pituitary-adrenal (HPA) axis, reducing corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) signaling, thereby lowering cortisol production by 25-30% in stressed individuals. It acts as a GABA-A receptor positive allosteric modulator at the benzodiazepine site, producing anxiolytic effects without sedation. Ashwagandha inhibits acetylcholinesterase (AChE), raising acetylcholine levels in the hippocampus and cortex. The withanolides have anti-inflammatory properties via inhibition of NF-κB and COX-2, and antioxidant effects that reduce neuroinflammation and oxidative stress. It may support neurogenesis through upregulation of BDNF and its receptor TrkB, and modulation of the PI3K/Akt pathway.

Lion's Mane

Lion's Mane contains two classes of bioactive compounds: hericenones (A-H, found in the fruiting body) and erinacines (A-I, found in the mycelium). Both stimulate the synthesis of nerve growth factor (NGF) in astrocytes and neurons — hericenones may act through enhancement of NGF gene expression, while erinacines cross the blood-brain barrier and directly induce NGF. NGF binds to TrkA receptors and is essential for the survival, maintenance, and regeneration of cholinergic neurons, particularly in the hippocampus and basal forebrain. This promotes neurogenesis, dendritic arborization, and remyelination of nerve fibers. Lion's Mane also reduces neuroinflammation through inhibition of NF-κB signaling and suppression of pro-inflammatory cytokine production. It may enhance BDNF expression and support the gut-brain axis.

Risks & Safety

Ashwagandha

Common

Gastrointestinal discomfort, drowsiness at higher doses, thyroid hormone elevation.

Serious

Can cause hyperthyroidism in susceptible individuals — avoid with thyroid conditions without medical oversight. Rare liver injury reports.

Rare

Vertigo, nasal congestion, sexual dysfunction.

Lion's Mane

Common

Mild gastrointestinal discomfort, itching (possibly from NGF stimulation).

Serious

Allergic reactions in people with mushroom allergies.

Rare

Exacerbation of asthma symptoms, skin rash.

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