Quick Answer: The Stamets Stack is a microdosing protocol combining psilocybin, Lion's Mane mushroom (Hericium erinaceus), and niacin (Vitamin B3), popularized by mycologist Paul Stamets. This synergistic combination is hypothesized to enhance neuroplasticity, cognitive function, and mood by leveraging psilocybin's ability to create neuroplastic "windows," Lion's Mane's stimulation of Nerve Growth Factor (NGF), and niacin's role in improving blood flow and neuroprotection. While anecdotal evidence and observational studies suggest benefits for mental health and cognitive enhancement, formal clinical trials on the stack as a whole are still emerging. The Stamets Stack: Lion's Mane, Psilocybin, and Niacin Explained In 2019, renowned mycologist and psychedelic researcher Paul Stamets introduced a microdosing protocol that has since gained significant traction within the wellness and scientific communities: the combination of psilocybin mushrooms with Lion's Mane mushroom ( Hericium erinaceus ) and niacin (vitamin B3). This unique blend, dubbed the "Stamets Stack," is rooted in a scientifically plausible hypothesis suggesting a synergistic effect on brain health and cognitive function. The rationale extends beyond simple supplementation, proposing a sophisticated interplay between these three components to foster neuroplasticity and overall mental well-being. Understanding the Components of the Stamets Stack Psilocybin: The Neuroplasticity Catalyst Psilocybin, the primary psychoactive compound found in certain mushrooms, is a potent inducer of neuroplasticity. Its mechanism involves modulating serotonin 5-HT2A receptors, which in turn influences the expression of brain-derived neurotrophic factor (BDNF) and TrkB receptor signaling [Grieco et al., 2022]. This process facilitates the growth of new synaptic connections and enhances the brain's ability to adapt and reorganize itself. These neuroplastic changes are considered fundamental to psilocybin's observed antidepressant, anxiolytic, and cognitive-enhancing effects [Zhao et al., 2024]. In the context of the Stamets Stack, psilocybin is administered at a sub-perceptual microdose, typically ranging from 0.1 to 0.3 grams of dried mushroom equivalent, ensuring therapeutic benefits without inducing a full psychedelic experience. Lion's Mane Mushroom: Supporting Neuronal Growth Lion's Mane mushroom ( Hericium erinaceus ) stands out as the most extensively researched non-psychedelic mushroom for its profound cognitive benefits. Its active compounds, particularly hericenones and erinacines, are known to stimulate the production of Nerve Growth Factor (NGF) [Contato et al., 2025]. NGF is a crucial protein essential for the growth, maintenance, and survival of neurons, playing a vital role in neurogenesis and neuronal repair [News-Medical, 2023]. The hippocampus and prefrontal cortex, brain regions critically involved in memory, learning, mood regulation, and often affected by conditions like depression, anxiety, and age-related cognitive decline, are particularly responsive to NGF stimulation [Alzdiscovery.org, 2025]. Stamets' hypothesis posits that Lion's Mane complements psilocybin by providing the necessary NGF to consolidate and maintain the new neural connections initiated by psilocybin, thereby potentially leading to more durable and significant neuroplastic changes than either compound could achieve alone. Niacin (Vitamin B3): Enhancing Delivery and Neuroprotection Niacin, or vitamin B3, is included in the Stamets Stack for its multifaceted contributions. Firstly, as a vasodilator, niacin increases blood flow throughout the body, including the brain and peripheral nervous system [Stamets, 2019]. This enhanced circulation is theorized to improve the delivery and bioavailability of psilocybin and Lion's Mane compounds to neural tissues, maximizing their therapeutic potential. Secondly, niacin possesses inherent neuroprotective properties and is a precursor to NAD+ (nicotinamide adenine dinucleotide), a coenzyme vital for cellular energy metabolism, DNA repair, and overall cellular health [Stamets, 2019]. The characteristic "niacin flush"—a temporary skin redness and tingling sensation—is often considered by some practitioners as an indicator of increased peripheral blood flow, though non-flush niacin forms are also used to mitigate this effect. The Synergistic Hypothesis: How the Stack Aims to Work The core principle of the Stamets Stack lies in the proposed synergy between its components. Psilocybin is believed to create a "neuroplastic window" by upregulating BDNF and promoting the formation of new neural pathways. During this period of heightened brain plasticity, Lion's Mane, with its NGF-stimulating properties, is thought to provide the building blocks and support necessary for these new connections to strengthen and become more permanent. Niacin then acts as a delivery enhancer, ensuring that both psilocybin and Lion's Mane compounds reach their targets effi