P21 — Research, Dosing & Price Guide

P21 is a synthetic peptide derived from the active region of ciliary neurotrophic factor (CNTF) that promotes neurogenesis in the hippocampus. It was developed to capture CNTF's neurotrophic benefits while being small enough to cross the blood-brain barrier. P21 increases neurogenesis and synaptic plasticity without the appetite-suppressing and weight-loss effects of full-length CNTF.

P21 is an 11-mer peptide that mimics the neurotrophic signaling of CNTF by inhibiting leukemia inhibitory factor (LIF) signaling and promoting the differentiation of neural progenitor cells in the hippocampal dentate gyrus. It enhances adult hippocampal neurogenesis — the birth of new neurons in one of the few brain regions where this occurs throughout life. P21 also increases dendritic complexity and synaptic density in existing neurons, improving the structural basis for memory formation. Its mechanism involves upregulation of BDNF and activation of the PI3K/Akt signaling pathway, which promotes neuronal survival and growth. Unlike full CNTF, P21 does not activate the JAK/STAT pathway responsible for appetite suppression and cachexia.

• Bhatt et al. (2013) in Neurobiology of Aging demonstrated P21 increased hippocampal neurogenesis and improved cognitive performance in aged rats
• Studies showed P21 rescued memory deficits in an Alzheimer's disease mouse model (3xTg-AD) by promoting neurogenesis and reducing tau pathology
• Research in the Journal of Alzheimer's Disease showed P21 treatment increased dendritic density and synaptic markers in the hippocampus
• Preclinical data demonstrated P21 improved spatial memory in the Morris water maze test after 30 days of treatment
• Li et al. (2015) showed P21 increased BDNF levels in the hippocampus and cortex of treated animals

• Intranasal: 50–100 mcg per nostril, once or twice daily
• Subcutaneous: 50–200 mcg once daily
• Cycle: 4–8 weeks on, 2–4 weeks off
• Start at the lower end to assess cognitive response before titrating up
• Morning administration preferred to align with peak cognitive demand periods
• Some protocols combine intranasal and subcutaneous routes for enhanced CNS delivery

Known Side Effects

• Headache — occasionally reported, usually mild and during the first week of use
• Nasal irritation — with intranasal administration, mild dryness or stinging
• Vivid dreams — reported by some users, consistent with enhanced hippocampal activity and memory consolidation during sleep
• Overstimulation — rare reports of mental restlessness at higher doses
• Very limited human safety data — most evidence is preclinical

Safety Profile

P21 has shown a favorable safety profile in preclinical studies with no reported organ toxicity or serious adverse events in animal models at research doses. However, human clinical trial data is essentially nonexistent, making its safety profile less well-established than many other nootropic peptides. The theoretical concern is that promoting neurogenesis in an uncontrolled manner could have unintended consequences, though no evidence of this has emerged. It is a research compound and should be treated as such. Individuals with neurological conditions should consult a physician before use.

Week 1–2: Subtle cognitive improvements — slightly better focus, improved word recall. Some users report more vivid dreams as hippocampal activity increases. Weeks 3–4: More noticeable cognitive enhancement. Learning new information feels easier, and memory consolidation improves. Users often report better spatial memory and navigation. Weeks 5–8: Peak neurogenesis effects. The newly born neurons are maturing and integrating into hippocampal circuits. Cognitive benefits are most pronounced. After cessation, benefits may persist for weeks as the new neurons continue to mature and integrate.

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