P021, also written P21 or Peptide 021, is an experimental peptide compound designed to mimic the brain-protective effects of ciliary neurotrophic factor (CNTF), a natural protein that supports nerve cell survival. It was developed at the New York State Institute for Basic Research in Developmental Disabilities as a possible treatment for Alzheimer’s disease, and is sold online as a “nootropic,” meaning a cognitive enhancer. It is unrelated to p21, the cell-cycle protein encoded by the CDKN1A gene.

The most important fact is that P021 has only been studied in mice, rats and cultured cells. No human trial has been published, and we found no study of it registered on ClinicalTrials.gov (ClinicalTrials.gov search). Nearly all of the published research comes from the laboratory that invented it, whose senior author holds patents on the compound, co-founded a company, Phanes Biotech, and is developing P021 as a drug (Mottolese et al., J Neurodev Disord 2024).

This page summarizes what the published animal research and regulators report. It is for education only and is not medical advice.

Property	Detail
Class	Unapproved synthetic peptide; CNTF-derived “peptide mimetic”
Origin	Short fragment of human CNTF with an adamantane-containing end group
Formula / weight (PubChem)	C₂₇H₄₂N₆O₈; 578.7 g/mol (CID 56599151)
Proposed mechanism	Blocks leukemia inhibitory factor (LIF) signaling and raises BDNF in animal brain
Studied doses	Only in animals, mostly mixed into feed (e.g. 60 nmol per gram of diet in mice)
Half-life	Developers report a plasma half-life of over 3 h in preclinical testing; no human data
Human data	None published
Approval	Not approved as a medicine by any regulator we could find
WADA status	Not named; unapproved substances fall under S0 (prohibited at all times)

What it is

From CNTF to a short peptide

CNTF itself has well-established neuroprotective effects, but whole neurotrophic proteins are poor drugs. Given outside the brain, CNTF and BDNF fail to reach the central nervous system and are degraded within a few minutes, and earlier attempts to treat Alzheimer’s disease with neurotrophic factors were halted because of poor brain entry, short half-life and severe side effects (Baazaoui and Iqbal, Biomolecules 2022). The Iqbal laboratory set out to find a small piece of CNTF that kept its activity.

Using antibodies to map CNTF’s most active region, the group first made an 11-amino-acid peptide called Peptide 6 (P6). They then trimmed it to a 4-amino-acid core (P6c) that still promoted new neuron formation in mice (Kazim and Iqbal, Mol Neurodegener 2016). The 2022 review places this core at amino acids 147–150 of CNTF (Baazaoui and Iqbal, Biomolecules 2022).

The adamantane modification

To make the core peptide survive longer and reach the brain, the researchers capped its starting end with an acetyl group and attached an adamantylated glycine to its far end. Adamantane is a rigid, cage-shaped, fat-soluble hydrocarbon. The stated aims were to increase blood-brain barrier permeability and slow breakdown by exopeptidases, enzymes that trim amino acids from the ends of peptides (Baazaoui and Iqbal, Alzheimers Res Ther 2017).

The resulting compound was first reported in 2010 under the name P21 (Li et al., FEBS Lett 2010), and later papers call it P021. PubChem lists it under both names, with CAS number 1246751-68-7 and the end group identified as a 3-carbamoyl-1-adamantyl amide (PubChem).

Molecule	What it is	Published research
CNTF	Full-length natural neurotrophic protein	Not covered here
Peptide 6 (P6)	11-amino-acid CNTF fragment	Rodent studies
P6c	4-amino-acid core of P6	Rodent studies
P021	P6c with acetyl cap and adamantylated glycine	Rodent and cell-culture studies only
ADAMAX	Semax sold with P021-style end groups (as marketed)	None

The P021 end group has been borrowed by sellers for other products. ADAMAX, for example, is marketed as Semax carrying the same adamantane-containing end group, although no published study has tested it.

How it works in the body

All mechanism and pharmacokinetic data come from animal and laboratory work by the developing group.

Proposed mechanism. The developers describe P021 as competitively inhibiting LIF signaling, which normally restrains new neuron formation, and increasing expression of brain-derived neurotrophic factor (BDNF, a protein that supports nerve cell growth and survival) (Baazaoui and Iqbal, Biomolecules 2022).
Downstream effects on tau. In Alzheimer’s model mice, higher BDNF was linked to reduced activity of glycogen synthase kinase-3β (GSK3β), an enzyme that adds phosphate groups to tau, the protein that forms tangles in Alzheimer’s disease (Kazim et al., Neurobiol Dis 2014).
Brain entry. In aged rats, the developers reported that P021 crosses the blood-brain barrier (Khatoon et al., J Alzheimers Dis 2015).
Stability and half-life. A 2016 review by the developers reported a plasma half-life of over 3 hours, over 95% stability in artificial intestinal fluid for 2 hours, and over 90% stability in artificial gastric juice for 30 minutes (Kazim and Iqbal, Mol Neurodegener 2016). The review does not state the species or dose behind the half-life figure, and it has not been measured in people.

Most studies gave P021 orally, mixed into the animals’ food. Mice in long-term studies received 60 nmol per gram of feed, which the authors calculated as about 162 nmol per mouse per day (Baazaoui and Iqbal, Alzheimers Res Ther 2017). These animal doses cannot be translated into a human dose.

Regulatory status

Drug approval

We found no FDA, EMA or other regulatory approval for P021, and no registered human trial (ClinicalTrials.gov search). Its developers describe it as a candidate they are working to develop as a treatment for Alzheimer’s disease (Mottolese et al., J Neurodev Disord 2024). It is not named among the controlled anabolic steroids in Schedule III (21 CFR 1308.13).

Sport

P021 is not named on the WADA list. Class S0 prohibits at all times any pharmacological substance not covered elsewhere on the list that has no current approval by a government health authority for human therapeutic use, explicitly including drugs under pre-clinical or clinical development (WADA 2026 Prohibited List). A pre-clinical compound like P021 fits that description.

What the research shows

There is no human research. The animal studies below were small, and almost all came from the developer’s laboratory.

Normal and aging animals

Healthy adult mice. Peripheral P021 improved learning and short-term and spatial memory in normal C57Bl6 mice, and increased formation and maturation of new neurons in the hippocampus (Li et al., FEBS Lett 2010).
Aged rats. In 22- to 24-month-old Fisher rats, chronic oral P021 reduced age-related decline in learning and memory, raised BDNF and restored synaptic markers (Bolognin et al., Neurobiol Aging 2014).
Tau in aged rats. In aged rats, P021 lowered tau in the brain and in cerebrospinal fluid toward young-adult levels, but did not lower amyloid-β/AβPP in cerebrospinal fluid (Khatoon et al., J Alzheimers Dis 2015).

Alzheimer’s disease mouse models

Most studies used 3xTg-AD mice, a strain engineered to develop both amyloid plaques and tau tangles.

Study	Treatment	Main reported findings
Kazim et al., Neurobiol Dis 2014	12 months in diet, starting at 9–10 months of age	Less abnormal tau; lower soluble amyloid-β, only a trend in plaques; improved cognition and neurogenesis
Baazaoui and Iqbal, J Alzheimers Dis 2017	In diet from 3 months of age, before visible pathology	Prevented neurodegeneration and tau and amyloid-β pathology; rescued memory; lower mortality
Baazaoui and Iqbal, Alzheimers Res Ther 2017	60 nmol/g feed from 3 to 21 months of age	Rescued dendritic and synaptic deficits and cognitive impairment
Wei et al., Alzheimers Res Ther 2020	Via the mothers’ diet, prenatal day 8 to postnatal day 21	Better cognition at 4 months; less tau and plaque at 22 months
Wei et al., J Alzheimers Dis 2021	In diet from birth to postnatal day 120	Prevented cognitive impairment; raised BDNF and synaptic proteins

In the 12-month treatment study, the effect on amyloid was limited: soluble amyloid-β fell, but plaque reduction did not reach significance (Kazim et al., Neurobiol Dis 2014). Each group in that study contained roughly 5–7 mice (Kazim and Iqbal, Mol Neurodegener 2016).

Other animal models

Down syndrome. In Ts65Dn mice, a Down syndrome model, P021 given to mothers in the diet (200 nmol per gram) from embryonic day 8 to weaning rescued developmental delay in pups and memory deficits in adulthood (Kazim et al., Sci Rep 2017).
Retinal degeneration. In aged rats treated for 3 months and 3xTg-AD mice treated for 18 months, P021 reduced retinal changes resembling age-related macular degeneration (Liu et al., Front Aging Neurosci 2019).
CDKL5 deficiency disorder. A group in Bologna, with the developer as a co-author, found that P021 corrected defects in a human neuronal cell line lacking CDKL5. In Cdkl5 knockout mice, however, chronic treatment did not raise BDNF, did not improve brain structure and gave only limited behavioral benefit (Mottolese et al., J Neurodev Disord 2024).

The CDKL5 study is a useful reminder that effects seen in cells, or in one animal model, do not always appear in another.

Side effects and risks

Unknown safety in humans

No human safety data exist. In animals, the developers reported no detectable immune reaction in rats (Khatoon et al., J Alzheimers Dis 2015) and no adverse effects in mice treated for up to 1 year (Kazim and Iqbal, Mol Neurodegener 2016). These are statements from the inventing group, not formal toxicology studies published for independent review.

Theoretical concerns

P021 is designed to change growth-factor signaling in the brain. Earlier attempts to treat Alzheimer’s disease with whole neurotrophic factors were halted in part because of severe side effects (Baazaoui and Iqbal, Biomolecules 2022). Whether a small fragment avoids such problems in people is unknown.

Product identity and quality

Products sold as “P21” or “P021” come from unregulated research-chemical channels. No pharmacopeial standard or published analysis of retail products exists, so the identity, dose, purity and sterility of a given product cannot be confirmed.

Conflict of interest

Nearly every P021 paper lists the inventor as an author. He holds patents on the composition and use of P021, is co-founder and chief scientific officer of Phanes Biotech, and is developing P021 as a therapeutic drug (Mottolese et al., J Neurodev Disord 2024). Independent replication is limited.

Key takeaways

A CNTF-derived research peptide. P021 is a 4-amino-acid fragment of ciliary neurotrophic factor with an adamantane-containing end group added to improve stability and brain entry.
Animal data only. Studies in mice and rats report better memory, more new neurons and less tau pathology, but no human trial has been published or registered.
Mostly one laboratory. Nearly all studies come from the inventing group, and the one partly independent mouse study found limited benefit.
Pharmacokinetics are preclinical. A plasma half-life of over 3 hours is reported from preclinical testing; nothing is known about its behavior in people.
Unapproved and prohibited in sport. No regulator has approved P021, and WADA’s S0 class prohibits unapproved substances like it at all times.

Sources

Li B, Wanka L, Blanchard J, et al. Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett. 2010;584(15):3359–3365. PubMed.
Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease. Mol Neurodegener. 2016;11(1):50. PubMed.
Baazaoui N, Iqbal K. Alzheimer’s disease: challenges and a therapeutic opportunity to treat it with a neurotrophic compound. Biomolecules. 2022;12(10):1409. PubMed.
National Center for Biotechnology Information. Ac-dggl-adamatanylglycine-NH2 (P021), PubChem CID 56599151. PubChem.
Bolognin S, Buffelli M, Puoliväli J, Iqbal K. Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound. Neurobiol Aging. 2014;35(9):2134–2146. PubMed.
Kazim SF, Blanchard J, Dai CL, et al. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer’s disease. Neurobiol Dis. 2014;71:110–130. PubMed.
Khatoon S, Chalbot S, Bolognin S, et al. Elevated tau level in aged rat cerebrospinal fluid reduced by treatment with a neurotrophic compound. J Alzheimers Dis. 2015;47(3):557–564. PubMed.
Kazim SF, Blanchard J, Bianchi R, Iqbal K. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome. Sci Rep. 2017;7:45561. PubMed.
Baazaoui N, Iqbal K. Prevention of amyloid-β and tau pathologies, associated neurodegeneration, and cognitive deficit by early treatment with a neurotrophic compound. J Alzheimers Dis. 2017;58(1):215–230. PubMed.
Baazaoui N, Iqbal K. Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound. Alzheimers Res Ther. 2017;9(1):45. PubMed.
Liu Y, Wei W, Baazaoui N, et al. Inhibition of AMD-like pathology with a neurotrophic compound in aged rats and 3xTg-AD mice. Front Aging Neurosci. 2019;11:309. PubMed.
Wei W, Wang Y, Liu Y, et al. Prenatal to early postnatal neurotrophic treatment prevents Alzheimer-like behavior and pathology in mice. Alzheimers Res Ther. 2020;12(1):102. PubMed.
Wei W, Liu Y, Dai CL, et al. Neurotrophic treatment initiated during early postnatal development prevents the Alzheimer-like behavior and synaptic dysfunction. J Alzheimers Dis. 2021;82(2):631–646. PubMed.
Mottolese N, Loi M, Trazzi S, et al. Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder. J Neurodev Disord. 2024;16(1):65. PubMed.
ClinicalTrials.gov. Search results for “P021”. US National Library of Medicine. Accessed October 2026. ClinicalTrials.gov.
World Anti-Doping Agency. The 2026 Prohibited List: International Standard. WADA.
Code of Federal Regulations. 21 CFR 1308.13, Schedule III. eCFR.

P21