Important limitations
- Individual claims and source links have not yet completed editorial verification.
- Evidence level, applicable study model, formulation, route and population remain unassigned.
Dosing & scaling, explained
The moderated mass amounts below are retained for comparison. Near-duplicates, mix-dependent volumes and device markings are excluded. This is educational source context, not a protocol or recommendation.
Mass amounts available for comparison
- Lower range100 mcgDose
Recorded example with no verified study backing; shown for amount literacy only.
- Mid range500 mcgDose
Recorded example with no verified study backing; shown for amount literacy only.
Only mcg or mg amounts are retained. The calculator derives mL, syringe units or pen clicks from the current vial strength, water volume and device.
No independently verified schedule
Evidence context
No clinical amount or schedule is inferred from this material. Source verification is pending, and every displayed amount remains educational context rather than guidance.
Storage, handling and interpretation
Product identity
Verify the exact compound, formulation and amount against the product label or certificate before calculation.
Storage & handling
Follow the product label, certificate and validated laboratory SOP; no universal storage assumption is applied here.
Prepared solutions
Label concentration and preparation date, use sterile technique where applicable, and follow a validated stability protocol.
Reported protocols for P21
What published studies and recent community write-ups report about amounts, timing and course length. 6 preclinical and 2 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.
| Context | Dose | Frequency | Route | Course | Source |
|---|---|---|---|---|---|
| Preclinical6 rows | |||||
| Preclinical: 3xTg-AD mice treated from the moderate-pathology stageFemale 3xTg-AD mice and wild-type controls, treatment started at 9-10 months of age | 60 nmol per gram of formulated diet | Continuous, in the food | Oral (medicated chow) | 6 or 12 monthsNone | Neurobiology of Disease (PubMed)2014 |
| Tau hyperphosphorylation at major Alzheimer-associated sites fell after both 6 and 12 months, soluble amyloid beta decreased with only a trend toward fewer plaques, and deficits in cognition, neurogenesis and synaptic markers were rescued, which the authors attribute to higher BDNF expression lowering GSK3-beta activity. This is a single-dose feeding study in one transgenic line; no dose-response work exists in any species. | |||||
| Preclinical: 18-month prevention study in 3xTg-AD miceFemale 3xTg-AD mice (32 treated, 35 vehicle) and 41 wild-type controls, started at 3 months of age | 60 nmol per gram of feed, about 162 nmol per mouse per day at 2.7 g of chow | Continuous, in the food | Oral (medicated chow) | About 18 months (3 to 21 months of age)None | Alzheimer's Research and Therapy (PubMed Central)2017 |
| Starting P021 6-9 months before overt plaque or tangle pathology prevented the loss of doublecortin-positive new neurons, preserved dendritic and synaptic markers and reversed cognitive impairment, with no weight loss, tumors or signs of pain recorded over the 18 months. Several synaptic markers moved only as trends and changes were region-dependent rather than uniform. | |||||
| Preclinical: prenatal to weaning treatment in the Ts65Dn Down syndrome modelPregnant Ts65Dn and wild-type dams (35 and 20) and their offspring | 200 nmol per gram of formulated diet, given to the mothers | Continuous, in the dams' food, reaching pups through the placenta and milk | Oral (dam diet) | 5 weeks, from embryonic day 8 to postnatal day 21Offspring switched to regular chow after weaning and were followed to about 7 months | Scientific Reports (Nature)2017 |
| Treated trisomic pups reached developmental milestones such as surface righting and cliff aversion sooner, and as adults showed less hippocampus-dependent memory impairment along with higher BDNF and phosphorylated CREB and lower GSK3-beta activity. Reduced STAT3 phosphorylation in offspring hippocampus was used as indirect evidence that the compound reached the brain; no brain concentration was measured. | |||||
| Preclinical: cognitive aging in old ratsFemale Fisher rats aged 19-21 months at the start (22-24 months at testing), with young adult controls | 500 nmol/kg (about 289 mcg/kg) in 10 mL/kg saline | Once daily, between 7 and 9 a.m. | Oral gavage | 88 daysNone | Neurobiology of Aging (PubMed)2014 |
| Treated old rats had shorter latencies in the Morris water maze, restored dentate gyrus neurogenesis, higher BDNF and TrkB signalling and partly restored synaptic proteins, and MR spectroscopy showed a reduction in the age-related rise in hippocampal myo-inositol. Maze performance improved but did not reach that of young rats, and FDG-PET glucose uptake was unchanged. | |||||
| Preclinical: CDKL5 deficiency model, the only in vivo test outside the originating labMale Cdkl5 knockout mice and wild-type littermates (39 animals across both arms) | 60 nmol per gram of diet (about 150 nmol per mouse per day) from weaning; 750 nmol per mouse by injection in adults | Continuous in food, or once-daily injections | Oral (medicated chow) for 70 days; intraperitoneal injection for 30 days | 70 days (juvenile arm) or 30 days (adult arm)None | Journal of Neurodevelopmental Disorders (PubMed Central)2024 |
| P021 restored proliferation, survival and maturation in CDKL5-knockout neuroblastoma cells, but neither the diet nor the five-fold higher injected dose raised hippocampal BDNF, corrected the neuroanatomical deficits or improved memory in the knockout mice; only muscular rigidity on a catalepsy bar improved. The compound's inventor is a co-author with declared patents and a company developing P021, so this is not an independent replication. | |||||
| Preclinical summary: healthy adult mice and rodent safety record8-10-month-old C57BL/6 mice (depot study); 3xTg-AD, wild-type and Cdkl5 knockout mice across the feeding studies | 25 nmol per day from subcutaneous extended-release pellets; 60 nmol per gram of feed in the long-term studies | Continuous release or continuous in the diet | Subcutaneous depot implant; oral | 35 days (depot); up to 18 months (diet)None | Alzheimer's Drug Discovery Foundation2025 |
| This 2025 foundation review records that the original 2010 study gave normal adult mice 25 nmol per day from a subcutaneous depot for 35 days and saw better object recognition and spatial memory with more new neurons in the dentate gyrus, and that up to 18 months of dietary P021 produced no weight loss, tumors or pain in mice. It states that human safety has never been assessed and quotes a plasma half-life of over 3 hours in mice from the developers' own reviews. | |||||
| Community-reported2 rows | |||||
| Community-reported daily figure | 500 mcg to 1 mg once daily most often cited; 100 mcg to 2 mg per day as the wider range; 250-500 mcg for new users | Once daily, in the morning | Subcutaneous from a reconstituted 5 mg vial (2 mL gives 2.5 mg/mL); intranasal also described | 4-8 weeksTime off between cycles, length not fixed | Community resource2026 |
| This 2026 guide states that every figure comes from vendor listings and forum discussion because no human trial exists, and flags the route mismatch: the rodent work used medicated chow, gavage and a depot implant while community use is subcutaneous or intranasal. Morning dosing is a convention based on reports of overstimulation or disturbed sleep at higher or later doses. | |||||
| Tiered subcutaneous and intranasal protocol | 100 mcg (beginner), 300 mcg (moderate) or 500 mcg (aggressive) subcutaneous; 500 mcg intranasal in weeks 1-2 rising to 1 mg in weeks 3-4 | Once daily in the morning | Subcutaneous into abdominal fat (10 mg vial in 2 mL), or nasal atomizer at 5 mg/mL giving 500 mcg per 0.1 mL spray | 4 weeks on (4-6 weeks in the common intranasal protocol)4 weeks off; some protocols 2-4 weeks off | Community resource2026 |
| This 2026 compound page reports that most community users prefer the intranasal route at 500 mcg to 1 mg a day and that many describe subcutaneous doses under 300 mcg as producing nothing noticeable, with any effect described as gradual over 3-5 weeks. It grades the compound research-only with no human safety profile and notes that the 2024 CDKL5 result did not reproduce the BDNF effect in vivo. | |||||
How a course is commonly described
- Weeks 1-2Community-reported
Community protocols start at 100 mcg subcutaneously or 500 mcg intranasally once each morning and describe this as a silent phase in which nothing is expected to be felt; transient headache or brain fog in the first days is the most common complaint reported.
- Weeks 3-4Community-reported
The intranasal protocol steps up to 1 mg a day and subcutaneous users move toward 300-500 mcg; reported changes are subtle shifts in recall and spatial memory, with vivid dreams sometimes mentioned. None of this has been measured in a controlled setting.
- Weeks 4-8Community-reported
Guides end the cycle somewhere between 4 and 8 weeks, with 4-6 weeks given as the usual stopping point for the intranasal course. The rodent studies the timing is borrowed from dosed continuously for 35 days to 18 months with no cycle at all.
- BreakCommunity-reported
A 4-week off period is the most-quoted pattern, with 2-4 weeks described in some protocols; the stated reason is the absence of long-term human safety data rather than any observed tolerance. Some users report a gradual return to baseline 8-10 weeks after stopping.
- Evidence checkCommunity-reported
As of August 2026 a ClinicalTrials.gov search returned no registered study of P021 of any kind, so there is no human pharmacokinetic, dose-ranging, safety or efficacy data behind any phase above; the rodent record comes almost entirely from one laboratory at a single dietary concentration.
- No human has received P021 in a registered study. The microgram doses, routes and 4-8 week cycles above are vendor and forum conventions; the rodent studies they borrow from used continuous dosing in food or by gavage for months, not short cycles.
- The widely quoted plasma half-life of over 3 hours comes from the developers' reviews and is described as a plasma stability figure in one of their primary papers; no human pharmacokinetic measurement exists and no brain concentration has been published.
- The only in vivo test outside the originating laboratory, in Cdkl5 knockout mice, did not reproduce the BDNF increase that the proposed mechanism depends on, even at a five-fold higher injected dose. P021 is not approved anywhere and is sold as a research chemical.
Sources for this section (9)
- Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease
- Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound
- Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer's-like memory deficits in the Ts65Dn mouse model of Down syndrome
- Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound
- Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder
- Cognitive Vitality Report: P021
Plus 3 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.
Overview
P21 (published as P021) is a small synthetic peptide built from a four-residue stretch of human ciliary neurotrophic factor (CNTF), with an acetyl group on the N-terminus and an adamantylated glycine amide on the C-terminus added to slow enzymatic breakdown and help it cross the blood-brain barrier. It was designed in Khalid Iqbal's laboratory at the New York State Institute for Basic Research and is reported to work by competing with leukemia inhibitory factor and raising BDNF expression, which in rodents increased hippocampal neurogenesis, lowered GSK3-beta activity and tau phosphorylation, and improved memory. Every published study is in mice, rats or cell culture, nearly all from the originating laboratory, and the one in vivo test run elsewhere (a CDKL5 deficiency model) did not reproduce the BDNF increase. No human trial has been registered, no regulator has approved it, and it is sold only as a research chemical in 5 mg vials.
What researchers are exploring
These themes organize the educational information currently available. Individual claims remain under source review and are not treatment claims.
- 1
What is P21?
Understanding P21's role as a CNTF mimetic
- 2
Research on P21
Development, mechanism of action, and therapeutic applications
What is known and what still needs verification
Available context is organized without assigning unsupported study models or evidence grades.
- Not graded
What is P21?
Understanding P21's role as a CNTF mimetic
- Not graded
Research on P21
Development, mechanism of action, and therapeutic applications
Amounts recorded for P21
These amount records are independent from vial strength, reconstitution volume and measuring device. A recorded source is not the same as study backing, and these values are not recommendations.
- 1Dose · lower endpointSign in for schedule, duration and source context.100 mcg
- 2Dose · upper endpointSign in for schedule, duration and source context.500 mcg
Chemistry identifiers
Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.
Sequence
Ac-Asp-Gly-Gly-Leu-Gly(adamantyl)-NH2 (the C-terminal residue is 3-aminoadamantane-1-carboxamide, written by the developers as adamantylated glycine)
Also listed as
P021, P-21, Peptide 021, P-21 nootropic peptide, Ac-DGGL(A)G-NH2, Ac-dggl-adamatanylglycine-NH2 (PubChem record title), UNII VV8CZC8PAS, GLXC-21260 (duplicate PubChem record CID 56589645)
InChIKey
LUJZBZPLIRWWGJ-ZKHAZHQOSA-N
IUPAC name
(3S)-3-acetamido-4-[[2-[[2-[[(2S)-1-[(3-carbamoyl-1-adamantyl)amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-4-oxobutanoic acid
Limitations and unknowns
Sources
1 link carried over from the earlier page, awaiting verification.