Onset
Not established. No human timeline data exists.
Protocol / Research Dosing Guide
P21 Dosage Guide: Reported Figures, Reconstitution and Evidence Limits
An evidence-organized P21 reference separating an entirely rodent evidence base from the vendor and community figures that circulate as a dose.
Last reviewed September 16, 202616 minute readResearch information only
Level 2 — Rodent research onlyNo human trial, pharmacokinetics or toxicologyNot FDA approved
P21 Quick Start
P21 (also written P-21 or P021) was developed in Khalid Iqbal's laboratory as an effort to reduce the neurotrophic activity of Cerebrolysin down to one defined molecule. Its published record is consistent and free of retractions, but it is entirely rodent work in disease and aging models. There is no human trial, no human pharmacokinetics and no toxicology dossier, so no dose has ever been established.
Why researchers care
Neurogenesis, synaptic plasticity and memory in preclinical models
Class
Synthetic adamantane-modified tetrapeptide (Ac-DGGLAG-NH2) derived from the active region of CNTF
Route reported
Oral and peripheral in the rodent studies; subcutaneous or intranasal in community reports
Cycle length
4–8 weeks with time off, as a community convention
Regulatory status
Not FDA approved; no registered clinical trials
Loading supplier information
P21 Dosing Protocol and Schedule
The supplied source reports a community and vendor figure of roughly 500 mcg to 1 mg once daily, within a broader cited range of about 100 mcg to 2 mg per day, usually reconstituted from a lyophilized vial and administered subcutaneously or intranasally, in the morning, for four to eight weeks.
| Phase or study | Amount | Frequency / evidence |
|---|---|---|
| Typical reported figure | About 500 mcg to 1 mg, once daily | Vendor copy and community reports |
| Broader cited range | About 100 mcg to 2 mg per day | Vendor copy and community reports |
| New-user references | About 250–500 mcg | Community reports |
| Timing | Morning, to avoid sleep disruption | Community convention |
| Cycle length | 4–8 weeks with time off | Community convention |
| Rest period | Not established | Not established |
None of these figures derives from human pharmacokinetic data, and no human safety data backs any cycle duration. There is also a route mismatch: the rodent studies used oral and peripheral administration, while community use is described as subcutaneous or intranasal.
P21 Supplies Needed
Neutral research-material planning only. This does not establish an appropriate amount or route.
Research planning item
Exact labeled research vial
Research planning item
Bacteriostatic water at a measured volume
Research planning item
U-100 insulin syringes
Research planning item
Alcohol prep swabs
Research planning item
Sharps container
Research planning item
Refrigeration for the prepared vial
Research planning item
Written concentration label with the preparation date
P21 Reconstitution Calculator
Vial-format concentration math
Concentration
2.5 mg/mL
Draw volume
0.2 mL
U-100 units
20
Mathematical draws
10
Arithmetic only. The entered amount is not a recommendation and does not establish suitability.
Best Time to Take P21: Morning or Night?
Morning or evening?
Morning is the community convention, based on reports of overstimulation or sleep disruption with later administration.
Daily or spaced?
Once daily is the reported pattern.
With food?
Not established for the routes reported in community use.
Missed amount?
No validated procedure exists.
P21 Route Comparison
| Format | What is reported | Evidence limit |
|---|---|---|
| Subcutaneous | The most commonly described community route | No human pharmacokinetic data |
| Intranasal | Also mentioned; local irritation is an anecdotal complaint | No exposure data |
| Oral or peripheral | The routes used in the rodent efficacy studies | Animal data does not map onto the routes people report using |
| Route conversion | Not established | No conversion exists between animal administration and human use |
Routes and amounts are not interchangeable unless a verified study explicitly establishes a conversion.
P21 Half-Life and Dosing Frequency
| Measure | Finding | Evidence limit |
|---|---|---|
| Human half-life | Not established | No human pharmacokinetic study exists |
| Blood-brain-barrier permeability | Reported as permeable in a 2015 aged-rat study | Animal finding |
| Frequency | Once daily is a community convention | Not pharmacokinetically derived |
| Repeat-cycle interval | Not established | No human data |
P21 Dosage Chart
| Route | Amount | Frequency | Source | Human validation |
|---|---|---|---|---|
| Subcutaneous or intranasal | 250–500 mcg | Once daily | Community report | No |
| Subcutaneous or intranasal | 500 mcg – 1 mg | Once daily | Vendor and community report | No |
| Subcutaneous or intranasal | Up to 2 mg | Once daily, upper cited range | Community report | No |
| Oral, rodent | Varies by study | Chronic dosing | Animal research | Not convertible |
Published study values describe those studies. Community-reported values are not validated dosing recommendations.
P21 Reconstitution Guide
Concentration: 2.5 mg/mL
| Entered amount | Volume | U-100 units |
|---|---|---|
| 0.5 mg | 0.2 mL | 20 units |
| 1 mg | 0.4 mL | 40 units |
| 1.5 mg | 0.6 mL | 60 units |
- 1.Confirm the labeled vial quantity, commonly 5 mg.
- 2.Choose and record the bacteriostatic water volume; 5 mg into 2 mL gives 2.5 mg/mL and into 2.5 mL gives 2 mg/mL.
- 3.Clean the stopper with an alcohol swab.
- 4.Add the liquid slowly down the vial wall.
- 5.Swirl gently until clear; do not shake.
- 6.At 2.5 mg/mL, 500 mcg is about 0.20 mL and 1 mg is about 0.40 mL.
- 7.Label the vial with the concentration and preparation date.
- 8.Keep the sealed vial cool and dark, and refrigerate once prepared.
Reconstitution does not establish identity, purity, sterility, stability, or an appropriate amount.
How P21 Works
Origin
P21 is derived from the active region of ciliary neurotrophic factor and carries an adamantane modification.
P21 Human Trials and FDA Status
Current status · verified September 16, 2026
Not FDA approved; no registered clinical trials
- No published human clinical trial of P21 exists: no Phase 1, no human pharmacokinetics, no toxicology dossier and no registered trials.
- Li 2010 introduced P21 (Ac-DGGLAG-NH2) and reported enhanced memory, neurogenesis and synaptic plasticity in normal mice.
- Bolognin 2014 reported reduced age-related cognitive decline in aged rats with chronic oral dosing.
- Kazim 2014 reported disease-modifying effects in a 3xTg-AD Alzheimer's model, including reduced tau pathology and preserved synapses.
- Khatoon 2015 reported reduced brain and CSF total tau in aged rats and blood-brain-barrier permeability.
- Kazim 2017 reported rescued memory deficits in a Down syndrome model with increased BDNF and phospho-CREB.
Who Should Avoid P21?
This is an evidence-gap and precaution list, not an approved prescribing label.
Pregnancy or breastfeeding
No safety data of any kind
Children or adolescents
No established protocol
Neurologic or psychiatric conditions
Effects and interactions are unknown
Concurrent medicines
No interaction studies
Anyone expecting cognitive enhancement in healthy people
No such data exists, even in animals
Long-term or repeated use
No human safety data and no published comprehensive toxicology
P21 Side Effects, Risks and Safety
Sleep disruption or overstimulationMost consistently reported anecdotally
Important limitation: The basis for the morning-dosing convention.
Headache, irritability or feeling wiredOccasionally mentioned
Important limitation: Anecdotal.
Injection-site reactionGeneric risk
Important limitation: Non-specific to P21.
Intranasal irritationGeneric risk
Important limitation: Non-specific to P21.
Chronic neurotrophic signalingTheoretical
Important limitation: A generic caution for any neurotrophic compound; no P21-specific cancer literature exists.
Human safety profileUnknown
Important limitation: No human toxicology or pharmacokinetic data.
P21 Timeline and Monitoring
Rodent study windows
Effects were measured over chronic dosing blocks in aging and disease models.
Community cycle
4–8 weeks is a convention, not a measured timeline.
Monitoring
No validated monitoring schedule or stopping rule exists.
P21 Benefits and Results: What the Evidence Shows
| Claim | Evidence level | What research shows | Important limitation |
|---|---|---|---|
| Memory and learning | Animal research | Improved maze learning in normal and model rodents | No human data |
| Neurogenesis and synaptic plasticity | Animal research | Consistent across studies | Single-lab weighting |
| Tau reduction | Animal research | Reduced brain and CSF total tau in aged rats | Model-specific |
| Cognitive enhancement in healthy people | Not established | No study has tested this | Unsupported claim |
P21 Storage and Handling
Sealed vial
Vendor guidance commonly calls for keeping it cool and away from light.
Prepared vial
Typically refrigerated per vendor instructions; no compound-specific stability study was identified.
Purity
Depends entirely on the supplier certificate of analysis.
Appearance
Cloudiness, discoloration or particles require qualified product review.
P21 Troubleshooting
Sleep disruption
The reported association is with higher amounts or later-day administration; morning use is the community convention.
Draw volume looks wrong
Recheck vial quantity, water volume, target unit and the U-100 scale.
Animal and community routes conflict
They do. Rodent efficacy used oral and peripheral administration, not subcutaneous or intranasal.
Cloudy solution
Do not assume it is usable; seek qualified product guidance.
Expecting a validated protocol
None exists. Every figure on this page is reported, not recommended.
A scheduled amount is missed
No validated missed-amount procedure exists.
P21 Comparisons
| Compound | Class or mechanism | Evidence | FDA status |
|---|---|---|---|
| P21 | CNTF-derived tetrapeptide acting via a BDNF cascade | Rodent studies only | Not approved |
| Cerebrolysin | Multi-peptide neurotrophic preparation | The starting point P21 was pared down from | Not FDA approved |
| Semax | ACTH(4–7) analogue | Preclinical and limited clinical literature | Not FDA approved |
| PE-22-28 | BDNF-pathway research peptide | Preclinical only | Not approved |
P21 Frequently Asked Questions
What is P21?
A synthetic adamantane-modified tetrapeptide, Ac-DGGLAG-NH2, derived from the active region of ciliary neurotrophic factor.
Is it FDA approved?
No, and there are no registered clinical trials.
Is there a human dose?
No. The 500 mcg to 1 mg figure is vendor and community derived, not trial validated.
What is the evidence base?
Rodent studies published roughly 2010–2019, much of it from the laboratory that created the compound.
What is the route mismatch?
Rodent efficacy used oral and peripheral administration, while community use is described as subcutaneous or intranasal.
What is its half-life?
Not established. No human pharmacokinetic study exists.
Does it work through CNTF signaling?
The authors attribute the effect largely to a BDNF-mediated cascade rather than classical CNTF receptor signaling.
What side effects are reported?
Anecdotally, sleep disruption or overstimulation, plus headache or irritability; there is no human safety data.
Is there a validated cycle?
No. The 4–8 week structure is a community convention.
What does the calculator do?
Concentration and volume arithmetic only.
Sources and Research
Coverage source
1. P-21 dosage coverage source
Community and vendor figures, route mismatch and reconstitution reference; not primary evidence.
Open direct sourceAnimal research
2. Li & Iqbal 2010, A neurotrophic peptidergic compound enhances memory and neurogenesis
Foundational mouse study introducing Ac-DGGLAG-NH2.
Open direct sourceAnimal research
3. Kazim et al. 2014, Disease modifying effect of a neurotrophic peptide mimetic in 3xTg-AD mice
Alzheimer's model study reporting reduced tau pathology and preserved synapses.
Open direct sourceAnimal research
4. Khatoon et al. 2015, Elevated tau level in aged rat CSF is reduced by treatment with a neurotrophic compound
Aged-rat study reporting reduced tau and blood-brain-barrier permeability.
Open direct sourceAnimal research
5. Kazim et al. 2017, Neurotrophic factor small-molecule mimetic rescues cognitive impairment in a Down syndrome model
Rodent study reporting increased BDNF and phospho-CREB and decreased GSK-3β.
Open direct sourceMissing information flagged for review
- Any human trial, pharmacokinetics or toxicology: Not established
- Established human dose and route: Not established
- Half-life: Not established
- Validated cycle and rest period: Not established
- Compound-specific stability study: Not established
- Drug interaction data: Not established