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Not medical advice. The Atlas is not a substitute for a clinician who can examine you.

NAP / Davunetide

NAPVSIPQ Neuroprotective Peptide (AL-108)

Evidence grade 2 of 5, Thin. Read how the Atlas grades evidence.

A once-promising clinical lead that has largely failed to deliver. Davunetide (NAP) completed the largest disease-modifying trial ever run in progressive supranuclear palsy, a randomised, double-blind, placebo-controlled Phase 2/3 in 313 patients (Boxer et al., Lancet Neurology 2014), and was negative on every primary, secondary, and exploratory endpoint, which halted development for that indication. Earlier small Phase 2 signals in amnestic MCI and schizophrenia (AL-108) were modest and inconsistent, so the honest read is preliminary human data plus one clearly failed pivotal trial; an intranasal formulation (CP201) is now in a pediatric Phase 3 for ADNP syndrome but has no efficacy readout yet, keeping this at grade 2.

FDA
Investigational and not approved for any indication. Its pivotal Phase 2/3 in progressive supranuclear palsy (n=313, 2010 to 2012) was completed and failed on all endpoints, which halted the original program. Intranasal CP201 holds FDA orphan drug and rare pediatric disease designations and entered a pediatric Phase 3 for ADNP syndrome in October 2024, with no efficacy readout yet.
WADA
Not listed on the WADA Prohibited List.

Reference only. Not medical advice.

What can go wrong

A failed drug lead, not a proven neuroprotectant; the pivotal PSP trial showed no benefit, intranasal delivery was associated with headache and nasal irritation, and current ADNP-syndrome use is unproven and investigational.

Talk to a clinician before taking this. The Atlas can tell you what has been studied about NAP / Davunetide. It cannot tell you how it would interact with your body, your history, or anything else you are taking, and nothing on this page is a reason to start.

An eight-amino-acid peptide (NAPVSIPQ) derived from Activity-Dependent Neuroprotective Protein (ADNP), discovered in the Gozes lab and developed as davunetide (AL-108). It reached human trials but its pivotal Phase 2/3 in progressive supranuclear palsy failed on all endpoints, and earlier signals in MCI and schizophrenia were small and mixed; it is now studied as intranasal CP201 for the rare pediatric ADNP syndrome.

What people take it for

These are the reasons people give for taking it. They are not effects it has been shown to have.

  • Alzheimer's neuroprotection
  • Cognitive-decline prevention

How it is supposed to work

Davunetide was designed to shore up the scaffolding inside brain cells. Neurons depend on tiny internal tracks called microtubules to move cargo and hold their shape, and in tau-related neurodegeneration those tracks fall apart as the tau protein that normally stabilizes them goes haywire. Davunetide, a small fragment of a natural brain-protective protein, helps keep tau attached to the microtubules and the tracks intact. In the lab it protected neurons against a wide range of insults, which made it a hopeful candidate for diseases like Alzheimer’s and related tauopathies.

Davunetide is an eight-amino-acid fragment of a natural brain growth factor called ADNP, activity-dependent neuroprotective protein, which glial cells release to protect neurons. It is given intranasally so it reaches the brain, and is also known as NAP, AL-108 and CP201. It is not an approved drug, and it is sold gray-market as a research compound.

Type
ADNP-derived octapeptide
Action
Stabilizes microtubules
Route
Intranasal
Tolerability
Good
Efficacy
Failed in trials
Approved
No

Elegant, Well-Tolerated, And It Didn’t Work

Davunetide is one of the cleaner cautionary tales in neuroscience: an elegant, well-pedigreed, genuinely neuroprotective peptide that did not work in its big human trials. Its mechanism is real and appealing, propping up the microtubule tracks that collapse in tau-driven neurodegeneration, and it was consistently protective in cell and animal models, with an early hint of memory benefit in people with mild cognitive impairment. But the decisive tests went against it. A large Phase 2/3 trial in progressive supranuclear palsy, a tau disease thought to be the ideal proving ground, found no benefit, and the cognitive-impairment trials showed no clear effect either. Crucially, it was well tolerated throughout, so its failure was about efficacy, not safety. Later analysis offered an explanation, that the peptide favors one form of tau that is prominent in Alzheimer’s but not in the disease that was tested, and a re-analysis raised a possible benefit in women, keeping a narrow line of research alive for a rare genetic condition linked to its parent protein. None of that has produced an approved drug. Yet it is now sold gray-market as a brain-boosting nootropic, a use its actual trials never tested and would not support.

Safety in detail

Davunetide was reasonably well tolerated across several hundred adult participants, with headache and nasal irritation the most common effects, but tolerability is not efficacy and no approved use exists.

  • Davunetide was consistently well tolerated across trials, given intranasally, so its failure was about efficacy, not safety.
  • For the gray-market nootropic use there is no approved product and no human safety data for that purpose.
  • There is no evidence it improves healthy cognition; its trials were in disease and failed.
  • The gray-market use trades on its pedigree rather than data.
  • Its honest clinical record is a string of negative efficacy trials.

Children and teenagers

Davunetide has no general pediatric use. Its only legitimate pediatric angle is research into a rare genetic condition linked to its parent protein, strictly within clinical settings. Gray-market nootropic use in children is inappropriate, being unapproved and unsupported by safety or efficacy data.

What people get wrong

Nothing recorded here yet. There is almost certainly something people get wrong about this one, and the blank space means we have not written it down, not that the record is clean.

Who profits, and who pushes back

Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.

There is no approved-drug economy here, since davunetide failed its major trials and its developer folded. A narrow line of development continues for a rare genetic condition, while gray-market vendors sell it as a nootropic on the strength of its neuroscience pedigree, alongside research-reagent sales. It is a failed drug with a gray-market afterlife.

How we got here

NAP was identified in the laboratory of Illana Gozes at Tel Aviv University as the shortest active fragment of Activity-Dependent Neuroprotective Protein (ADNP), a protein Gozes originally characterised. Rights were licensed from Ramot, the university technology-transfer company, to Allon Therapeutics of Vancouver, which developed it under the code AL-108 (intranasal) and AL-208 (intravenous) and gave it the INN davunetide, carrying it through Phase 2 studies in amnestic MCI and schizophrenia and the failed Phase 2/3 in progressive supranuclear palsy around 2010 to 2012. After that failure halted the program, the intranasal asset was later picked up by Coronis Neurosciences as CP201 and licensed onward to ExoNavis, which obtained FDA orphan drug and rare pediatric disease designations and began a pediatric Phase 3 in ADNP syndrome (Helsmoortel-Van der Aa syndrome) in October 2024.

Around 1999 a neuroprotective fragment of the brain protein ADNP, named NAP, was identified, and it showed strong protection in preclinical models. Developed as intranasal davunetide, it produced an early memory hint in mild cognitive impairment but no clear benefit, and a large Phase 2/3 trial in progressive supranuclear palsy failed, leading its developer to fold. Later work explained the failure through tau selectivity and raised a possible benefit in women, while the compound acquired a gray-market afterlife as a nootropic.

  1. ~1999NAP is identified as a neuroprotective fragment of the protein ADNP.
  2. 2000sStrong preclinical neuroprotection drives development as intranasal davunetide.
  3. 2008-2012An early memory signal appears in cognitive impairment, without clear benefit.
  4. 2012-2014A large progressive-supranuclear-palsy trial fails, and the developer folds.
  5. 2019-2023Tau-selectivity and possible female-benefit analyses keep a narrow thread alive.

The numbers behind the grade

Type
ADNP-derived octapeptide
Action
Stabilizes microtubules
Route
Intranasal
Tolerability
Good
Efficacy
Failed
Approved
No

The people taking it

An elegant, well-tolerated neuroprotective peptide that stabilizes the brain’s microtubule scaffolding but failed its major Alzheimer’s-spectrum and progressive-supranuclear-palsy trials, now sold gray-market as a nootropic on its pedigree rather than evidence.

Davunetide’s gray-market users are nootropic and brain-health biohackers, people worried about cognitive decline, and neuroprotection seekers drawn by its neuroscience pedigree and intranasal route. Its legitimate relevance is to research populations with specific tau diseases and a rare genetic condition linked to its parent protein.

A neuroprotective peptide that failed its major trials in progressive supranuclear palsy and cognitive impairment despite good tolerability and an elegant mechanism, with narrow ongoing development and a gray-market nootropic use. Not approved.

Set against the alternatives

Against other tau- and microtubule-directed drugs, such as the microtubule stabilizer that also failed and proved toxic in tauopathy trials, davunetide shares a difficult clinical record for the whole approach. Against the broader graveyard of neuroprotection candidates, it is a familiar story of compelling preclinical promise undone in late trials. And against other gray-market nootropic peptides like semax, cerebrolysin and dihexa, it shows the same pattern of a real neuroscience pedigree being resold as brain enhancement without evidence. Its strength is an elegant, well-tolerated mechanism; its defining feature is that it did not work.

What we do not know

  • Whether the possible benefit in women and the rare-disease threads hold up.
  • Whether any tau- or microtubule-directed approach can succeed clinically.
  • Whether the tau-selectivity insight enables a better-targeted trial.
  • How to translate neuroprotection from animals to humans at all.

What could change

Rare-disease developmentA narrow line continues for a genetic condition linked to its parent protein.Female-subgroup hypothesisA possible benefit in women remains unconfirmed.Tau-targeting insightIts preference for one tau form may guide better-aimed trials.Hard fieldTau and neuroprotection drug development remains very difficult.

The market for this

What follows describes how this is bought and sold. It is not a buying guide and it is not an endorsement of any seller.

Available only through gray-market research vendors, which is not a route to an approved or proven product. It failed its efficacy trials and has no evidence for the nootropic use it is marketed for; the neuroscience pedigree is real, but the clinical trials were negative and the nootropic use was never tested. For cognitive concerns, see a clinician rather than buy a failed drug, and treat the brain-booster framing with strong caution.

Gray-market and research-grade davunetide is moderately priced, and the cost buys a failed-trial compound rather than a proven treatment.

Davunetide comes from research synthesis and gray-market suppliers as intranasal or research material, with no approved or human-grade product.

Not an approved productIt is not sold as an approved medicine.Research and gray-marketIntranasal and research material is sold gray-market.Niche developmentA narrow pharmaceutical thread continues for a rare disease.

What this entry does not yet cover

What follows is unfinished work on our side, not a finding about NAP / Davunetide.

Nothing outstanding on this one.

Sources

The studies that matter

  • Mechanismpreclinical

    Derived from the neuroprotective protein ADNP, it stabilizes microtubules by recruiting tau and protects neurons against many insults.

  • Early memory signalMCI trial

    A trial in mild cognitive impairment hinted at a short-term-memory benefit but showed no clear overall effect.

  • PSP failurePhase 2/3

    A large trial in progressive supranuclear palsy found no benefit, though the peptide was well tolerated.

  • Tau selectivity2019

    Later work showed it favors the 3-repeat form of tau, prominent in Alzheimer’s but not in the 4-repeat disease that was tested.

  • Subgroup and rare-disease threads2023 onward

    A re-analysis suggested possible benefit in women, and research continues for a rare genetic condition linked to its parent protein.