PSP trial
Trial- Dose
- 30 mg
- How often
- Twice daily, nasal spray
- How long
- 52 weeks
313 people with progressive supranuclear palsy, randomized 1:1 against placebo at 48 centers. No difference on either main measure; more nosebleeds and nasal discomfort.
Human studiesADNP-derived microtubule-stabilizing peptide (investigational)
Davunetide
NAP, NAPVSIPQ, AL-108 (nasal spray), AL-208 (IV), CP201
- Common dose
- Trial doses only: 5–60 mg a day by nose
- Cycle
- No set cycle
- Form
- In trials only
An 8-amino-acid piece of ADNP (activity-dependent neuroprotective protein), a protein essential for brain development. In cells and mice it steadies microtubules, the internal scaffolding and transport tracks of nerve cells, and reduces the abnormal tau that builds up in Alzheimer’s disease and progressive supranuclear palsy.
Evidence. Tested in about 750 people in controlled trials from 2006 to 2012. The largest, 313 people with progressive supranuclear palsy given a nasal spray for a year, showed no benefit (2014); smaller trials in memory impairment and schizophrenia missed their main thinking measures. Later reanalyses by the inventor’s group report benefit only in women, but no new trial has been registered and nothing is approved.
What it’s used for
None of these uses is approved. Uses tested in people come first, then claims that rest on animal studies or user reports.
- Progressive supranuclear palsy
- TrialFailed: in a 313-person, year-long trial, twice-daily nasal davunetide didn’t slow decline versus placebo. Later reanalyses by its inventor’s group report benefit in women only, which no trial has tested.
- Mild cognitive impairment and memory
- TrialUnproven: in 144 adults with amnestic mild cognitive impairment, 12 weeks didn’t change the main memory score; 2 single tests hinted at benefit.
- Schizophrenia
- TrialUnproven: in 63 adults, 12 weeks didn’t improve thinking scores, but a test of everyday skills improved versus placebo (p=0.048). No larger trial followed.
- Memory after heart bypass surgery
- TrialUnproven: one IV dose around bypass surgery in 234 adults didn’t change thinking versus placebo, per the sponsor; a 2025 reanalysis reports benefit in men.
- Alzheimer’s disease
- AnimalUnproven: in Alzheimer’s-model mice it reduced abnormal tau and improved memory. It has never been tested in people with Alzheimer’s dementia.
- ADNP syndrome in children
- AnimalUnproven: in mice lacking one copy of the Adnp gene, daily doses partly reversed developmental and memory problems. Its licensee says a children’s trial began in 2024; none is registered.
Trial: tested in people, with the result. Animal: cell or animal studies only.
Every compound’s uses, by body system: evidence map, and by condition: conditions A to Z.
Status
- Approval
- Not approved anywhere. A US orphan drug designation for progressive supranuclear palsy (January 2010) and an EU one (March 2010, withdrawn April 2013) preceded the failed trial. ExoNavis Therapeutics, its licensee since 2021, says it holds US orphan and rare pediatric disease designations for ADNP syndrome and planned a phase 3 study from late 2024; no such trial is registered (ClinicalTrials.gov, October 2026).
- US compounding
- Never nominated for pharmacy compounding, so it appears on none of FDA’s 503A or 503B bulk substance category lists (503A list updated May 14, 2026).
- European Union
- No marketing authorization. An EU orphan designation for progressive supranuclear palsy (March 2010) was withdrawn at the sponsor’s request in April 2013.
- United Kingdom
- No marketing authorization (MHRA).
- Canada
- No marketing authorization (Health Canada). Its first developer, Allon Therapeutics, was based in Vancouver.
- Australia
- No marketing authorization. Davunetide isn’t named in the Poisons Standard (October 2026).
- Sport (WADA 2026)
- Likely banned in sportNot named on the 2026 list. With no approval anywhere, it falls under S0 non-approved substances, banned at all times; it isn’t a hormone or growth factor of the kind S2 names. The 2027 list adds peptides to S0’s examples; no change.
Category 2 is FDA’s list of bulk substances that may present significant safety risks in compounding. The 503A bulks list adds substances that pharmacies may compound with. Advisory committee votes are advice; FDA makes the final decision. Sport status follows the WADA Prohibited List in force since January 1, 2026; athletes should confirm with their anti-doping organization. Checked October 5, 2026. Status outside the US checked October 7, 2026 against EMA, MHRA, Health Canada and TGA records. By country: EU, UK, Canada, Australia. Status of every compound.
How it works
Davunetide is NAP, an 8-amino-acid piece of ADNP (activity-dependent neuroprotective protein), which nerve cells need to develop normally. Through a short SIP motif it binds EB1 and EB3, proteins that ride the growing tips of microtubules, the internal scaffolding and transport tracks of nerve cells. In cells and mice this steadied microtubules, supported dendritic spines, the small bumps where synapses form, and reduced abnormal tau, the protein that tangles in Alzheimer’s disease and progressive supranuclear palsy.
AnimalMainly from cell and animal studies; not shown in people.
Not known
Whether nasal doses reach the human brain at active levels hasn’t been shown, and trials found no clear benefit. Whether the effects reported only in women are real needs a trial designed to test them.
Protocol
Trial
Boxer 2014
30 mg twice daily as a nasal spray for 52 weeks in 313 people with progressive supranuclear palsy. It did no better than placebo.
Trial
Morimoto 2013
5 mg once daily or 15 mg twice daily as a nasal spray for 12 weeks in 144 adults with amnestic mild cognitive impairment; no significant effect on the main memory score.
Community
No established dose outside trials, and research vials aren’t commonly sold. Figures quoted online couldn’t be cross-checked.
- Frequency
- Twice daily in the largest trial; once daily in some arms
- Route
- Nasal spray in trials (AL-108); a single IV infusion in one heart-surgery trial (AL-208)
- Cycle
- No established cycle. Trials ran 12 to 52 weeks of continuous daily use.
No set cycle, shown over 26 weeks
Common protocols
The ways Davunetide is most often run, each tagged with where it comes from.
Memory-impairment trial
Trial- Dose
- 5 mg once daily, or 15 mg twice daily
- How often
- Nasal spray
- How long
- 12 weeks
144 adults with amnestic mild cognitive impairment, 2:1 drug to placebo. The main memory score didn’t differ from placebo; 2 single tests hinted at benefit.
Schizophrenia trial
Trial- Dose
- 5 or 30 mg a day
- How often
- Nasal spray, added to usual medicines
- How long
- 12 weeks
63 adults. Thinking scores didn’t differ from placebo; a test of everyday skills (UPSA) improved (p=0.048).
Heart-surgery trial (IV form)
Trial- Dose
- 300 mg (100–200 mg in an open-label run-in)
- How often
- A single IV infusion
- How long
- Once, around bypass surgery
234 adults having coronary bypass. The sponsor reported no difference in thinking versus placebo; the results were never published in full.
Taking it
Where it goes
Trials used a nasal spray, a few sprays into each nostril; one surgery trial gave a single IV infusion. Injection under the skin hasn’t been tested in people.
If you miss a dose
No published guidance outside trial protocols. Skip the missed dose and take the next one as usual; don’t double up.
What to expect
- 52 weeks, progressive supranuclear palsy
Disease scores worsened by the same amount on davunetide and placebo: median 11.8 points on the PSP Rating Scale in both groups (p=0.41).
Trial - 12 weeks, mild memory impairment
No significant difference on the composite memory score, with signals in 2 single tests of memory and attention (Morimoto 2013).
Trial - 12 weeks, schizophrenia
No change in thinking scores versus placebo; everyday-skills scores improved, with effect sizes of 0.74 at 5 mg and 0.48 at 30 mg (Javitt 2012).
Trial - Reanalyses, 2023–2026
The inventor’s group reported slower decline in women with PSP and sex-specific effects in the memory and surgery trials. None of these analyses was planned in advance.
Trial
Side effects and what to do
Nosebleeds, runny nose or nasal discomfort
PSP trial: nosebleeds 12% vs 8% on placebo, runny nose 10% vs 5%, nasal discomfort 10% vs under 1%.
Restlessness
Posted results of the schizophrenia trial: 13 of 41 people on davunetide vs 2 of 22 on placebo.
Palpitations
One serious case in 21 people on 30 mg a day in the schizophrenia trial; none on placebo.
Serious events and deaths
PSP trial: 54 serious adverse events in each group, with 11 deaths on davunetide and 10 on placebo, in line with the disease.
Unknown beyond a year
No one has taken it for longer than 52 weeks in a published study.
Stop and get medical help
Stop and get medical help for heavy or repeated nosebleeds, a racing or irregular heartbeat, hives, swelling of the face or throat, or trouble breathing.
Can it cause …?
The side effects people ask about most, answered one by one. Each answer says where it comes from.
- Trouble sleeping
- Not reportedNot reported as a sleep problem in published trials; restlessness was more common on davunetide in one small trial.
- Acne, rash or skin changes
- Not reportedNo skin reactions reported more often than placebo; the main side effects were inside the nose.
- Anxiety, low mood or irritability
- TrialRestlessness was posted for 13 of 41 people on davunetide vs 2 of 22 on placebo in a 12-week schizophrenia trial.
- Low or high blood sugar
- Not reportedNot more common than placebo; high blood sugar after bypass surgery occurred in both groups of the IV trial.
- Fast heartbeat or blood pressure changes
- TrialOne serious case of palpitations among 21 people on 30 mg a day in the schizophrenia trial; none on placebo.
- Cancer risk
- Not reportedNot reported in trials of up to a year; longer-term risk hasn’t been studied.
- TirednessHeadacheNausea or vomitingDiarrhea or constipationDizzinessHair lossWater retention or swellingJoint or muscle painMore hungerLiver strainKidney problems
- Not reportedNot among the side effects reported more often than placebo in trials of up to 313 people for 52 weeks.
Trial: reported in human studies. Not reported: studied in people and not reported. A side effect that hasn’t been reported can still happen, especially with long or high-dose use. Any of these across every compound: the side-effect finder.
Who should avoid it
No product label covers davunetide, so these come from human studies and from precautions based on how it works. Most important first.
- Nosebleeds, nasal disease or recent nasal surgery
- TrialIn the largest trial the spray caused more nosebleeds, runny nose and nasal discomfort than placebo.
- Pregnancy or breastfeeding
- PrecautionNo human safety data exist. Mouse studies gave it during pregnancy to shield the fetus from alcohol damage, not to test safety.
- Anyone relying on product quality
- PrecautionNo medicine exists; powder sold online is unregulated, so identity, amount and sterility are unchecked.
Interactions
No interaction studies have been published, and no product label lists any. In the schizophrenia trial it was added to people’s usual antipsychotic medicines, with no interaction reported.
Trial: seen in human studies, or a group those studies left out. Precaution: follows from how it works or from a related drug, and hasn’t been tested. This isn’t a complete list: a pharmacist or doctor can check a specific medicine or condition. Every documented interaction, by medicine: drug interactions.
Special situations
What’s known about pregnancy, breastfeeding, kidney and liver problems, age and surgery. Where nothing has been studied, the row says so.
- Pregnancy
- PrecautionNo human data. Mouse studies gave it during pregnancy to shield the fetus from alcohol damage, not to test safety.
- Breastfeeding
- PrecautionNo human data; it isn’t known whether it passes into breast milk.
- Kidney problems
- PrecautionNot studied in kidney disease, and how the body clears it hasn’t been published.
- Liver problems
- PrecautionNot studied in liver disease, and how the body breaks it down hasn’t been published.
- Older adults
- TrialMost trial participants were older adults with progressive supranuclear palsy or memory impairment; side effects were mainly in the nose.
- Children and teens
- PrecautionNot approved for any age. Its licensee says a phase 3 in children with ADNP syndrome began in 2024; no such trial is registered.
- Surgery and anesthesia
- TrialOne trial gave a single IV dose during heart bypass surgery in 234 adults, with no safety concerns reported by the sponsor. No data for the nasal spray.
Trial: from human studies. Precaution: not studied, so the caution follows from how it works or from a related drug. Ages are given as approved or studied; this site never gives doses for children. Across every compound: pregnancy, breastfeeding, kidney disease, liver disease, older adults and surgery.
Tracking and pairing
Worth tracking
- Nosebleeds or nasal irritation
- Restlessness or sleep changes
- Heart rhythm symptoms such as palpitations
Often paired with
Usually run on its own.
Human studies
4 key published human studies, with how many people took part. Animal studies aren’t listed here.
-
No difference from placebo on the PSP Rating Scale (median change 11.8 vs 11.8, p=0.41) or daily-living scale (p=0.92); more nosebleeds (12% vs 8%) and nasal discomfort (10% vs under 1%).
- Design
- Randomized, double-blind, placebo-controlled phase 2/3 trial at 48 centers in 6 countries
- Dose
- 30 mg twice daily, nasal spray
- Length
- 52 weeks
Boxer et al., Lancet Neurol 2014, PMID 24873720
-
Generally safe and well tolerated; no significant difference on the composite memory score, with possible signals in 2 tests of memory and attention.
- Design
- Randomized, double-blind, placebo-controlled, ascending-dose phase 2 trial in amnestic mild cognitive impairment
- Dose
- 5 mg once daily or 15 mg twice daily, nasal spray
- Length
- 12 weeks
Morimoto et al., Dement Geriatr Cogn Disord 2013, PMID 23594991
-
No significant change in MATRICS thinking scores (p=0.45); everyday-skills (UPSA) scores improved across arms (p=0.048), with effect sizes of 0.74 and 0.48.
- Design
- Randomized, double-blind, placebo-controlled trial in schizophrenia, added to antipsychotics
- Dose
- 5 or 30 mg a day, nasal spray
- Length
- 12 weeks
Javitt et al., Schizophr Res 2012, PMID 22169248
-
The sponsor had found no difference in thinking overall; this reanalysis by the inventor’s group, of 176 people with complete data (only 19 treated women), reported lower nerve-injury markers and better verbal memory in treated men.
- Design
- Post hoc analysis by sex of a randomized, double-blind, placebo-controlled phase 2 trial (234 randomized, 2006–2008)
- Dose
- One IV infusion of 300 mg (100–200 mg in a run-in)
- Length
- Single dose around coronary bypass surgery
Gozes et al., Transl Psychiatry 2025, PMID 41173865
Trials under way
No ongoing trial of davunetide is registered, and none has finished recently without publishing its results. Checked on ClinicalTrials.gov, October 7, 2026. Every compound: trials under way.
Limits of the evidence
Four controlled trials gave it to about 750 people for up to a year. The largest, 313 people with progressive supranuclear palsy, was clearly negative; the others missed their main memory or thinking measures, apart from an everyday-skills score in 63 people with schizophrenia. Benefits in women come from unplanned reanalyses by the inventor’s group, which holds patents on sex-specific use. Only the nasal spray was tested repeatedly, and use beyond a year is unstudied.
How it’s supplied
Nasal spray, 5 mg once daily to 30 mg twice daily, in adult trials of 12–52 weeks; one 300 mg IV dose around heart surgery. Not sold. Sprayed into the nose once or twice daily by participants, in trials that ended in 2012. No trial has been registered since. It’s available only in clinical trials, so the calculator and dose log don’t apply.
No medicine or ready-made product is sold. The trials used a ready-made nasal spray and, once, an IV solution. Powder sold online as davunetide or NAP is uncommon and unregulated.
Datasheet
- Half-life
- No reliable value has been published.
- Type
- Peptide, 8 amino acids
- Molecular weight
- 824.9 g/mol
- Formula
- C36H60N10O12
- Sequence
- NAPVSIPQ
- Storage before use
- Freezer (−20 °C) for long-term storage, kept dry and dark.
- After mixing or opening
- Fridge (2–8 °C) once in solution.
- Molecule: Residues 354–361 of human ADNP (UniProt Q9H2P0); FDA GSRS UNII GF00K3IIWE (CAS 211439-12-2, PubChem CID 9832404, INN 9063). Formula and weight calculated for the free peptide; GSRS shows a charged form (C36H59N10O12)
- Storage: Community Common research-chemical practice; the trial sprays’ storage rules were never published
Every compound side by side: the half-life chart and the storage chart.
Identifiers
- CAS number
- 211439-12-2
- UNII (FDA)
- GF00K3IIWE
- PubChem CID
- 9832404
- DrugBank
- DB12613
- ATC code
- None assigned
- Development codes
- AL-108 (nasal spray), AL-208 (IV), NAP, CP201; INN 9063
- Brand names
- None; never approved
- First described
- Described in 1999 by Illana Gozes’s lab, Tel Aviv University, within the newly sequenced ADNP protein (Bassan et al.).
Every compound’s numbers: the identifiers table.
Product form and quality
Trials used a ready-made nasal spray (AL-108) and an IV solution (AL-208); neither is sold. Powder sold online as davunetide or NAP is unregulated; like most synthetic peptides it may be an acetate or trifluoroacetate salt, so peptide content is below powder weight.
Cautions
- Failed its largest trial: in 313 people with progressive supranuclear palsy, a year of twice-daily nasal spray did no better than placebo on either main measure.
- The spray caused more nose problems than placebo in that trial: nosebleeds 12% vs 8%, runny nose 10% vs 5%, nasal discomfort 10% vs under 1%.
- Claims that it works in women come from after-the-fact reanalyses by the inventor’s group, which holds patents on sex-specific use and works with the company developing it. No trial was designed to test this.
- Not approved anywhere, and no trial has been registered since 2012. Nothing sold online is checked for identity, purity or sterility.
Questions
What is davunetide?
An 8-amino-acid piece of ADNP (activity-dependent neuroprotective protein), a protein essential for brain development. In cells and mice it steadies microtubules, the internal scaffolding and transport tracks of nerve cells, and reduces the abnormal tau that builds up in Alzheimer’s disease and progressive supranuclear palsy.
How does davunetide work?
Davunetide is NAP, an 8-amino-acid piece of ADNP (activity-dependent neuroprotective protein), which nerve cells need to develop normally. Through a short SIP motif it binds EB1 and EB3, proteins that ride the growing tips of microtubules, the internal scaffolding and transport tracks of nerve cells. In cells and mice this steadied microtubules, supported dendritic spines, the small bumps where synapses form, and reduced abnormal tau, the protein that tangles in Alzheimer’s disease and progressive supranuclear palsy. Whether nasal doses reach the human brain at active levels hasn’t been shown, and trials found no clear benefit. Whether the effects reported only in women are real needs a trial designed to test them.
Is davunetide FDA-approved?
Not approved anywhere. A US orphan drug designation for progressive supranuclear palsy (January 2010) and an EU one (March 2010, withdrawn April 2013) preceded the failed trial. ExoNavis Therapeutics, its licensee since 2021, says it holds US orphan and rare pediatric disease designations for ADNP syndrome and planned a phase 3 study from late 2024; no such trial is registered (ClinicalTrials.gov, October 2026). Never nominated for pharmacy compounding, so it appears on none of FDA’s 503A or 503B bulk substance category lists (503A list updated May 14, 2026).
What is the usual davunetide dose?
From human studies (Boxer 2014): 30 mg twice daily as a nasal spray for 52 weeks in 313 people with progressive supranuclear palsy. It did no better than placebo. Morimoto 2013: 5 mg once daily or 15 mg twice daily as a nasal spray for 12 weeks in 144 adults with amnestic mild cognitive impairment; no significant effect on the main memory score. These are the amounts sources reference, not recommendations.
How is davunetide given?
Sprayed into the nose once or twice daily by participants, in trials that ended in 2012. No trial has been registered since. It isn’t sold: it’s available only in clinical trials.
Who should avoid davunetide?
No product label covers davunetide, so these come from human studies and from precautions based on how it works. Nosebleeds, nasal disease or recent nasal surgery: In the largest trial the spray caused more nosebleeds, runny nose and nasal discomfort than placebo. Pregnancy or breastfeeding: No human safety data exist. Mouse studies gave it during pregnancy to shield the fetus from alcohol damage, not to test safety. Anyone relying on product quality: No medicine exists; powder sold online is unregulated, so identity, amount and sterility are unchecked.
How should davunetide be stored?
Before mixing: Freezer (−20 °C) for long-term storage, kept dry and dark. After mixing: Fridge (2–8 °C) once in solution. This is common practice; no product label covers it.
Is davunetide banned in sport?
Probably. Not named on the 2026 list. With no approval anywhere, it falls under S0 non-approved substances, banned at all times; it isn’t a hormone or growth factor of the kind S2 names. The 2027 list adds peptides to S0’s examples; no change.
Has davunetide been studied in people?
Yes. The human studies section lists 4 published studies. The largest, from 2014, included 313 people. No difference from placebo on the PSP Rating Scale (median change 11.8 vs 11.8, p=0.41) or daily-living scale (p=0.92); more nosebleeds (12% vs 8%) and nasal discomfort (10% vs under 1%).
How long has davunetide been studied in people?
Trial 52 weeks: 157 people with progressive supranuclear palsy were assigned 30 mg twice daily by nose (Boxer 2014).
Does davunetide come in other forms, like a pill or nasal spray?
Trial Tested as a nasal spray (AL-108) for up to 52 weeks and as a single IV infusion (AL-208) during heart surgery. Injection under the skin hasn’t been tested in people.
Can you drink alcohol while taking davunetide?
No study No data. No study has looked at davunetide and alcohol together in people.
Can davunetide be taken with semaglutide or tirzepatide?
No study No study has combined them. No interaction is known, but none has been looked for.
What happens if you take too much davunetide?
Trial No overdose data. Trials used up to 60 mg a day by nose and a single 300 mg IV dose. Call Poison Help (1-800-222-1222), or emergency services for severe symptoms.
Sources
- Boxer et al., randomized placebo-controlled phase 2/3 trial of davunetide in 313 people with progressive supranuclear palsy (Lancet Neurol 2014) PMID 24873720
- Morimoto et al., randomized placebo-controlled trial of AL-108 in 144 adults with amnestic mild cognitive impairment (Dement Geriatr Cogn Disord 2013) PMID 23594991
- Javitt et al., randomized placebo-controlled trial of davunetide in 63 adults with schizophrenia (Schizophr Res 2012) PMID 22169248
- Gozes et al., post hoc sex analysis of the PSP trial (Transl Psychiatry 2023) PMID 37845254
- Bassan et al., discovery of ADNP, containing the NAP sequence (J Neurochem 1999) PMID 10037502
- EMA orphan designation EU/3/10/728, davunetide for progressive supranuclear palsy (2010; withdrawn April 2013)
For the protocol details
- ClinicalTrials.gov NCT00505765 posted results (schizophrenia trial adverse events) NCT00505765
- Gozes et al., post hoc sex analysis of the AL-208 bypass-surgery trial, with its design and safety summary (Transl Psychiatry 2025) PMID 41173865
- Shapira et al., post hoc reanalysis of the PSP trial in women (Mol Psychiatry 2026) PMID 42399413
For how it works, who should avoid it and the limits of the evidence
- Oz et al., the NAP motif binds microtubule end-binding proteins and regulates dendritic spines (Mol Psychiatry 2014) PMID 25178163
- Matsuoka et al., NAP reduces tau pathology and improves memory in a mouse model (J Pharmacol Exp Ther 2008) PMID 18199809
- Spong et al., NAP given to pregnant mice in a fetal alcohol model (J Pharmacol Exp Ther 2001) PMID 11303069
- Gozes et al., sex-dependent reanalysis of the memory-impairment trial, with the patent disclosure (Transl Psychiatry 2024) PMID 39358355
For uses, the side-effect questions, special situations, trials, identifiers and status outside the US
- Hacohen-Kleiman et al., NAP in Adnp-deficient mice, a model of ADNP syndrome (J Clin Invest 2018) PMID 30106381
- ClinicalTrials.gov NCT00505765 posted results; FDA GSRS UNII GF00K3IIWE; EMA orphan designation EU/3/10/728; Australian Poisons Standard, October 2026
Doses tagged Community come from public dosing guides and user reports, checked against at least two of them. Those sites aren’t named here because many of them sell peptides or earn commissions on them.