Side-by-side · Research reference

ACE-031vsAdamax

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 2HUMAN-REVIEWED10/44 cited

BAnimal-StrongHUMAN-REVIEWED20/47 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Adamax

ACTH(4-10) Analogue · Russian Nootropic

1.4×BDNF protein ↑Dolotov 2006

3×BDNF mRNA (exon III)Dolotov 2006

1.6×trkB phosphorylationDolotov 2006

Intranasal · Research Use Only

01Mechanism of Action

Parameter

ACE-031

Adamax

Primary target

Myostatin, GDF11, activin A — TGF-β superfamily ligands

Melanocortin receptors (MC-Rs) in hippocampus and cortex

Pathway

Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition

ACTH(4-10) fragment → MC-R binding → BDNF/trkB upregulation → neurotrophic signaling

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Increased hippocampal BDNF expression, trkB tyrosine phosphorylation, enhanced conditioned avoidance learning, circadian rhythm normalizationDolotov 2006 Arushanian 2008

Feedback intact?

—

Non-endocrine — devoid of adrenal axis effectsvan 1978

Origin

Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025

ACTH(4-10) fragment with modified amino acid sequence at positions 8, 9, 10Teter 2001

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

Adamax

Clinical dosing

Weekly or biweekly SQ injections (exact doses undisclosed pre-halt)

Phase 2 DMD trial protocol not fully published.

—

Black market products

Variable purity; 12/14 tested products contained target protein plus contaminantsReichel 2025

SDS-PAGE revealed multiple protein bands; quality control absent.Reichel 2025

—

Evidence basis

Phase 2 trial discontinued — incomplete dataset

Animal (rodent, rabbit) studies; minimal human RCT data

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

—

Duration investigated

12–24 weeks (trial cut short)

—

Animal dose (rat)

—

50 mcg/kg body weightDolotov 2006

Single intranasal application; produced maximal BDNF response.

Route

—

IntranasalDolotov 2006 Smolnik 2000

Frequency

—

Single-dose or chronic administration protocols

Chronic dosing normalized circadian rhythms; single-dose produced acute BDNF elevation.

Human dose (exploratory)

—

Not established — limited human data

ACTH(4-10) and analogs dosed 30–60 mcg intranasally in early human studies.

Timing

—

Variable — chronic administration for circadian effects

04Side Effects & Safety

Parameter

ACE-031

Adamax

Epistaxis (nosebleeds)

Significant incidence in Phase 2 DMD trial — primary safety signal

—

Telangiectasia

Dilated capillaries / spider veins observed

—

Vascular abnormalities

Mechanism: ActRIIB/ALK1 pathway disruption affects vascular homeostasis

—

Injection site reactions

Local erythema, induration (biologics class effect)

—

Antibody development

Potential for anti-drug antibodies (Fc-fusion proteins); incidence not reported

—

Black market contaminants

12/14 tested products contained multiple unidentified proteins alongside ACE-031Reichel 2025

—

Cardiovascular effects

—

ACTH(4-10) fragments may have pressor and cardioaccelerator actions at high dosesGruber 1984

Effects attenuated by α/β-receptor antagonists; observed at 30–1000 nmol/kg IV in rats.

Natriuretic effect

—

ACTH(4-10) exhibited natriuretic activity at lower doses (7 nmol/kg)Gruber 1984

Behavioral suppression

—

Suppression of aggression, reduced orientation-cognition reactions in rabbitsTeter 2001

May reflect anxiolytic or stress-dampening profile.

Long-term safety

—

Unknown — chronic human safety data lacking

Absolute Contraindications

ACE-031

·History of vascular disorders (epistaxis, telangiectasia, HHT)
·Pregnancy (TGF-β pathway critical for fetal development)
·Active malignancy (myostatin inhibition may affect tumour growth)
·Use of non-pharmaceutical grade ACE-031 (contamination risk)Reichel 2025

Adamax

·Pregnancy and lactation (precautionary; no data)
·Active cardiovascular instability (due to potential pressor effects)

Relative Contraindications

ACE-031

·Coagulation disorders or anticoagulant use (epistaxis risk)
·Hereditary hemorrhagic telangiectasia (HHT) family history
·Cardiovascular disease (vascular remodeling effects unknown)

Adamax

·Hypertension (monitor BP if using higher doses)
·Renal impairment (natriuretic effects may alter electrolyte balance)

05Administration Protocol

Parameter

ACE-031

Adamax

1. Pharmaceutical status

ACE-031 is not FDA-approved or commercially available. Phase 2 development was discontinued in 2011 due to safety concerns. Any ACE-031 on the black market is unregulated research chemical.

Add sterile water or bacteriostatic water to lyophilised vial per manufacturer guidance. Roll gently — do not shake. Ensure clarity before use.

2. Black market quality

12 of 14 tested black market ACE-031 products contained the target protein but also carried multiple unidentified protein contaminants detectable by SDS-PAGE. Two products contained no ACVR2B-immunoreactive material.Reichel 2025

Intranasal administration is the primary route in animal and exploratory human studies. Delivered via nasal spray or dropper to ensure mucosal absorption.Dolotov 2006 Smolnik 2000

3. Detection in sport

ACE-031 is prohibited under WADA S4.3 (Myostatin Inhibitors). Gel electrophoresis and Western blotting using ACVR2B-specific antibodies can detect the ~58.4 kDa protein in biological samples.Reichel 2025

Variable. Single-dose protocols for acute cognitive tasks; chronic daily dosing for circadian rhythm normalization and sustained neuroprotection.

4. Clinical trial route

Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.

Lyophilised: room temperature, light-protected. Reconstituted: refrigerate 2–8 °C, use within manufacturer-specified timeframe.

06Stack Synergy

ACE-031

— no documented stacks

Adamax

+ Semax

Moderate

View Semax →

Both Adamax and Semax are ACTH(4-10)-derived nootropics acting via melanocortin receptors and BDNF upregulation. Adamax has distinct amino acid modifications at positions 8-10, potentially offering complementary receptor binding profiles or metabolic stability. Stacking may amplify neurotrophic signaling and cognitive enhancement, though direct synergy studies are absent. Theoretical multi-pathway benefit.

Adamax: Research dose intranasal
Semax: 300–600 mcg intranasal
Frequency: Once daily, morning or pre-cognitive task
Primary benefit: Enhanced BDNF upregulation, cognitive performance, neuroprotection