Cerebrolysin

Cerebrolysin is a mixture of small peptides and amino acids made from purified pig brain tissue, used for stroke recovery and dementia-related cognitive decline. It's given as an injection or IV infusion and has been used clinically abroad for about 50 years, approved in over 50 countries, though it's not a single peptide but a proprietary blend, and it is not FDA-approved in the US. Its strongest evidence doesn't back up that use: a major systematic review found no real benefit on survival after stroke, plus more serious side effects than placebo, and its largest dedicated stroke trial missed its main goal.

Cerebrolysin has been studied mainly for stroke and cognitive recovery. Its largest, strongest trial (CASTA, in acute ischemic stroke) did not meet its main goal, and a 2023 Cochrane review found moderate-certainty evidence of no benefit on death in acute stroke plus a moderate-certainty increase in non-fatal serious adverse events versus placebo. The cognitive and recovery uses people pursue are not supported by this strongest evidence. A few newer 2026 studies in patients who also had clot-removal reported better outcomes, but they were not randomized and their authors call them preliminary.

Not FDA-approved in the US for any indication. Cerebrolysin has never been submitted for FDA approval despite ~50 years of clinical use internationally. Available exclusively in the US as a research compound or through gray-market import from jurisdictions where it is approved (Russia, Eastern Europe, Asia). Not DEA-scheduled. WADA status: not explicitly named on the 2026 Prohibited List as of last review; the broader peptide-mixture / neurotrophic class is not currently a WADA-targeted category. Critically: the 2023 Cochrane systematic review (Ziganshina et al., 7 RCTs, 1,773 participants) found moderate-certainty evidence of NO clinical benefit on all-cause death in acute ischemic stroke and moderate-certainty evidence of increased non-fatal serious adverse events with Cerebrolysin compared to placebo (RR 2.39, 95% CI 1.10 to 5.23).[⁴] This Cochrane finding is the load-bearing safety-evidence anchor for the entry.

Cerebrolysin is not FDA-approved in the US; the strongest available review found no benefit on death in acute stroke and a possible increase in non- fatal serious adverse events. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Cerebrolysin is not FDA-approved in the US for any indication. The product has never been submitted for FDA approval despite ~50 years of clinical use internationally. Cerebrolysin is available exclusively in the US as a research compound or through gray-market import. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ The strongest available evidence (2023 Cochrane systematic review) finds NO clinical benefit on the primary outcome of all-cause death in acute ischemic stroke and a moderate-certainty signal of increased non-fatal serious adverse events with Cerebrolysin compared to placebo. The Ziganshina 2023 *Cochrane Database of Systematic Reviews* meta-analysis pooled 7 RCTs (1,773 participants) and reached moderate-certainty conclusions: (a) all-cause death: RR 0.96, 95% CI 0.65 to 1.41 — no benefit on the primary clinical-outcome endpoint; (b) total serious adverse events: RR 1.16, 95% CI 0.81 to 1.66 — no difference in total SAE rates; but (c) non-fatal serious adverse events: RR 2.39, 95% CI 1.10 to 5.23 — moderate-certainty evidence of a doubled non-fatal SAE rate with Cerebrolysin, with the signal more prominent in the 30 mL × 10 days (cumulative 300 mL) dosing regimen (RR 2.87, 95% CI 1.24 to 6.69 in subgroup analysis).[⁴] This Cochrane finding is the load-bearing safety-evidence anchor for the entry — the strongest available evidence does not support clinical benefit in the most-studied indication and surfaces a safety signal that should anchor risk-benefit framing. A cluster of newer (2026) studies in the mechanical-thrombectomy-adjunct setting reported favorable functional outcomes, but every one of them is observational and non-randomized, and their own authors describe the findings as hypothesis-generating pending RCT confirmation — they do not displace this RCT-based Cochrane conclusion.[⁶][⁷]

⚠️ Cerebrolysin is a complex mixture, not a single peptide — exact composition is proprietary to Ever Neuro Pharma and varies batch-to-batch in characterized components. Unlike single-molecular-entity peptides like the GLP-1 ra family or the GHS-axis cluster where the active species is rigorously defined, Cerebrolysin is the aqueous output of standardized enzymatic hydrolysis of purified porcine brain tissue. The product specification describes ~25% peptide content (peptides <10 kDa) plus ~75% free amino acids and metabolic intermediates. The specific peptides responsible for the hypothesized neurotrophic effect have not been individually characterized in published literature — the mechanism is described in terms of "BDNF-like" and "NGF-like" activity rather than at the specific-molecular-species level. This is a fundamentally different evidence base from rigorously-defined-active-species peptides like semaglutide or hexarelin and warrants honest framing.

⚠️ The CASTA Phase IV trial (the largest and methodologically-strongest Cerebrolysin trial in the published literature) had a negative primary endpoint in acute ischemic stroke. The Heiss 2012 *Stroke* CASTA trial enrolled 1,070 patients with acute ischemic hemispheric stroke within 12 hours of symptom onset, randomized to Cerebrolysin 30 mL daily IV (n=529) or placebo (n=541) for 10 days, with 90-day follow-up. The primary endpoint — combined global directional test of modified Rankin Scale, Barthel Index, and NIH Stroke Scale — showed no significant difference between treatment groups.[³] A post-hoc subgroup analysis suggested a trend favoring Cerebrolysin in severely affected patients (NIHSS >12), with cumulative 90-day mortality 20.2% placebo vs 10.5% Cerebrolysin in this subgroup (HR 1.97, lower CI bound 1.00) — but this is a post-hoc finding from a trial that did not meet its primary endpoint, requiring confirmation by a subsequent prospective trial that has not been completed.[³] The Phase IV CASTA trial's neutral primary endpoint is the largest single-trial evidence base for Cerebrolysin in acute stroke and should anchor the entry's clinical-evidence framing.

⚠️ Cerebrolysin dosing is in milliliters of solution, not milligrams of peptide — fundamentally different from the rest of the Vialwise library. Standard clinical-trial doses are 10–60 mL IV per day, typically administered as a slow IV infusion (in 100–250 mL saline carrier) over 60–90 minutes daily for 10–21 days. The CASTA Phase IV stroke trial used 30 mL daily for 10 days (cumulative 300 mL).[³] Research-community use varies but typically follows the clinical-protocol convention of IV or IM administration measured in milliliters. The Vialwise calculator is designed for mg/mcg dosing of single-peptide compounds and may not apply cleanly to Cerebrolysin's mL-dosing convention — verify any Cerebrolysin protocol against published clinical-trial dosing rather than against the calculator output.

According to PubMed-indexed research, Cerebrolysin is not a single peptide but rather a complex mixture of low-molecular-weight peptides and free amino acids derived from porcine brain tissue via standardized enzymatic hydrolysis manufactured by Ever Neuro Pharma (Austria; formerly Ebewe Pharma).[¹][²] The product has been in clinical use since the 1970s and is currently approved in over 50 countries — primarily Russia, Eastern Europe, China, South Korea, Mexico, and parts of the EU — for indications including acute ischemic stroke, vascular dementia, Alzheimer's disease, and traumatic brain injury. The specific molecular composition is proprietary and varies batch-to-batch within Ever Pharma's standardized specification (~25% peptides <10 kDa + ~75% free amino acids and metabolic intermediates).[²][⁴]

Mechanism (hypothesized). Based on articles retrieved from PubMed, Cerebrolysin is hypothesized to act via neurotrophic and neuroprotective signaling pathways mimicking endogenous neurotrophic factors.[²] Preclinical models in cerebral ischemia and neurodegeneration suggest activity at multiple converging targets including the BDNF (brain-derived neurotrophic factor), NGF (nerve growth factor), and GDNF (glial cell-derived neurotrophic factor) signaling axes, plus inhibition of calpain-mediated apoptotic pathways activated during ischemic injury. The specific active molecular components within Cerebrolysin's mixture have not been individually identified in published literature — the mechanism is described in terms of aggregate "BDNF-like" and "NGF-like" activity rather than at the specific-molecular-species level. This is a fundamentally different evidence base from rigorously-defined-active-species peptides in the rest of the Vialwise library.

Evidence-integrity caveat on the mechanism literature (2026). During 2026, a cluster of the preclinical Cerebrolysin papers that the neurotrophic-mechanism hypothesis rests on — animal-model and transgenic-model studies of "BDNF-like / NGF-like" neurotrophic and neurogenic effects — were retracted or flagged with Expressions of Concern, including manufacturer-affiliated (EBEWE / EVER Neuro Pharma) papers and papers from the Masliah group.[⁵] This entry does not cite any of the retracted or flagged papers, so none of the citations below rests on withdrawn work. But the honest framing is that a portion of the wider preclinical literature underpinning the neurotrophic story is now discredited, and the mechanism should be read as hypothesized, not established — with even less weight placed on the preclinical mechanism narrative than the clinical-trial evidence already warrants.

CASTA Phase IV trial (Heiss 2012, Stroke).[³] The CASTA trial is the largest and methodologically-strongest published RCT of Cerebrolysin in acute ischemic stroke. Multicenter trial across 50+ centers in Asia. 1,070 patients with acute ischemic hemispheric stroke within 12 hours of symptoms onset, randomized to Cerebrolysin 30 mL daily IV infusion (n=529) or placebo / saline solution (n=541) for 10 days, with 90-day follow-up. Primary endpoint: combined global directional test of modified Rankin Scale, Barthel Index, and NIH Stroke Scale. Results: Primary endpoint showed no significant difference between treatment groups. Post-hoc subgroup analysis by severity (NIHSS) suggested a trend favoring Cerebrolysin in severely affected patients (NIHSS >12): OR 1.27, lower CI bound 0.97 for NIHSS; cumulative 90-day mortality 20.2% placebo vs 10.5% Cerebrolysin in the severe subgroup (HR 1.97, lower CI bound 1.00). The authors concluded the trial's confirmatory primary endpoint was neutral but suggested the severity-stratified post-hoc finding should be confirmed by subsequent trials.[³] A subsequent confirmatory trial in the severely-affected subgroup has not been completed.

Cochrane systematic review (Ziganshina 2023).[⁴] The most recent and methodologically-strongest evidence-synthesis for Cerebrolysin in acute ischemic stroke is the Ziganshina 2023 *Cochrane Database of Systematic Reviews* meta-analysis. The review pooled 7 RCTs (1,773 participants) including 1 RCT of the Cerebrolysin-like compound Cortexin (272 participants). Authors evaluated risk of bias and judged most studies as unclear-to-high risk of bias across multiple domains; the Cerebrolysin manufacturer Ever Neuro Pharma supported 3 of the included studies (totally or partially). Findings: (a) All-cause death: RR 0.96, 95% CI 0.65 to 1.41, moderate-certainty evidence — Cerebrolysin probably has no effect on all-cause death in acute ischemic stroke. (b) Total serious adverse events: RR 1.16, 95% CI 0.81 to 1.66, moderate-certainty evidence — no significant difference in total SAE rates. (c) Non-fatal serious adverse events: RR 2.39, 95% CI 1.10 to 5.23, moderate-certainty evidence — Cerebrolysin probably increases non-fatal SAEs, with the signal more prominent in the 30 mL × 10 days regimen (RR 2.87, 95% CI 1.24 to 6.69 in subgroup analysis). The Cochrane conclusion: "Cerebrolysin or Cerebrolysin-like peptide mixtures derived from cattle brain [sic — Cerebrolysin itself is porcine-derived; the "cattle brain" phrasing is an inconsistency inside the Cochrane abstract, quoted here verbatim] probably have no beneficial effect on preventing all-cause death in acute ischaemic stroke. Moderate-certainty evidence suggests that Cerebrolysin probably has no beneficial effect on the total number of people with serious adverse events. Moderate-certainty evidence also indicates a potential increase in non-fatal serious adverse events with Cerebrolysin use."[⁴] This Cochrane finding is the load-bearing safety-evidence anchor for the entry.

Newer lower-certainty evidence (2026) — tiered below the Cochrane anchor. A cluster of 2026 publications examining Cerebrolysin as an adjunct to mechanical thrombectomy in acute ischemic stroke reported *favorable* results, which is a different direction from the RCT-based Cochrane conclusion. Every one of them is observational and non-randomized, and each set of authors explicitly frames the result as preliminary and requiring randomized confirmation. In the Afridi 2026 systematic review and meta-analysis (*Brain and Behavior*), which pooled 3 observational studies totalling 294 participants, participants receiving Cerebrolysin as a thrombectomy adjunct had a higher rate of good functional outcome (mRS 0–3) at follow-up, RR 1.56 (95% CI 1.25 to 1.93), a lower rate of symptomatic intracranial hemorrhage, RR 0.12 (95% CI 0.03 to 0.48), and lower mortality, RR 0.36 (95% CI 0.18 to 0.68) — the authors flag the small sample size and observational design as limits on inference.[⁶] In the Staszewski 2026 propensity-matched cohort (*Translational Stroke Research*), participants treated after endovascular thrombectomy showed higher 12-month functional independence, adjusted OR 6.10 (95% CI 1.64 to 22.66); the authors describe the finding as hypothesis-generating and call for multicenter randomized confirmation.[⁷] Alrabadi 2026 (*Journal of Clinical Neurology*) is a pooled analysis of recent studies addressing hemorrhagic-transformation risk in the same adjunct setting.[⁸] These do not overturn the Cochrane conclusion. They sit lower on the evidence hierarchy — observational rather than randomized, small, in a different (post-thrombectomy) population, and with authorship concentrated in enthusiast- and manufacturer-adjacent groups. The Ziganshina 2023 Cochrane review remains the strongest available evidence for Cerebrolysin in acute ischemic stroke, and its mixed-to-negative conclusion stands.[⁴] The accurate summary is that the evidence base is mixed and unsettled, with the randomized evidence negative and the newer favorable evidence low-certainty and unconfirmed.

Other indications beyond acute stroke. Cerebrolysin has been studied in published trials for vascular dementia, Alzheimer's disease, and traumatic brain injury — with results similarly mixed across the indication base. In traumatic brain injury, the Boontoterm 2025 prospective cohort (*Asian Journal of Neurosurgery*) followed 340 participants with moderate TBI and nonoperative lesions for 6 months and reported higher survival in the Cerebrolysin group (59.4% vs 27.8%) — but the study was single-blind and non-randomized by the authors' own description, which substantially limits causal inference, and it is not an RCT.[⁹] The CAPTAIN-series TBI trials are frequently referenced in the Cerebrolysin literature but are not cited in this entry and should not be treated as an established benefit finding here. Multiple meta-analyses of Cerebrolysin in dementia indications report small effect sizes with substantial heterogeneity. The broad pattern across indications is that manufacturer-supported trials and Russian/Eastern European/Asian-published trials report favorable trends, while methodologically-strong randomized-evidence synthesis (including Cochrane) reaches moderate-to-no-benefit conclusions with safety signals. The 2026 observational thrombectomy-adjunct cluster is a genuine exception to the shorthand that "Western-published evidence is uniformly negative" — it is Western-published and favorable, but it is observational and low-certainty, so it widens the uncertainty rather than resolving it.[⁶][⁷][⁸]

Regulatory status (international). Cerebrolysin is approved in over 50 countries including Russia, Ukraine, China, South Korea, much of the former Soviet Union, parts of Eastern Europe (Poland, Czech Republic, Slovakia, Romania, Hungary), Austria (manufacturer's home country), Mexico, and parts of the Middle East. Approved indications vary by jurisdiction — typically including some combination of acute ischemic stroke, vascular dementia, Alzheimer's disease, and traumatic brain injury. Many EU member states do not have Cerebrolysin approved — its approval pattern in the EU is uneven and reflects the mixed clinical-evidence base.

Regulatory status (US — current). Cerebrolysin is not FDA-approved in the US for any indication and has never been submitted for FDA approval despite ~50 years of international clinical use. The compound is not on the FDA 503A bulks list for compounding. Cerebrolysin is available in the US exclusively as: (a) a research compound from research-supply chains; (b) a gray-market import from jurisdictions where it is approved; or (c) for personal-use import under FDA's "personal importation" policy for non-controlled products not approved in the US (an enforcement-discretion policy, not a legal exemption). Not DEA-scheduled.

Regulatory status (sport — WADA). Cerebrolysin is not explicitly named on the 2026 WADA Prohibited List as of last review. The broader peptide-mixture / neurotrophic class is not currently a WADA-targeted category. Users in regulated sport should verify the current WADA status directly via the WADA Prohibited List and their National Anti-Doping Organization before any use.

Common research interests. Despite the mixed published-evidence base, Cerebrolysin is used in research-community contexts for: - Post-stroke neurorehabilitation — extrapolating from the post-hoc severe-subgroup-favorable finding in CASTA Phase IV.[³] The dominant research-community use case in stroke survivors seeking neurological recovery support. - Putative cognitive-enhancement effects — extrapolating from the dementia / vascular dementia / Alzheimer's published-trial evidence base. Research-community use in healthy adults for cognitive enhancement is not supported by the published evidence — the trial evidence is in clinical-disease populations. - Post-traumatic brain injury recovery — extrapolating from the published TBI trial and cohort literature, including the single-blind, non-randomized Boontoterm 2025 cohort.[⁹] Research-community use is reported but the evidence base is mixed and no randomized trial establishes benefit. - Putative neuroprotective effect during age-related cognitive decline — research-community use case extrapolating from the dementia trial evidence; published evidence for cognitively-healthy adult use is essentially absent.

Commonly reported

• Infusion-related vasomotor symptoms (flushing, palpitations, vertigo, sensation of heat) — typically transient during the IV infusion; managed by slower infusion rate
• Injection-site reactions — at IM injection sites; typical for porcine-derived products
• Headache — common; usually mild
• Mild GI symptoms (nausea, anorexia) — common; usually mild
• Mild dizziness or vertigo — common during early treatment days
• Asthenia / fatigue — common; usually mild
• Diaphoresis / sweating during infusion — common; manage with slower infusion rate
• The Cochrane non-fatal SAE signal is moderate-certainty evidence and merits attention in the context of an unapproved-in-the-US product with mixed published-evidence base. The specific SAEs driving the elevated RR are not detailed in the Cochrane review but appear to include cardiovascular events and other non-fatal medically-significant events.
• Long-term safety in repeated treatment cycles is not characterized in published Cochrane-grade evidence. Most published trials are 10–21 day single-cycle studies.
• Porcine-derived product immunogenicity is a theoretical concern for sensitized individuals; the Ever Pharma manufacturing process is designed to minimize this risk but does not eliminate it.

Serious

• The Cochrane 2023 systematic review found moderate-certainty evidence of increased non-fatal serious adverse events with Cerebrolysin (RR 2.39, 95% CI 1.10 to 5.23, n=1,335 across 3 trials).[⁴] The specific non-fatal SAEs are not specified in detail in the Cochrane review.
• Severe hypersensitivity reaction / anaphylaxis — rare but documented; porcine-derived product warrants vigilance; immediate medical evaluation warranted
• Severe vasomotor reaction during infusion (severe hypertension or hypotension; arrhythmia) — warrants immediate suspension of infusion and medical evaluation
• Hypertensive crisis — theoretical risk in patients on concurrent MAOI therapy; immediate medical evaluation warranted
• Seizure — rare but reported in some Cerebrolysin trials; immediate medical evaluation warranted
• Allergic reaction (hives, swelling, difficulty breathing) — warrants immediate medical evaluation

Known hypersensitivity to Cerebrolysin or porcine-derived products — contraindicated

Severe renal impairment — caution; amino-acid load may worsen uremic encephalopathy

Concurrent MAOI therapy — caution per manufacturer label; hypertensive crisis risk

Active grand mal epilepsy or status epilepticus — caution; seizure risk

Pregnancy and lactation — no controlled human data; default to contraindicated

Pediatric use — Cerebrolysin is used in pediatric neurological indications in some jurisdictions (Russia, China) but is not FDA-approved for pediatric use

Active acute psychosis — caution; the published evidence base does not establish safety in this population

Regulatory note (US): Cerebrolysin is not FDA-approved in the US for any indication and is not legally compoundable through US 503A pharmacies. US use is exclusively via research-supply chains or personal-import gray-market.

Regulatory note (sport): Not explicitly named on the 2026 WADA Prohibited List as of last review. Users in regulated sport should verify directly.

Not DEA-scheduled.

Critical: The 2023 Cochrane systematic review found moderate-certainty evidence of NO clinical benefit on all-cause death in acute ischemic stroke and a moderate-certainty signal of increased non-fatal serious adverse events.[⁴] This is the strongest available evidence base and should anchor risk-benefit decision-making.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

Systematic review

a study that pools and evaluates the results of many trials.

Serious adverse event

a medically significant harm reported during a study.

Intravenous (IV)

delivered into a vein.

1. Ever Neuro Pharma GmbH (Austria; formerly Ebewe Pharma). Cerebrolysin product specification and manufacturing history, 1970s–present. Aqueous mixture of low-molecular-weight peptides and free amino acids derived from purified porcine brain tissue via standardized enzymatic hydrolysis. ~25% peptide content (peptides <10 kDa) + ~75% free amino acids and metabolic intermediates per Ever Pharma product specification. Approved in 50+ countries (Russia, Ukraine, China, South Korea, much of Eastern Europe, parts of EU, Mexico, parts of the Middle East). Source for: Ever Pharma manufacturer history; the porcine-brain-derived peptide-and-amino-acid-mixture product specification; the international regulatory-approval pattern; the never-submitted-to-FDA US regulatory status.
2. Hong Z, Moessler H, Bornstein N, Brainin M, Heiss WD. (2009). A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA. International Journal of Stroke, 4(5):406–412 (October 2009).(PMID 19765131)
3. Heiss WD, Brainin M, Bornstein NM, Tuomilehto J, Hong Z; for the CASTA Investigators. (2012). Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Stroke, 43(3):630–636 (March 2012; published online January 26, 2012).(PMID 22282884 · NCT00868283)
4. Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K. (2023). Cerebrolysin for acute ischaemic stroke. Cochrane Database of Systematic Reviews, 10:CD007026 (October 11, 2023).(PMID 37818733)
5. Retraction and Expression-of-Concern record, Cerebrolysin preclinical neurotrophic-mechanism literature (2026). Three representative notices: (a) Expression of Concern — Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin. Acta Neuropathologica.(PMID 41817815)
6. Afridi et al. (2026). Efficacy and Safety of Cerebrolysin as an Adjunct to Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Observational Studies. Brain and Behavior, 16(3):e71252 (March 2026).(PMID 41880098)
7. Staszewski et al. (2026). Cerebrolysin after Endovascular Thrombectomy in Stroke: 12-Month Functional Outcomes in a Propensity-Matched Cohort. Translational Stroke Research, 17(2) (published 2026-02-25).(PMID 41739286)
8. Alrabadi et al. (2026). Cerebrolysin and Risk of Hemorrhagic Transformation: A Pooled Analysis of Recent Studies. Journal of Clinical Neurology, 22(2):235–236 (March 2026).(PMID 41775380)
9. Boontoterm et al. (2025). Neuroprotective Effects of Cerebrolysin in Moderate Traumatic Brain Injury with Nonoperative Lesions: A 6-Month Prospective Cohort. Asian Journal of Neurosurgery, 21(2):241–250 (published 2025-11-19).(PMID 42110924)

• Oxytocin — same mechanism class
• P021 — same mechanism class
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• Selank — same mechanism class
• Semax — same mechanism class
• Glutathione — shared research area