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Introduction
In this article, I’m going to tell you how to use an extract from the brains of pigs to rehabilitate your brain, reduce anxiety and depression, reduce withdrawals from drugs, delay tolerance development from drugs, protect yourself from neurodegenerative disease, and more.
How I Found Cerebrolysin
1. I developed an essential tremor in childhood that worsened tremendously when I developed more brain damage in my twenties.
2. I developed an almost crippling anxiety disorder in my 20’s also.
As my research developed, I came to understand that increases in neurogenesis and brain plasticity were those that most helped me overcome my anxiety disorder. Surprisingly, as they did so, I began to heal from my essential tremor. Consequently, I’ve devoted a lot of time in the last two years to the study of neurogenesis – the reason I have a long series on serotonin.
Cerebrolysin is one of the only commercially available formulation of actual neurotrophic molecules. When I discovered it, I experimented with it so extensively that I think I may be the single human who has most used Cerebrolysin.
In this article, I’ll tell you what Cerebrolysin is and what it’s effects are, before I take you through a tour of the most interesting rodent studies on Cerebrolysin followed by a survey of the human clinical studies, which are extensive. Finally, at the end of the article, I’ll tell you how to get Cerebrolysin and how I use it.
What is Cerebrolysin?
In 1949, Gerhart Harrer discovered that enzymatic hydrolysis of brain tissues produced a substance that stimulates nerve cells. It was subsequently registered as a drug in Austria by 1954, known as FPF1070, and has since become a commonly used medicine in East Asia and Eastern Europe, though it has yet to gain popularity in North America and Western Europe.
Cerebrolysin is a protein-based mixture of free amino acids (20%) and active, low molecular weight amino acid sequences (80%) that include the brain growth factors brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNF).
Cerebrolysin’s Consistent Effects
1. Endogenous growth factors:
a. Cerebrolysin administration upregulates nerve growth factor[1], brain derived neurotrophic factor[2], and IGF-1[3].
2. Oxidative stress and inflammation:
a. Cerebrolysin administration consistently reduces markers of inflammatory cytokines (e.g. TNF-a), reduces markers of oxidative stress, increases glutathione activity, and consequently protects neurons from apoptosis[4].
3. GSK-3B:
a. Like donepezil[5], Cerebrolysin has been shown to inhibit glycogen synthase kinase-3-beta (GSK-3B)[6].
b. Inhibition of GSK-3B and cyclin-dependent kinase 5 (CDK5) activity are the reasons Cerebrolysin decreases beta amyloid deposition and microtubule-associated protein tau phosphorylation[7].
4. Plastic changes:
a. Cerebrolysin induces plastic changes to dendritic morphology. Chronic Cerebrolysin exposure in aging rodents increases dendritic spine density and dendritic length in pyramidal neurons of the PFC and granule cells of the dentate gyrus[8].
b. Cerebrolysin reverses endothelial permeability dysfunction by reducing proinflammatory and pro-coagulation proteins and by increasing tight junction proteins[9].
Interesting Rodent Studies
1. Cognitive deficits:
a. In a rodent model of diabetes-induced cognitive decline using streptozotocin, Cerebrolysin treatment reduced HbA1c% elevations, attenuated body weight loss due to diabetes, enhanced learning and memory, reduced serum TNF-a and increased IGF-1beta, glutamate, and serotonin levels. Authors concluded that Cerebrolysin is neuroprotective against diabetes-induced cognitive decline[10].
b. In a rodent model of aging related cognitive deficits, Cerebrolysin dose-dependently improved antioxidant markers, reduced markers of oxidative stress like malondialdehyde, and reduced apoptosis while improving memory[11].
2. Parkinson’s disease:
a. In the 6-OHDA rodent model of Parkinson’s disease, post-treatment of rodents with Cerebrolysin restored midbrain and striatum dopamine levels, normalized MDA and NO levels, and replenished glutathione activity in the midbrain[12].
b. In the MPTP rodent model of Parkinson’s, sustained release, nanoparticle Cerebrolysin treatment had similar effects[13].
3. Alcoholism:
a. Concurrent Cerebrolysin treatment in rodents exposed to ethanol counteracts ethanol-induced oxidative stress and apoptosis[14].
4. Morphine withdrawal:
a. In a rodent model of morphine withdrawal, pre-treatment with Cerebrolysin limited withdrawal symptoms and heat shock protein elevation while not affecting morphine tolerance[15].
b. In another rodent model of morphine tolerance and withdrawal, concurrent Cerebrolysin treatment delayed tolerance development and attenuated symptoms of withdrawal from morphine[16].
5. Sleep deprivation:
a. Sleep-deprived animals experience memory deficits that can be attenuated by concurrent Cerebrolysin administration, likely via reducing oxidative stress at the hippocampus[17].
6. Depression:
a. In a rodent model of reserpine-induced depression due to reduced monoamine activity, Cerebrolysin pre-treatment improved antioxidant status, reduced TNF-a, elevated BDNF, norepinephrine, serotonin, and dopamine, and reduced depressive symptoms similarly to fluoxetine[18].
7. Pain:
a. In a rodent model of mechanical neuropathic pain (called allodynia), Cerebrolysin was effective in reducing mechanical neuropathic pain but not the peripheral inflammation[19].
8. Hyperthermia:
a. In a rodent model of whole-body hyperthermia[20], pre-treatment with Cerebrolysin dose-dependently attenuated reductions in blood-brain barrier permeability and reduced overall neuronal damage due to the heat.
b. In a review paper studying the use of Cerebrolysin for heat strokes, authors concluded that it was the best neuroprotective drug available[21].
9. Schizophrenia:
a. In a rodent model of schizophrenia[22], 30-day Cerebrolysin treatment reduced amphetamine-induced locomotion, increased social activity, ameliorated dendritic retraction and spine loss and dendritic pathology and neuronal loss in the prefrontal cortex and NAcc. The authors conclude that Cerebrolysin may benefit the management of schizophrenic symptoms.
Diabetic Neuropathy
In a 1997 placebo-controlled longitudinal study[23] of 20 diabetics, patients who received 20 mL daily for a period of 10 days experienced reduced diabetic neuropathy pain for at least a period of 6 weeks.
Vascular Dementia
The second most common cause of dementia is vascular, where disordered blood flow to the brain produces cognitive impairment.
A Cochrane meta-analysis was first conducted in 2013 and later updated in 2019[24] on all 6 RCTs that have used Cerebrolysin to treat vascular dementia. Four of the trials used Cerebrolysin treatments once a day, 5 days a week, and for only four weeks, while two trials used a longer treatment duration of 24 weeks. The authors conclude the Cerebrolysin improves cognitive function in vascular dementia in a duration-dependent fashion, and that effect sizes are limited due to study design (i.e. a very long duration study should show more attenuation of disease progression).
Alzheimer’s Disease
Cerebrolysin was FDA-approved in the US as a treatment for Alzheimer’s disease.
In 2007, a meta-analysis of 6 RCTs studying mild-to-moderate Alzheimer’s disease patients found that 30 mL of Cerebrolysin given daily for 5 days a week for a total of 5 weeks led to a significant improvement in clinical global impression. The outcome was further confirmed by a 2015 meta-analysis[25].
In 2009, Alvarez et al[26]. showed that Cerebrolysin treatment dose-dependently reduced serum TNF-a and increased dissociable IGF-1 in Alzheimer’s disease patients.
A 2010 RCT[27] on 133 patients with moderate to severe Alzheimer’s disease tested the safety and efficacy of Cerebrolysin treatment. Patients were stratified to receive either 10, 30, or 60 mL diluted in saline 5 days a week for 4 weeks followed by 2 days a week for another 8 weeks. Cerebrolysin improves global clinical function at all three doses with a dose-dependent effect.
In a 2011 RCT on 130 mild-to-moderate Alzheimer’s disease patients found that Cerebrolysin treatment was as effective as donepezil treatment and that the combination of the two was superior to either for clinical endpoints[28].
In 2016, Alvarez et al.[29] conducted a RCT on 158 patients with mild-to-moderate Alzheimer’s disease using 10 mL of Cerebrolysin given intravenously 5 times a week for weeks 1-4 and 13-16, with some arms employing donepezil at 5 or 10 mg and a placebo. They found that while Cerebrolysin alone or in combination with donepezil could increase serum BDNF, donepezil could not do so alone. Together, they produced a synergistic effect on serum BDNF as donepezil potentiates Cerebrolysin’s effect. The effect of Cerebrolysin on BDNF disappeared 3 months into discontinuation, but that period could have been extended if donepezil was used. Finally, APoE4 carriers exhibited the best results from the therapy and APoE4 carriers with higher initial serum BDNF levels responded the best of them.
In 2020, Alvarez et al.[30] showed that Cerebrolysin and the combination of Cerebrolysin and donepezil (but not donepezil alone) could synergistically contribute to reductions in VEGF in markedly ill Alzheimer’s disease patients, but not in mild-to-moderate cases. VEGF is thought to rise as a response to pathological conditions in AD, though it is thought to offer neuroprotective effects[31]. The indirect effect of Cerebrolysin reducing VEGF likely indicates its effect on the causal pathology.
Traumatic Brain Injury
A meta-analysis covering all human studies on Cerebrolysin and TBIs 2018 and prior found a statistically significant improvement in outcomes on the Glasgow Outcome Scale and modified Rankin Scale scores[42].
In 2019-20, the CAPTAIN I RCT trial[43] was designed to determine whether Cerebrolysin’s neuroprotective and neurotrophic effects could attenuate outcomes from TBIs in 46 patients. Patients given 50 mL/day for 10 days following by 10mL/day for 2 more 10 day periods fared better than controls. Later, the CAPTAIN II RCT trial, performed with a larger cohort of 139 patients found that the treatment improved mult-dimensional TBI outcomes. Finally, the authors confirmed the results of the two trials with a meta-analysis[44].
It was later shown that age, processing speed, and attention as measured by the MMSE, PSI DSC, and PSI SS metrics is predictive for human TBI patients’ stroke recovery following Cerebrolysin treatment[45].
Ischemic Stroke
A 2012 meta-analysis found that Cerebrolysin treatment was effective for acute hemorrhagic stroke[46].
In 2012, the largest RCT[47] using Cerebrolysin in humans for stroke recovery was performed - on 1070 patients. Patients were given parenteral Cerebrolysin at 30 mL/day for 10 days with aspirin or saline with aspirin, beginning within 12 hours after the stroke. The authors studied the neuroprotective effects of Cerebrolysin on mortality from stroke and found that Cerebrolysin favorably improved mortality only in those most severely affected patients, but this result diminished when groups are not stratified by stroke severity.
The 2015-16 CARS RCT trials[48][49] investigated whether stroke patients who receive parenteral Cerebrolysin treatment (30 mL/d for 21 days, once daily, beginning 24-72 hours after the stroke onset) recover motor function in their upper extremities faster. Previous human studies had initiated Cerebrolysin treatment very close to or before stroke onset and used it for less time, thereby mostly exhibiting the neuroprotective effects of Cerebrolysin, as opposed to the effects of neurogenesis and neuroplasticity. With 21 days of treatment and a delayed start, Cerebrolysin was still found to have a small to moderate beneficial effect while being well tolerated. This result was confirmed by a 2017 meta-analysis by the same authors that combined both of the CARS trials[50].
A 2018 meta-analysis of 9 RCTs using Cerebrolysin to treat human stroke patients confirmed that 30-50ml of Cerebrolysin given once daily for 10-21 days, when treatment initiates within 72 hours of the ischemic stroke, attenuates early neurological deficits from strokes[51].
Despite this evidence, the Cochrane review[52] failed to support the use of Cerebrolysin for acute ischemic stroke.
Recently[53], Cerebrolysin has been shown to be a beneficial add-on for acute stroke, in part because of lowering the risk of hemorrhagic complications after recanalization therapy.
Children with Autism
A 2003 observational study employing 0.1 mL of Cerebrolysin injected intramuscularly daily for 5 days on children 27 children with autism and Asperger’s found positive benefit in all the children with Asperger’s and most of the children with autism.
In a 2017, an observational study[32] was performed on autistic children aged 4-6 years stratified according to whether they had exogenous (organic) or endogenous autism. Though both improved following Cerebrolysin treatment, the exogenous group recovered markedly better than the endogenous group.
In 2018, an Iranian research group sought to determine whether Cerebrolysin treatment could improve behavioral, verbal, and nonverbal develop in 36 Autistic children aged 3-10. The authors used a protocol of 0.1mL/kg Cerebrolysin injected intramuscularly thrice weekly the first month, followed by twice for the next two weeks and once for the final two weeks. The CARS questionnaire was used to assess autistic traits from the treated group. The authors suggest that the frequency of intramuscular injections is prohibitive and that sustained release formulations may be desirable.
In 2020, Iraqi practitioner Al-Mosawi[33] treated 24 patients with typical autism, 17 patients with atypical autism, and 4 patients with Asperger’s syndrome with Cerebrolysin and either 3, 2, or 1 antipsychotic, sometimes including citicoline. After 6 months of treatment, all patients exhibited qualitative improvements.
Children with Cerebral Palsy
Cerebral palsy is characterized by motor difficulty, mental retardation, seizures, and other neurological problems. It is the most common cause of permanent neurological disability in children and thought to be caused by brain damage suffered in early life that is not progressive.
In 2016, an Iranian clinical trial[34] investigated the effects of Cerebrolysin on 50 children suffering from cerebral palsy, between the ages of 1.6-6.2 years old. The Cerebrolysin group was treated with 0.1 mL/kg of body weight intramuscularly once daily for 10 days followed by once weekly for 4 months. The Cerebrolysin group had significantly improved motor function 4 months after the trial.
A second, 2017 Iranian clinical trial[35] investigated the effect of Cerebrolysin treatment on spastic cerebral palsy patients aged between 2-6 years old. 0.1mL/kg was injected intramuscularly 5 days a week for a month, and only once a week for the third month. In the second month, it was injected 4 times the first week, 3 times the second week, and so on. Using the Modified Ashworth score to assess motor spasticity, the authors found that Cerebrolysin attenuated spasticity the first month, after which improvements ceased, and that age of onset of treatment was a determining factor.
In 2020, an Iraqi researcher[36] examined the effects of 3 mL of Cerebrolysin and 3 mL of citicoline (375 mg) injected every other day for 30 days on a two-year-old boy exhibiting cerebral palsy due to kernicterus. Kernicterus occurs when excess bilirubin accumulates in the grey matter of the brain in early life, due to hyperbilirubinemia. The authors observed minor improvements in the boy’s condition.
High Risk Pre-term Infants
In an Egyptian RCT of high risk pre-term infants (born less than 32 weeks during a pregnancy, 6 months after their corrected birth date), treatment of 0.1 mL/kg of body weight given once weekly for 3 months greatly reduced the motor, language, and interpersonal deficits of the infants
Children with Rare Conditions
Rett Syndrome is a rare X-linked dominant genetic disorder that exclusively affects females. In a case study on a 3-year-old girl with Rett Syndrome who was previously hypotonic, ataxic, and had unusual upper limb motor function, 1 mL of Cerebrolysin injected intramuscularly daily for 10 days followed by a month of 3 mL injected every third day with oral citicoline. The girl experienced dramatic improvement in all measures[37].
An Iraqi practitioner named Aamir Al-Mosawi produced a case report[38] of four children suffering with myelomeningocele, a type of spina bifida associated with defects in the bones and membranes surrounding the spinal cord. Using a mixture of Cerebrolysin (1-5mL, every day to every third day) treatments and nandrolone decanoate (25 mg, intermittently), the practitioner described remarkable improvements in function in the three patients he treated.
In 2020, Al-Mosawi published a case study[39] of his success using a protocol combining 3-5 mL of Cerebrolysin, 1 mg of the antipsychotic trifluoperazine (or another antipsychotic, like prochlorperazine), and 3 mL of citicoline to treat idiopathic mental retardation in a children, who in turn exhibited progressive improvements in symptoms.
In 2020, Al-Mosawi also produced a case study[40] on a 9-year-old boy with Charcot Marie Tooth disease, the progressive and hereditary motor and sensory disease with no cure. Treated with 3 mL of Cerebrolysin every 3 days, Al-Mosawi observed remarkable qualitative improvements in motor and sensory-dependent action.
In 2020, Al-Mosawi[41] treated two 4-year-old Iraqi boys suffering from Wohlfart Kugelberg Welander syndrome, a progressive, autosomal recessive condition which gradually causes difficulty with gait and movement. Leaving the boy with less severe symptoms as a control, Al-Mosawi found that Cerebrolysin improved the symptoms of the treated child while the control’s symptoms remained constant.
So, Where Can I Get Cerebrolysin?
At www.cosmicnootropic.com, use the discount code “LEO”.
Some Guidelines from Personal Experience
1. Select which ampule size you want according to how much you plan to inject.
a. 2 mL ampules are good for maintenance doses, while 5 mL or 10 mL ampules are most useful for neuroprotection and intense recovery.
2. Never store opened Cerebrolysin. Once it opens, it will go bad within minutes when exposed to oxygen and light.
3. Tools you’ll want:
a. Consider visiting healthwarehouse.com.
b. Consider using an 18-21 gage, 5 mL syringe to withdraw the fluid.
c. Consider replacing that needle with a 28-30 gage needle after withdrawing, for the intramuscular injections.
4. Where to inject?
a. Some like to inject closer to their brains – chest, shoulders, traps, neck can all work.
b. Some like to inject 2 mL at a time before moving the needle an inch away and injecting again.
5. What sort of protocol?
a. 2 mL twice a week is significant.
b. 10-60 mL for 5-10 days in a row is what I would use for a withdrawal, followed by a maintenance dose.
c. Some people use a heavy dose once a week, since the research shows it has a trailing effect.
References
[1] Ubhi, K., Rockenstein, E., Vazquez‐Roque, R., Mante, M., Inglis, C., Patrick, C., ... & Masliah, E. (2013). Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease. Journal of neuroscience research, 91(2), 167-177. [2] Shishkova, V. N., Zotova, L. I., Maljukova, N. G., Sutjusheva, I. R., Kan, N. V., Gasanova, E. M., & Kerimova, E. I. (2015). An assessment of cerebrolysin effect on BDNF level in patients with post stroke aphasia depending on carbohydrate metabolism disorders. Zhurnal nevrologii i psikhiatrii imeni SS Korsakova, 115(5), 57-63. [3] Alvarez, X. A., Sampedro, C., Cacabelos, R., Linares, C., Aleixandre, M., García-Fantini, M., & Moessler, H. (2009). Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer's disease patients treated with the neurotrophic agent Cerebrolysin. The The International Journal of Neuropsychopharmacology, 12(7), 867-872. [4] Abdel-Salam, O. M., Mohammed, N. A., Youness, E. R., Khadrawy, Y. A., Omara, E. A., & Sleem, A. A. (2014). Cerebrolysin protects against rotenone-induced oxidative stress and neurodegeneration. Journal of Neurorestoratology, 2, 47-63. [5] Noh, M. Y., Koh, S. H., Kim, S. M., Maurice, T., Ku, S. K., & Kim, S. H. (2013). Neuroprotective effects of donepezil against A β42‐induced neuronal toxicity are mediated through not only enhancing PP 2 A activity but also regulating GSK‐3β and n AChR s activity. Journal of neurochemistry, 127(4), 562-574. [6] Rockenstein, E., Torrance, M., Mante, M., Adame, A., Paulino, A., Rose, J. B., ... & Masliah, E. (2006). Cerebrolysin decreases amyloid‐β production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease. Journal of neuroscience research, 83(7), 1252-1261. [7] Rockenstein, E., Ubhi, K., Trejo, M., Mante, M., Patrick, C., Adame, A., ... & Masliah, E. (2014). Cerebrolysin™ efficacy in a transgenic model of tauopathy: role in regulation of mitochondrial structure. BMC neuroscience, 15(1), 1-11. [8] Juárez, I., González, D. J., Mena, R., & Flores, G. (2011). The chronic administration of cerebrolysin induces plastic changes in the prefrontal cortex and dentate gyrus in aged mice. Synapse, 65(11), 1128-1135. [9] Teng, H., Li, C., Zhang, Y., Lu, M., Chopp, M., Zhang, Z. G., ... & Fleckenstein, B. (2021). Therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability. Neuroreport, 32(5), 359-366. [10] Georgy, G. S., Nassar, N. N., Mansour, H. A., & Abdallah, D. M. (2013). Cerebrolysin ameloriates cognitive deficits in type III diabetic rats. PloS one, 8(6), e64847. [11] Pourmemar, E., Majdi, A., Haramshahi, M., Talebi, M., Karimi, P., & Sadigh-Eteghad, S. (2017). Intranasal cerebrolysin attenuates learning and memory impairments in D-galactose-induced senescence in mice. Experimental gerontology, 87, 16-22. 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[23] Biesenbach, G., Grafinger, P., Eichbauer-Sturm, G., & Zazgornik, J. (1997). Cerebrolysin in treatment of painful diabetic neuropathy. Wiener medizinische Wochenschrift (1946), 147(3), 63-66. [24] Cui, S., Chen, N., Yang, M., Guo, J., Zhou, M., Zhu, C., & He, L. (2019). Cerebrolysin for vascular dementia. Cochrane Database of Systematic Reviews, (11). [25] Gauthier, S., Proano, J. V., Jia, J., Froelich, L., Vester, J. C., & Doppler, E. (2015). Cerebrolysin in mild-to-moderate Alzheimer's disease: a meta-analysis of randomized controlled clinical trials. Dementia and geriatric cognitive disorders, 39(5-6), 332-347. [26] Alvarez, X. A., Sampedro, C., Cacabelos, R., Linares, C., Aleixandre, M., García-Fantini, M., & Moessler, H. (2009). Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer's disease patients treated with the neurotrophic agent Cerebrolysin. The The International Journal of Neuropsychopharmacology, 12(7), 867-872. [27] Alvarez, X. A., Cacabelos, R., Sampedro, C., Aleixandre, M., Linares, C., Granizo, E., ... & Moessler, H. (2011). Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer’s disease: results of a randomized, double‐blind, controlled trial investigating three dosages of Cerebrolysin. European journal of neurology, 18(1), 59-68. [28] A Alvarez, X., Cacabelos, R., Sampedro, C., Couceiro, V., Aleixandre, M., Vargas, M., ... & Moessler, H. (2011). Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with cerebrolysin and donepezil. Current Alzheimer Research, 8(5), 583-591. [29] Alvarez, X. A., Alvarez, I., Iglesias, O., Crespo, I., Figueroa, J., Aleixandre, M., ... & Moessler, H. (2016). Synergistic increase of serum BDNF in Alzheimer patients treated with cerebrolysin and donepezil: association with cognitive improvement in ApoE4 cases. International Journal of Neuropsychopharmacology, 19(6), pyw024. [30] Alvarez, X. A., Alvarez, I., Martinez, A., Romero, I., Benito, C., Suarez, I., ... & Moessler, H. (2020). Serum VEGF predicts clinical improvement induced by Cerebrolysin plus donepezil in patients with advanced Alzheimer’s disease. International Journal of Neuropsychopharmacology, 23(9), 581-586. [31] Alvarez, X. A., Alvarez, I., Aleixandre, M., Linares, C., Muresanu, D., Winter, S., & Moessler, H. (2018). Severity-related increase and cognitive correlates of serum VEGF levels in Alzheimer’s disease ApoE4 carriers. Journal of Alzheimer's Disease, 63(3), 1003-1013. [32] Chutko, L. S., Yakovenko, E. A., Surushkina, S. Y., Kryukova, E. M., & Palaieva, S. V. (2017). The efficacy of cerebrolysin in the treatment of autism spectrum disorders. Zhurnal nevrologii i psikhiatrii imeni SS Korsakova, 117(9), 71-75. [33] Al-Mosawi, A. J. (2020). Our experience with childhood pervasive developmental disorders (Autism and Asperger Syndrome): Cure is Possible. EC Clinical and Medical Case Reports, 3(4), 01-08. 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