Cerebrolysin

 

cerebrolysin

Cerebrolysin is a mixture of neuropeptides and free amino acids derived from a young porcine brain. It is considered as one of the most potent nootropics available. Since it was discovered in the late 1940s and used since 1954, Cerebrolysin also one of the oldest and most studied nootropics. Despite its high efficiency, the fact that the only way to administer it is injections keeps it from being popular among nootropic users.

Cerebrolysin contains 15% of 24 various neuropeptides such as enkephalins, neurotensin, substance P and 85% of 17 free L-amino acids.

 

History of clinical usage and studies of Cerebrolysin

Cerebrolysin was discovered in 1949 by Austrian scientist Gerhart Harrer, who worked at University of Innsbruck. He found that the process of enzymatic hydrolysis of the brain tissue produces substances that can stimulate nerve cells.

The drug was registered in Austria in 1954. First publications of clinical trials dated 1954-55.

In 1954, H. Lenz successfully used Cerebrolysin in the treatment of absence seizures and narcolepsy.

In the 1955 year, H. Hetzel and E. Niedermeyer found that this substance can awake patients from hypoglycemic coma. The EEG abnormities typical for hypoglycemia also disappeared.

K.Kundratitz in 1957 used intravenous Cerebrolysin injections to treat severe cases of mental deterioration.

F.Kramer in 1959 published his research dedicated to its usage in the treatment of cerebrovascular diseases.

In 1960, Rudolf Dreyer in his work “Die Behandlung der Epilepsien” also noted that this substance can be used in a complex treatment of epilepsy.

During the next years, as Cerebrolysin spread to more countries, the number of publications about its clinical usage in the treatment of various neurological disorders started to grow exponentially. As of today, it is approved in 44 countries worldwide.

In 1973, it was used in the Soviet Union for the first time, in the treatment of cerebral atherosclerosis. The Russians not only used this nootropic in their medical practice but also worked on the development of its substitute. They started working on Cortexin in the late 1970s and finished the development at the beginning of 1980s. Currently, Cortexin is not the only Cerebrolysin analog available. Several manufacturers from CIS countries produce Cerebrolizat, which is the closest and cheapest analog to this drug.

In 1975 K. Boehme found that Cerebrolysin enhances the effect of tricyclic antidepressants. The drug leaflet also suggests that concomitant administration with antidepressants or MAO inhibitors may lead to cumulative effects. In the presence of such effects, the reduction of antidepressants dosage is advisable.

J.Wenzel in 1977 confirmed neurotrophic effects of the drug. He found that injections of Cerebrolysin to newborn rats stimulate the growth of hippocampal neurons, promote dendritic branching and increase the number of synaptic contacts.

Since 1980, the technology of production has changed. The changes affected the processes of purification of the hydrolysate and the quality control of both raw materials and finished product. So, modern C and the old one back from 1954 are not the same.

Double-blind, placebo-controlled trial performed in 2000 by Chinese scientists evaluated the efficiency of the drug in the treatment of Alzheimer’s disease. In this study, the patients that received treatment with Cerebrolysin showed statistically significant improvement in NAI, MMSE and SCAG scores compared with placebo group.

Studies continue to this day. For example, in 2016 there are 38 studies was published in PubMed and 21 on Russian science citation index.

 

Mechanism of action and Pharmacological effects

Since Cerebrolysin is a mixture of various peptides and amino acids, its exact pharmacology is still not clear. Each neuropeptide has its function. Here is the information I was able to get about how it works:

  • Protection of neurons against damaging conditions (Neuroprotective action). The drug prevents the formation of free radicals and decreases the concentration of lipid peroxides. Suppress glutamate excitotoxicity and prevents neuronal death caused by ischemia and hypoxia.
  • Metabolic regulations. This includes improvement of brain energy metabolism and intracellular protein synthesis.
  • Neurotrophic activity, which is similar to natural nerve growth factors by its action. Cerebrolysin stimulates neuronal differentiation and sprouting, supports the survival of neurons. In the experimental model of Alzheimer’s, it was shown to slow down the process of neurodegeneration.
  • Neuromodulatory effects include restoration of impaired cognitive functions, improvement of concentration and the processes of memorization and the recall of memory. This nootropic also has a positive effect on the mood.

 

Usage in medical practice

Here are the list of official indications for use along with some related researches. On-label uses include:

Dementia of various origins. In a group of 40 patients with degenerative and vascular dementia, the treatment with 20ml of Cerebrolysin daily for ten days demonstrated success. Analysis by SCAG and Geriatric rating scale revealed significant improvement of cognitive functions. Patients’ assessment of their clinical status was also improved. In a placebo-controlled trial on multi-infarct dementia patients, the main group treated with 30ml daily for 28 days showed improvement in EEG results, abstract reasoning, and memory tests. Another placebo-controlled study with the same dosage and treatment duration were performed on 479 patients with senile dementia of Alzheimer’s type. The main group showed statistically significant improvement of SCAG scores. According to the Clinical Global Impression rating scale, the efficiency of the course was significant for 61% of patients and moderate for 38.3%. In the control group, results were moderate for 20%, while the health condition of 60% patients did not change.

Alzheimer’s disease. Currently, Alz is one of the most widespread neurodegenerative diseases. It is also one of the indications for Cerebrolysin use. According to several studies, this drug can inhibit the generation of amyloidogenic proteins that involved in neurodegeneration and restore the process of neurogenesis. After the course of treatment, patients increased their attention span, memory, and ability to recall information.

Parkinson is the second most common neurodegenerative disease after Alzheimer’s. Cerebrolysin can be used as a part of complex treatment in the early stages of Parkinson’s disease. The first scientific publications about its usage on Parkinson patients dated 1987.

Cerebral blood flow disorders. A study performed in 1994 on acute ischemic stroke patients showed that patients received 10-30ml of C daily for 20 days improved their neurological status and cerebral functions more compared to the control group. Multicentre randomized controlled trials performed in 2001 and 2005 also showed, that the treatment with high Cerebrolysin dosages (50ml) resulted in significant regression of neurological symptoms and improvement in functional recovery.

Traumatic brain injuries. Just like with other Nootropics, one of the indications for use is TBI. The reason for that is its neuroprotective action.

It is also used in pediatric practice, just like Cortexin. This includes prenatal brain injuries, cerebral palsy, developmental disorders and Attention Deficit Hyperactivity Disorder (ADHD). According to the study performed in 1999 on the kids with ADHD, about 60% of patients showed improvement of their symptoms after the treatment. EEG results before and after therapy were also different.

 

Dosage and how to take

Anything up to 5ml should be injected intramuscular, up to 10ml intravenous, dosages up to 50ml should be administered by slow infusion.  The length of the course is 10-20 days of daily injections.

Here are the daily dosages suggested by the manufacturer for clinical use:

  • Acute conditions, including Ischemic stroke, traumatic brain injuries, and complications after neurosurgical procedures: 10-50ml.
  • Residual period of stroke, traumatic brain, and spinal cord injury: 5-50ml.
  • Psycho-organic syndrome and depression: 5-30ml.
  • Alzheimer’s and vascular dementia: 5-30ml.
  • In the pediatric practice: 0.1-0.2ml per one kg of body weight.

A lot of people ask if there are any other ways to administer Cerebrolysin without injections. Actually, injections are the only way suggested by the instructions. But just for informational purposes, I’ll share some studies and trials where it was taken without intramuscular or intravenous injections.

At the beginning of the article I mentioned work of K.Kundratitz dated 1957. He mentioned that he used Cerebrolysin in his practice, and the course consists of 30-40 injections, “Subkutan oder intramuscular” which means “subcutaneously or intramuscular.”

In the study performed in 2000 on Elderly patients, the drug was administered orally.

Also in several studies on rats, it was administered subcutaneously and intranasally.

Summing all this up, there is almost no evidence of successful usage without injections, only a few trials, mostly on the animals. So if you want to try this Nootropic, IM injections seem to be the only way. Also, according to some anecdotal experiences of the nootropic community, using it intranasally not only less effective but may lead to severe side effects as well.

 

Cerebrolysin side effects

Although this drug considered safe and non-toxic, adverse reactions are still possible. Here is the list of side effects according to the drug leaflet:

  • Sweating, dizziness, increased heart rate and arrhythmia caused by the fast injection. To avoid that, it should be injected slowly.
  • Loss of appetite, diarrhea, constipation, nausea.
  • Irritability, insomnia.
  • Allergic reactions, characterized by headaches, pain in the neck, limbs or lower back.
  • Headaches, depression.

Contraindications for use include hypersensitivity to the components, acute kidney disorders, and epileptic status.

 

Conclusion

Cerebrolysin at this moment is one of the best nootropics by the safety/efficiency ratio. It is highly studied and effective in both on-label clinical application and for the most off-label users, according to anecdotal experiences of the Nootropic community. But the side effects are still possible, and you have to deal with injections to take it. Also, if you overcame your fear of needles, you may look upon Cortexin, a more modern analog of Cere, which has the less efficient dosages and the length of the course.

 

 

 

References

  1. Vostrikov V.V, Shishliannikov G.Z, Zelentsov K.E, Vostrikov M.V, Shabanov P.D “Cerebrolysin in the practical medicine.”
  2. Lenz H. “Aminosäuregemisch bei Petit mal und narkoleptischen.”
  3. Hetzel H. “Die Wirksamkeit von Gehirnhydrolysaten beim hypoglykaemischen Koma.”
  4. Wenzel M, Wenzel J, Grosse G, Lindner G, Kirsche W, Matthies H. “The effect of amino acids on the in-vitro differentiation of hippocampal neurons-morphometric and electron microscopic studies on ribosomes, protein synthesis and synaptogenesis.”
  5. Jovnir I.K, Broshik N.S, Krotiuk L.N “The usage of cerebrolysin on patients with cerebral atherosclerosis.”
  6. Alvarez XA, Lombardi VR, Corzo L, Pérez P, Pichel V, Laredo M, Hernández A, Freixeiro F, Sampedro C, Lorenzo R, Alcaraz M, Windisch M, Cacabelos R. “Oral Cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects.”
  7. Dreyer R. “Die Behandlung der Epilepsien.”
  8. Verischagin N.V, Lebedeva N.V “Mild forms of vascular dementia: cerebrolysin effects.”
  9. Ruether E., Husmann R., Kinzler E. et al “28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer’s disease.”
  10. Zavadenko N.N “Nootropic compounds in pediatric practice and children neurology.”
  11. Balenty E., Grasmugg B. “Erste Ergebnisse der Anwendung von Cerebrolysin an Patienten mit Morbus Parkinson.”

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