What is Noopept? Can it really improve memory and cognition, and is it safe?

Answer:

Noopept (N-phenylacetyl-L-prolylglycine ethyl ester -- JSC LEKKO Pharmaceuticals), also known as omberacetam, is promoted as a "nootropic," a substance taken to enhance memory, cognitive function and/or mood. It was synthesized in 1996 by researchers in Russia, where it is apparently currently sold as a drug for improving learning and memory and improving cognitive function after brain damage (such as from concussion or stroke). The evidence for these uses, however, is largely based on animal studies, and two studies in people which were not placebo-controlled.

It is not an approved drug in the U.S., nor is it permitted to be sold as a dietary supplement. (Drugs that are chemically similar to Noopept, including piracetam, aniracetam, oxiracetam and phenylpiracetam, are also not permitted to be sold as supplement ingredients in the U.S.)

Noopept should not be taken by people with high blood pressure or certain other medical conditions, as discussed below.

Efficacy
Noopept has been shown in animal studies to reach the brain when taken orally (Boiko, Bull Exp Biol Med 2000), and appears to be converted into a substance that closely resembles a naturally-occurring brain peptide, cycloprolylglycine, which may influence the brain's reaction to anxiety and stress (Gudasheva, Eur J Drug Metab Pharmacokinet 1997; Seredenin, Bull Exp Biol Med 2002). Noopept has been found to reduce anxiety and learned helplessness (which can occur in anxiety or depression) in rats (Uyanaev, Bull Exp Biol Med 2006; Koliasnikova, European Neuropsychopharmacology Meeting 2011).

Also in rats, Noopept has been shown to stimulate nerve-growth factors in the hippocampus, a part of the brain which is important for emotion and memory (Ostrovskaya, Bull Exp Biol Med 2008), as well as improve memory after damage to the frontal cortex (Romanova, Bull Exp Biol Med 2000). In rat models of Alzheimer's disease, Noopept improved spatial memory and increased the immune response to amyloid-beta peptides (which form plaques in the brain associated with Alzheimer's disease) (Ostrovskaya, J Psychopharmacol 2007).

As described below, there appear to be only two studies on the effects of Noopept on cognition and/or mood in people. Both were limited studies which did not include a placebo control, and both focused on people with vascular brain disease, stroke, or concussion. There do not appear to be any studies showing Noopept improves cognition or mood in healthy people without impairment.

One two-month study among fifty-three people in Russia age 50 or older with mild cognitive disorders (including brain disease such as vascular dementia and traumatic brain injury) compared the effects of Noopept with piracetam; however, there was no placebo group. Although both groups experienced improvements, those who those who took 20 mg of Noopept daily (10 mg twice per day) had more improvement on most measures of cognition and mood, with fewer adverse effects, than those who took 1,200 mg of piracetam (Neznamov, Neurosci Behav Physiol 2009). Overall, among those who took Noopept, 42.9% of those with brain disease with emotional dysregulation and 70% of those with post-concussive syndrome had significant improvements, compared to just 25% and 16.7%, respectively, among those who took piracetam. It should be noted, however, that two people taking Noopept dropped out of the study after experiencing increases in systolic blood pressure which required treatment.

A second, open label study among 60 people in Russia who had a stroke found that those who took 20 mg of Noopept daily for twelve months had mild, but significant improvement in cognitive function after 2 months of taking Noopept compared to a control group who did not take Noopept (but apparently did not take a placebo); however, the study does not appear to report measures of cognitive function at 12 months, so it's not known whether there was a  benefit after one year (Amelin, Zh Nevrol Psikhiatr Im S S Korsakova 2011).

Safety
In one of the clinical studies noted above, Noopept was taken for 56 days and was generally well-tolerated; however, two people experienced increases in systolic blood pressure which required treatment. Other side effects included increased sleep disturbance and irritability (Neznamov, Neurosci Behav Physiol 2009).

The package insert by JSC LEKKO Pharmaceuticals indicates that allergic reactions can occur, and that it can cause a severe rise in blood pressure in people with high blood pressure. It also states that it should not be taken by anyone under the age of 18, women who are pregnant or lactating, people with kidney or liver disease. (It also cautions anyone with lactase deficiency, lactose intolerance or glucose-galactose malabsorption against taking, but this appears to be due to the fact that the pill provided by the manufacturer contains certain excipients, like lactose.) According to the manufacturer, it should not be taken with alcohol, drugs with a stimulating effect, or blood-pressure lowering drugs.

Noopept is not an ingredient Generally Recognized as Safe (GRAS) in the U.S. and there do not appear to be long-term safety studies.

Dosage
JSC LEKKO Pharmaceuticals recommends taking 10 mg of Noopept twice daily, in the morning and afternoon, after eating. It also recommends taking for between 1.5 to 3 months, and stopping for one month before continuing again, if needed (the reason for this recommendation is not clear).

Products sold on the Internet containing Noopept typically provide 10 mg per recommended daily serving (one capsule) and cost about $20 for a 3 month supply. Some brands, however, provide higher amounts (30 mg) per capsule. 

Is it Legal?
In the U.S., Noopept is not approved as drug nor can it be legally sold as dietary supplement. The FDA considers Noopept to be an analog of the compound piracetam, which, similarly, is not an approved drug in the U.S. and cannot legally be sold as a dietary supplement (FDA 2016; FDA Warning Letter 2010; FDA Enforcement Report 2013). However, some memory and cognitions supplements listing Noopept and/or its analogs on their labels continue to be sold in the U.S. Some of these products have been tested and confirmed to contain high doses of these drugs or combinations of these drugs, leading to concerns about the quality and safety of these supplements.

Piracetam is approved as a drug in other countries, but not in the U.S. In the United Kingdom piracetam is prescribed for myoclonus (uncontrolled jerking of muscles in the arms or legs), and has also been proposed for improving cognition and symptoms of dementia, although the evidence for this is mixed (Flicker, Cochrane Database Syst Rev 2001; Winblad, CNS Drug Rev 2005).

Bottom Line
There is no evidence that Noopept will improve cognition and memory in healthy individuals and there is only preliminary evidence that it can do so in people with brain diseases or have suffered brain trauma. It appears to be generally well tolerated but its safety has not been established. It should not be taken by people with high blood pressure or those taking blood-pressure lowering medication or stimulant medication, people with kidney or liver disease, or women who are pregnant or lactating.