Racetams

Authored by Robert Chen • 
July 10, 2016

Racetams are a class of synthetically made compounds that share a pyrrolidone nucleus.1Racetams have been used for cognitive improvement in dementia patients, in memory recovery following stroke, and as nootropic substances in healthy people. Commonly used racetams include piracetam2, aniracetam, oxiracetam, and pramiracetam.

It is important to note that there are several different subtypes of racetams. There are racetams that serve as cognitive enhancers, or nootropics. There are a subset of racetams that act as antiepileptic drugs (levetiracetam, brivaracetam, seletracetam). Furthermore, there are several racetams that have unknown clinical efficacy (nefiracetam, nebracetam, rolipram, dimiracetam).1

racetam examples Figure 1. Racetams share a pyrrolidone nucleus. Examples of racetams are shown above.

Pharmacology of Racetams

Currently, there is no strict, scientifically validated mechanism for racetam function. However, multiple studies have found evidence that racetams can bind at glutamate receptors that are co-located with cholinergic receptors, in order to raise acetylcholine levels.3Studies have shown that racetams activate the AMPA receptor, which increases glutamate levels.3

Racetams and Mental Performance

Most of the studies surrouding racetams such as piracetam have centered around the treatment of neurological disorders, including mild cognitive impairment, Alzhiemr's disease, and cognitive deficits following cerebrovascular diseases such as stroke.1

Memory

A study in 344 rats found that a combination of piracetam with choline supplementation resulted in improved performance on memory tasks, in both acute and chronic settings. It was found that administration of piracetam and choline in conjunction was more effective in improvement in memory retention compared to administration of either compound alone. The effect was greater when administered every day for 1 week compared to one single administration.4

In humans, piracetam has been the most widely studied. A study on 56 hospitalized geriatric patients (ages 65 to 80) were given either 2400 mg of piracetam of placebo over a period of two months. It was found that piracetam did not result in significantly different changes in memory compared to placebo.5

In one study, oxiracetam in doses of 800 mg to 2400 mg per day was shown to improve memory performance in some patients with mild to moderate dementia, when taken for a period of 1 to 6 months.2

Attention

A number of studies have assessed the effects of racetams on attention. Racetams have been shown to improve attention in patients with neurological diseases such as Alzheimer's disease6and epilepsy.7

While there have been various informal accounts of using racetams for improvements in attention in cognitive diseases, the use of racetams in normal subjects has not been studied extensively in controlled scientific settings.8One study showed that oxiracetam in doses of 800 mg to 2400 mg per day has been shown to improve performance on attention-based tasks in some patients with mild to moderate dementia, when taken for a period of 1 to 6 months.2

Creativity

While there are various anecdotal accounts of creativity modulation via racetams such as aniracetam, coluracetam, and oxiracetam, there is a limited amount of rigorous scientific research supporting its use.9

Adverse Effects of Racetams

It is important to note that there are several known adverse effects of racetams. Side effects of piracetam include anxiety, insomnia, drowsiness and agitation.1Furthermore, many racetams including piracetam carry high addictive potential.8,10Most studies on piracetam report low rates of adverse effects. However, headaches were present in 15% of the study subjects in one study on racetams for cognitive deficits from cerebrovascular disorders11. High blood pressure was found in 18% of subjects in a study on cerebrovascular disorders and traumatic brain injury.12Drowsiness was reported in two studies, for epilepsy and autism.13,14Sleep disturbances were found in 12% of patients in a study involving racetams for the treatment of chronic fatigue syndrome.15

Editor's Note

We agree that racetams have potential to serve as cognitive enhancers. However, most of the research on racetams have been performed on humans with cognitive deficits such as dementia. There is limited research on the effect of racetams on healthy adults. Furthermore, there are known side effects associated with racetams, such as anxiety, insomnia, and agitation. Furthermore, racetams are not classified as Generally Regarded as Safe (GRAS) substances by the FDA. For this reason, we do not recommend using racetams habitually for purposes of cognitive enhancement.

  1. Malykh, A. G., & Sadaie, M. R. (2010). Piracetam and piracetam-like drugs. Drugs, 70(3), 287-312.

  2. Gouliaev, A. H., & Senning, A. (1994). Piracetam and other structurally related nootropics. Brain research reviews, 19(2), 180-222.

  3. Copani, A., Genazzani, A. A., Aleppo, G., Casabona, G., Canonico, P. L., Scapagnini, U., & Nicoletti, F. (1992). Nootropic Drugs Positively Modulate α‐Amino‐3‐Hydroxy‐5‐Methyl‐4‐Isoxazolepropionic Acid‐Sensitive Glutamate Receptors in Neuronal Cultures. Journal of neurochemistry, 58(4), 1199-1204.

  4. Bartus, R. T., Dean, R. L., Sherman, K. A., Friedman, E., & Beer, B. (1981). Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats. Neurobiology of Aging, 2(2), 105-111.

  5. Abuzzahab Sr, F. S., Merwin, G. E., Zimmermann, R. L., & Sherman, M. C. (1977). A double blind investigation of piracetam (Nootropil) vs placebo in geriatric memory. Pharmakopsychiatrie, Neuro-Psychopharmakologie, 10(2), 49-56.

  6. Croisile, B., Trillet, M., Fondarai, J., Laurent, B., Mauguiere, F., & Billardon, M. (1993). Long‐term and high‐dose piracetam treatment of Alzheimer's disease. Neurology, 43(2), 301-301.

  7. Piazzini, A., Chifari, R., Canevini, M. P., Turner, K., Fontana, S. P., & Canger, R. (2006). Levetiracetam: an improvement of attention and of oral fluency in patients with partial epilepsy. Epilepsy research, 68(3), 181-188.

  8. Husain, M., & Mehta, M. A. (2011). Cognitive enhancement by drugs in health and disease. Trends in cognitive sciences, 15(1), 28-36.

  9. Rose, S. P. (2002). 'Smart drugs': do they work? Are they ethical? Will they be legal? Nat Rev Neurosci, 3(12), 975-979. doi:10.1038/nrn984

  10. Fond, G., Micoulaud-Franchi, J. A., Macgregor, A., Richieri, R., Miot, S., Lopez, R., ... & Repantis, D. (2015). Neuroenhancement in healthy adults, part I: pharmaceutical cognitive enhancement: a systematic review. Journal of Clinical Research & Bioethics, 2015.

  11. Batysheva, T. T., Bagir’, L. V., Kostenko, E. V., Artemova, I. Y., Vdovichenko, T. V., Ganzhula, P. A., ... & Otcheskaya, O. V. (2009). Experience of the out-patient use of memotropil in the treatment of cognitive disorders in patients with chronic progressive cerebrovascular disorders. Neuroscience and behavioral physiology, 39(2), 193-197.

  12. Neznamov, G. G., & Teleshova, E. S. (2009). Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin. Neuroscience and behavioral physiology, 39(3), 311-321.

  13. Fedi, M., Reutens, D., Dubeau, F., Andermann, E., D'Agostino, D., & Andermann, F. (2001). Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy. Archives of neurology, 58(5), 781-786.

  14. Wasserman, S., Iyengar, R., Chaplin, W. F., Watner, D., Waldoks, S. E., Anagnostou, E., ... & Hollander, E. (2006). Levetiracetam versus placebo in childhood and adolescent autism: a double-blind placebo-controlled study. International clinical psychopharmacology, 21(6), 363-367.

  15. Boiko, A. N., Batysheva, T. T., Matvievskaya, O. V., Manevich, T. M., & Gusev, E. I. (2007). Characteristics of the formation of chronic fatigue syndrome and approaches to its treatment in young patients with focal brain damage. Neuroscience and behavioral physiology, 37(3), 221-228.

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