Piracetam
Piracetam (brand name: Nootropil®, Myocalm®), is a nootropic, (though it is only called so by off-label users, see 'As a nootropic' below). It is a cerebral function regulating drug which, it is claimed, is able to enhance cognition and memory, slow down brain aging, increase blood flow and oxygen to the brain, aid stroke recovery, and improve Alzheimer's, Down's Syndrome, dementia, and dyslexia, among others.[1] Piracetam's chemical name is 2-oxo-1-pyrrolidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid (pyroglutamate). Piracetam is a cyclic derivative of GABA. It is one of the racetams. Though largely ignored in the United States, piracetam is commonly prescribed in Europe for a variety of conditions. However, in some places, due to its non-toxic nature and its general health benefits it is seen more as a food supplement than as a drug. One of its general health effects is said to be toning of damaged nerves and muscles (although this is scientifically unverified). It is safe for use by itself as a non-prescription drug in a reasonably healthy person.
Effects
Several meta-reviews of literature on piracetam indicate that piracetam increases performance on a variety of cognitive tasks among dyslexic children, though this may reflect its enhancement of cross-hemispheric communication and of cognitive function in general, rather than a specific improvement in whatever causes dyslexia. Piracetam also seems to inhibit brain damage caused by a variety of factors including hypoxia and excessive alcohol consumption.[2][3]
Piracetam has been studied in an extensive number of clinical experiments, and has shown positive results in the treatment of post-stroke aphasia, epilepsy, cognitive decline following heart and brain surgery, dementia,[4] and myoclonus.[5][6]
Piracetam appears to increase communication between the two hemispheres of the brain, and increases activity of the corpus callosum.[7][8][9]
Mechanisms of action
The mechanism of action of piracetam is not known, although it is hypothesized to act on ion channels or ion carriers, thus leading to non-specific increased neuron excitability, while explaining its lack of agonistic or inhibitory effect on synaptic action (quite unlike most neurotransmitters), and its low toxicity.[10] It has been found to increase blood flow and oxygen consumption in parts of the brain.[11]
Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors which are implicated in memory processes.[12] Furthermore, Piracetam may have an effect on NMDA glutamate receptors which are involved with learning and memory processes. Piracetam is thought to increase cell membrane permeability.[12][13] Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Ca2+, K+).[10] It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brain. [14][15] Piracetam appears to increase the synthesis of cytochrome b5[16], which is a part of the electron transport mechanism in mitochondria. It also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle. [17]
History
Piracetam was first synthesized in 1964 by scientists at the Belgian pharmaceutical company UCB led by Dr Corneliu E. Giurgea. The drug was the first of the so-called nootropics ("smart drugs" or "cognitive enhancers"), that is, substances which purportedly enhance mental performance. The term nootropic was coined by Giurgea. Nootropil was launched clinically by UCB in the early 1970s and remains an important product of that company in Europe.
Approval and usage
Piracetam is primarily used in Europe, Asia, South America and the US. Piracetam is legal to import into the United Kingdom and the United States for personal use with or without prescription as with other prescription-only drugs [citation needed]. As of June of 2006, piracetam is sold in the United States as a dietary supplement. It has become popular as a cognitive enhancement drug among students, who often buy it in bulk as a powder and then consume it with orange juice to mask the strong, bitter taste. 2 weeks of piracetam enhanced verbal memory in healthy college students in a double-blind, placebo-controlled study.[18] It is used by parents as a treatment for childhood autism, though no study has yet produced results which would support such a use.
Aging
Piracetam appears to reverse the effects of aging in the brains of mice.[19][20]
Piracetam appears to reduce levels of lipofuscin in the rat brain. [21] (Lipofuscin accumulation is common symptom of aging and alcoholism).
Alcoholism
Piracetam appears to be effective in treating alcoholism or its symptoms. [22] [23] [24] [25] [26] [27]
Alzheimer's and senile dementia
Piracetam appears to be effective for improving cognition in Alzheimer's disease and senile dementia patients. [28] [29] [30] [31] [32]
Clotting, coagulation, vasospastic disorders
Piracetam is useful as a long term treatment for clotting, coagulation, and vasospastic disorders such as Raynaud's phenomenon[33] and deep vein thrombosis[12][34] It is an extremely safe anti-thrombotic agent which operates through the novel mechanism of inhibiting platelet aggregation and enhancing blood cell deformability.[12] Because traditional anti-thrombotic drugs operate through the separate mechanism of inhibiting clotting factors, co-adminsitration of piracetam has been shown to highly complement the efficacy and safety of traditional Warfarin/Heparin anti-coagulation therapy.[35] The most effective treatment range for this use is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart.[34] Piracetam is currently being investigated as a complement or alternative to Warfarin as a safe and effective long term treatment for recurring deep vein thrombosis.[34]
Stroke, ischemia and symptoms
Piracetam has been found to improve cognition after stroke, and reduce symptoms, such as aphasia[36]. It also improves cognition in cases of chronic ischemia. [37] [38]
Dyspraxia and Dysgraphia
Due to its supposed effect on nerves and muscles it is sometimes prescribed as an aid to Muscle or dexterity training. There has not been a specific study as to whether it is beneficial in this aspect. Vinpocetine, another purported nootropic with which piracetam is indirectly synergesic, is confirmed to help with these conditons to a certain degree.
Schizophrenia
Piracetam improves cognitive performance as with normal people, but does not improve or worsen chronic schizophrenia.[1]
Dosage
Piracetam is usually supplied in 800 mg tablets or capsules. Some bulk or nutritional suppliers supply it in a powder form. The recommended dosage varies based on the indication, usually ranging from 1.6-9.6 grams daily (2-12 pills daily). Some people report faster results when taking 1-2 pills every hour for 4-6 hours or taking 4-8 pills at once for the first few days to notice an effect.
For blood coagulation, clotting, and vasospastic disorders such as Raynaud's phenomenon or deep vein thrombosis, the most effective treatment range is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart.[33][12][34]
It has been studied up to 45 grams daily without major side effects.[citation needed]
It has no known LD-50 in humans when taken orally.[10]
Contraindications
Piracetam is contra-indicated in patients with severe renal impairment (renal creatinine clearance of less than 20 ml per minute), hepatic (liver) impairment and to those under 16 years of age. It is also contraindicated in patients with cerebral haemorrhage and in those with hypersensitivity to piracetam, other pyrrolidone derivatives or any of the excipients.
Special warnings and precautions for use
Due to the effect of piracetam on platelet aggregation, caution is recommended in patients with underlying disorders of haemostasis, major surgery or severe haemorrhage.
Abrupt discontinuation of treatment should be avoided as this may induce myoclonic or generalised seizures in some myoclonic patients.
As piracetam is almost exclusively excreted by the kidneys caution should be exercised in treating patients with known renal impairment. In renally impaired and elderly patients, an increase in terminal half-life is directly related to renal function as measured by creatinine clearance. Dosage adjustment is therefore required in those with mild to moderate renal impairment and elderly patients with diminished renal function.
Side effects
Piracetam has been found to have very few side effects, and those it has are typically "few, mild, and transient."[39] A large-scale, 12-week trial of high-dose piracetam found no adverse effects occurred in the group taking piracetam as compared to the placebo group.[40] Many other studies have likewise found piracetam to be well-tolerated.[41][42][39]
Symptoms of general excitability, including anxiety, insomnia, irritability, headache, agitation, nervousness, and tremor - are occasionally reported.[43][44]. Such symptoms seem more likely reported in connection with caffeine consumption (coffee), or with monosodium glutamate (a common additive in many processed foods). Effects can be reduced with magnesium supplements. Headache from use of piracetam may be alleviated by coadministration of an acetylcholine biosynthetic precursor, or a drug with cholinergic effects, such as choline bitarate, choline citrate, lecithin, cyprodenate or centrophenoxine.[citation needed]
Many users report decreased levels of tolerance for alcohol. Some users not only notice decreased levels of tolerance for alcohol, but also a dis-interest in consuming alcoholic drinks at all. Many user also report synergistic effects with cannabis. There is also a large amount of anecdotal evidence that piracetam potentiates serotonergic psychedelic drugs such as psilocybin mushrooms or LSD. Also used synergesically with hydergine.
References
- UCB Pharma Limited (2005). "Nootropil 800mg & 1200mg Tablets and Solution". electronic Medicines Compendium. Datapharm Communications. Retrieved 8 December.
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- ^ James South, "Piracetam - the original nootropic", International Antiaging Systems
- ^ "Can nootropic drugs be effective against the impact of ethanol teratogenicity on cognitive performance?" Eur Neuropsychopharmacol. 2001 Feb;11(1):33-40.
- ^ "Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation." Neurotoxicology. 2002 May;23(1):19-31.
- ^ "Clinical efficacy of piracetam in cognitive impairment: a meta-analysis." Dement Geriatr Cogn Disord. 2002;13(4):217-24.
- ^ "Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy." Arch Neurol. 2001 May;58(5):781-6.
- ^ "Effectiveness of piracetam in cortical myoclonus." Mov Disord. 1993;8(1):63-8.
- ^ Giurgea, C. & Moyersoons, F., "The pharmacology of corticol evoked potentials" Arch Int Pharmacodyn Ther 199, (1972) pp.67-78.
- ^ Buresova, 0. & Bures, J., "Piracetam induced facilitation of interhemispheric transfer of visual information in rats", Psychopharmacologia 46, (1976) pp.93-102.
- ^ Okuyama, S. & Aihara, H., "Actions of nootropic drugs on transcallosal response of rats", Neuropharmacol 27, (1988) pp.67-72.
- ^ a b c AH Gouliaev, A Senning, "Piracetam and other structurally related nootropics" Brain Research. Brain Research Reviews. 1994 May;19(2):180-222.
- ^ "Cerebral blood flow effects of piracetam, pentifylline, and nicotinic acid in the baboon model compared with the known effect of acetazolamide." Arzneimittelforschung. 1996 Sep;46(9):844-7.
- ^ a b c d e "Piracetam--an old drug with novel properties?" Acta Pol Pharm. 2005 Sep-Oct;62(5):405-9.
- ^ "Piracetam: novelty in a unique mode of action." Pharmacopsychiatry. 1999 Mar;32 Suppl 1:2-9.
- ^ Grau, M. et al, "Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat", Gen Pharmac 18 (1987) pp.205-211.
- ^ Nickolson, V. & Wolthuis, 0., "Effect of the acquisition - enhancing drug Piracetam on rat cerebral energy metabolism", Biochem Pharmacol 25, (1976) pp.2241-2244.
- ^ Tacconi, M. & Wurtman, R. "Piracetam: physiological disposition and mechanism of action" in Advances in Neurology, vol. 43 (1986) S. Fahn et al, ed. Raven Press: NY.
- ^ Grau, M. et al, "Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat", Gen Pharmac 18 (1987), pp. 205-211
- ^ "Increase in the Power of Human Memory in Normal Man through the Use of Drugs" Psychopharmacology 49, 307-309 (1976).
- ^ Pilch, H. & Mueller, W. "Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged by not of young mice", Psychopharmacol 94,(1988) pp.74-78.
- ^ Stoll, L. et al,"Age-related deficits of central muscarinic cholinergic receptor function in the mouse: partial restoration by chronic Piracetam treatment", Neurobiol Aging 13, (1991) pp. 39-44.
- ^ Paula-Barbosa, M. et al, "The effects of Piracetam on lipofuscin of the rat cerebellar and hippocampa; neurons after long-term alcohol treatment and withdrawal", Alcoholism: Clinical and Experimental Research 15, (1991) pp. 834-838.
- ^ Skondia, V. & Kabes, J., "Piracetam in alcoholic psychoses: a double-blind, crossover, placebo controlled study", J Int Med Res 13, (1985) pp.185-187.
- ^ Buranji I, Skocilic Z, Kozaric-Kovacic D. "Cognitive function in alcoholics in a double-blind study of piracetam, Lijec Vjesn 1990 Mar-Apr;112(3-4):111-4.
- ^ S Kalmár, Adjuvant therapy with parenteral piracetam in alcohol withdrawal delirium, Orv Hetil (2003) 144: pp.927-30.
- ^ Dencker SJ, Wilhelmson G, Carlsson E, Bereen FJ. "Piracetam and chlormethiazole in acute alcohol withdrawal: a controlled clinical trial." J Int Med Res 1978;6(5):395-400.
- ^ Meyer JG, Forst R, Meyer-Wahl L. "Course of alcoholic predelirium during treatment with piracetam: results of serial psychometric tests (author's transl)", Dtsch Med Wochenschr 1979 Jun 22;104(25):911-4
- ^ Binder S, Doddabela P. "The efficacy of Piracetam on the mental functional capacity of chronic alcoholics (author's transl)", Med Klin 1976 Apr 23;71(17):711-6
- ^ Croisile, B., et al, "Long-term and high dose treatment of Alzheimer's disease", Neurol 43', (1993) pp.301-305.
- ^ DeBerdt, W., "Interaction between psychological and pharmacological treatment in cognitive impairment", Life Sci 55, (1994) pp.2057-2066.
- ^ Ferns, S. et al, "Combination choline/Piracetam treatment of senile dementia" Psychopharmacol Bull 18 (1982), pp. 96-98.
- ^ Smith, R. et al "Comparison of therapeutic response to long-term treatment with lecithin versus Piracetam plus lecithin in patients with Alzheimer's disease" Psychopharacol Bull 20 (1984), pp. 542-545.
- ^ Branconnier, R. "The efficacy of the cerebral metabolic enhancers in the treatment of senile dementia", Psychopharmacol Bull 19, (1983), pp.212-19.
- ^ a b "Treatment of the Raynaud's phenomenon with piracetam." Arzneimittelforschung. 1993 May;43(5):526-35.
- ^ a b c d "Platelet anti-aggregant and rheological properties of piracetam. A pharmacodynamic study in normal subjects." Arzneimittelforschung. 1993 Feb;43(2):110-8.
- ^ "The treatment of severe or recurrent deep venous thrombosis. Beneficial effect of the co-administration of antiplatelet agents with or without rheological effects, and anticoagulants." Thromb Res. 1995 Jun 15;78(6):469-82.
- ^ DeBerdt, W., "Interaction between psychological and pharmacological treatment in cognitive impairment", Life Sci 55, (1994) pp. 2057-2066.
- ^ Herrschaft, H., "Effects and therapeutic efficacy of nootropic drugs in acute and chronic cerebral ischaemia in man", in Pharmacology of Cerebral Ischemia. (1989) J. Kriegelstein, ed. CRC Press: Boca Raton, FL.
- ^ Platt, D. et al, "On the efficacy of Piracetam in geriatric patients with acute cerebral ischaemia: a clinically controlled double blind study", Arch Gerontal Geriatrics 16, (1993) pp.149-164.
- ^ a b "Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo." Neurol Neurosurg Psychiatry. 1998 Mar;64(3):344-8.
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- ^ "Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy." Arch Neurol. 2001 May;58(5):781-6.
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See also
- Dysgraphia and Dyspraxia
- Choline - piracetam is synergistic with choline
- Cholinergic
- Hydergine - piracetam is synergistic with hydergine
- Nootropic
- Vinpocetine
- Other Racetams
External links
- Erowid Piracetam Vault
- Erowid Piracetam FAQ
- Collection of Scientific Abstracts on Piracetam
- Piracetam (Nootropyl) by Ward Dean, M.D., and John Morgenthaler
- Nootropics - Reviewing The Smart-Drugs, By James South, MA
- Piracetam - The Original Nootropic, By James South, MA
- Research Abstracts on Piracetam