Piracetam

Piracetam (brand name: Nootropil®, Myocalm®), a leading Nootropic, is a cerebral function regulating drug which is claimed to be 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. Piracetam's chemical name is 2-oxo-pyrrolidone, or 2-oxo-1-pyrrolidine acetamide. 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.

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.

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, and myoclonus, and some believe that understanding the mechanism through which it works can teach us about the role of inter-hemispheric communication in the brain.

Mechanisms of action
The mechanism of action of piracetam is not known. It has been found to increase blood flow and oxygen consumption in parts of the brain.

Piracetam may facilitate movement of information between the brain's two hemispheres via the corpus callosum, and improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors which are implicated in memory processes. 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. Finally, Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Ca2+, K+). It has been found to increase oxygen consumption in the brain.

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. 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. As of June of 2006, piracetam is not regulated in the United States (it is neither a controlled substance nor a prescription drug but instead sold 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. It is used by parents as a treatment for childhood autism, though no study has yet produced results which would support such a use.

Piracetam is useful as a long term treatment for clotting, coagulation, and vasospastic disorders such as Raynaud's phenomenon and deep vein thrombosis It is an extremely safe anti-thrombotic agent which operates through the novel mechanism of inhibiting platelet aggregation and enhancing blood cell deformability. 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. 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. 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.

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.

It has been studied up to 45 grams daily without major side effects.

It has no known LD-50 in humans when taken orally.

Contraindications
Piracetam is contra-indicated in patients with severe renal impairment (renal creatinine clearance of less than 20 ml per minute), hepatic 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.

Undesirable effects
Piracetam has been found to have very few side effects, and those it has are typically "few, mild, and transient."

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.

Many other studies have likewise found piracetam to be well-tolerated.

Headache from use of piracetam may be aleviated by coadministration of an acetylcholine biosynthetic precursor, such as choline bitarate, choline citrate, or lecithin.

Many users report decreased levels of tolerance for alcohol.