Racetams and CDP-Choline: Two Nootropics that Stack with Think Gum

“Nootropic Stacks” like Racetams and CDP-Choline synergize with the ingredients in Think Gum

This blog post was guest authored by Jack Baldwin.  Jack is the founder of Focus Supplements and has a Management and Economics degree from Kings College London.

What is Oxiracetam?
Oxiracetam is part of a family of compounds called the racetams. All racetams are pyrrolidone derivatives, the first of which was piracetam. Corneliu E. Giurgea first synthesized Piracetam in 1964 (1), he later coined the term ‘nootropic’ in 1972 (2). All racetams share a 2-pyrrolidone core structure, modifications of this core structure result in changes in solubility, absorption, potency, pharmacological action and even taste!

Racetam Chemistry
Racetam Chemistry

As can be seen on the diagram above, the only difference between Piracetam and Oxiracetam is a single hydroxyl group, however the two molecules are significantly different. Three of the major differences are that Oxiracetam requires a lower dosage than Piracetam due to its increased potency, has a subtle stimulatory effect and in comparison to Piracetams unpleasant bitter and sour taste, Oxiracetam has a pleasant sweet taste.

Oxiracetam has the ability to increase our memory and attention via acetylcholine. Oxiracetam is known to significantly increase acetylcholine utilization, by increasing the production of acetylcholine via a process called high affinity choline uptake (HACU) (3). During this process, dietary or supplemented Choline is pulled into neurons. Once Choline is inside a neuron, it is turned into acetylcholine.  In addition to increasing HACU, Oxiracetam also enhances the release of acetylcholine from activated neurons (4).

What is CDP-Choline?
Cytidine diphosphate-choline, also known as CDP-Choline is a molecule that combines Cytidine and Choline with two phosphate groups. The molecule itself does not seem to have any pharmacological action; instead the molecule is quickly hydrolyzed in the intestines to form both cytidine and choline. Cytidine is then converted in to uridine. This means that CDP-Choline is essentially a pro drug for uridine and choline. Both of these compounds are naturally present in our diet. Choline is a precursor for acetylcholine, and thus increased levels of choline will ultimately lead to higher brain levels of acetylcholine. Uridine is a major component of our RNA and has the ability to increase cellular membrane synthesis and increase dopamine receptor density.

Reasons for combining Oxiracetam and CDP-Choline
As discussed earlier, Oxiracetam increases the utilization of acetylcholine by increasing acetylcholine production via HACU and enhancing acetylcholine release in activated neurons. Increased acetylcholine utilization and release will eventually lead to a depletion of acetylcholine levels in the brain, which most commonly results in a headache but will also decrease the efficacy of Oxiracetam. To prevent this, it is wise to supplement Choline via a Choline source such as CDP-Choline. Since Oxiracetam increases HACU the supplemented Choline is quickly taken up by neurons and turned into acetylcholine. An added benefit of using CDP-Choline as a Choline source is that its uridine content may also further aid in the production of acetylcholine (5).

How to take
It is recommended to take 800 mg of Oxiracetam and 250 mg of CDP-Choline once or twice a day. Since Oxiracetam and CDP-Choline both have a pleasant sweet flavor it is possible to incorporate the powders in to a drink. For example, one could mix the juice of half a lemon with 250 ml of water and then add 800 mg of Oxiracetam and 250 mg of CDP-Choline to sweeten the drink. Keep in mind if you want to do this, you’ll need a proper scale to measure out your powders. You can buy Oxiracetam and CDP-Choline powder here. If you do not have a proper scale you can purchase one here or you can simply purchase Oxiracetam tablets here and CDP-Choline tablets here.

Adding an Extra Boost: Vinpocetine and Caffeine
The combination of Oxiracetam and CDP-Choline will subtly increase one’s ability to stay focused and retain information at a higher rate. However on highly demanding days subtle simply isn’t going to cut it. Adding Vinpocetine and Caffeine, will provide an extra boost that will allow you to cope with more demanding days. Vinpocetine is a semisynthetic derivative of a compound called Vincamine, which is naturally present in the lesser periwinkle plant. Vinpocetine seems to increase memory via various different mechanisms. It has been shown that Vinpocetine is a sodium and calcium channel inhibitor (6), and it appears that inhibiting these channels can increase memory (7). Vinpocetine also interacts with the alpha-adrenergic receptors (8), and it seems that this is in part responsible for its memory enhancing effects (9). Vinpocetine also increases blood flow in the brain(10), this is important because neurons need blood to function and thus increased blood flow could lead to increased functioning of neurons. Caffeine is a naturally occurring alkaloid found in many plant species, the most common of which being coffee and tea. Caffeine is the most commonly used stimulant in the world. It acts by blocking a family of receptors called the adenosine receptors (11). These receptors cause a myriad of effects when they are activated. One of these effects is that it makes us feel sleepy, thus blocking these receptors causes us to feel more alert (12). Caffeine also increases the amount of acetylcholine receptors and acetylcholine release in the brain (13), (14) and thus is additive to the acetylcholine effects of Oxiracetam and CDP-Choline. A handy formulation of Vinpocetine and Caffeine in gum form called Think Gum can be purchased here.

References
1.    Giurgea CE, Greindl MG, Preat S (1983). “Nootropic drugs and aging”.Acta Psychiatr Belg83 (4): 349–58.
2.    Gazzaniga, Michael S. (2006). The Ethical Brain: The Science of Our Moral Dilemmas (P.S.). New York, N.Y: Harper Perennial. p. 184.
3.    Spignoli G, et al (1986) Effect of oxiracetam and piracetam on central cholinergic mechanisms and active-avoidance acquisition . Clin Neuropharmacol.
4.    Raiteri M, Costa R, Marchi M. (1992) Effects of oxiracetam on neurotransmitter release from rat hippocampus slices and synaptosomes . Neurosci Lett.
5.    Wang L, Albrecht MA, Wurtman RJ (2007). Dietary supplementation with uridine-5′-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat . Brain Res.
6.    Tretter L, Adam-Vizi V The neuroprotective drug vinpocetine prevents veratridine-induced {Na+}i and {Ca2+}i rise in synaptosomes . Neuroreport. (1998)
7.    Tóth, E., Kiss, B., Gere, A., Kárpáti, E., Törley, J., Pálosi, É, . . . Szporny, L. (1997). 1-Oxa-3,8-diazaspiro[4.5]decan-2-one derivatives with a potent inhibitory effect on neural Ca-uptake and protecting action against TET-induced brain edema and memory and learning deficits. European Journal of Medicinal Chemistry, 32(1), 27-38.
8.    Gaál L, Molnár P (1990) Effect of vinpocetine on noradrenergic neurons in rat locus coeruleus . Eur J Pharmacol.
9.    Lemon N, et al (2009) Locus coeruleus activation facilitates memory encoding and induces hippocampal LTD that depends on beta-adrenergic receptor activation . Cereb Cortex.
10.    Lim, C., Cook, P., & James, I. (1980). The effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteers. British Journal of Clinical Pharmacology, 9(1), 100-101.
11.    “Caffeine”. DrugBank. University of Alberta. 16 September 2013.
12.    Porkka-Heiskanen T (2011) Methylxanthines and sleep . Handb Exp Pharmacol.
13.    Shi D, et al (1993) Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain . Cell Mol Neurobiol.
14.    Acquas E, Tanda G, Di Chiara G (2002) Differential effects of caffeine on dopamine and acetylcholine transmission in brain areas of drug-naive and caffeine-pretreated rats .Neuropsychopharmacology.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s