July 29, 2015
Importance of understanding the dose-response curve
For many chemicals and supplements, and the nootropics are no exception here, there is a sweet spot where maximum benefit is reached, known in pharmacology jargon as being in the optimal range or therapeutic window. Piracetam is a near perfect example as it exhibits a striking U-shaped dose-response curve. Rhodiola, L-theanine, phenibut, noopept and most of the nootropics and other substances have a ceiling that, once reached will not increase in more pronounced positive effects even with increased intake. In these cases, the old adage that less is more can be clinically shown to be true. As a result a basic understanding of the dose-response curve and the practice of minimum effective dosing can be vital for using supplements safely, efficiently and effectively.Sometimes Less is MoreWith many things less is actually more. Take for instance the case of common psychoactives like alcohol or caffeine. People use caffeine to block adenosine receptors carrying their signal that the body is tired which causes the body and brain to feel more alert. Excess of caffeine however can lead to a state of jittery, nervousness that may keep you up all night, but if you can’t get your trembling fingers to behave then chances are it won’t be much help focusing your mind and getting the task at hand done. Alcohol is a GABAergic, which means it affects the brain’s natural relaxation pathways, but with increase of the substance you increase effects but past a certain level the likelihood of increase of negative side effects is greater than the possibility of increased benefit. To a certain degree, more caffeine or more alcohol may produce a greater desired effect but at some point you will pass the u-shaped peak, or “bell curve,” of the dose-response curve at which time you begin treading in the territory of increased peripheral effects without increase in desired effects. To use our previous examples, you might still be awake and ready to finish the work you’re late on, but if you can’t keep your fingers still due to caffeine jitters or if you’re losing your lunch due to over-indulgence in alcohol then you’ll find you’ve passed up the “sweet spot” and will only find increase in undesired effects without any added desired effect.
Piracetam, perfect model of the bell shaped dose-response curvePiracetam is one of the best examples of the U-shaped bell curve dose-response with the optimal range lying between 2.4 - 4.8 grams per dose, 2-3 times per day. On average, efficacy of piracetam increases sharply as the user approaches the peak of the dose-response curve and benefit drops and negative peripherals increase as you go past the peak of the bell curve right there at 4-4.8 grams. In addition to minding the dosage-response curve, keeping in mind the concept of minimum effective dosage should protect against habituation and keep your monthly supplement bill more manageable in addition to resulting in less chance of negative side effects. Also, remember that cycling weekly and monthly is a good idea. Starting out the week with one cup of coffee and possibly a lower dose of a racetam or other psychostimulant. Remember many of these compounds will build up after use for several days so building up to largest dose in the middle of the week and amping back down towards the weekend is a good idea. In short, just remember the bell curve and try to follow the curve to the maximum dosage at the middle of the week and gently back down. As always make sure you consult with a physician if you’re taking any prescription medications or are currently under a doctor’s care for any current medical condition.
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