Looking for a good pramiracetam stack? Maybe I can point you in the right direction.
Phenylpiracetam and pramiracetam are my favorite racetams, by a long shot. Subjectively, phenylpiracetam feels like a mild psychostimulant. It seems to improve cognitive tempo, and make me feel a little more on point. Based on tentative evidence, it may improve long-term memory consolidation and have anti-amnesic effects.
Pramiracetam has a fairly unique mechanism of action. Thus the a good pramiracetam stack is a little different from typical nootropic stacks. Let’s start off with a quick summary of our recommended pramiracetam stack:
|Pramiracetam||HACU, aldosterone system, other mechanisms|
|CDP Choline||Prodrug for uridine and choline|
|Modafinil (low-dose, 50mg)||Wakefulness-promoting agent|
|Methylene Blue||BBB permeable antioxidant, mitochondrial bioenergetics enhancer|
|Standard neuroprotective supplements||Vitamin D, l-theanine, curcumin|
Pramiracetam Mechanism of Action
Pramiracetam seems to help long-term potentiation and memory consolidation without affecting working memory. Unlike other racetams, pramiracetam doesn’t affect glutamate receptors. For example, piracetam modulates AMPA-type glutamate receptors 1). This activity contributes to its nootropic effects. Instead, pramiracetam increases high-affinity choline uptake (HACU) in a manner analogous to coluracetam.
Role of Aldosterone
Aldosterone receptors may also contribute to piramiracetam’s mechanism.
Aldosterone is a steroid hormone best known for its role in regulating blood pressure. It also regulates electrolyte balance (sodium and potassium) and volume status. Because aldosterone promotes fluid retention, drugs that block the effect of aldosterone treat hypertension.
Aldosterone has a prominent role in the kidneys and adrenals. But apart from this role, Aldosterone is also a neurosteroid that acts in the brain. Aldosterone has poor blood brain barrier permeability. Even so, a small subset of neurons are sensitive to aldosterone 2).
Pramiracetam either behaves like aldosterone in the brain or increases the activity of aldosterone. Aldosterone increases sympathetic tone, which mediates the fight-or-flight physiological response. So, pramiracetam may indirectly enhance adrenaline/noradrenaline signaling in the brain. These neurotransmitters are important for long-term memory formation. (Consider the flashbulb effect as an example of this.)
Removal of the adrenals, which produce adrenaline/noradrenaline abolishes the effect of pramiracetam. This result is consistent with pramiracetam’s effect on aldosterone and sympathetic tone. 3) So far, our account of pramiracetam’s mechanism is speculative. Too little research has been done to make definitive conclusions.
CDP-choline provides the extra choline needed to support pramiracetam’s cholinergic action. Pramiracetam is a high-affinity choline uptake enhancer. This means that pramiracetam helps cholinergic neurons absorb more choline. Choline is the precursor to acetylcholine, important for memory and cognition. CDP-choline is a prodrug for choline with nootropic properties.
I tend to benefit from nootropics that increase arousal. So, I’ve added modafinil to this pramiracteam stack because it promotes wakefulness. From the above diagram, you can see how both too much and too little arousal impairs cognitive performance.
Sensitive individuals who are low-dose responders might want to avoid combining the two. The mixture of pramiracetam and modafinil can be anxiety-promoting (anxiogenic). Thus, it’s always advised to start at the lowest possible doses.
Methylene blue synergies well with pramiracetam. Methylene blue is a potent REDOX cycler that enhances the efficiency of mitochondria. It’s this action that may improve cognition. Methylene blue is under clinical investigation by TauRx for the treatment of Alzheimer’s disease.
One disadvantage of methylene blue is that it’s a nitric oxide synthase inhibitor. Nitric oxide is kind of a double-edged sword in the brain. On the one hand, it’s associated with neurotoxicity. So, it dilates blood vessels and plays an indispensable role in long-term potentiation (LTP). Nitric oxide synthase inhibition might detract from the therapeutic effects of methylene blue.
Pramiracetam, it turns out, is a nitric oxide synthase inducer. Increasing nitric oxide synthase expression might offset some of methylene blue’s effects on nitric oxide.
Methylene blue also stacks well with pramiracetam because it’s neuroprotective. Use neuroprotectants to hedge against the theoretical risk of excitotoxicity.