4 replies to this topic

[iseethelight]

I started taking piracetam and choline for  memory and motivation issues 9 months ago. I stopped it about 2 weeks ago. It almost ruined my life. Now before I proceed, disclaimer: I believe the reason I reacted like this to piracetam / choline is because I'm sensitive to acetylcholine increase, so if you're not, piracetam/choline may work well for you. 

 

Now that it's out of my system,  I'm starting to realize how different my behavior became during that period. The scary thing is, while you're on it, you think that your behavior is amazing and that you're superior.

 

I literally accomplished nothing productive in those 9 months and that time  period seemed to have been a  flash. I started many projects but never stuck to anything. 

I became manic, narcissistic and depressed (alternating between the 3 on a weekly basis). I had bouts of anger, depression and euphoria. I simply became reckless.

 

I felt smart during those months but seemed to have retained nothing I learned in that time span. Before I started my stack, I was learning to play the guitar, learning spanish and french, mastering billiard and cooking etc, I stopped all of that 2 weeks into my stack. I mismanaged my money, spent recklessly and isolated myself. 

 

I spent a lot time sleeping, it doesn't matter how much I slept the night before, I'd need at least two long naps during the day. I was constantly dizzy with joint pain.

 

I even started spending lots of time on social media posting shirtless gym pics on instagram, something I would never do before. I did amass a huge following so I managed to humiliate myself to thousands of people. I think such attention seeking behavior is reserved for women, not real men. 

 

Now I'm not saying  piracetam and choline are bad. What I'm saying that stack is that it's not for everyone. So be careful. 

 

Now I've started taking an anti-cholinergic and I feel much better. I don't plan on taking it long term but the fact that I feel better and calmer on it, means that increase in ach does me no good.

 

Edited by iseethelight, 17 September 2015 - 07:16 PM.

[CaptainJ]

Thank you for sharing this.  I'm curious if I may be in the same camp, although it seems I tend to notice changes more slightly, if at all, than the majority of folks I read from.  I was looking this up because I had some racetams left that I havent taken often in a long time, but I have no choline or lecithin to take with them, and was trying to remind myself which was the best to buy.  After reading this, I am reconsidering and am curious to hear from you or anyone what is the best way to test if choline is something beneficial for me or otherwise?

 

I also share/have shared some of the problems you listed above, and am curious if you think they were more attributable to piracetam/choline?  I have memory issues and my life has been flashing by for too long, and while new things fascinate me, I have not been able to stick with them and often have trouble learning new things.  Hence, I actually bothered to log in just now, vs just reading like usual, because I am tired of life flashing by and would like to understand better how my brain responds to things.  Doctors haven't been able to help much, so I am trying to make myself learn.  Until reading this, I had no idea choline could do that and was/kind of still am(?) on here trying to get an idea of which kind I should buy.  Thanks in advance to anyone who says anything, and thank you for sharing that OP with us.  

[gamesguru]

isochromo

oxidative stress

who what where when why how

did somebody say something

 

Oxidative Stress in a Model of Toxic Demyelination in Rat Brain: The Effect of Piracetam and Vinpocetine

We studied the role of oxidative stress and the effect of vinpocetine (1.5, 3 or 6 mg/kg) and piracetam (150 or 300 mg/kg) in acute demyelination of the rat brain following intracerebral injection of ethidium bromide (10 μl of 0.1%). Results: ethidium bromide caused (1) increased malondialdehyde (MDA) in cortex, hippocampus and striatum; (2) decreased total antioxidant capacity (TAC) in cortex, hippocampus and striatum; (3) decreased reduced glutathione (GSH) in cortex and hippocampus (4); increased serum nitric oxide and (5) increased striatal (but not cortical or hippocampal) acetylcholinesterase (AChE) activity. MDA decreased in striatum and cortex by the lower doses of vinpocetine or piracetam but increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC. GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide. Vinpocetine and piracetam displayed variable effects on regional AChE activity.

 

Malondialdehyde (MDA) is a marker for oxidative stress, so the meaning of the correlation between high MDA and higher doses of vinpocetine & piracetam is that the body is trying to respond to a state of increased oxidation.  Not good.

[metabrain]

I had the same issues with Piracetam over time which is why I stopped taking it I noticed that it seems to build up in my system over time.

[gamesguru]

One possible explanation for the tolerance is upregulated presynaptic autoreceptors (which modulate neurotransmitter release), perhaps ampa or nmda glutamate, iGluR or mGluR, nicotinic or muscarinic^[1] cholinergic.

In particular, I am attracted to NMDARs which piracetam potently upregulates, or AMPA^[2], for which piracetam is a positive allosteric modulator.  Even tho it upregulates NMDARs, perhaps it upregulates them also presynaptically, or otherwise tells the presynaptic terminal, hey man, stop dispensing so much glutamate over there, we're saturated with (positively allosterically modulated AMPA) receptors here.

 

Effects of piracetam and meclofenoxate on the brain NMDA and nicotinic receptors in mice with different exploratory efficacy in the cross maze test
A population of outbred mice of the ICR strain was divided into two subpopulations according to their high (EH mice) or low (EL mice) exploratory efficacy in the closed cross maze test. In addition, the EH and EL mice differed in the number of binding sites of (i) [G-3H]-MK-801 with NMDA receptors from hippocampus and (ii) [G-3H]-nicotine with nicotine cholinoreceptors (nACh) from neocortex. A subchronic administration of the cognition enhancer piracetam (200 mg/kg, once per day for 5 days) increased by 70% the number of binding sites of NMDA receptors in the EL mice. At the same time, this treatment decreased the density of neocortical nACh receptors in both EL and EH mice (by 55% and 40%, respectively). A subchronic administration of the cognition enhancer and anti-oxidant meclofenoxate (100 mg/kg, once per day for 5 days) also decreased the density of neocortical nACh receptors in both EL and EH mice (by 48% and 20%, respectively). However, meclofenoxate also increased by 41% the number of binding sites of NMDA receptors in the EH mice.

 

The anti-dementia drug nefiracetam facilitates hippocampal synaptic transmission by functionally targeting presynaptic nicotinic ACh receptors.
Nefiracetam, a pyrrolidone derivative developed as an anti-dementia drug, persistently potentiated currents through neuronal nicotinic acetylcholine (ACh) receptors (alpha7, alpha4beta2) expressed in Xenopus oocytes, and the potentiation was blocked by either the selective protein kinase C (PKC) inhibitors, GF109203X and staurosporine, or co-expressed active PKC inhibitor peptide. In primary cultures of rat hippocampal neurons, nefiracetam increased the rate of nicotine-sensitive miniature excitatory postsynaptic currents, without affecting the amplitude, and the increase was inhibited by GF109203X. In addition, the drug caused a marked increase in the glutamate release from electrically stimulated guinea pig hippocampal slices, and the effect was abolished by the nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. Nefiracetam induced a long-lasting facilitation of synaptic transmission in both the CA1 area and the dentate gyrus of rat hippocampal slices, and the facilitation was inhibited by alpha-bungarotoxin and mecamylamine. Such facilitatory action was still found in the hippocampus with selective cholinergic denervation. The results of the present study, thus, suggest that nefiracetam enhances activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals [long term → possible downregulation], and then leading to a sustained facilitation of hippocampal neurotransmission. This may represent a cellular mechanism underlying the cognition-enhancing action of nefiracetam. The results also provide the possibility that nefiracetam could be developed as a promising therapeutic drug for senile dementia or Alzheimer's disease.

 

Presynaptic NMDA receptor mechanisms for enhancing spontaneous neurotransmitter release [again chance of DR].
NMDA receptors (NMDARs) are required for experience-driven plasticity during formative periods of brain development and are critical for neurotransmission throughout postnatal life. Most NMDAR functions have been ascribed to postsynaptic sites of action, but there is now an appreciation that presynaptic NMDARs (preNMDARs) can modulate neurotransmitter release in many brain regions, including the neocortex. Despite these advances, the cellular mechanisms by which preNMDARs can affect neurotransmitter release are largely unknown. Here we interrogated preNMDAR functions pharmacologically to determine how these receptors promote spontaneous neurotransmitter release in mouse primary visual cortex. Our results provide three new insights into the mechanisms by which preNMDARs can function. First, preNMDARs can enhance spontaneous neurotransmitter release tonically with minimal extracellular Ca(2+) or with major sources of intracellular Ca(2+) blocked. Second, lowering extracellular Na(+) levels reduces the contribution of preNMDARs to spontaneous transmitter release significantly. Third, preNMDAR enhance transmitter release in part through protein kinase C signaling. These data demonstrate that preNMDARs can act through novel pathways to promote neurotransmitter release in the absence of action potentials.