Somewhat Advanced: Drugs for School

[TCMVegas]

Drugs for School

Hi all. I've read into the literature myself to some degree, but material on ACh and NMDA receptors is... dense, to say the least.

I was hoping for your help on what I'm planning to use this semester. Basically, I'm taking a difficult math course this summer; so I want to get my ass motivated, and be on top of my cognitive game! Memory is key, as is motivation...

Drug List

Bupropion 150mg:
The NE effects outweigh the DA effects 10:1 by my calculations, including all active metabolites. I've found in the past that the NE boost really gets me anxious (good for work ethic), and behaviorally more like the stereotype of the socially awkward and nervous math major who works a lot. However, bupropion is apparently an anticholinergic, being an antagonist at nicotinic ACh receptors (nAChR), but not at muscinaric ACh receptors (mAChR). Research shows that nicotine enhances memory by NAChR agonism.

SO: I'm thinking that bupropion would then indeed impair memory, and perhaps best replaced by another stimulant such as methylphenidate, due to this anticholinergic action. Is this a reasonable conclusion to draw? I don't think I'd notice if my memory got 25% worse, so better safe than sorry?


Piracetam(approx 100mg/Kg) with Choline:
Sekio posted this paper in the past, whose pubmed link has gone dead:

NSFW:

In an attempt to gain some insight into possible approaches to reducing age-related memory disturbances, aged Fischer 344 rats were administered either vehicle, choline, piracetam or a combination of choline or piracetam. [...] Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (p less than 0.05), but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. In a second study, it was shown that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated administration (1 week) of the piracetam/choline combination was superior to acute injections. Regional determinations of choline and acetylcholine revealed interesting differences between treatments and brain area. Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine levels were much more subtle (only 6-10. No significant changes following choline administration were observed in the hippocampus. However, piracetam alone markedly increased choline content in hippocampus (88 and tended to decrease acetylcholine levels (19. No measurable changes in striatum or cortex were observed following piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either drug alone, and in certain cases the effects were much less pronounced under the drug combination. [...] The results of these studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with either drug alone

There's decades of research behind the memory-enhancing effects of piracetam, caused by upregulation of NMDA receptors. Wouldn't this be expected to cause increased vulnerability to excitotoxicity? I'm not sure how NE/DA stimulants affect glutamatergic activity, butI suspect that they increase it. Shouldn't this be a serious concern? Scarily, PubMed has no results regarding piracetam and excitotoxicity.

Wikipedia on NMDA and excitotoxicity:

NSFW:

Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions[2] (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.

Nicotine gum:
Nicotine improves memory, and could potentially be used when working to counter the nAChR antagonism from bupropion? I'm sure the truth isn't so straightforward, is picking up use of nicotine gum really something advisable, ignoring addiction potential?


(This post was originally going to be a PM to Epsilon Alpha, but a PM of this size would be wholly unethical! )

 

[TCMVegas]

Sekio's previous commentary on the article above:

TL;DR.
1. Piracetam plus choline is more effective than either alone.
2. Taking piracetam/choline every day for several weeks will give better effects than taking it only once or twice.
3. Choline increases levels of choline and acetylcholine in the brain. Piracetam increases levels of choline, and decreases levels of acetylcholine (by a small amount). Combining the two results in a milder effect on neurotransmitters than either drug alone. (closer to increasing choline and keeping ACh the same)

 

[sekio]

SO: I'm thinking that bupropion would then indeed impair memory

I'm not sure nicotinic antagonists actually carry a cognitive penalty. (at least, buproprion doesn't... do people not use it as an ADD treatment?)

Scarily, PubMed has no results regarding piracetam and excitotoxicity.

I would hazard a guess that's because it's non-excitotoxic... just because a drug interacts with NMDA does not make it an excitotoxin.

Honestly, you are likely to see better results setting up an aerobic excercise regimen and micro-managing your diet (if you are the kind of person who eats Mcdonalds and drives to school) rather than playing with nootropics. More green vegetables and more oxygen to your brain is always a good idea.

Avoid the nicotine if you can. Too much potential for a messy situation where you become a regular snuff-dipper, and the short duration does not lend itself well to regular usage.

Consider caffeine as a stimulant; it is relatively physically benign and quite effective if dosed correctly. (don't eat 200mg of caffeine one day and then complain it makes you jittery)

 

[AlphaMethylPhenyl]

Reports of bupropion-induced cognitive impairment can be found all across the internet. I took 300mg for three years; when I came off it I couldn't believe my intelligence. Its used for ADD sometimes but its pretty inferior to other treatments. Seroquel is used for ADD too.

Caffeine is great. Highly recommended.

Nicotine works, perhaps better than most psycho-stimulants, but he's right (as always): short duration/addictive potential.

Exercise/diet is your best bet.

Wish Limitless wasn't just a movie.

 

[TCMVegas]

I'm not sure nicotinic antagonists actually carry a cognitive penalty. (at least, buproprion doesn't... do people not use it as an ADD treatment?)

It seems fair to conclude that if bupropion is a significant antagonist, that it should indeed cause memory impairments. Here's a couple of papers about this:

http://www.sciencedirect.com/science/article/pii/0014299995006281..

The effect of nicotine was tested on retrieval 24 h after training on a passive avoidance task. Intraperitoneal (i.p.) injection of nicotine (0.25–1.5 mg/kg) increased the step-down latency in mice dose dependently. Pretreatment with the nicotinic receptor antagonist mecamylamine (0.5–1 mg/kg) decreased, whereas pretreatment with the dopamine D1 receptor antagonist SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol maleate) (0.01, 0.05 and 0.1 mg/kg) and the β-adrenoreceptor antagonist propranolol (10 mg/kg) increased the nicotine response. The dopamine receptor D2 receptor antagonist sulpiride (5–10 mg/kg), the anti-muscarinic agent atropine (2.5–10 mg/kg), the peripheral nicotinic receptor antagonist hexamethonium (0.01–0.5 mg/kg), the α-adrenoceptor antagonist phenoxybenzamine (1 and 10 mg/kg) and the peripheral dopamine D2 receptor antagonist domperidone (5 and 10 mg/kg) did not change the response induced by nicotine. Single administration of the antagonists did not cause response; however, a high dose of domperidone (10 mg/kg) and propranolol alone increased the step-down latencies. It may be concluded that a nicotinic receptor mechanism is involved in the nicotine-induced improvement of memory retrieval.

http://onlinelibrary.wiley.com/doi/...7/08)38:3/4<188::AID-DDR7>3.0.CO;2-I/abstract

Nicotine has been found by a variety of investigators to improve memory in rats, monkeys, and humans. Recent studies have helped to determine the behavioral and pharmacological nature of critical nicotine effects on memory function. Other nicotinic agonists, including ABT-418, GTS-21, or lobeline, can also significantly improve memory performance. Conversely, nicotinic antagonists, such as mecamylamine, can impair memory. Nicotine can reverse memory impairments caused by aging or by lesions to hippocampal connections. The observation that nicotine improves memory performance when it is administered by chronic infusion is potentially important for the development of treatments of cognitive impairment. Nicotinic agonists show promise for the development of novel treatments for cognitive disorders. Some characteristics of nicotine, nicotinic receptors, and the nature of the disorders to be treated, however, present challenges to the development of nicotinic-based treatments. Drug Dev. Res. 38:188–195 © 1996 Wiley-Liss, Inc.

Avoid the nicotine if you can. Too much potential for a messy situation where you become a regular snuff-dipper, and the short duration does not lend itself well to regular usage.

I'm staying away from tobacco as a certainty, my understanding is that nicotine gum is relatively innocuous. I have noticed the addictive potential, so I do understand that risk. However, I'm not sure what you mean about the short duration being bad, seems nicer than having a 24-hour stimulant like bupropion, for example.