16 replies to this topic

[Raptor87]

A few days ago I took some paracetamol with a cup of coffee. After that I had better focus and I sensed a relief in my daily workload.

Does this stack elevate concentration and focusing abilities?

Do painkillers perhaps elevate blood- oxygen levels?

What can you do to elevate oxygen- levels in the brain?

[Ampa-omega]

maybe just because of pain reduction caffeine is know for that as well, it could be from reducing inflammation.

[Raptor87]

Hmm... I was thinking that maybe its the blood- pressure in the brain that gets lowered which gives a sense of relievement and indirectly reduces agitation. I was as some call it, in the zone! I was actually surprised because the effects were pretty good and I have stimulants prescribed!

[Delta Gamma]

Try looking at the chronic inflammation-cognition link on google scholar, same with the depression-inflammation link.
COX-2 inhibitors are looking more and more promising for the adjacent treatment of several neurological disorders as well as lessening cognitive impairment by them.

http://jama.ama-assn...2/18/2237.short
http://www.sciencedi...006322308008950
http://www.nature.co...ll/nrn2297.html

If you like the effects you get from NSAID's try the old 81mg of ASA a day the FDA so heavily endorses.

[Raptor87]

My mom suffers from rheumatism, could I have some element of it that impairs my cognition?

These articles were age related but Im not that old, Im only 28. What do you guys say?

And painkillers usually scare the hell out of me. Is there a safe way to treat this kind of problem?

[manic_racetam]

Paracetamol/Acetaminophen [AKA tylenol] is a non-narcotic analgesic/fever-reducer, not an NSAID. It actually isn't even an anti-inflammatory and works differently on pathways in the body than NSAID's.

If you really think the paracetamol had this effect for you then a good starting point might be this article, to get some leads on it's possible mechanisms in the body. Also make sure to stay under 1,000mgs per day, since it can cause liver damage.

[thedevinroy]

Actually I believe it in part has to do with metabolism of caffeine, xanthines in coffee, and paracetamol all being broken down by the p450 enzymes (primarily CYP1A2 from what I gather). Taking them together makes them stick in your system longer, thereby giving the caffeine more time to block more adenosine receptors, increasing dopamine levels and norepinephrine levels. Sustained release / high dose caffeine has this effect on me as well. Muscle tension, tunnel vision, and heightened anxiety.

cAMP accumulation also occurs from caffeine's PDE inhibition. At first, this thwarts the dopaminergic and noradrenergic actions in the pre-frontal cortex, but cAMP also induces tyrosine hydroxylase which will cause more dopamine and norepinephrine to counteract the signal reduction. Prolonged caffeine stimulation thus improves effects on focus given time. Hard to say if this can happen in a few days or a few weeks, so this might not be the effect from competitive metabolism.

I also believe the COX enzyme uses a tyrosine analogue, which may increase tyrosine's half-life as well. Tyrosine being a precursor of dopamine, this could be causing an effect you are experiencing. I can't tell for sure because it looks like an analogue, not true tyrosine. Perhaps the answer is in the previous conversion enzyme or perhaps this is a dead end. Perhaps this analogue (Tyr385) is also used to make dopamine or is a receptor ligand or an inhibitor of metabolism or transport. Hard to say... not knowing much about Tyr385.

Just ideas.

Edited by devinthayer, 18 October 2011 - 07:52 PM.

[thedevinroy]

The competitive enzyme inhibition gets deeper... looks like something in coffee inhibits COX-2 enzyme as well, thereby extending the half-life of Paracetamol, which extends the half-life of caffeine, which prevents paracetamol from becoming mutagenic (those darn p450 enzymes).

EDIT: http://www.ncbi.nlm....rm=COX-2 coffee

There is a lot more on coffee and the COX-2 enzyme.

Edited by devinthayer, 18 October 2011 - 08:03 PM.

[thedevinroy]

Seems the cAMP and tyrosine hydroxilase activity are pretty closely linked, and fast, within minutes. Not weeks.

http://www.brimr.org/Roskoski/61.pdf

[noos]

paracetamol
We previously showed that acetaminophen administration to rats increases forebrain serotonin levels as a result of the inhibition of liver tryptophan-2,3-dioxygenase (TDO). In this study we determined whether aspirin alone and in combination with acetaminophen could further influence brain serotonin as well as norepinephrine levels and if so whether the status of the liver TDO activity would be altered. The results show that acetaminophen alone increases brain serotonin as well as norepinephrine levels with a concomitant inhibition of liver TDO activity. In contrast, aspirin did not alter the levels of these monoamines but increased serotonin turnover in the brain while acetaminophen decreased the turnover. When combined with acetaminophen, aspirin overrides the reduced serotonin turnover induced by acetaminophen. This report demonstrates the potential of these agents to alter neurotransmitter levels in the brain.

PMID: 15214507 [PubMed - indexed for MEDLINE]


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paracetamol PARA may activate opiate receptors that in turn may increase 5-HT levels, at least in the cerebral cortex and in the pons, thus provoking an analgesic effect. Indeed, in the mechanism of action of PARA, a 5-HT-mediated antinociception is of interest because central 5-HT activation may potentiate the effect of opioids, as observed in rats (Baraldi et al., 1983) and humans (Bentley and Head, 1987). These potentially regulatory and interactive mechanisms between 5-HT and opioid transmission in nociception are supported by the finding that the analgesic effect of PARA depends on an intact 5-HT neurotransmission and is antagonized by the opioid antagonist naloxone.
http://jpet.aspetjou.../280/2/934.full

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acetylsalicylic acid and acetaminophen affect the enzymes responsible for the catabolism of tryptophan, which is a precursor for the mood elevating neurotransmitter serotonin
http://eprints.ru.ac.za/194/

Edited by noos, 18 October 2011 - 09:01 PM.

[thedevinroy]

+1 for Noos. I love you.

I always wondered why acetaminophen helped with my coffee hangovers so well... it affects SE and NE levels... plus opoid and COX-2? Wow, dog, that's a bone to the ER in the land of analgesic seduction. No wonder... so taking coffee with acetaminophen from now on to cure my head pains and give me that extra jolt. Oh, and I'm allergic to aspirin, so this might work as a nice replacement super synergy.

[Raptor87]

Interesting stuff.

Thank you for sharing the information. You guys are gold!

[rastilin]

Yeah that's really interesting. I've noticed the same effect actually and it makes my workload much easier. Though if it affects Serotonin, how dangerous would it be to to use as part of a stack?

[nupi]

I would be a bit worried in its hepatoxicity when it comes to its use in a long term stack - in fact, I pretty much refuse to take it these days for that reason. Then again, I respond well to Aspirin (which, aside of the nasty interactions it can have, seems to be actually good for you in many ways) and Ibuprofen, so no real reason not to use those.

[rastilin]

If it's just liver damage, I can take my chances. Especially if I use less than the recommended daily levels of paracetamol, enough to improve focus and get my work done; not enough to go near the daily limits and with occasional weeks of nothing to recover. I'm much more worried about possible problems arising from Serotonin issues, which is why I never touch St John's Wort and stuff like that. I'm worried there's a risk that you'll become dependent and your new baseline level will be with it in your system, so now you're back where you started and you can't get off whatever you're taking or you'll be crushingly depressed and incapable of working.

I'd like to avoid ibouproufen because I'm doing more exercise, anything that removes inflammation may also stop muscles responding to effort. No idea about aspirin though; what have you noticed from it?

[nupi]

I use it for head-aches and colds.

But it definitely has other effects, blood-thinning being the most obvious one (good for heart disease and stroke prophylaxis).

[thedevinroy]

I would be a bit worried in its hepatoxicity when it comes to its use in a long term stack - in fact, I pretty much refuse to take it these days for that reason. Then again, I respond well to Aspirin (which, aside of the nasty interactions it can have, seems to be actually good for you in many ways) and Ibuprofen, so no real reason not to use those.

Actually, caffeine competitively inhibits the enzyme that makes Paracetamol hepatoxic.