11 replies to this topic

[Mind_Paralysis]

So, I have been jonesing about how I seem to have found a fairly safe, side-effects free and above all - SUBTLE anxiolytic - Acetaminophen. (Tylenol, Paracetamol, Alvedon, Panadol, etc)

 

However, other than the liver strain which can be countered by limiting the dose, there seems to be some fear of long-term cognitive effects...

 

http://www.forbes.co...t-j-js-tylenol/

 

Mainly about decreased memory and cognition - BUT...! The research seems to indicate developing brains - not fully matured ones. So, what do you think guys? Is Acetaminophen debilitating for adults, or is the potential danger only in the embryonic state?'

 

As far as I can see, this is the ONLY study that came to this conclusion...? Other studies, such as this one, seems to imply that it's actually neuro-protective:

 

http://www.medscape....rticle/704809_5

 

And in closing, there's the suspicion that it simply inhibits emotion all-together:

http://neurocritic.b...blunt-your.html

 

 

[Duchykins]

Not worth the risk when other routes are available.

 

However, given the series of studies that found that tylenol reduced nonallergic histamine-mediated adverse effects from NAC, it might follow that tylenol can reduce arousal in general via this effect on histamine alone (you do need some histamine for intellectual, psychological, sexual health and overall "energy"). 

 

If this is the case, and if this is your goal, then there are safer ways to reduce histamine or block some of its effects.

[Mind_Paralysis]

Perhaps not. It is FRIGHTENINGLY CHEAP tho', and very easily obtained - and the effects seem to be immediate, in comparison to SSRI's and NRI's, which usually takes quite some time to reach any effect whatsoever.

 

I will admit, that the ratio between cost and availability is the main reason I'm interested in it.

 

I must say, that it's a rather perplexing chemical - some doses are nootropic and neuroprotective, others are quite dangerous and toxic.

 

 

I'm mainly interested in seeing if Acetaminophen can be used as a replacement for SSRI's, in treating stimulant-induced anxiety, mainly in periodic treatment, as the anxiety I get from stimulants have a rising scale, so continous anxiolytic treatment isn't really necessary - and obviously I want to replace methylphenidate with some more benign options, so my use of Acetaminophen is not intended for long-term consumption.

 

Edited by Stinkorninjor, 22 July 2015 - 11:49 PM.

[Flex]

I would say that its safe.

Just look for the differences of cigarette smoke to prenatal (embrio), adolescence and Adult stages/ages.

 

Btw: Paracetamol is a FAAH, so perhaps its anxiolytic through this (?) but I´ve forgott whether its actually bioactive, can pass the BBB &etc.

 

[Mind_Paralysis]

I would say that its safe.

Just look for the differences of cigarette smoke to prenatal (embrio), adolescence and Adult stages/ages.

 

Btw: Paracetamol is a FAAH-inhibitor, so perhaps its anxiolytic through this (?) but I´ve forgotten whether its actually bioactive, can pass the BBB &etc.

 

Interesting. It doesn't seem to be actual Acetaminophen that has this effect, but rather it seems to be one of its active metabolites:

AM404 - the metabolite that is believed to be responsible for the analgesic effect.
 

 

Earlier work on the mechanism of AM404 suggested that the inhibition of fatty acid amide hydrolase (FAAH) by AM404 was responsible for all of its attributed reuptake properties, since intracellular FAAH hydrolysis of anandamide changes the intra/extracellular anandamide equilibrium.^[3]However, this is not the case, as newer research on FAAH knockout mice has found that brain cells internalize anandamide through a selective transport mechanism which is independent of FAAH activity.^[4]This mechanism is inhibited by AM404.

 

 

Good ol' Tylenol... it keeps surprising us with undreamt of secrets, even 70 years later...

 

Anyways, here are the two studies that showed the anxiolytic effects of Acetaminophen:
 

"Acetaminophen Reduces Social Pain"

http://pss.sagepub.c...ontent/21/7/931

 

"The Common Pain of Surrealism and Death Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats"

http://pss.sagepub.c...956797612464786

 

I think the basic idea, seems to be that there is some mutual part of the processing of both emotional and physical pain, and it's through the inhibiting of this process, that Acetaminophen works.

[Mind_Paralysis]

I just noticed this brand-spanking-new study as well, which shows synergistic effects of Acetaminophen with SSRI's:

 

"Paracetamol potentiates the antidepressant-like and anticompulsive-like effects of fluoxetine." http://www.ncbi.nlm....pubmed/25340977

This quote is of perticular interest...

 

In addition, coadministration of paracetamol and fluoxetine/AM404 at subeffective doses produced synergistic effects, indicating that subthreshold doses of fluoxetine and paracetamol may enable better management in depression and obsessive-compulsive disorder comorbid patients.

 

 

It implies, that the synergistic effect may actually be quite powerful, and a combination of the two may actually be very useful in eliminating the troublesome side-effects of both... No risk of liver-toxicity, and no risk of cognitive impairment from the SSRI - the low dose could enable patients to circumvene the withdrawal symptoms with a laundry-list of strange neurological effects that going off an SSRI gives you.

[Flex]

wow nice finds.

The article: Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats

gave me a further insight how people tick, i.e. why some dont want to face something unconfortable and look, unconsciously for a more comfortable one.

 

when You´ve mentioned the emotions, I´ve remebered this:

 

Tylenol May Blunt Emotions, and Not Just Pain

http://well.blogs.ny...just-pain/?_r=0

 

Compared with those who took the placebo, those who took Tylenol were about 20 percent less likely to rate images as extremely pleasant and 10 percent less likely to rate them extremely unpleasant.

Although the mechanisms remain unclear, previous research suggests that Tylenol reduces pain by acting on the insula, a part of the brain that, among other functions, influences social emotions.

 

I´ve read that chronic tobacco also decreases the insula activity

 

Down-regulation of amygdala and insula functional circuits by varenicline and nicotine in abstinent cigarette smokers.

http://www.ncbi.nlm....pubmed/23506999

 

Btw: be careful about SSRI induced PSSD

Found this about SSRI & cognitive impairments:

https://www.reddit.c...ive_impairment/

 

Honestly, I´m a bit sceptic that all side effects are avoidalbe by lowering the SSRI dose because, if I´m not mistaken, some effects are not depend on thze increase of Serotonine but on the SSRI molecule per se.

Will recherche my claim and update it.

Edited by Flex, 23 July 2015 - 03:53 AM.

[Mind_Paralysis]

Ey Flex, did you find that study regarding the molecular structure of SSRI's? Sounds fairly interesting, if that is the case.

 

My theory about reducing the side-effects is simply that usually, side-effects and positive effects go hand in hand - but as far as I can see, Tylenol is merely synergistic with SSRI's through a completely different path-way.

It should hold some water then.

[Junk Master]

Very interesting.  What do you guys think of the hepatotoxicity of Tylenol, especially in those who drink moderately?  Is it overstated?  Would milk thistle negate some of the risk?

[Flex]

cant say much but Tylenol is used for suicide, so..

"fun fact": the death comes ~3 days after the liver is killed

 

If You dont get any answers, You could ask it on ask-a-doc on reddit

[Mind_Paralysis]

Not sure about that hepatoxicity - we do know that it's the most commonly used painkiller of them all tho', and because of that simple fact, there should be a decent amount of people that accidentally drink while they're on it - yet we don't see any abnormally huge numbers of liver-related death-cases among the western population.

 

Like Flex says, I wouldn't recommend it tho' - best to be on the safe side, especially with these higher doses that we're talking here.

 

Personally I'm a teetotaller tho' - I don't smoke tobacco, marijuana, drink coffee, tee, or drink alcohol. I usually stay away from junk-food as well. I was on 50 mg Agomelatine for a while as well, and that has actually been proven to be hepatoxic as well, but I didn't notice anything, so I'm not really worried

Edited by Stinkorninjor, 04 August 2015 - 12:12 AM.

[jack black]

This is very interesting info. OP, thanks for posting this. If paracetamol indeed works on CB1 receptor, it should be synergistic to the effects of

• Epigallocatechin
• Epicatechin
• Kavain
• Yangonin

based on: https://en.wikipedia...receptor_type_1

 

next time i pop some tylenol, I'll chase it with green tea or kava extract.