# Article: Could Acetaminophen Ease Social Anxiety?



## LostPancake (Apr 8, 2009)

this is pretty interesting. maybe it would be good to carry around some painkillers - if you get rejected, take a pill. it would probably reduce some of the learned anxiety, as the pain is probably what wires the amygdala to fear similar situations in the future.



> Could Acetaminophen Ease Social Anxiety?
> 
> Could a drug designed to reduce physical pain take the edge off social rejection? A study due to be published in Psychological Science says that physical and social pain appear to overlap in the brain. Acetaminophen, the active ingredient in Tylenol, appears to relieve social pain as well as physical ailments.
> 
> ...


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## korey (Apr 25, 2006)

I used to get awfully contorted and tense during social situations, and it became seriously problematic for my back after a while - so much so that my psych switched me from Xanax to Valium at one point so I could benefit from Valium's muscle relaxant effects in addition to its antianxiety effects. I still sometimes get very tense in social situations (ie grocery store), but now it's due more to frustration than anxiety. When I catch myself tensing up, I can make myself physically relax in seconds thanks to some of the stuff I've learned through progressive relaxation. I only need to take Tylenol now for headaches and body aches due to physical exertion, lol.


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## Vini Vidi Vici (Jul 4, 2009)

LostPancake said:


> this is pretty interesting. maybe it would be good to carry around some painkillers - if you get rejected, take a pill. it would probably reduce some of the learned anxiety, as the pain is probably what wires the amygdala to fear similar situations in the future.


makes sense....acetaminophen i think either inhibits the reuptake, or inhibits the degredation of anandamide, and endogenous cannabinoid in the brain. Andandamide functions similarly to THC, .....knockout mice engineered without Cannabinoid receptors show increased social fear in response to rejection, and a decreased ability to tolerate rejection and adjust to negative events, such as painful stimuli, ect...therfore, rasing anandamide would cause a benefit to such individuals/mice


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## Vini Vidi Vici (Jul 4, 2009)

> Endocannabinoids mediate anxiolytic-like effect of acetaminophen via CB1 receptors
> 
> Acetaminophen (Paracetamol), a most commonly used antipyretic/analgesic agent, is metabolized to AM404 (N-arachidonoylphenolamine) that inhibits uptake and degradation of anandamide which is reported to mediate the analgesic action of acetaminophen via CB1 receptor. AM404 and anandamide are also reported to produce anxiolytic-like behavior. In view of the implication of endocannabinoids in the effect of acetaminophen, we contemplated that acetaminophen may have anxiolytic-like effect. Therefore, this possibility was tested by observing the effects of various doses of acetaminophen in mice on anxiety-related indices of Vogel conflict test and social interaction test. The results from both the tests indicated that acetaminophen (50,100, or 200 mg/kg, i.p.) or anandamide (10 or 20 μg/mouse, i.c.v.) dose dependently elicited anxiolytic-like effect, that was comparable to diazepam (2 mg/kg, i.p.). Moreover, co-administration of sub-effective dose of acetaminophen (25 mg/kg, i.p.) and anandamide (5 μg/mouse, i.c.v) produced similar anxiolytic effect. Further, pre-treatment with AM251 (a CB1 receptor antagonist; 1 mg/kg, i.p.) antagonized the effects of acetaminophen and anandamide with no per se effect at 1 mg/kg dose, while anxiogenic effect was evident at a higher dose (5 mg/kg, i.p.). None of the treatment/s was found to induce any antinociceptive or locomotor impairment effects. In conclusion, the findings suggested that acetaminophen (50, 100, or 200 mg/kg, i.p.) exhibited dose dependent anxiolytic effect in mice and probably involved endocannabinoid-mediated mechanism in its effect.


http://cat.inist.fr/?aModele=afficheN&cpsidt=21965815


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## Vini Vidi Vici (Jul 4, 2009)

according to this study.....you would need in between 3 and 5 grams of Acetaminophen to recreate the results in a human. i dunno if that would hurt somebodys liver or not....it probably would.


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## Duke of Prunes (Jul 20, 2009)

Sounds like a first class ticket to a screwed up liver.


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## Keith (Aug 30, 2008)

Duke of Prunes said:


> Sounds like a first class ticket to a screwed up liver.


:ditto that stuff is brutal on the liver in high quantities


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## 7skulls (Jan 4, 2010)

Vini Vidi Vici said:


> http://cat.inist.fr/?aModele=afficheN&cpsidt=21965815


Hm, AM404 looks good. Definitely would like to know how to get it without intoxicating myself with acetaminophen ...


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## meyaj (Sep 5, 2009)

I think co-administration with sufficient N-Acetylcysteine could likely deal with any liver toxicity, as it would allow the glutathione supply to keep up with APAP's toxic metabolites.

Of course, I wouldn't bet on this enough to start doing it for myself, nor would I know the appropriate dosage of NAC, but it's probably something worth looking into.


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## LostPancake (Apr 8, 2009)

Vini Vidi Vici said:


> makes sense....acetaminophen i think either inhibits the reuptake, or inhibits the degredation of anandamide, and endogenous cannabinoid in the brain. Andandamide functions similarly to THC, .....knockout mice engineered without Cannabinoid receptors show increased social fear in response to rejection, and a decreased ability to tolerate rejection and adjust to negative events, such as painful stimuli, ect...therfore, rasing anandamide would cause a benefit to such individuals/mice


hmm, that's interesting - i was wondering why they were using acetaminophen instead of something else. i was thinking of trying it with ibuprofen.

so i was looking it up on wikipedia and it says it may protect against alzheimers and parkinsons also (and protect the other dopamine-producing neurons as well?).



> In some studies, ibuprofen showed superior results compared to a placebo in the prophylaxis of Alzheimer's disease, when given in low doses over a long time.[8] Further studies are needed to confirm the results before ibuprofen can be recommended for this indication.
> Ibuprofen has been associated with a lower risk of Parkinson's disease, and may delay or prevent it. Aspirin, other NSAIDs, and paracetamol had no effect on the risk for Parkinson's.[9] Further research is warranted before recommending ibuprofen for this use.
> http://en.wikipedia.org/wiki/Ibuprofen


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## UltraShy (Nov 8, 2003)

Could they try that study with something a tad more potent such as oxycodone or morphine?

I didn't see any mention of how significant the Tylenol result was. Given that it only took a mere half century to find this use for Tylenol, I'm guessing the effect isn't very potent otherwise it might have become obvious many decades ago.

Oops, I forgot the DEA loves liver failure, hates potential for drug addiction. This is hard to understand given that drug addiction, at worst, can only kill you which is what liver failure is certain to do.


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## Cedilla (Dec 25, 2009)

I was taking Vicodin 7.5/750 and Lortab 7.5/500 all of December, and most of November for pain, about 3-5 a day, and my anxiety, depression seemed much better when I was on them. When I quit them, I had some mild withdrawal, but after a few days of full body muscle aches, and runny nose, and an overall crappy mood, as well some other unpleasant side effects I feel much better than I did at the beginning of November.

I chalked up the mood uplifting effects to the Hydrocodone, because I have taken plenty of APAP in my lifetime, and it never made me feel anything, not even pain relief, although I have never taken acetaminophen for such a long period of time before.


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## UltraShy (Nov 8, 2003)

I personally don't even use Tylenol for pain because it doesn't do anything for me.


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## Cedilla (Dec 25, 2009)

For me the only OTC drugs that help with minor pain is Naproxen Sodium, and Ibuprofen.


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## jim_morrison (Aug 17, 2008)

Paracetamols (acetaminophen) most useful application is probably realistically for reducing fever, ibuprofen is probly most useful for reducing fever and also for reducing inflammation. As for pain though in general, these OTC meds probly won't do a whole lot for anything more than a mild headache.


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## BradPit (Apr 8, 2008)

_Tylenol_ 3 with Codeine would be more effective for social anxiety
or oxycodone to take the edge off social rejection

interesting http://www.ocdla.com/blog/social-anxiety-phobia-research-225#more-225


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## Vini Vidi Vici (Jul 4, 2009)

BradPit said:


> _Tylenol_ 3 with Codeine would be more effective for social anxiety
> or oxycodone to take the edge off social rejection


true dat man. codeine almost completely eliminates my Social Anxiety, 10mg makes my anxiety gone like 80%. i assume if i used it frequently tho it wouldnt be as effective.


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## pita (Jan 17, 2004)

Interesting study. Personally, I stay away from tylenol.


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## meyaj (Sep 5, 2009)

BradPit said:


> _Tylenol_ 3 with Codeine would be more effective for social anxiety
> or oxycodone to take the edge off social rejection


I assume you brought up tylenol 3 because of its combination of both an opioid AND apap. Oxycodone, though, shouldn't theoretically be any more effective at taking taking "the edge off" social rejection than any other particular opioid at an equipotent dose, although, for some people, such a dose of codeine in particular might be quite high.

In this case, maybe percocets are ideally effective (oxycodone + APAP.) But for me, oxycodone is an extremely "dirty" feeling opioid and just serves to make me irritable. I've tried a bunch of different opioids and oxycodone also seems to have the strongest impact on cognition for an equipotent (in terms of analgesia) dose. Oxycodone/percocets are a bit stronger, but in my own experience, if you wanted such a combo in a single pill for whatever reason, Vicodin is much cleaner feeling and pro-social for me. Tramadol combos would probably be a good option as well.

Though there's no real reason why, if you want the APAP, you have to settle for an opioid with a pre-dosed combination of APAP. It's very inexpensive, and allows you much greater control, to just buy tylenol to take in addition to a pure opioid. Aside from the obvious choice of buprenorphine (to mitigate tolerance and whatnot), fentanyl isn't very sedating relative to its analgesic effects, very clean feeling, and a 72-hour patch might be a preferred formulation for such a use. Hydromorphone is also, IMO, far more preferable to oxycodone for this. These are quite powerful and are highly sought after for recreational use though. But in my opinion, hydrocodone is quite a suitable enough opioid for the task anyways, and although in Canada, and I believe in the US as well, there are no pure hydrocodone products, it's typical combination with APAP might be what you desire anyways.



Vini Vidi Vici said:


> true dat man. codeine almost completely eliminates my Social Anxiety, 10mg makes my anxiety gone like 80%. i assume if i used it frequently tho it wouldnt be as effective.


10mg? Wow, I can't even really feel 60. That's one of the issues with codeine... it's a prodrug and the enzyme responsible for metabolizing it into morphine is wildly variable among different people. Responses can be difficult to predict.

10mg is quite small though. A Tylenol 3 is, everywhere that I'm aware of, 30mg, and Tylenol 3's are generally considered to be quite weak.

You can actually buy Tylenol 1's over the counter here in Canada, without any ID or anything like that. The only thing is it's literally over the counter and you have to ask the pharmacist for it, who can only give you two bottles at a time, but even then you can buy bottles with as many as 200 pills. So you can buy 400 pills at a time and always buy some more the next day, or just go to a different store... not much of a restriction, it was really only put in place to keep tourists from stocking up excessively.

Each pill contains 300mg tylenol, 15mg caffeine, and 8mg codeine per pill. They make an equivalent with aspirin instead of tylenol, and so for pain (or occasionally a little boost from the caffeine + codeine content), I'll take two of each. They're dirt cheap too.

I believe some (though not many) states also allow the sale of it over the counter. I wish 10mg dealt with my SA so effectively... I'd already have my solution and wouldn't be trying all these other drugs out if it did!


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## the chosen one (Jan 8, 2010)

you know whats weird? i actually thought about and tried this the other day and i think it might really work. i knew i was going to see someone i liked the other day and it was nervous about it so i took a few tylenol before i leftand it really did help. like someone else said if you did this alot it would probably damage your liver but as kind of a stop-gap soloution i really think this could help.


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## Vini Vidi Vici (Jul 4, 2009)

yeah it is interesting that codeine has such a strong effect on me....but so does alcohol, usually. a very small amount of it, like 3 ounces of wine, can considerably lower my social anxiety and makes me motivated/happy and want to do things. dude i really REALLY wish the US sold Tylenol 1 OTC.....but i understand why they dont, it would be abused like crazy, tonsa people would kill their livers. but anyway, codiene+caffeine+tylenol sounds like an awesome combination, saying that i already take the latter 2 quite frequently. but if i took codeine every day, im pretty sure i would get completey tolerant in 2-3 weeks, and very soon end up worse off than i was without it.


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