I know from my experience APAP helps my headaches, I accidentally placebo-tested it myself when I mistook my Cimeditidine for APAP several times in my medication organizer a couple years ago.
The cimetidine I consumed entirely failed to alleviate my headaches' severity for the few months I was erroneously taking them for headaches instead of acetaminophen... Conversely, when previously I had
actually been taking APAP, my headaches' pain-levels were quite noticeably reduced.
When I went to buy more Paracetamol, under the hunch that the bottle of my generic acetaminophen was just a bad batch, I realized I opening the bottle and comparing tablets, that I had mixed up my cimetidine tablets with the similiar shaped acetaminophen tablets.
Once I returned to taking
actual acetaminophen, my headaches were once again effectively treated (not fully resolved albeit), and I could actually function at work once again when I took them at the first sign of a headache.
So, at least for headaches, they help me when a accidentally blinded-plaebo did not.
I've also found when combining APAP with Aspirin, that my headaches are even more alleviated.
I have also found Tylenol to be helpful with aches and pains - severe pain though, I imagine its not truly much help.
Though a just brief search of the journals, there are many studies that show its antinociceptive properties. There are many double blind studies on the effectiveness of APAP for different types of pain.
Additionally there innumerous rodent-tests (tail-flick tests etc) showing a non-insignificant reduction in rodent behaviors indicative of pain in rodents after being administered APAP.
But as far as APAP increasing the RECREATIONAL value of opioids... UNLIKELY:
Unless APAP is inducing liver damage, and effectively reducing your ability to metabolize oral opioids, I don't see any pharmocomechanical mechanism that would increase the narcotic properties of coadministered opioids.
Perhaps there is SOME competive inhibition of the CYP-450 cytochrome in a manner other than hepatotoxicity, but I don't see literature supporting it as a potent inhibitor of the main enzymes that are responsible for opiate metabolism.
Obviously if it were, it wouldn't be included in many Codeine preparations, as Codeine is merely a prodrug of Morphinr - i.e. Codeine is not centrally active as an opiate until it is Metabolized in the liver in Morphine.
In conclusion:
- APAP does have evidence of pain reduction via clinical and animal testing. So in that regard, perhaps its alleged NSAID effects would help with Pain relief when coadministered with opioids - but not their euphoric/opiate properties.
- APAP does not show any mechanism by which it could potentiate Opiate receptor agonism or affinity, nor does it exhibit the Cytochtlme P450 inhibitive properties, properties that would reduce the liver's first past metabolism efficiency - thus having no effect on plasma concentrations via competitive inhibition of the the relevant P450 enzymes.
- APAP is a hepatotoxin though, and liver damage will increase the potency of orally administered Opioids (excluding Codeine), so maybe this a possible mechanism for potnetiation.
The only way I feel it could really make oral opioids more recreations is somewhat a placebo effect, but I have felt first hand... I know that for the taste and "head feel" of acetaminophen (particularly on any empty stomach, and when you take the medicine simultaneously with food or drink in that GI-state) does lends itself to what some people refer to as a "body high" - and I do find that feeling/taste/sinus-sensation enjoyable in combination with orally administered opioids. Perhaps that is what people are noticing as the opioids being stronger. So perhaps that perceived pleasurable-sensation is slightly bumping-up your braind endorphins enough to potentiative the euphoric properties of opipids. But that is a lot of "IFs", and primarily a psychological effect not a pharmacological effect.
Please let me know what you think of my hypothesises here. Thanks.
