Effects - Tramadol vs Tramadol w/apap

[Adultswimmer]

If this has been answered in another thread, I apologize; I was not able to find what I was looking for.As a long time opiate user, AFOAF said that Tramadol w/apap gave a much more intense euphoria than Tramadol without apap, though the dosage amounts were similar, as were all other factors except the date. I should mention that AFOAF takes brand names and had injested hydrocodone some 4 hours prior with each type of Tramadol. This is not the first time SWIM has said the same thing but I am having a hard time understanding why. Is there an explanation to this or is it a perception only? (of course perception is everything)

[Gradient]

Adultswimmer,

Tramadol with APAP should be no more euphoric than Tramadol without. APAP is another name for acetaminophen, or Tylenol. In fact, the presence of acetaminophen in the tablets limits the amount that one might consider ingesting due to potential liver toxicity at higher doses (4000mg max recommended in one day). Most individuals favor performing cold-water-extractions (CWE) to remove this very compound from other pharmaceutical opioid preparations (I'm not sure such a proceedure would be successful with Tramadol, however).

I feel that you're right - can only be perception in this case. My guess is that the individual may have done something prior to the particularly euphoric experience that may have potentiated the effects of Tramadol. Acetaminophen has absolutely no recreational value whatsoever.

[Master_Khan]

Originally Posted by Gradient

Acetaminophen has absolutely no recreational value whatsoever.

By itself yes; but isn't it a 'potentiator' ?

[Gradient]

Master_Khan,

There are indeed anecdotal sources suggesting that acetaminophen might enhance the subjective effects of some opiates. There is no reason to believe this would occur at the neural level, however - acetaminophen has no activity at the µ-opioid receptor, and therefore wouldn't potentiate Tramadol's action at the receptor that confers euphoria. Acetaminophen is a COX enzyme inhibitor (enzyme largely responsible for inflammation and fever), which serves as an anti-inflammatory agent.
However, as Adultswimmer suggested, perception is critical when characterizing an experience with any given compound. If one experiences minor alleviation of aches and pains by the additional disparate action of acetaminophen, one may indeed experience 'potentiation'. This is distinct from, say, ingesting cytochrome inhibitors to decrease the degradation of opioids in the body by liver enzymes - this directly enhances the activity of opioids at the µ-opioid receptor, thereby potentiating the euphoric effects.

In sum, compared to other known methods of potentiating the euphoric component of the effects of opiates, acetaminophen (or APAP) should not be considered to be a desirable or effective option due to the potential for liver toxicity. There are far more effective ways to enhance the effects of opiates, most of which have an extremely friendly side-effect profile (grapefruit juice, cimetidine, anti-histamines).

Master_Khan, are you familiar with any individuals who can attest to the efficacy of acetaminophen as a potentiating agent for opiates? I can't find any actual data regarding any potential interaction of opioids and the COX enzyme, so there could indeed be a significant interaction that isn't obvious.

Reputation Comments on this post:

That is just an excellent response, very helpful!

[honourableone]

Never mind

[jon-q]

Your friend could well be speaking the truth; Acetaminophen/APAP and Ibuprofen are often added to various opioids/opiates to increase their analgesic qualities, the effect is called “Drug Synergy” Simply defined, it means that the whole is greater than the sum of it’s parts. Tramadol/APAP drug synergy is often used to good effect in terms of pain relief, and may give slightly increased euphoria.
APAP can be harmful when taken in high doses or when small doses are taken over extended periods of time, It’s debatable whether or not the benefits one would get from Tramadol/APAP drug synergy will outweigh the potential risks.
Q

[Gradient]

Originally Posted by jon-q

Tramadol/APAP drug synergy is often used to good effect in terms of pain relief, and may give slightly increased euphoria.
Q

jon-q,

Out of curiosity, are you suggesting that there may be a chemical interaction between the two compounds that may induce increased euphoria? I believe that the use of the general phrase, drug synergy, describes the combination's increased efficacy at relieving pain and inflammation specifically, rather than inducing increased euphoria (since that isn't the proposed use for Ultram, or most other opiate medications). This is likely why Tramadol (w/o acetaminophen) is sometimes prescribed for depression/opiate withdrawal while Ultram is generally reserved for moderate pain management.

If you were basically asserting that the combination may result in increased euphoria due to the fact that acetaminophen will simply operate to relieve pain - and that makes most people happy in general - then that's what I was trying to get at with this (my apologies if I was unclear!):

Originally Posted by Gradient

However, as Adultswimmer suggested, perception is critical when characterizing an experience with any given compound. If one experiences minor alleviation of aches and pains by the additional disparate action of acetaminophen, one may indeed experience 'potentiation'. This is distinct from, say, ingesting cytochrome inhibitors to decrease the degradation of opioids in the body by liver enzymes - this directly enhances the activity of opioids at the µ-opioid receptor, thereby potentiating the euphoric effects.

I think it might be important to keep in mind that acetaminophen is often added to preparations of compounds that are commonly used recreationally to discourage recreational use. Here's a quote I pulled from wikianswers (not definitive, obviously) on the subject regarding acetaminophen in oxycodone preparations:

"Acetaminophen is a non-narcotic analgesic pain killer, which is found in many different over-the-counter (OTC) medications like Tylenol. Acetaminophen is often combined with low-strength narcotic opiate/opioid painkillers such as Lortab, Percocet, Endocet, ect. It is usually added to these medications to add to the pain relieving effects, and to discourage recreational drug abuse. In high doses, acetaminophen is highly toxic to the liver and can cause liver damage or failure. Due to this, taking large doses of such combination medications is VERY dangerous and potentially fatal. If one insists upon abusing such drugs, there are methods to separate the acetaminophen from the oxycodone-hcl, but I will not discuss this because I do NOT condone drug abuse. On most prescription bottles for these combination medications (oxycodone-hcl with acetaminophen), you will see the letters APAP. This indicates the presence of acetaminophen in the medication."

Hope this helps!

[Master_Khan]

Thankyou for your insightful response gradient. I think you hit it on the head when you said that the relief of pain could be the juice. Swim takes opies for pain but no denying the pleasure. It's OK to feel OK!

[jon-q]

Quote:
Originally Posted by jon-q
Tramadol/APAP drug synergy is often used to good effect in terms of pain relief, and may give slightly increased euphoria.
Q

jon-q,

Out of curiosity, are you suggesting that there may be a chemical interaction between the two compounds that may induce increased euphoria?

I think we may have gotten some of our wires crossed. No Gradient, I’m not suggesting there’s a chemically based reaction between Tramadol or Opiates/Opioids and APAP/NSAID.

Firstly Swim isn’t advising anybody to try and potentiate Tramadol with APAP or any type of NSAID, let’s be clear about that.


Pains in general will divert/reduce any “High-like” effects, so it stands to reason anything that effectively reduces pain may help increase any euphoric effects.
Various studies have shown and support the existence of “Drug Synergy” in terms of pain relief. For example, Codeine, Dihydrocodeine, Hydrocodone, Oxycodone and various other Opioid/Opiate based drugs including Tramadol show markedly increased analgesic qualities when combined with NSAID/APAP. I’m not suggesting this will automatically increase euphoria in the same manner; I simply suggested that it might be possible? I accept it’s also possible any feelings of euphoria might also be reduced; the truth is that despite scientists knowing of this phenomenon for over 30yrs there appears to be very little research in to the actual cause and effects.
Medically speaking drug synergy is used to lower the amount of opiate/opioids needed to produce an equivalent degree of analgesia, if you’re suggesting this doesn’t exist? Then I’m afraid I am going to disagree with you on that.

How effectively euphoria is increased is something we can debate, it’s doubtful any significant increase will be achieved especially in the case of Tramadol, hence my original quote “MAY slightly increase euphoria”.

BTW sorry for the delay Gradient.
Q

This paper may shed some more light on the subject.

Selective potentiation of opioid analgesia by nonsteroidal anti-inflammatory drugs: Departments of Pediatrics, Anesthesiology and Neurology, Laboratory of Molecular Neuropharmacology, Memorial Sloan Kettering Cancer Center


Article outline}

Opioids are often used in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of moderate to severe pain. In this study we have examined interactions between these two classes of drugs. NSAIDs are inactive in the radiant heat tail-flick test, an assay of moderate to severe pain in which opioids are effective. In this assay, ibuprofen potentiated the analgesic actions of hydrocodone and oxycodone, shifting their ED50 values by 2.5-fold and 4.6-fold despite its inactivity when given alone. These opioid/NSAID interactions were dependent upon both the opioid and the NSAID. Neither aspirin nor ketorolac influenced hydrocodone actions in this model and ibuprofen did not potentiate fentanyl or morphine analgesia. Together, these studies demonstrate potent interactions between selected combinations of opioids and NSAIDS and may help explain the clinical utility of combinations.

Reputation Comments on this post:

Perfect response!

[Gradient]

Originally Posted by jon-q

Pains in general will divert/reduce any “High-like” effects, so it stands to reason anything that effectively reduces pain may help increase any euphoric effects.
Various studies have shown and support the existence of “Drug Synergy” in terms of pain relief. For example, Codeine, Dihydrocodeine, Hydrocodone, Oxycodone and various other Opioid/Opiate based drugs including Tramadol show markedly increased analgesic qualities when combined with NSAID/APAP. I’m not suggesting this will automatically increase euphoria in the same manner; I simply suggested that it might be possible? I accept it’s also possible any feelings of euphoria might also be reduced; the truth is that despite scientists knowing of this phenomenon for over 30yrs there appears to be very little research in to the actual cause and effects.
Medically speaking drug synergy is used to lower the amount of opiate/opioids needed to produce an equivalent degree of analgesia, if you’re suggesting this doesn’t exist? Then I’m afraid I am going to disagree with you on that.

jon-q,

I think we're in firm agreement here . Thanks for that comprehensive clarification. I think you're absolutely correct, and thanks for that quote - it sums up the intended interaction between the two compounds quite nicely.

[Content]

The issue with Tamadol/APAP usually is that it is in something around 35 tramadol/350-650 apap so its not a very good dose