Possible Grapefruit Juice Potential for Greater Tramadol Experience

[DrMuffy]

Grapefruit Juice Potential for Greater Tramadol Experience

SWIdr recently did a little research on the effects of grapefruit juice on tramadol. It seems that a tramadol experience (potentiated by grapefruit juice) can be much more stronger based on some people's (including himself) experiences. So SWIdr decided to see if there was anything relating grapefruit juice (directly and or indirectly) to the tramadol experience. He is not very educated when it comes to the termonology of pharmacology and such, so he apologizes if he uses terms incorectly and or contradicts himself. SWIdr very much welcomes: Corrections, additional information, and replies to his findings.

The following exerpt is talking about codeine and tramadol:
“Both agents are prodrugs; that is, the parent compound is essentially devoid of analgesic activity but the active demethylated metabolites—morphine in the case of codeine and O-demethyl tramadol in the case of tramadol—are responsible for the analgesic activity.”
source- http://jada.ada.org/cgi/content/full/135/3/298

"(+/-)-Tramadol is a synthetic analogue of codeine. It is a central analgesic with a low affinity for opioid receptors. Its selectivity for mu receptors has recently been demonstrated, and the M1 metabolite of tramadol, produced by liver O-demethylation, shows a higher affinity for opioid receptors than the parent drug. The rate of production of this M1 derivative (O-demethyl tramadol), is influenced by a polymorphic isoenzyme of the debrisoquine-type, cytochrome P450 2D6 (CYP2D6)."
source- http://opioids.com/tramadol/index.html

-SWIdr’s Notes: Grapefruit Juice has been known to interfere with the metabolism of codeine and a lot of other drug’s. Grapefruit juice works mainly on the P450 cytochromes and can tie up the liver. It seems that some people do not metabolize tramadol it into its M1 active O-demethyl metabolite, which produces greater effects than other metabolites of tramadol. So grapefruit juice may help with the o-demethylation of tramadol, which would explain the greater effects for users of tramadol who potentate it with grapefruit juice.

“With prodrugs like codeine and tramadol, people who metabolize them poorly exhibit little analgesic activity with the intake of these drugs because they do not form the necessary active metabolites, while people who metabolize them extensively readily form the active metabolites and exhibit significant analgesia.”
source- http://jada.ada.org/cgi/content/full/135/3/298

-SWIdr’s Note: This is why some can feel the (recreational) effects of tramadol, while some do not, since their livers metabolize poorly and cannot create O-demethyl tramadol, which is its M1 metabolite.

SWIdr's Conclusion- Grapefruit juice does seem to help with tramadol experiences one way or another. According to the information SWIdr found: grapefruit juice plays an important potentiating factor by helping with the metabolism. Besides helping the experience last longer and such, it seems to help with the o-demethylation of tramadol, which creates a stronger experience. Again SWIdr welcomes: Corrections, additional information, and replies to his findings and or sources.

Reputation Comments on this post:

	Good intelligent research. Great member.
	A little late, but very good post!
	Good, informative post

[RTR]

Swin knows this isn't grapefruit juice, but Smin had 300mg of Tramadol around 10:30am and was really nice. At 5:00pm, the buzz was gone and Swim still had some pain relief. Swim Decided to drink some Arizona Raspberry Iced Tea and in a couple minutes a buzz started to kick in and lasted for about 40 minutes. Swim would like it if swiys would also try this tea with their Tramadol.

[DrMuffy]

SWIdr will most definatly try to test out this experiment SWIY talks about. Meanwhile he has been testing out tramadol doses with and without grapfruit juice. Without the juice, its definatly not as fun, but who knows, could be placebo....

[Swimster]

Swim had positive effects too. With Grapefruit-Juice. He though it was just a myth at first. But it seems to take the pre-end of the ride and turn it back into a Buzz-"Prefix", if you know what swim means. It was strange to belive at first for he.

[DrMuffy]

SWIdr tried tramadol without grapefruit juice tonight, and did NOT experience effects at the normal grapfruitjuice potentiated dose (which was 150-300mgs). He had to use 800mgs of tramadol to obtain the same opiate effects, exept there was much more Serotonin and Norepinephrine activity, which stimulated SWIdr way more than usual, which was undesirable (sp?). This experiment also compliments SWIdr's findings, but of course it could have been placebo (but he highly doubts it).

[Bajeda]

Thats a rather high dose of Tramadol, and much more risky. If swiy's tolerance is so high that he needs to use that level dose he sould consider cutting back and/or abstaining for a while.

Some files in the archive may be of interest to swiy, particularly the one documenting recreational use of Tramadol.

[DrMuffy]

Originally Posted by Bajeda

Thats a rather high dose of Tramadol, and much more risky. If swiy's tolerance is so high that he needs to use that level dose he sould consider cutting back and/or abstaining for a while.

Some files in the archive may be of interest to swiy, particularly the one documenting recreational use of Tramadol.

Thanks you so much SWIbejeda!! Theses articles were very helpful, not to mention interesing. Yes, 800 mgs of Tramadol is a very high dose, but SWIdr is trying to ween himself of of it, (and he usually takes smaller doses anyways).

[Swimster]

No joke!! Swim heard 400mg's was a 24H max, And this was the max he ever took! Seisures and other risks are real possible, even at doses as low as 200mg's!

So SwiDr. should be carefull!! Altough, Swiy has done things worse than this, like taking Tram with caffeine!(MAOI,risk of SerotoninSyndrome,Ouch!) So don't feel bad. SwiDr. should of checked out doses, first tho.(perhaps erowid).

Anyway, perhaps Placebo, tho. I heard other substances, that this rumor associated with, was a false myth.

[DrMuffy]

^^^^^^^^^
Now that would be bad, yikes!! SWIdr is pretty sure his tolerace and the effects of the grapefruit juice/tramadol are not placebo (since he has been experimenting for over 10 days now with the substance).


Yes SWIdr uses lesser doses most of the time (when using grapfruit juice), also SWIdr forgot to mention he took 1 mg of clonazepam with the second dose of tramadol to help avoid seizures (if in fact it does help). SWIdr regret this stupidly high dose, which could have ended up much worse, and will try to avoid other large doses in the future!

[Bajeda]

Originally Posted by DrMuffy

Yes SWIdr uses lesser doses most of the time (when using grapfruit juice), also SWIdr forgot to mention he took 1 mg of clonazepam with the second dose of tramadol to help avoid seizures (if in fact it does help). SWIdr regret this stupidly high dose, which could have ended up much worse, and will try to avoid other large doses in the future!

Swiy should be extra cautious with such actions as taking other substances with the Tramadol, even if it helps in some regards! Tramadol is known to be much more dangerous when taken with other CNS depressants, as you saw with the files in the archive!

Take care now, swiy doesn't want to have any problems weaning himself off Tramadol use!

[DrMuffy]

Originally Posted by Bajeda

Swiy should be extra cautious with such actions as taking other substances with the Tramadol, even if it helps in some regards! Tramadol is known to be much more dangerous when taken with other CNS depressants, as you saw with the files in the archive!

Take care now, swiy doesn't want to have any problems weaning himself off Tramadol use!

Very true!! SWIdr realized how messed up he could have been since most of those tramadol ODs involve benzos, yikes !!! Well SWIdr is going to keep doing with the lower doses of tramadol with grapefruit juice, until he slowely weens off the substance.

Warning: Doing these experiments/recreational abuse all these days in a row has created quite a tolerance and even an addiction to the substance, so if anyone elso decides to try this combo, BE CAREFUL!!!

[Bajeda]

Originally Posted by DrMuffy

Very true!! SWIdr realized how messed up he could have been since most of those tramadol ODs involve benzos, yikes !!! Well SWIdr is going to keep doing with the lower doses of tramadol with grapefruit juice, until he slowely weens off the substance.

Be sure to stay healthy and try to keep active so swiy doesn't keep the weaning process in mind too much.

Some Kava or Valerian or some other nice calming and euphoric ethno could possibly be helpful as swiy gets down to much lower doses.

[Paracelsus]

As far as I know, the enzymes responsible for O-demethylation of substances like codeine, DXM and tramadol is CYP2D6. From most circumstantial evidence it seems that grapefruit inhibits this enzyme, making the O-demethylation slower. That potentiates DXM, makes codeine weaker and should make tramadol weaker (in theory). Since grapefruit does without doubt potentiate tramadol, other mechanisms are probably responsible for the potentiation. (Please correct me if I'm wrong somewhere).

SWIMs tramadol+grapefruit experiment from last night:

SWIM drank grapefruit juice from two grapefruits over the course of an hour.

After finishing the grapefruit juice, SWIM consumes 200mg Tramadol HCl (in liquid form).

First effects were felt about 60 minutes after consumption and consisted of warmness, some itching and some sedation.

After another hour, the experience gets more and more intoxicating and sedating. ~ 30 minutes later, SWIM decides to take a nap.

SWIM didn't really fall asleep, but didn't stay awake either. He just lay on his bed with eyes closed, and he thinks he dreamt a little (he can't remeber what). It was strange, SWIM was semi-conscious, not being able to decide of he was just thinking about something or dreaming about it.

After some 45 minutes, SWIM forced himself to get out of the bed and stay awake. The itching got quite uncomfortable, but it was no big deal.

After 30 minutes, the tiredness overwhelmed SWIM and he decided to go to bed. The tramadol was still acting quite powerful, so SWIM put himself into a lateral position (to prevent choking on vomit - better safe than sorry/dead) and slowly faded into that familiar dreamlike state. The bad thing was that SWIM was getting tired, but not able to fall asleep.

SWIM spent half the night in that dreamy state, but he was getting bored of it and trying to get some sleep, but it wouldn't come until about 4-5 AM (GMT+2.00). And SWIM had to wake up at 06.30.

Mild pain relief was still noticeable 15 hours after consumption.

Maybe SWIM will try a herbal downer to help him sleep next time. If there's gonna be a next time.

[DrMuffy]

^^^^^^^^^
Yeah SWIdr kinda got confused with th whole O-demethylation part, but knew that grapefruit (usually speeds thing up, so he just kinda conclued that it worked on hat liver process also. This experience was a good exemple of either a placebo effect (doubt it) or a real emaple of grapefruit juice potentiating Tramadol (somehow)......Say, in't DXM a (distant) member of the opiate family, so maybe it could be some molecular structers had th same OH group or something else....(SWIdr doesn't know his termonolgy of pharmacology and mplecules, so please excise him for mis9information).

[Swimster]

The bad thing was that SWIM was getting tired, but not able to fall asleep.

This is Extremely common! Swim believes that the end part(which lasts like 8hrs or so depending on dose), is the comedown part, in which, at first seems pleasant(unusually), but gets exsausting after say around 5 hours! Anyway, it can seem hallucigenic, or something similar, when trying to sleep, and almost impossible. <i>Note:by "Hallucigenic", swim is not comparing to any real hallucinations, but rather a sort of ironic weirdness.

[DrMuffy]

^^^^^
Yes many people experience these side effects of Tramadol, but other's dont. (According to erowid): the onset is about 15 minutes, it "coming up" part can differ from person to person, but it usully last anywher from 15 minutes to an hour, the plateau can last from 2-8 hours, and the comedown is about 5 hours.
SWIdr doesn't have the effect mentioned above, but of course he does also take Soma and Xanax with his Tramadol sometimes, so those could explein it. Also the half life of tramadol is about 8 hours or so, so when it leaves your system, so do most of the good/bad parts, which would leave one in a semi-depressed state (it acts on the Serotonin and Norepinephrine receptors too), but the effects of the Serotonin and Norepinephrine may still keep one slightly stimulated.

[delphinen]

Tramadol binds to opiate receptors in 15 to 30 minutes after ingestion. After 2 to 3 hours, it gets metabolized to the lovely O-demethyl, which binds too far more to opiate receptors than Tramadol, and its also too much stronger.

[Nicaine]

SWIM thinks a carefully planned dosing regimen could be far more effective than grapefruit juice, although the two methods could of course be combined. He actually started experimenting with this yesterday, but cut it short when his kratom arrived. It did seem to be working very well for the short time he tried it.

(1) Take 50mg of Tramadol.
(2) Take another 50mg 1 1/2 hours later.
(3) Take another 50mg 2 hours later, and continue taking 50mg ever 2 hours until the desired effect is reached. One should not exceed the daily 400mg limit.

This is based on the fact that the parent drug has a half life of ~5 hours, and the active metabolite 9+ hours. IMO the worst method would be to take a large loading dose... the best would be to dose small/often and allow the active metabolite to build up in the bloodstream, while giving the parent drug time to clear.

[Psych0naut]

Originally Posted by Swimster

This is Extremely common! Swim believes that the end part(which lasts like 8hrs or so depending on dose), is the comedown part, in which, at first seems pleasant(unusually), but gets exsausting after say around 5 hours! Anyway, it can seem hallucigenic, or something similar, when trying to sleep, and almost impossible. <i>Note:by "Hallucigenic", swim is not comparing to any real hallucinations, but rather a sort of ironic weirdness.

I think what SWIY is describing is what is called the nod. A state where one is half asleep and drifting through weird dreams, but still half awake as well. This happens with all opiates and opioids in high doses, SWIM has experienced this with tramadol and opioids as well.

[Paracelsus]

In SWIMs experience with tramadol, the nod came before the comedown part (wanting to sleep but not being able to). Also, SWIM has found this comedown to be unique to tramadol, not occuring with other opiates. But SWIMs experience with opiates is limited (opium, codeine, DHC, tramadol)

[Swimster]

Originally Posted by Paracelsus

In SWIMs experience with tramadol, the nod came before the comedown part (wanting to sleep but not being able to). Also, SWIM has found this comedown to be unique to tramadol, not occuring with other opiates. But SWIMs experience with opiates is limited (opium, codeine, DHC, tramadol)

For swim, he is mildly stimulated on the rise, but when he starts to come-down with the tired like effect, he nods.

Also, SWIM has found this comedown to be unique to tramadol, not occuring with other opiates.

Well some people hardly even consider Tramadol to be an opiate[tramadol only has some of the common opiate characteristics].

[monkeygone2heaven]

swim is confused. if tramadol is related to codeine, and grapefruit juice is supposed to actually decrease codeine potentiation (as swim gathered from the opiate potentiation thread it's good for other opiates, bad for codeine)... does it still work with tramadol?

[Swimster]

^^well this topic go's a little more into biology[enzymes and stuff]

[Paracelsus]

Originally Posted by monkeygone2heaven

swim is confused. if tramadol is related to codeine, and grapefruit juice is supposed to actually decrease codeine potentiation (as swim gathered from the opiate potentiation thread it's good for other opiates, bad for codeine)... does it still work with tramadol?

I don't know how it works, but SWIM knows the potentiation of tramadol with grapefruit isn't just a placebo effect. And SWIM is immune to placebo.

[Bajeda]

Originally Posted by Paracelsus

And SWIM is immune to placebo.

I seriously doubt that anyone is completely immune to placebo. If you are aware of what you are doing and approach new combinations or substances that hold promise a bit incredulously I think there is a lesser chance of encountering the placebo effect. I still don't think you can discount it entirely though.

Anyways, on to swim's report....




Swim currently weighs one hundred and sixty pounds. He had been using Tramadol fairly regularly for about a month but took a break recently so he has little to no tolerance, and the SSRI effects should have worn off in the meantime. The diminished tolerance swim has may make it more difficult to evaluate the specific impact of grapefruit juice potentiation on the Tramadol experience, but he feels that his memory of previous Tramadol experiences without tolerance is good enough to allow for some judgement. Swim also wanted to smoke cannabis throughout the experiment, so that could throw him off a bit, but he has smoked cannabis on un-potentiated Tramadol before so he may be able to notice a difference between the effects.


12:30... Swim ingested 150mg 'Tamolan' generic Tramadol along with 350ml of grapefruit juice. Grapefruit juice isn't really swim's thing, so his stomach felt queasy after drinking the glass.

12:50... Swim begins eating a nice plate of pasta for lunch. He wanted to have a beer with the meal but thought he better not.

13:15... Swim is feeling good all-around. The mood lift is much more prominent than swim remembers from before, as is the body buzz. Things are looking good.

13:40... Swim starts to smoke a fat hash-filled joint. After only a few puffs all the jitters from the Tramadol disappear.

13:55... Swim has finished smoking. He feels a very mellow yet trippy high. Not really any anxiety or rapid tangential thought processes to fend off. Sensory perceptions are heightened more than they usually would be from just smoking cannabis by itself.

14:15... Swim took a shower. Afterwards he need some water to quench his thirst, as he feels a bit 'heated'. He is still very cheery and basking in euphoria, though his mental state has calmed considerably as he turned off the music to help him chill out.

14:45... Swim is debating whether or not to take another 50mg of Tramadol. I think he will wait a bit and decide then. Swim is feeling very 'up' and happy right now, and his body is light and full of energy. Cognition is slowed somewhat, but swim is more able to focus on single trains of thought better than when he smokes cannabis alone or with a bit of tramadol normally.

14:55... Now swim is chatting with himself in the chat room. This is interesting... He is having too much fun to really think about it though, his mind is pretty erratic at the moment, but he is still very cheerful.

15:05... Swim takes another 50mg with only a swig of grapefruit juice.

15:10... Swim could really go out and dance at this point. Instead, he cranks up the music and just goes nuts in his room. This feels almost like a good first plateau DXM trip, except less trippy as the cannabis high is wearing off. Swim is very euphoric, giddy, energetic, almost speedy.

15:20... There is a greatly enhanced level of auditory input for swim. It makes him want to smoke sinicuichi to add to it and maybe distort the hearing more. This is great for music though, at the moment it sounds even better than when swim is stoned. Swim feels he may want to smoke another joint soon though, as the previous high isn't as strong and he is getting a bit on the speedy and jittery side.

17:35... Swim smoked another moderately sized joint. He is feeling a heavy stoning effect and is tripped out, though he is still experiencing a good deal of euphoria. Some slight visual distortions, such as when he looks at paintings and his vision is a bit fuzzy so he sees movement. Nothing especially intense, but still cool nonetheless. Swim's mind doesn't feel as clouded, though its difficult to perform some not too complicated tasks, and swim's motor-control isn't functioning at its best!

18:50... Swim washed down another 50mg Tramadol with some grapefruit juice. He is feeling a bit jittery, but pretty good on the whole. Swim is feeling heated again, but its most likely due to the air conditioning being off at the moment.

20:15... Swim smoked another medium size joint. He is feeling less trippy effects this time around, but pleasant euphoria and mellowness. Swim made a mixed drink with about two shots or so of alcohol. He isn't going to go over that amount, and knows mixing alcohol with Tramadol is an additional risk. He wants to see how the alcohol synergizes with the potentiated Tramadol and cannabis. Swim waited until this point as he doesn't feel the very strong effects he was feeling earlier, but still fairly pleasant ones.

20:50... Swim feels 'weighty' in the limbs. If he stops concentrating on anything its like he goes directly in a Zen state. Great euphoria and level mindset shortly after finishing the drink. Very enjoyable.

22:00... Smoked another joint. Swim is feeling very blazed right now. There is still euphoria present, but the energy is a bit lacking by this time. Swim is trying to concentrate on something, so we'll see how that goes.

23:10... Swim was nodding off a bit, though he has stopped now. Cognition is still not functioning at optimal levels. Should be time to try and go to sleep soon.

1:00... Swim is very level headed now. Not much in the way of noticeable effects, though swim can't say he noticed an obvious come-down period of any related effects. Rather, he is in the process of a nice smooth, gradual decline. Time is passing by very slowly. Swim could go to sleep if he wanted, but he is going to listen to a little soothing music first so he can appreciate it in his current state before he tires enough to really want to sleep.

10:00... Swim ended up sleeping in a bit more than he wanted. He woked up feeling groggy and a little dehydrated. Tiny bit of a headache.

10:30... Swim ate breakfast and drank some coffee. He is bright and energized again. No euphoria really, but it feels as though there are some lingering Tramadol effects. He is good to go about his day.




Swim tried the Tramadol + grapefruit juice potentiator combo the next day as well, though without all the cannabis consumption. He would definitely agree that the effects stretch out and last longer when Tramadol is consumed with grapefruit juice, though its harder for him to directly evaluate any changes in potency or other effects. I do believe he was much more energized than normal though, especially when he added cannabis to the mix. It was a very nice high, and I think if swim takes tramadol and grapefruit juice again he will also smoke cannabis, as it took the edge off the more irritable effects and produced some interesting synergy as well.

The alcohol mixed nicely as well, but left swim a bit hungover the next day, and probably contributed a good deal to his dehydration as well. Swim only drank two shots, and he was propelled upwards quite a bit. Before swim has mixed Tramadol and alcohol (stupidly at that time) to a greater extent but didn't get the very euphoric effect he got with the two shots on the grapefruit potentiated Tramadol. I don't think swim would venture to try alcohol with Tramadol again, especially if it were potentiated by grapefruit juice, as the potential for pleasure isn't worth the annoying side effects and dangers involved.