• N&PD Moderators: Skorpio

Strong potentiation of Tramadol with grapefruit juice

El_Toro

Bluelighter
Joined
Jul 23, 2006
Messages
411
Hi,

I have been using Tramadol too frequently for my liking due to its amazingly fast AD effect (I am not too keen on the opioid-like effect from the mu agonism). Anyway, having read about the metabolism of Tramadol via the different enzymes and in an attempt to boost the survival of the parent drug (tramadol) instead of the metabolising into O-desmethyltramadol, I have ingested 750 mls of white grapejuice 24 hours prior to dosing a typical dose of 200mgs. Since one of the enzymes responsible for its metabolism is CYP3A4, I wanted to see if it would work.

Well, after a typical and common dose of 200mgs on empty stomach, I am finding that Tramadol's 5HTP releasing and NE reuptake properties have been profoundly potentiated. Typically, at 2 hours post ingestion I would start feeling the conversion of tramadol into the O-desmethyl version yet I am feeling at aprox T: +2.30, with a very agitated sensation and uncomfortable head high. Jaw tension is increased as so is agitation, so much that I am fearing of seizure activity as my muscles are twitching much more than commonly with this dose. My pupils are slightly more enlarged than usual so I am wary of any serotonin toxicity (I have cyproheptadine and benzodiazepines at hand). I did once experiment with this same susbatnces but at a dose of only 100mgs of Tramadol and again, found a very strong potentiation of the parent drug.

In any case, and due to the lack of literature regarding this matter, I am reporting this and would actually like to get some discussion going on and/or feedback on this mechanism of action and Tramadol's overall AD affinity, which I find is not as much discussed as its opioid effect. I would have otherwise posted this in trip reports but would like to have an open discussion in the aforementioned topics.

Thanks
 
I would be worried about potentiating the seizure risk, while this seems like something I would like to try also I would probably take a benzo to try to reduce the risk. This isn't probably something that someone primarily after the opiod affects should do as the metabolism is nessecary for that (I think).
 
I am on Trams. I take 5x50mg instant release caps. I have always taken with grapefruit juice (fresh) sometimes It is accompanied by a nice high, sometimes not. Always relief of chronic pain syndrome but only about 25% that Fent 2.1mg gave.
Never any feeling of seizure risk at that dose even whilst undergoing strenuous activity (surfing).
Hope this contributes something.
Hari Om
edtree

Edit: There is the 'Ultimate Tramadol Discussion Thread' here:http://www.bluelight.ru/vb/showthread.php?t=409372
It seems alive but for some reason I cannot post there. Hope it helps : )
 
Last edited:
3A4 does metabolize both tramadol and O-desmethyl tramadol and a 3A4 inhibitor would be expected to potentiate both... but it's still 2D6 that does the O-demethylation AFAIK. Doesn't 3A4 demethylate that characteristic opioid tertiary amine? I dunno, maybe there was just so much potentiation the OP didn't notice the slowly building O-desmethyl action until later than normal.
 
Thought that struck me on the way back from the grocery store: if tramadol can be inactivated by N-demethylation, and O-desmethyl tramadol can be inactivated by N-demethylation and also by glucuronidation at the exposed hydroxy group, a 3A4 inhibitor really might increase the tramadol/O-des ratio.
 
After reading another thread I tried taking the grapefruit juice an hour before dropping 150mg of Trams then waited 2hr and b.d'd the other 150, had the best Tram ride ever for the whole day. Was something like just after a coke rush but for around 8 hrs! Next day was a bitch though big W.D's indeed am now trying the same thing but with 200 bd'd.
and btw grapefruit juice and b.ding the dose definitely worked for me : )
Hari Om
edtree
 
Last edited:
Top