Grapefruit Juice Potential for Greater Tramadol ExperienceSWIdr 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.