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  #1  
Old 27-04-2009, 04:21
Gradient Gradient is offline
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Potentiating Tramadol

Tramadol is a fully-synthetic opioid pro-drug with SSNRI activity. Upon ingestion, the digestive cytochrome enzymes - the cytochrome P450 family specifically - metabolize Tramadol into five distinct compounds. O-Desmethyltramadol, one of the five, has a markedly high affinity for the -opioid receptor, far more so than Tramadol itself. The same enzymes that convert Tramadol to its 5 metabolites, cytochrome P450, ionize these metabolites for water-soluble excretion. Therefore, the metabolism of Tramadol revolves entirely around the metabolic activity of cytochrome P450 in the liver.

Cimetidine (Tagamet) is a potent inhibitor of the cytochrome P450 enzyme, in addition to acting as a pH neutralizer. Therefore, if one were to ingest cimetidine prior to ingestion of Tramadol, one would likely experience a reduction of effects. However, if one were to wait until ingested Tramadol had time to be converted to its metabolites (30-180 mins), the ionization of the metabolites of Tramadol should be inhibited. This would be expected to enhance and prolong the effects of Tramadol at the -opioid receptor considerably. In sum, in order to potentiate the effects of Tramadol with cimetidine, timing and sequence is key.
In addition, subsequent to regular administration of recommended doses of cimetidine, the liver will up-regulate the expression of the enzymes responsible for converting Tramadol to its more potent metabolites. In other words, after ingesting cimetidine for a regular interval of time, one will become more sensitive to the effects of Tramadol. It should be noted, however, that this dynamic would render an individual less sensitive to other non-synthetic and semi-synthetic opiates over time.
A friendly chimp has revealed that this has been a highly effective and reliable method of potentiation. He doesn’t ingest Tramadol without cimetidine anymore. It should be noted that grapefruit juice has indeed been noted to be a cytochrome P450 inhibitor as well, though not quite as potently as cimetidine. This method should produce no anticipated ill-effects, as the magnitude of effects will never exceed the SSNRI activity inherent to the initial dose ingested. So long as one takes care not to initially ingest too-high a dose, this method of potentiation will not enhance SSNRI activity – rather, it should selectively enhance -opioid activity because it's the metabolites, not Tramadol, that are being enhanced.

Hope this helps to get the most bang-for-your-milligram in as safe a way as possible ! Since this method of potentiation is so distinct from typical methods for the majority of other opiates, I figured it warranted a thread of its own - I apologize if this was a mistake. I'd be quite interested to know if this works for any other chimps out there.

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Added subsequent to Richard_smoker's post: I've confirmed that the CYP2D6 is indeed responsible for both the metabolism of Tramadol to its five metabolites, as well as the ionization of o-desmethyltramadol for excretion. Therefore, the described relationship is likely to exist.

Here's a quickie abstract that suggests that cimetidine does indeed inhibit the cytochrome P450 family, and CYP2D6:
http://jcp.sagepub.com/cgi/content/abstract/40/2/193

Here's another to suggest that the O-demethylation of Tramadol is done by CYP2D6:
http://www.springerlink.com/content/910gnjjd610h24pu/

Here's a surprisingly nice wikipedia entry on the metabolism of O-Desmethyltramadol, which is indeed carried out by CYP2D6:
http://en.wikipedia.org/wiki/O-Desmethyltramadol

Please let me know if any are interested in reading the full article from either of those abstracts - I'll be happy to post them up.

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However, this doesn't necessarily mean that I'm correct! There is no study on this specific interaction (including the sequencing of ingestion of the compounds). Please suggest any potential issues with this theory that we might iron out, I'd greatly appreciate it!

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Thanks for sharing this interesting information
amazing infromation, well formatted and easy to use. Thanks!
Excellent post, this is the kind of information DF is good for.

Last edited by Gradient; 03-03-2014 at 21:15. Reason: Checked on cytochrome enzyme upon Richard_smokers suggestion
  #2  
Old 27-04-2009, 04:47
Richard_smoker Richard_smoker is offline
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Re: Guide to Harmlessly Potentiating Tramadol

hmmm... you know there are several different specific subtypes of the CYP (cytochrome 450) enzyme. I can tell you a much more effective way of enhancing the drug than this approach.

Some information about which specific type of P450 enzyme breaks the tramadol down, and which one breaks down the O-Desmethyltramadol.

If there's any data out there for which enzyme breaks down the O-Desmethyl, then if that enzyme is DIFFERENT than the one which breaks down tramadol itself, then someone could presumably take a specific inhibitor of THAT p450 enzyme. this would allow the tramadol to convert into the 'better' drug which would accumulate in a hypothetical person's bloodstream because its break-down enzyme would be unavailable (cuz it's being inhibited).
  #3  
Old 27-04-2009, 04:56
Gradient Gradient is offline
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Re: Guide to Harmlessly Potentiating Tramadol

Quote:
Originally Posted by Richard_smoker View Post
hmmm... you know there are several different specific subtypes of the CYP (cytochrome 450) enzyme. I can tell you a much more effective way of enhancing the drug than this approach.

Some information about which specific type of P450 enzyme breaks the tramadol down, and which one breaks down the O-Desmethyltramadol.

If there's any data out there for which enzyme breaks down the O-Desmethyl, then if that enzyme is DIFFERENT than the one which breaks down tramadol itself, then someone could presumably take a specific inhibitor of THAT p450 enzyme. this would allow the tramadol to convert into the 'better' drug which would accumulate in a hypothetical person's bloodstream because its break-down enzyme would be unavailable (cuz it's being inhibited).
Richard_smoker,

Quite true. However, to the best of my knowledge, it is indeed the same enzyme: CYP2D6.

Here's a quickie abstract that suggests that cimetidine does indeed inhibit CYP2D6:
Quote:
Originally Posted by Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers
Systemic adverse effects of timolol ophthalmic solution given at usual therapeutic doses have been well characterized. Timolol is partially metabolized by cytochrome P450 (CYP) 2D6. Cimetidine inhibits the activity of cytochrome P450, including CYP2D6, leading to reduced systemic clearance of concomitant drugs. Coadministration of cimetidine has been speculated to affect the pharmacological effects of timolol ophthalmic solution, resulting in increased blood concentration. To evaluate whether administration of cimetidine with timolol ophthalmic solution increased the degree of beta-blockade, 12 healthy Japanese male volunteers ages 19 to 26 received cimetidine (400 mg), on oral placebo, timolol maleate 0.5% (0.05 mL to each eye), or placebo eye drops in a randomized, double-blind, Latin-square design. The oral drug alone was given for 3 days, and on the 4th day, eye drops were applied after oral drug administration. At baseline and 1, 3, and 6 hours after eye drop administration, blood pressure and heart rate (HR) were measured before and after exercise. Intraocular pressure (IOP) was measured at rest. A visual analog scale (VAS) was used to assess subjective bodily feelings in exercise tolerance after every physical exercise. The exercise HR, exercise systolic blood pressure (SBP), and resting SBP were reduced following timolol with and without cimetidine compared with the placebo (p < 0.01, respectively). Administration of cimetidine with timolol ophthalmic solution resulted in additional reductions of the resting HR and IOP. VAS detected a significant reduction in exercise tolerance from timolol ophthalmic solution (p < .05). In conclusion, administration of cimetidine with timolol ophthalmic solution increased the degree of beta-blockade.
The metabolism of O-Desmethyltramadol is indeed carried out by CYP2D6.

Therefore, cimetidine would be expected act to inhibit the metabolism of Tramadol to its metabolites if ingested first - but would act to inhibit the metabolism of its metabolites if ingested subsequently.

Last edited by Gradient; 18-12-2012 at 20:04. Reason: wikipedia link
  #4  
Old 27-04-2009, 08:41
Gradient Gradient is offline
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Re: Guide to Harmlessly Potentiating Tramadol

I'm not sure that one would need the metabolite to be ionized by the same enzyme as the pro-drug. One might consider the enzyme-substrate interactions as more of a temporal spectrum of activity - therefore, most of the Tramadol will be metabolized before the o-desmethyltramadol is able to reach phase II metabolism. This is why I think the sequencing is key.

It takes a given amount of time for all of the Tramadol to be metabolized, sure. However, given the fact that about an hour subsequent to ingestion, these enzymes have had plenty of time to perform phase I hepatic metabolism - the majority of psychoactivity derived from any given dose will be determined by the amount of Tramadol converted within that first hour of metabolism. Therefore, the rate at which o-desmethyltramadol will be ionized by CYP6D4 will hinder the effects more than the metabolism of any remaining (few molecules left) Tramadol might contribute.

I agree with your assertion that there will inevitably be some Tramadol left to be potentially converted after an hour has passed. However, the amount of o-desmethyltramadol in circulation after that first hour will likely outweigh the potential for additional o-desmethyltramadol to be generated from the remaining Tramadol after an hour has passed. In other words - I agree that there will be some remaining Tramadol that will fail to be converted to its 5 metabolites, but I believe that the enhancement of o-desmethyltramadol by inhibition of phase II hepatic CYP6D4 metabolism will serve to outweigh any potential additional metabolites from Tramadol.

I suppose one might consider it to be a question of 'do the benefits outweigh the positives?' - in this case I believe it will. Of course, if one wished to re-dose with more Tramadol, ingesting cimetidine would be quite counter-productive. However, this was a guide to potentiate Tramadol - not to get the best experience out of Tramadol (saving money, low on supply, etc...) I do, however, feel that the interaction you've brought up is indeed central to the fact that this method will not generate serotonin syndrome from a reasonable dose - there is indeed a limit as to how much o-desmethyltramadol can be generated from any given dose.

Last edited by Gradient; 01-08-2013 at 22:43.
  #5  
Old 04-06-2009, 19:23
Gradient Gradient is offline
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Re: Guide to Harmlessly Potentiating Tramadol

My chimp has consistently observed that mild muscle-relaxants markedly enhance the general effects of Tramadol. When taken about 30 mins subsequent to ingestion of Tramadol, both carisoprodol and methocarbomol have noticeably generated a much higher level of analgesia and mood-lift than either of the substances alone. With only 100mg Tramadol and 800mg methocarbamol, the chimp observes effects he associates with 300mg+ Tramadol. The chimp hasn't tried NSAIDs in combination with Tramadol, but would be interested to see if there is a similar dynamic.

Has anyone else observed this relationship between mild muscle relaxants and Tramadol?

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  #6  
Old 06-06-2009, 20:47
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Re: Guide to Harmlessly Potentiating Tramadol

swim has taken over 800mg Tram in one sitting and felt nothing. perhaps swim will try this next time there is a chance.
  #7  
Old 13-09-2009, 08:10
The baine The baine is offline
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Re: Guide to Harmlessly Potentiating Tramadol

Just to add a report my friend gave me:

He started dosage just before the peak of the response curve of the M1 metabolite with cimetidine. It canceled out all effects. even when he was feeling the mu action. his dosages were 300mg tramadol and 400 mg cimetidine. Since then he tried various dosages and timings based an scientific charts then by pure speculation. All in all it was a waste of tramadol and cimetidine for that matter.
  #8  
Old 05-11-2009, 06:17
shivakiva2112 shivakiva2112 is offline
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Re: Harmlessly Potentiating Tramadol

^Including cimetidine in all cases reduced the effects of the tramadol? Did your friend give sufficient time between experiments to account for tolerance (mild though it may be)? Possibly he has a slower isoform of the CYPXXX enzyme (forgot which)? Just offering pure speculation here, this is a very interesting topic.
  #9  
Old 07-11-2009, 19:50
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Re: Harmlessly Potentiating Tramadol

Great post with lots of information but SWIM has some further question around the chemical O-Desmethyltramadol found in Tramadol.

SWIM has recently found himself being able to get hold of O-Desmethyltramadol own its own and pure. SWIM had 5g of this chemical in his possesion his is has not used any yet as he is very unsure of the effects, dosage due to the lack of information on this chemical outside of its effect in tramadol. Do any SWIY who are more literate in science maybe give SWIM a rough idea on effects, potency, dosage and best route of administration (most efficient). SWIM is thinking of IV'ing but is also considering insufflating.

SWIM hopes his post isnt seen as going too off-topic as at the moment reading up on Tramadol is the closest he can get to finding information on said chemical.

SWIM made a thread on this chemical here : - http://www.drugs-forum.com/forum/sho...d.php?t=105916

Thank you.
  #10  
Old 03-10-2011, 22:49
Wayne Brady Wayne Brady is offline
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Re: Guide to Harmlessly Potentiating Tramadol

Quote:
Originally Posted by killersnowman View Post
swim has taken over 800mg Tram in one sitting and felt nothing. perhaps swim will try this next time there is a chance.
My cat in a hat has taken 400mg of Tramadol on its own and felt only an uncomfortable speediness (he does not do well with many speedy substances) with only slight opiate effects. He read that taking a small amount of benzodiazepine along with tramadol is relatively safe and even prescribed in some cases.

So, he decided to try it out. He took .5mg phenazepam (in PG solution) and three 50mg Tramadol pills (crushed up and parachuted.) It should be noted that he has natural (and also a self inflicted tolerance on top of that haha) tolerance to, for lack of a better blanket term, downers.

Okay, anyway, he was trashed! He felt like he just ate 100mg of morphine for about six hours! He did not feel any of the benzo except that the nod was crazy and it may have contributed to that. No comedown either. That was probably because of the super-duper long half life of Phenazepam, it likely kept him chilled out and able to sleep.

One other thing that may be relevant and help sort out some of this enzyme stuff is that hydrocodone does absolutely nothing for my feline unless cimetidine is taken.

As Spucky said, it is a strange drug.

Hope this post was helpful, I don't recommend anyone mix painkillers, especially ones that are less well known and strange like Tramadol with benzos. There are those out there who really know what they're doing (and unfortunately some that just wanna "get fucked up") and they are going to do it anyway, be careful, always start with low doses please

Sorry if this is off-topic and also for the overuse of parenthesis lol.

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Last edited by Wayne Brady; 24-02-2012 at 04:40. Reason: there, their, they're confusion
  #11  
Old 04-10-2011, 00:41
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Re: Harmlessly Potentiating Tramadol

VERY interesting stuff. I have been interested in the significant (albeit dangerous) dual potentiation of 5-HT and tramadol with SSRI's. FYI I wouldn't throw grapefruitjuice in there just for kicks though since it may interact in ways we can't predict.

Last edited by GeographyGeography; 18-01-2013 at 04:56.
  #12  
Old 15-10-2011, 20:53
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Re: Harmlessly Potentiating Tramadol

What dose is appropriate for potentiating this [Tramadol], and other opiates?

In a Swimmie's times past, he has tried adding Cemetidine for other opiates. Is there a difference in the level of potentiation, specific to Tramadol? As I recall, the Swimmer's Cimetidine doses ranged from 300mg to 750mg, or there about.

I suspect the dose was too low for proper effect?
  #13  
Old 22-10-2011, 05:20
Travis Tea of Justice Travis Tea of Justice is offline
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Re: Guide to Harmlessly Potentiating Tramadol

Quote:
Originally Posted by Gradient View Post
Has anyone else observed this relationship between mild muscle relaxants and Tramadol?
Tiddles has! Tiddles is my cat's third weakest alternative avatar (or MCTWAA for short ) Specifically with carisoprodol. Even a normal therapeutic dose of carisoprodol will mildly improve the tramadol experience for Tiddles.

By far the best potentiator MCTWAA has found for tramadol is gabapentin, although it would probably be more accurate to state that the tramadol potentiates the gabapentin since it works best if the gabapentin is taken around four hours after dosing the tramadol and if the two are taken in the wrong order then neither works very well and it's a royal waste of drugs. None of us know the mechanism for these effects I'm afraid. I'm sure Tiddles would love to hear anyone's ideas on the subject though

Some caveats are that:

Tiddles seems to be a hypermetaboliser of both tramadol and gabapentin (lucky imaginary cat avatar!) and gets way better results in terms of analgesia and positive mood changes than most users report. He doesn't know whether it would work for well for more ordinary avatars but speculates that it would still be better than either drug alone.

MCTWAA gets far less out of gabapentin if he doesn't follow the following rules:

Eat a smallish, medium-to-high fat, snack shortly before each dose.
Do not exceed 1g (1000mg) per dose.
Space each dose 30-60 mins apart.
If more than three of these doses are wanted during a day then separate each cluster of 3 up-to-1g doses at least four hours apart.
Swallow each dose with plenty of regular soda (cola seems best).

I could post more detail on the reasons for the gabapentin rules if anyone's interested but it's basically because absorption of gabapentin by the body is rather low compared to most drugs and if the whole day's amount were to be taken in one go on an empty stomach with water then most of it would be wasted and one's cat's avatar wouldn't!

Tiddles has never had supplies of tramadol and pregabalin at the same time and therefore has no idea if the strong similarity between pregabalin and gabapentin would mean that it work well with tramadol. He finds it just like gabapentin but better on it's own on the rare occasions he can get some though so he's prepared to bet that it would, probably even better. In the same vain he tortures himself from time to time imagining just how wonderful a combo tapentadol and pregabalin might be but that's getting in to the realms of pure speculation for MCTWAA! If you know any creature that's tried it please let me know what it reports so that I can pass it on to him

Peace, Travis
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Old 24-10-2011, 01:42
Gryzor Gryzor is offline
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Re: Harmlessly Potentiating Tramadol

So does anyone have info on exactly what dosages are needed and the space of time to take Cimetidine and Tramadol for potentiation? I'm prescribed 400mg Tramadol a day for ADHD/Dysthymia, some recent abstracts and scientific discoveries are truly showing trams worth.
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Old 12-03-2012, 18:35
ruca ruca is offline
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Re: Harmlessly Potentiating Tramadol

hi guys!
well, i know this thread is not new but while i was browsing on how to potentiate tramadol i "stumbled" on it..
at first,i have to admit, i was a bit frustated, for almost everyone was mentioning stuff such as"cimetidine(if im not mistaken or mispelling) and here in portugal i did never found anything of the sorts,maybe it has a different brand name but..not that"popular(i'd know if it was!!)..
but something real nice happened while i was browsing and reading this very tread ...although im by no means an opiate or benzo first timer,quite the opposite,i have a real good tolerance to both(and im not even that clean),i combined 500mg of tramadol with 40 mg of diazepam and...bam!slow but surely,it did hit me in a way i was not expecting.for sure it s not the same as a stronger opiod/opiate but still the effect is quite enjoyable...it s like it acts a s a real good anti depressive(as stated before by a lot of people)but also has some influence on my creative process as a plastic artist,even though it has some strange effect on my eyes,it s like i momemtraly loose focus or something..
i know i dont really add much info but still i wanted to sahre my tramadol/diazepam combo..quite enjoyable..
stay safe mates
r
  #16  
Old 13-03-2012, 23:56
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Re: Harmlessly Potentiating Tramadol

Mr. Gradient... I have a question.
If cimetidine works in the way your friend has described to you, how long in his approximation must one wait to re-dose tramadol?

It was said that taking cimetidine daily will further potentiate the effects of tramadol down the road. This seems contrary to the idea that cimetidine taken after tramadol potentiates and taken before, negates its effectiveness. Do any of your research animals or friends have a week or so of data to confirm said phenomena of cimetidine related reverse tolerance to tram? I'll admit I know little of the physiological purpose and mechanism of cimetidine but these facts seemed incompatible and I could not find a clear resolution within your posts, thank you.

Anyone who wants to answer please do. Also, I agree with Ruca, lets have a consensus on how long one should wait after taking tram to take cimetidine; it seems several of you could produce answers on good authority. Gradient says 30-180 min, no offense but thats a rather loose approximation, what amount of delay worked best for your friend's research animals?
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Old 14-03-2012, 23:20
Wayne Brady Wayne Brady is offline
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Re: Harmlessly Potentiating Tramadol

Quote:
Originally Posted by ruca View Post
something real nice happened while i was browsing and reading this very tread ...although im by no means an opiate or benzo first timer,quite the opposite,i have a real good tolerance to both(and im not even that clean),i combined 500mg of tramadol with 40 mg of diazepam and...bam!r
Anyone else haven any benzo/tramadol experience? This seems to be a nice combo. The more I read the more I think this may not be as bad as it sounds. The benzo may even make recreational Tramadol dosages safer by raising the seizure threshold. Obviously, I am speculating about something potentially dangerous so take this for what it is.
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Old 29-03-2012, 13:02
Gryzor Gryzor is offline
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Re: Harmlessly Potentiating Tramadol

Quote:
Originally Posted by Wayne Brady View Post
Anyone else haven any benzo/tramadol experience? This seems to be a nice combo. The more I read the more I think this may not be as bad as it sounds. The benzo may even make recreational Tramadol dosages safer by raising the seizure threshold. Obviously, I am speculating about something potentially dangerous so take this for what it is.
Yes I know someone who took it daily with benzos with weed on top sometimes. Never was in danger or found it dangerous but never went apesh!t or above 500mg a day + 40mg valium or equivalent. Works well together lasts a long time and is good on depression yeah....for a while. 2 difficult drugs to get off.
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Old 29-03-2012, 16:06
Gradient Gradient is offline
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Re: Harmlessly Potentiating Tramadol

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Originally Posted by EncyclopediaHumanica View Post
If cimetidine works in the way your friend has described to you, how long in his approximation must one wait to re-dose tramadol?

It was said that taking cimetidine daily will further potentiate the effects of tramadol down the road. This seems contrary to the idea that cimetidine taken after tramadol potentiates and taken before, negates its effectiveness.

lets have a consensus on how long one should wait after taking tram to take cimetidine; it seems several of you could produce answers on good authority. Gradient says 30-180 min, no offense but thats a rather loose approximation, what amount of delay worked best for your friend's research animals?
I see three separate, well considered questions. All of them, unfortunately, can only be confronted with speculation; metabolic enzyme expression and activity vary tremendously between individuals - due to both genetic and environmental factors - including sensitivity to enzyme substrates, baseline expression of cytochrome isotypes, and rates of upregulation (or down) of cytochrome isotypes to name a few issues. All of this to say: I am unable to tell you what will work for you with any certainty.

I assume you're referring to the statement I made concerning increased expression of cytochrome isotypes induced by regular administration of cimetidine? The issue you bring up is quite valid; this idea may only be effective if cimetidine is always ingested in the manner I've described - as tramadol will more effectively be converted to its metabolites due to upregulated expression of inhibited cytochrome enzymes in response to regular cimetidine inhibition.

Again, I'd like to re-iterate that this is mostly speculation fueled by some personal observation. I'm happy to discuss any other potential problems.
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Old 03-02-2013, 09:10
Miss Malcontent Miss Malcontent is offline
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Re: Harmlessly Potentiating Tramadol

Today I took

20mgs temazepam - around 3:30 this arvo

{Then about an hour later...}

2 x 50mg Tramal SR (tramadol slow release)
-crushed and swallowed

{Then roughly 2 hours later}

2 x 50mg Tramal SR - crushed and swallowed
And
10mg temazepam

---------------------

Wish I'd payed more attention to timing sorry.

Result is though I didn't feel much to start with it definitely crept up on me.
Feeling quite pleasant, heavy body stoned feeling that makes you think moving is going to suck but doesn't when you do move or get up. Not as messed up as I'd like to be but a nice relaxed high. I'm really not sure as to what is potentiating or synergizing with what because Tramadol and Temazepam on their own do nothing for me.

Also I should add that last night was the first block of sleep I had after a 4 day sleep deprived Speed binge so I don't know if these things are enhanced from already being a little foggy and surely still a little sleep deprived.

Also I heard that taking codeine when or after tramadol peaks is the thing to do. Is it around the peak or after to get the best out of codeine?
  #21  
Old 05-01-2014, 15:08
Gryzor Gryzor is offline
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Re: Harmlessly Potentiating Tramadol

The best way to 'potentiate' harmlessly....is to take your desired tramadol dose in a pyramid pattern going downwards every 20 minutes for example if you plan on 400mg take 200mg then +t0:20 100 or 150mg then 30 mins later take last remaining dose. This allows CYP2D6 to intermittantly recover and produce more O-Desmethyltramadol.
Bioavailability is well known to go up with constant dosing of tramadol but its best use it once a day. Taking it over a time period of 45 mins or so.

There is some guide available that adds grapefruit juice, antihistamines, otc painkillers and citmetidine to produce the ultimate potentiation of tramadol but its not worth putting all that crap into your system for the sake of waiting and taking your tablets every 10 mins.
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Old 18-02-2014, 18:54
jljar5 jljar5 is offline
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Re: Harmlessly Potentiating Tramadol

Cimetidine is listed as a "weak inhibitor" Source: Wikipedia/Others all the strong or moderate ones are SSRI, SNRI, both, and there's like one anti fungal. But the risk of serotonin syndrome would prompt me to advise people to NOT mix anti-depressants. Source: Wikipedia/others

Here's a thread about potentiating with Benadryl (not even listed as a CYP2d6 Inhibitor, but quite a bit of anecdotal evidence) http://www.drugs-forum.com/forum/showthread.php?t=33839

I've tried cimetidine to potentiate many things (CYP2d6 is a VERY commonly used enzyme) at doses up to 1200mg and noticed no definitive effects, beyond possible very slight placebo. I've tried it with many types of opiates (the only other 2d6 worth potentiating imo) even ones not listed and NO effects at least for me.
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Old 24-02-2014, 03:04
Deveraux Deveraux is offline
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Re: Potentiating Tramadol

Some guy I met in Hong Kong told me he finds the combination of Tramadol with Carisoprodol to be highly enjoyable. He used it for a completely different experience than Tramadol alone though.
While he finds 200mg of Tramadol to leave him highly functional, energetic, talkative, and can work and still be as or even more productive, combining it with 700mg Carisoprodol makes for a far mellower experience.
The combination seems to give him a very relaxed, while still euphoric and energetic. He found that having 200mg Tramadol with 1050mg Carisoprodol was enjoyable but the sedation was too strong and he kept dozing off and waking up again, it was very entertaining for a while but the synergy between the stimulation from the Tramadol and the sedation from the Carisoprodol got to be annoying for a moment. He found the need to stand up and walk around to prevent him from dozing off.
The combination of 200mg Tramadol with 700mg with Carisprodol was much more enjoyable, giving him a very relaxed time, finding a middle point between the sedation and the stimulation. While the tramadol alone is for him ideal to be more active, the combination with Carisoprodol is better suited for being with someone chatting on a couch, maybe playing video games or watching a movie.
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Old 03-03-2014, 14:47
jljar5 jljar5 is offline
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Re: Potentiating Tramadol

First off for reference, I'm 180 lb male, Ex-heroin addict so I have a high natural tolerance now (like it only goes down so far) and now I just chip or do pills, usually snorting or iv depending what it is. 2 iv op 80s will have me nodding (I think it takes 2 cuz you get like 2/3 out of that TimerX crap) with no tolerance, or about 80mg iv morphine. So it's relatively high, even when I have taken months off of anything. I haven't been physically dependent in over 4 years. So on to the post:

I could DEFINITELY see that Deveraux, Soma (carisoprodol) potentiates opiates better than pretty much any pill (dxm makes opiates stronger but by a different way, it actually temporarily LOWERS your opiate tolerance.. Very cool, but I digress..), I've read it's up to 60%

As far as me personally, oxycodone, even hydrocodone (which is pretty weak to me), WITH carisoprodol is like freakin black tar heroin. seriously.. It potentiates the opiate a lot, then it also has this SUPER euphoric rush, almost similar to alcohol, the lightheaded/euphoric feeling but somas are fairly short acting so you but sedation does build up as you continue to use them to maintain the buzz and you will start to nod HARD at some point. Be VERY CAREFUL any combination of CNS depressants is dangerous.
So I Could definitely see it w tramadol.. I have chronic severe stomach pain, so I'm trying tramadol, anywhere from 100mg, to 400mg at a time (I am aware max daily dose recommendation is 400mg) and when I take more than 200mg at a time I add clonazepam and sometimes on top of that, some Pharma GABA (pure GABA, supplement OTC) and/or gabapentin (Neurontin) to prevent the dreaded tonic clonic seizures that can be induced by the lowered threshold from increasing doses of tramadol.

I have access to carisoprodol as well, I just need a way to go get it (Not havin a car SUCKS lol) but I think I will try that combo, and compare it to my many many other encounters with opiates and see how it stacks up. Thanks for the post.

Also Deveraux, I wonder, How long does the Soma last him???
I may be a fast metabolizer (pretty sure I am) but I need to start out with 700 mg (2 pills) and then take 1-2 more every 45 -90 min to maintain the same level (I am not taking any medications that are it's cyp450 inhibitors or anything like that)
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Old 03-03-2014, 20:22
Deveraux Deveraux is offline
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Re: Potentiating Tramadol

Well that'd be hard to answer since usually tramadol has for him first an stimulating phase to be followed by a much more relaxing phase. The carisoprodol is taken at the beggining so as to have the stimulation from the trams counter the sedation from the soma, while still having the nice body high and potentiating the trams, but he never redosed on the soma himself but rather just went to bed afterwards. (Just to clarify, while from what I've seen here most people likes to take some time between tramadol doses to potentiate the opioid side of it and tone down the stimulation, this guy loves the stimulatory part of it)
Taking into account that carisoprodol has a relatively short (2 hours) half life it would make sense to re-dose.
If you're trying to potentiate the opioid side of it, considering the dosages you've been taking, I'd probably take 100mg Tramadol + 700mg clarisoprodol, adding another 100mg tramadol at T+1:00 and probably a second 700mg clarisoprodol somewhere in between T+2:00 and T+3:00.
This I say from my position in which I don't ussually redose trams and 200mg is my ideal dosage, having nastier side effects when going over it, if your tolerance is high and can handle bigger doses you can probably adjust them.

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