Co-administered Caffeine might significantly aid intestinal absorption of MDMA

[crOOk]

For those who care about it, a study from 2007 that totally needs to be linked on bluelight... I know MDMA absorption has been a topic of debate here before, but I've never heard any anecdotes regarding the combination with caffeine. Anyway, here's the abstract. The library locked my card during my manic episode, so I can unfortunately not paste anything past this, nor can I supply the study by request.

Interactions between 3,4-methylenedioxymethamphetamine, methamphetamine, ketamine, and caffeine in human intestinal Caco-2 cells and in oral administration to rats.

Abstract

Amphetamine-type stimulants (ATSs) are often abused orally in the form of tablets for recreational purposes. The ATS tablets contain one or more active ingredients such as 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (MA), ketamine (KA), and caffeine (CF). The aim of this work is to determine whether such components in tablets interact with each other in intestinal absorption. The interactions between MDMA, MA, KA, and CF in the uptake and permeation by human intestinal epithelial Caco-2 cell line were investigated in monolayer cultures. MDMA, MA, and KA mutually inhibited the uptakes by Caco-2 cells. The inhibition of MA uptake by KA was the greatest of all combinations (72.6% inhibition). Similarly, MDMA, MA, and KA mutually inhibited the permeation from the apical to the basolateral side through Caco-2 cells. Although CF did not affect the uptakes of MDMA, MA, and KA, CF enhanced the permeation of MDMA in comparison to MDMA alone. In addition, the interaction of MA with KA and that of MDMA with CF in intestinal absorption were investigated by oral administration to rats. The area under the plasma concentration-time curve of MA significantly decreased by co-administration with KA in comparison to MA alone, while that of MDMA significantly increased by co-administration with CF in comparison to MDMA alone. The results in rats were similar to those in Caco-2 cells. These findings suggest that the intestinal absorption of similar compounds with amine moieties such as MDMA, MA, and KA are mediated by a common transport system, and that CF affects the absorption of MDMA in a different way from the transport system. In human, intakes of ATS tablets mixed with such components might result in similar interactions in intestinal absorption to those in Caco-2 cells and rats.
Source: Kuwayama K, Inoue H, Kanamori T, Tsujikawa K, Miyaguchi H, Iwata Y, Miyauchi S, Kamo N, Kishi T.
National Research Institute of Police Science,
Kashiwanoha, Kashiwa, Chiba, Japan.
[email protected]

 

[FlippingTop]

Thanks for this. I guess that is why SO many pills on ecstacydata have caffeine in them!

I will try 200mg caffine before my next MDMA dose in 2 weeks time.

 

[pofacedhoe]

i find caffeine makes the mdma high unsettled and anxious. an unpleasant addition

 

[Josair]

I can send the paper should anyone want it, but:

The abuse of ATS (amphetamine-type stimulant) has become a serious social problem not only in Japan but also all over the world. The ATS tablets contain one or more active ingredients such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), methamphetamine (MA), etc. [2–8]. These components are similar to each other in their pharmacological and toxicological effects, and they affect the central nervous system

Orly? Note that they also included ketamine in that bunch of 'similar substances'.

Anyway, I think that brewed coffee is mildly acidic. Am I wrong or MDMA is better absorbed in a more basic gastric environment?
Still, if the numbers they give are correct there is a huge difference... might be worth a try. Maybe more interesting, oral ketamine seems to inhibit the absorption of oral MDMA (and vice-versa), kittyflippers should take note

 

[crOOk]

i find caffeine makes the mdma high unsettled and anxious. an unpleasant addition

Unless you're consuming a gram of caffeine per day anyway that is... In which case it might very well still aid absorption. But yeah I hear you, I prefer my rolls nice and mellow.

 

[crOOk]

I can send the paper should anyone want it, but:

Orly? Note that they also included ketamine in that bunch of 'similar substances'.

Anyway, I think that brewed coffee is mildly acidic. Am I wrong or MDMA is better absorbed in a more basic gastric environment?
Still, if the numbers they give are correct there is a huge difference... might be worth a try. Maybe more interesting, oral ketamine seems to inhibit the absorption of oral MDMA (and vice-versa), kittyflippers should take note

You are either misquoting them on purpose or you really haven't understood why the word ketamine was used in that abstract. Why oh why would either of those scenarios apply to a bluelighter in ADD?!
Regarding pH... you're kinda right, but your intestines are pretty well buffered. Choosing rectal route over oral will increase absorption rate immensely. pH varies considerably between different regions of the GI tract. In fact, the activity of H3O+ can physiologically vary by a factor of ~100.000.000 from as low as pH1 in the stomache to pH10 in the brown parlor (these aren't average values, but they can coexist and are no cause for concern). Think of how reliably mdma hits people with the expected intensity for the respective dosage. If a miniscule amount of substance was able to change your intestinal pH at any time, you'd be in deep shit.

edit: not literally you wouldn't. ;D

edit2: well, maybe

 

[chaos_destroy]

Probably worth noting that caffeine has been shown to increase MDMA induced hyperthermia and serotonin depletion both of which are associated with so-called neurotoxicity.

Heres a review on the topic

Vanattou-Saifoudine, N., R. McNamara, et al. (2012). Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators. Br J Pharmacol 167(5): 946-959.

Abstract:
Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption.

 

[danharper01]

When I combine caffeine with my MDMA I definitely get more negative side-effects.

 

[Darksidesam]

i find caffeine makes the mdma high unsettled and anxious. an unpleasant addition

+1

Also, isn't caffeine + MDMA more neurotoxic?

My only experience with mdma and caffeine deliberately was when i made up a 90mg crystal mdma/ 70mg caffeine capsule.

The sweat just ran down my head as i come up,

As someone who mods ED and see's people posting every day,
Just saying i don't ever advise Caffeine and MDMA in fact i advise people against this combination.

 

[King Kong]

The doses used in rat are pretty high: 10 mg/kg for MDMA and 50 mg/kg for caffeine. Is it realistic? I know it’s difficult to establish parallels between rats and humans…

Also, the difference in Cmax is quite surprising! The addition of caffeine almost doubles the absorption (from 0.36 to 0.62 ug/mL). I am pretty sure if such effect occurs in humans too, we would have heard a lot more about the combination of MDMA and caffeine…

 

[crOOk]

Guys, I hope you are all aware of the fact that increased absorption might lead to a higher peak plasma concentration of MDMA, ergo more side effects. With MDMA dosage is extremely critical in my experience. There's a ton of 120mg rolls floating around here when I last check (I don't use rolls, nor am I in the "scene" myself aside from a few contacts). With 120mg is really an ideal dosage for most people. 170 might have you feel like utter crap. I'm just proposing, maybe many of those added sides would also appear on a higher dosage?? Plus, caffeine has some pretty bad side effects itself, I wouldn't do this unless you have a tolerance for it which ime pretty much eliminates any subjective effects except from keeping withdrawls locked out.

 

[crOOk]

The doses used in rat are pretty high: 10 mg/kg for MDMA and 50 mg/kg for caffeine. Is it realistic? I know it’s difficult to establish parallels between rats and humans…

Also, the difference in Cmax is quite surprising! The addition of caffeine almost doubles the absorption (from 0.36 to 0.62 ug/mL). I am pretty sure if such effect occurs in humans too, we would have heard a lot more about the combination of MDMA and caffeine…

I'm surprised noone else has tackled that issue. Ofc this in no way says anything about absorption in the human intestines, nor does the study claim such mechanism to have been observed. It does allow for experimentation though and we might now when people report back. Call me irresponsible for posting this.

Regarding the second part of your post, consider what I said in the post above and note how many people have experienced a shitload of negative sides with the combo... Makes me kinda curious tbh. If I didn't have tons of issues atm I'd probably try administering 70mg inside a 500ml energy drink (got a huge caffeine tolerance, 1g per day). I have no tolerance for MDMA, but 70mg will not cause me to experience any of the intense empathogenic surges I get from MDMA.

Combining this with a regular MDMA dose would be idiotic tbh.

 

[crOOk]

Probably worth noting that caffeine has been shown to increase MDMA induced hyperthermia and serotonin depletion both of which are associated with so-called neurotoxicity.

Heres a review on the topic

Vanattou-Saifoudine, N., R. McNamara, et al. (2012). Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators. Br J Pharmacol 167(5): 946-959.

Abstract:
Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption.

Relative to an equal plasma concentration of MDMA? I can't access the study, my library account is locked. What I read are a number of claims for which I could think up various explanations on the spot. I do not see any actual data being quotes, not is MDMA to be considered a psychostimulant imho. I think they are using data of other stimulants to prove their point about caffeine+mdma here. Would be cool if I could see a pdf with the full article...

No where is it stated that serotonin depletion is induced. I don't even know if such a thing has ever been observed. They are referring to serotonergic toxicity which isn't really a medical term at all imho. That would by my udnerstanding mean "toxicity caused by the neurotransmitter serotonin or by activation of it's proteine targets by another molecule" through common mechanisms maybe. Something along those lines.

Now IF they were meaning to refer to "serotonin toxicity" than this is a medical term which is equal to serotonin syndrome. Now this is not some invisible enemy that just sneaks up on you without your knowledge, hits you out of nowhere and causes sudden death. :D It's a clinical diagnosis determined by a patient presenting the following symptoms according to Sternbach's critera:

-Recent addition or increase of a serotonergic agent - check lol
-Absence of other aetiologies (infections substance abuse or withdrawal symptoms) - wait whut?!
-No recent addition or increase in a neuroleptic agent - I really hope noone is gonna try to roll when on them mind control pills
-At least 3 of the following:
Mental status changes - fuck yes
Agitation
Myoclonus - this is similar to an intense twitch, like when you're falling asleep. Ever seen someone od on GHB?
Hyperreflexia - lowered threshold for a reflex to be triggered, note: this also occurs when youre sleep deprived!
Diaphoresis - sweating
Shivering
Tremor
Diarrhea
Incoordination
Fever - definitely a fever at over 38.5, this is subject to debate and psychological temperature varies between times of day. other factors play a huge role too. a tricky subject really when talking about the average joe's party roll.

according to dunkley et al these features are really the only ones needed to determine serotonin toxicity:
-clonus (inducible, spontaneous or ocular)
-agitation
-diaphoresis
-tremor
-hyperreflexia

Mind you this really doesnt apply to your rolls according to Sternbach's criteria... Imho they are absurd though lol. I still do not know what exactly is referred to by "serotonergic toxicity" and exactly how the level of it was determined. Curious to find out though, in case anyone can send over the study.

 

[chaos_destroy]

How does one go about adding a paper to a post? In the mean time these are the main papers it references. The last one says that caffeine does not alter MDMA plasma levels in rodents.

Camarasa, J., D. Pubill, et al. (2006). "Association of caffeine to MDMA does not increase antinociception but potentiates adverse effects of this recreational drug." Brain Res 1111(1): 72-82.

McNamara, R., A. Kerans, et al. (2006). "Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love")." Neuropharmacology 50(1): 69-80.

Vanattou-Saifoudine, N., R. McNamara, et al. (2010). "Mechanisms mediating the ability of caffeine to influence MDMA ('Ecstasy')-induced hyperthermia in rats." Br J Pharmacol 160(4): 860-877.

 

[Hammilton]

The doses used in rat are pretty high: 10 mg/kg for MDMA and 50 mg/kg for caffeine. Is it realistic? I know it’s difficult to establish parallels between rats and humans…

Um... No. 50mg/kg of caffeine would be equal to 4500mg for a 200lb person. Even for a 150lb person, that'd be 3400mg. Those are doses that may well cause seizures in a human.

For the MDMA that'd be 900mg for a 200lb person, for 680mg for a 150lb person. Extremely huge doses. I dunno if they'd kill you, but they'd have a real good chance. I feel bad for the rats.

Why is that these sorts of studies always use ridiculous doses? Why intentionally put a rat through such a terrible experience for this sort of data? There are good reasons to give rats high doses of drugs. Determining whether caffeine increases the absorption of MDMA is not one of them. At all.

I'm not remotely against animal testing. It's a great thing, but frankly, this is inhumane.

 

[amanitadine]

Likely because realistic doses don't Get the dramatic effects that gets a paper published. Standard operating procedure for this sort of thing.

 

[endotropic]

Um... No. 50mg/kg of caffeine would be equal to 4500mg for a 200lb person. Even for a 150lb person, that'd be 3400mg. Those are doses that may well cause seizures in a human.

For the MDMA that'd be 900mg for a 200lb person, for 680mg for a 150lb person. Extremely huge doses. I dunno if they'd kill you, but they'd have a real good chance. I feel bad for the rats.

Why is that these sorts of studies always use ridiculous doses? Why intentionally put a rat through such a terrible experience for this sort of data? There are good reasons to give rats high doses of drugs. Determining whether caffeine increases the absorption of MDMA is not one of them. At all.

I'm not remotely against animal testing. It's a great thing, but frankly, this is inhumane.

Due to differences in metabolism and body mass/surface area ratio the rule of thumb is that you divide doses in mice by 12 and doses in rats by 6 to try and approximate human doses. That's just a rough approximation though, if you want more accuracy you can do something more like this:

Dose translation from animal to human studies revisited
http://www.fasebj.org/content/22/3/659.full

Or you can just assume that all scientists are being controlled by some mysterious propaganda puppet master in order to sully the names of our wonderful drugs

 

[Solipsis]

i find caffeine makes the mdma high unsettled and anxious. an unpleasant addition

Yes, true for me as well.

For me alkaline antacid substances such as magnesium aluminum oxide seem to work quite well in combination with PEA stimulants like M1 or MDMA.
I'm sure if MDMA absorption has passed often as a subject here... this must be one of the more known / popular strategies? Still, I have no actual empirical evidence that the difference in stomach makeup is big enough to change absorption significantly.

Anyway, back to the caffeine.

 

[Josair]

I was wondering whether 'caffeine aid intestinal absorption of MDMA' and 'caffeine makes rolling less pleasant/more neurotoxic' can in fact be (partly) two sides of the same coin...
more (faster) absorption -> higher plasma levels -> stronger effects (maybe even unpleasant, though i'll admit that i'm maybe pushing it too far here) -> worse comedown/more damage

 

[Solipsis]

Hmm, well depends...
Realizing how this was meant: no, because I read the 'less pleasant' remark as jitteriness of caffeine (+ basically all other negative effects of it) as a function of caffeine without the payoff.
Yes you are right though that any effective action of MDMA comes with baggage.

IMO it's just not the same though.
Subjective judgement is where it is at anyway at the end of the day, and people should decide for themselves whether they find any potentiation of positive effects worth the negatives. Agreed that subjectively, when having taken the combination there is no important difference anymore between what one drug contributes rather than the other (>> amalgamation) ... I still think it matters because it is expected that even if there are benefits from combining with caffeine, the side-effects (mainly the adrenergic ones) would be out of proportion with those positives.
Well at least, my expectation. :D And/or actual experiences with the combo I can remember, that would only be guarana / coca cola not caffeine powder, though and at the back of memory shelves.

My question in return though is: do we know what kind of caffeine dose would be optimal for this beneficial effect? If it is low enough then it becomes so much more likely that it is an acceptable trade-in. Otherwise I would probably recommend the antacid, differently (higher and less spaced apart) dosing of MDMA, and keep it at that.