Research Regarding Redosing and “3 Month Rule”

[heatlessbbq]

I like that 3 month rule when it comes to MDMA breaks.

 

[Negi]

Ok @Negi hasn’t come back to refute anything yet. I’d just like to add one more thing that only makes my argument stronger.

While yes there is rough “species to species” dosage transition charts, they are rough at best. As is the case with MDMA, where dosages actually correlate pretty well rat to human.

In this study..

Effects of Dose and Route of Administration on Pharmacokinetics of (±)-3,4-Methylenedioxymethamphetamine in the Rat
Michael H. Baumann, Dorota Zolkowska, [...], and Marilyn A. Huestis

They talk about the MDMA cMax values for 2mg/kg in rats was similar to 1.5mg/kg in humans.

So with this in mind, we can now assume that many of these research studies are actually safer than you once assumed.. Wouldn’t you agree Negi?

-GC

Sorry about not replying earlier, I'm not much of a bluelight regular anymore so I don't login very often.

This is quite an interesting paper. First off we have some great news. I'm not sure if you read enough of the paper to see it, but 10mg/kg is back on the menu!

Administration of 10 mg/kg MDMA in our study produced a robust 5-HT syndrome but no long-term 5-HT depletion, suggesting that this dose is not neurotoxic under the conditions used here.

The fact that different papers have very different opinions on this is a little concerning, but hey, maybe these were the rats with more anti-oxidants you were talking about.

Here is the money shot so to speak:

Administration of 2 mg/kg MDMA by intraperitoneal and subcutaneous routes produced an MDMA Cmax of ∼200 ng/ml, a concentration close to the MDMA Cmax in humans who receive 1.3 to 1.7 mg/kg by the oral route under controlled conditions

I should note that the "intraperitoneal and subcutaneous routes" both involve MDMA being injected into the rats, either under the skin or directly into the organ cavity. Not quite analogous to the average human MDMA user.

Just below that section, this popped up:

MDMA t1/2 was ∼45 min for rats given 2 mg/kg, and this interval is much shorter than the t1/2 of 7 to 9 h observed in humans

I feel this is pretty significant, one can imagine that if MDMA is hanging around for nearly 10 times as long in humans, it might have a little more of an impact than the short time it is present in a rat. The authors recognize this and propose a solution:

Given the rapid MDMA clearance in rats, repeated intraperitoneal or subcutaneous injections of low-dose MDMA in this species might be an acceptable model for single oral doses in humans.

Hopefully future studies will test this proposed protocol, I would be very interesting to see if it provides different results. By the way, I checked all the previously cited papers in the thread - except for when they were deliberately trying to deliver a neurotoxic dose, MDMA was always delivered as a single full dose injection. Lets keep our fingers crossed that someone in the future will re-run them with a more acceptable model for replicating the effects of human oral doses.

As for the significant difference in the correlation of rat to human doses compared to the paper I had posted, I can't say much about that. The differences between the papers is relatively stark. From my paper:

However, what is most apparent is that a dose of 2 mg/kg in humans produces a peak plasma concentration that is only achieved by giving approximately 7 mg/kg to rats.

I will note that the paper I cited also the used more than just the peak plasma concentration to make that judgment, it also used the rise in temperature produced by MDMA:

given that a 100 mg MDMA dose (1.4 mg/kg) provokes a 0.6°C oral temperature rise in humans (Farré et al.2007) and a similar increase in rectal temperature is seen following an approximate fourfold higher dose (5 mg/kg IP) to rats (Colado et al.1995).

When it comes down to it though, the paper I cited for rat to human dosing is a review paper, comparing five different human studies and six different rat studies. This paper is the results of a single study. As you have said:

I tend to look at the information as a whole from many research article sources

For now I'll rely more heavily on the review paper to make my dosing decisions. However I'm pretty interested in why the other paper has such different results. When I have time (or am seriously procrastinating) I might go through and compare it to the different rat studies in the review paper. Maybe it's the type of rats they used? I'm curious to find out.

 

[Inds]

G_Chem, I don't have the study Swim15 introduced me but I can find it later. The problem with mdma is the degradation of reuptake sites and the average time it took to regenerate was I believe 5.8 months in that paper. You'll always have a lower serotonin ceiling if you roll regularly and it'll take months or years before you finally notice the unfixable damage you did. The immediate damage is not noticeable because it's only after too many reuptake sites are lost that the low serotonin levels become the new established norm.

Also, I don't trust rat studies. You can't extrapolate rat data to human. Even the mg/kg isn't comparable because rats have way better excretion systems than us. What 10 mg/kg is for them could be 1 mg/kg for us.

 

[Juicy Zack]

Lol ya I tend to write novels...

In summary it’s not wise to redose more than once in a single night with MDMA (beyond a small booster not long after the first) both in terms of neurotoxicity and overall pleasurable effects.

Which is something people already know..

But then I also deconstruct the whole “3 month rule” and show why it’s more of rule based around averages per year. And in fact it may even be safer to consume closer together so long as you keep your antioxidant system “topped off.”

Based on research along with my own use.. If your use is kept to 4-8 times a year max, and you keep up on your antioxidants, there’s no worries.

-GC

How can one keep their antioxidants “topped off”??

PS - Newbie here

 

[TripSitterNZ]

How can one keep their antioxidants “topped off”??

PS - Newbie here

Take anti oxidant vitamin supplements daily or eat alot of fruit and vegetables like tomatoes which are rich in anti oxidants. Keeps you looking younger and protects your body from free radical damage

 

[Swim15]

How can one keep their antioxidants “topped off”??

PS - Newbie here

Have a diet high in antioxidants containing foods (fruits, vegetables, healthy oils, green tea, etc) and low in things that decrease antioxidant status (refined sugar, processed foods, trans fats, etc).

Supplements in the forms of greens powders, polyphenol extracts, fish oils, ala, or things that boost glutathione are all good options to further increase antioxidant status but won’t make up for a shit diet.

 

[Negi]

One thing to keep in mind if people are trusting the various "supplement" regiments to protect them from the effects of more aggressive MDMA use is that the evidence surrounding the protective nature of many of them is pretty thin. I would recommend everyone read this reddit post by Dr Matthew Baggott, one of the world's top MDMA researchers who has been studying it for nearly 20 years.



In some cases people are taking oral supplements based on a single study where they were injected directly into the brains of rats.

 

[Swim15]

^In a lot they were proven to do more than that though. Metformin and some others are also probably more effective than most of those and not mentioned.

Look at the benefit vs cost vs possible reward. What’s it cost to take those supplements during a roll? Less than $1-2. If you aren’t willing to spend a couple bucks to potentially protect the most important thing in your body then you shouldn’t be rolling lol.

 

[Negi]

Sure, take them if you want. But when people in the thread are saying stuff like:

I’ll finish with my own personal data. I’ve been rolling for 15yrs, and have found that there doesn’t seem to be any downsides to rolling b2b SO LONG AS I TAKE THE PROPER ANTIOXIDANTS!!!
[...]
Most can’t follow all the rules required to safely roll b2b.. Most can’t keep it to one reasonable dose the first night. Eating healthy the days before and after. Taking antioxidant supplements.

They are ascribing much more to the supplements than "eh, it's $2 and it will probably help".

 

[Swim15]

Sure, take them if you want. But when people in the thread are saying stuff like:



They are ascribing much more to the supplements than "eh, it's $2 and it will probably help".

Yeah you’re right, that’s a little extreme.

That said, there is most definitely some good literature and knowledge of mechanisms to support their use.