Comment · Thu, April 25, 2013
MDMA: The 'Dont Re-dose' advice?
Original post in this thread
KosherDev · 25 points
So this came up in another thread and people suggested I make my way over here for a more specific answer.
We've all heard the general advice of not re-dosing on mdma to minimize any potential harmful after effects. It makes sense but is it the act of just 'taking more' that could cause issues, or is it the actual time separation?
So the example. You take an initial 120mg dose, and then a subsequent 60mg dose an hour or so later for a grand total of 180mg.
Vs.
One initial dose of 180mg.
Are they equally 'bad' or does the subsequent dosage cause more complications than one large initial dose? If so, why?
What they were answering
susquehannock · 1 points
I was just wondering if there was any information if one method was 'worse' than the other if the dosage was the same.
Hmmm. Well I would be amazed to learn that there were any studies or models that could be applied to the difference between taking 120 then 60, vs taking 180.
I think all you can get is anecdotal commentary.
But lets wait and see, there's enough action on your post now so that if anyone DOES have a model that applies, they will find this post and write about it.
my anecdotal commentary is that 120 plus 60 is somewhat better, because the comedown is not as big of a shock. Some dysphoria is inevitable during comedown tho. That dysphoria is not what I would ever have classified as a neurotoxic effect, tho, sure, I can imagine people suggesting that it was.
My anecdotal take on the dysphoria is that it's sad to return to baseline after you have enjoyed 4-5 hours of an extraordinarily satisfying mental state.
I don't like it when a great book I am reading is over, either. I don't attribute that to neurotixicity, altho I would certainly describe it as a state of lowered serotonin.
u/MisterYouAreSoDumb
There are multiple studies showing the increased metabolism to neurotoxic metabolites due to re-dosing.
http://www.ncbi.nlm.nih.gov/pubmed/20388857
> The pharmacokinetics of MDMA follows a nonlinear model, which results in a disproportional
MDMA increase in plasma; with increasing MDMA intake, a relatively higher concentration of the parent MDMA is found in plasma compared with MDMA metabolites (de la Torre et al., 2000). This
nonlinear kinetic model presented for MDMA at high dose levels has
been attributed to autoinhibition or metabolic inactivation of CYP2D6
by the parent compound (de la Torre et al., 2000; Van et al., 2006).
This means that initial doses inhibit certain enzymes, mainly CYP2D6, causing future doses to follow secondary metabolic pathways (i.e. CYP3A4), which causes greater than normal amounts of neurotoxic metabolites to be created.
Here is one proving the non-linear pharmcodynamics in humans.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663855/
>This study used a rigorous scientific design to perform an extended pharmacokinetic analysis
of MDMA and three metabolites, HMMA, MDA, and HMA, characterizing Cmax, Tmax,
AUC∞, detection windows, t1/2, Vd/F, CL/F, and metabolite ratios for up to 143 hours after
dosing. Low (1.0 mg/kg) and high (1.6 mg/kg) oral MDMA doses were administered to 17
volunteers of both genders, including, for the first time, black participants. Strengths of this
study include measurement of HMMA and HMA concentrations after low and high MDMA
doses, more frequent and extended plasma sampling (up to 143 hours post dose versus 48 hours
or less in earlier reports), and participants who resided on a closed research unit with 24-hour
monitoring to prevent self-administration of MDMA or other drugs. This study provides
support for the theory of MDMA nonlinear pharmacokinetics within the range of doses used
recreationally and provides preliminary information on gender differences in drug elimination.
>
The predominant theory of nonlinear pharmacokinetics of MDMA and HMMA is mechanism-
based inactivation of CYP2D6 by MDMA. In vitro data suggest that a metabolic complex
formed by the methylenedioxyphenyl ring inhibits O-methylation.
Large doses are bad too, but the main problem is extending the time the plasma concentrations of metabolites remain high. Re-dosing is a sure way to significantly extend the plasma time of the toxic metabolites. This is why I always suggest inhibiting at least CYP3A4, if not CYP2D6. Then I suggest increasing urinary acidity at the end of your roll so that you can urinate out most of the MDMA before it has a chance to fully metabolize.