Repeated regular Intermittent MDMA use protects against damage from binge

[Jabberwocky]

Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats.


We have recently shown that chronic intermittent exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) completely blocks the reduction in serotonin transporter (SERT) binding and the hypoactivity seen following a subsequent MDMA binge treatment. The present study determined whether a similar neuroprotective effect also occurs in rats given the same intermittent MDMA exposure in adulthood. Adult male Sprague-Dawley rats were given either MDMA (10 mg/kg x 2) or saline, every fifth day, from postnatal day (PD) 60 to PD 85. The MDMA-induced latency until seminal plug production was reduced over the course of intermittent treatments. After a 1-week wash-out period, animals received either a low- or high-dose MDMA binge (2.5 or 5.0 mg/kg x 4). Core body temperature was measured during and after the binge to determine the effects of MDMA pretreatment on MDMA-induced hyperthermia. Spontaneous motor activity was determined the next day, and cortical and hippocampal samples were collected at 1 week postbinge to measure serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations as well as [3H]citalopram binding to SERT. Hyperthermia occurred more rapidly and seminal discharge was more common in the MDMA-pretreated group compared to the MDMA-naïve group in animals given the low-dose binge. MDMA preexposure protected animals from the reductions in cortical 5-HT levels and SERT binding produced by the high-dose binge and blocked the postbinge hypoactivity. These findings indicate that chronic, intermittent MDMA exposure in adulthood induces neuroprotective effects similar to those seen with adolescent treatment. However, there was also evidence for drug-induced sensitization in adults that was not observed in adolescents. Thus, altered drug sensitivity in chronic Ecstasy users may depend not only on the frequency and pattern of use but also on the age of the user.



Well well well.... it seems the wait 3 month crowd is just plain wrong


also:

[h=1]Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats attenuates the effects of a subsequent challenge with MDMA or a 5-hydroxytryptamine(1A) receptor agonist.[/h]
http://www.ncbi.nlm.nih.gov/pubmed/16434566

 

[Cotcha Yankinov]

Boy you are really an MDMA crusader ^.^

Upregulation of antioxidant defenses is supposedly known to happen with amphetamines. Theory being with prescription dose escalation that the brain is given a chance to build up its defenses (and hence that binge dosing a naive animal may not be a relevant model for specifically prescription protocol adhering patients).

But I see drug induced sensitization in adult rats is still present with MDMA according to your study. A single dose of amphetamine can increase locomotor activity for a year, I would not be surprised if there were similar findings with certain MDMA administration protocols. But yeah, 3 month rule is actually still a good rule. MDMA can have serious negative side effects especially in some people and it's not something you want to overdo, especially in young people. Even if just for 5HT2B related reasons it would be good not to do it 100 times a year..

 

[Jabberwocky]

Even if just for 5HT2B related reasons it would be good not to do it 100 times a year..

I think that is also overblown based on recreational dose, the peak concentrations barely reach the level to induce fibrosis in susceptible individuals, and only then for a few hours.

 

[aced126]

Link to the first paper?

The 3 month wait period isn't suggested for the sole purpose as to avoid neurotoxicity (in fact I'd say that reason is a small contributor anyway). It is for many other more important reasons. MDMA is a special drug, unlike any other class, where frequent dosing almost always results in the empathic part of the experience dissolving, with people left with a more dopaminergic and fiendy type high (losing the magic). Also, dosing too often for many results in feeling mentally quite poor, due to depleted serotonin and what not, and these comedowns tend to get worse with frequent dosing. Finally, I have seen myself many people who use it frequently start to consume a lot each night, trying to chase something uncatchable, and end up spending loads on what is really not that full of an experience anymore. And as we have seen, lots of people can also start to develop mental health issues like anxiety and depression. I know a few people who went on SSRIs directly because of their MDMA usage.

MDMA is one of the best drugs, but it needs to be respected and done very infrequently to get the most out of it. With MDMA, less is more.

After an initial MDMA dose, SERT is internalised and downregulated as a homeostatic mechanism in response to increased serotonin concentration in the synaptic cleft. However, constantly administering MDMA will result in a greater depletion of serotonin due to constant inhibition of TPH and such. As a result this overall might result in less serotonin synthesis and vesicular release which would lead to increased SERT synthesis and upregulation. 5HT autoreceptors could also be playing a role here. At the very worst, you could have SERT upregulated but a small amount of axons actually dying, but when you then viewed where [3H]-citalopram was binding to, it would look as though nothing has really happened. It's unwise to interpret the results of this study as "it's alright to take MDMA often", especially when the reason for not taking it often isn't that based on neurotoxicity prevention, as mentioned earlier. It is the growing consensus that regular MDMA usage might not actually kill 5HTergic axons, and if it does they simply regrow, but there are many other ways frequent dosing can fuck you up, so I wouldn't do it.

***

Also I've just read a few of your posts regarding advice on MDMA dosing and I have to say, it's truly terrible. I mean, all I need to do is quote a part of this post from you: "I have it on very good information that you can take 2 grams of (tested) MDMA over a weekend and be back to normal in a week or so."

http://www.bluelight.org/vb/threads...stions-(3-Days-Later)?p=13777757#post13777757

In the interest of harm reduction, could you please stop trying to use science incorrectly to back up truly awful suggestions like that. Science is a tool to understand the truth, not to fool yourself. And anyways, you need nothing more than common sense to be able to undoubtedly advise against doing 2 grams of MDMA over a weekend. Please in the interest of Bluelight user safety and harm reduction, stop handing out dangerous advice.

 

[terarc]

^ well said

 

[Cotcha Yankinov]

^Thanks Aced, and I'll add that going around the posts wherein people are having severe issues from MDMA, including the recovery and support thread, and labeling everyone's issues "HPA axis dysregulation" is not only insensitive but most likely factually incorrect and just plain not helpful.

I realize many people think MDMA is harmless (on the level of cannabis) but the truth is that, especially to a vulnerable individual, it can cause serious long term issues. Permanently life altering issues.

 

[Cotcha Yankinov]

I think that is also overblown based on recreational dose, the peak concentrations barely reach the level to induce fibrosis in susceptible individuals, and only then for a few hours.

There is a study showing about 30% of young adult MDMA abusers had valvular heart disease, while none in the control group (I think around 30-40 people in each group) had valvulopathy.