Reversal Of MDMA induced Hyperthermia

[Unlucky]

I wanted to share with you guys the findings of Jon E Sprague who discovered that a commonly used medication for heart failure also happens to reverse the effects of mdma induced heyperthermia and rhabdomyolysis.

I found it intersting that a medication used for another purpose is able to be benefical in other ways. I also felt sharing this information could prove useful in saving someones life someday.

Carvedilol is commonly used as a non-selective beta blocker in the treatment of mild to moderate congestive heart failure which was actually and coincidently discovered by the same specialist whos treating my Neurological condition Professor Murray Essler, but when I randomly contacted a thermoregulatory scientist Jon E Sprague over the net back in 2002 for my temperature problems I was suprised to find that he had also discovered using Carvedilol for the purpose of reversing Mdma induced hyperthermia..a bizzare coincidence?

After recomendation from Jon Sprague and my neurologist Professor Essler I tried Carvedilol for my existing temperature problems but unfortunately it was a little too late as the effects of Carvedilol only work on hyperthermia during the neurotoxic response.

As jon Sprague stated " the 1 and
3-adrenergic receptors contribute to the mediation of 3,4-methylenedioxymethamphetamineinduced hyperthermia and drugs targeting these receptors, such as carvedilol, treat the psychostimulant-induced hyperthermia and its sequelae. Other nonselective -blockers like dantrolene (also used for reversing hyperthermia) may be of little or no benefit in MDMA-induced hyperthermia. Because Carvedilol completely reverses established hyperthermia and reduces elevations in serum CK levels induced by MDMA, it may, on the other hand, be an ideal candidate for the treatment of MDMA toxicity.

Carvedilol blocked the hyperthermic effects of MDMA when administered 15 mins before or after MDMA treatment. Moreover, carvedilol administration at the time of peak hyperthermia (1 hr post-MDMA, showing robust hyperthermia) completely reversed MDMA induced hyperthermia and significantly reduced muscle cell damage.

Jon E Sprague was nice enough to send me a .pdf of his findings if anyones interested I can send you the full report.

 

[kaskelot]

This is interesting. It'd be nice to have a copy.

 

[IlostaMadge]

That's fascinating, I think that this mechanism would reduce the neurotoxicity somewhat as well, studies have shown that the neurotoxicity varies dependant on temperature (as does methamps toxicity).

Off topic, but low dose selegiline as an MAO B inhibitor reduces MDMA neurotoxicity dramatically due to preventing breakdown of DA and MDMA metabolites, this means that the fine axon terminals don't suffer from oxidative damage.
It's bizarre, studies have shown that MDMA directly injected into the brain can release serotonin without the inherent neurotoxicity that MDMA carries, which means it might be a metabolite, but the exact metabolite is unknown, it is thought to be a monoamine though, as MAO B inhibition prevents damage.

Elevation of body temperature can seriously worsen possible MDMA-induced toxicity; and the thermogenic effect of MDMA is magnified in a hot environment like an indoor rave. Certainly, hypothermia-inducing agents are (partially) neuroprotective against Ecstasy damage; and the primary role of dopamine in MDMA-induced toxicity may actually be to elevate body temperature via its increased action on the dopamine D1 receptors rather than its uptake into the depleted serotonergic axon terminals. But consensus on the molecular mechanisms behind MDMA megadose-induced damage remains elusive.

 

[mad_scientist]

Coadministration of prazosin and pindolol also blocks MDMA hyperthermia quite effectively, but if carvedilol does it by itself then thats much more convenient only having to use one drug instead of two. Dantrolene combats rhabdomyolysis pretty well but if your MDMA overdose has progressed that far then you're in deep trouble regardless!

 

[kaskelot]

That's fascinating, I think that this mechanism would reduce the neurotoxicity somewhat as well, studies have shown that the neurotoxicity varies dependant on temperature (as does methamps toxicity).

Off topic, but low dose selegiline as an MAO B inhibitor reduces MDMA neurotoxicity dramatically due to preventing breakdown of DA and MDMA metabolites, this means that the fine axon terminals don't suffer from oxidative damage.
It's bizarre, studies have shown that MDMA directly injected into the brain can release serotonin without the inherent neurotoxicity that MDMA carries, which means it might be a metabolite, but the exact metabolite is unknown, it is thought to be a monoamine though, as MAO B inhibition prevents damage.

On topic: To me that seems quite established, the connection between different degrees of hyperthermia and neurotoxic strain, but I'm no scientist and has mostly mundane sources. If there is a direct correlation, it would be interesting to know in more detail what methamphetamine and MDMA has in common in this aspect, if it's metabolites or serotonergic effects or something more obscure, and also I'd like to know if the same pattern is appliable to mephedrone or piperazines with serotonergic effects, among other semilegal or similar compunds sold as MDMA-/ecstasy-substitutes on the market.

Off topic: That's fascinating.
So, MAO-B-inhibitors have been shown to reduce neurotoxic potential in MDMA? If so, then selegiline would make an excellent safety belt. If I haven't misunderstood the pharmacology, MAO-B-inhibitors such as selegiline does not call for specific diet or such, or affect the MDMA-experience negatively due to decrease in any of the sought after transmittor substances.

I have it, but have not read all of it, do you know if Julie Hollands book on ecstasy elaborates on these subjects along these lines?

 

[fastandbulbous]

I think they use dantrolene for controlling hyperthermia with other drugs etc., but it's a bit toxic in itself so it's not exactly risk free.

Selegeline is a known risk for hyperthermia when taken with other sympathetic amines, so not really a safety belt at all

 

[Enabled]

Not to mention the increased possibility of developing amphetamine psychosis.

Super fun in combo though.

 

[Limpet_Chicken]

Fast, just how bad is dantrolene?

From what I've read it sounds like small doses could be used as a muscle relaxant with opiates, I know its directly acting on muscles rather than CNS active as are conventional muscle relaxants, but it sounds like it could be alright.

Or am I barking up the wrong tree totally?