MDMA neurotoxicity prevention

[JWills20]

See this paper from Gary Gudelsky and colleagues: http://www.ncbi.nlm.nih.gov/pubmed/7698172

This paper used ridiculously large doses of both MDMA and DOI/MeODMT. Neither of which are very similar to classic psychedelics, including LSD, nor are the doses near to human recreational usage. So there's no way this paper supports your comment that

Classical psychedelics, including LSD, increase the neurotoxicity of MDMA.

. Many people combine psychedelics with MDMA successfully. Sure, the comedown might be harsher and the experience can be mind-bending but a significant increase in neurotoxicity - unlikely. Especially since neurotoxicity from MDMA is highly unlikely to actually occur at human recreational doses anyway (100-300mg).

Taking an SSRI before MDMA greatly reduce the emotional effects of MDMA.

This is correct.

MDMA and anti depressants can cause seratonin syndrome

This is not correct. Remember that serotonin syndrome = massive amounts of serotonin in the brain. So if SSRI's reduce the amount of serotonin released from MDMA, and hence why the emotional effects are reduced, serotonin syndrome is the absolute opposite to that.

 

[terarc]

Yeah I don't think that study really proves that psychedelics increase neurotoxicity. Even if those effects were replicated in humans at normal doses with all psychedelics, less serotonin afterwards and more dopamine during might make you feel shit but doesn't necessarily equal 'damage' or neurotoxicity. As I've already said, MDMA injected directly into the brain causes no damage even though serotonin and dopamine are released, so obviously levels of either of those aren't causing the problem. The best current theory is that the issue comes from metabolites created by a certain enzyme, which can be inhibited by things like Prozac and certain other SSRIs, by certain supplements, maybe grapefruit juice etc. there's a very interesting post on reddit by a guy who's done a lot of research into it but I cannot find a link right now. I think the only damage resulting from something outside of these metabolites is down regulation or reduction of serotonin receptors due to abuse of the drug over a period of time, which can be avoided simply by not abusing it, and perhaps remedied by something like Saint johns wort which upregulates and promotes neurogenesis of those receptors.

But again, you really are overplaying the risks here. by all means take precautions of course, that's never bad, but playing around with pharmaceuticals in combo with MDMA requires some care, and if you're not sure of anything, the 'damage' you'll get from one average dose of MD as a one off is nothing you're gonna notice or miss, and even if you did, you'll be feeling fine again a week or two later

 

[MBaggott]

This paper used ridiculously large doses of both MDMA and DOI/MeODMT. Neither of which are very similar to classic psychedelics...

You seem to be unfamiliar with the scientific term "classical psychedelics". It doesn't just mean drugs that played in big stadiums in the 1970s. It means psychedelics that have their trippy effects by stimulating 5-HT2A receptors. See, for example, the beginning of this Richard Glennon review: http://eywa.maps.org/w3pb/new/1991/1991_glennon_1136_1.pdf

My other comment is that people's experience taking a drug combination is not evidence for or against neurotoxicity. We can't really measure it in living people, so when anyone says anything about MDMA neurotoxicity they are either talking about animal studies or they are deeply confused.

As I've already said, MDMA injected directly into the brain causes no damage even though serotonin and dopamine are released, so obviously levels of either of those aren't causing the problem. The best current theory is that the issue comes from metabolites created by a certain enzyme, which can be inhibited by things like Prozac and certain other SSRIs, by certain supplements, maybe grapefruit juice etc.

The neurotoxic metabolite theory isn't proven or widely accepted in science. While infusing MDMA into rat brain hasn't caused toxicity, it is hard to do that in a way that keeps the concentrations high for hours, which we know is needed for the neurotoxicity. Instead, the MDMA drains from the brain compartment into the larger body compartment. The result is that the levels of MDMA don't stay high enough for long enough to cause toxicity. So the brain studies aren't a clear result.

Two other theories of toxicity are that dopamine gets oxidized to a known neurotoxin (this was Dave Nichol's theory) and that the serotonin neurons basically get overworked to death ("energy exhaustion") with the high metabolic activity depleting energy sources and increasing oxidative stress. My guess is that the truth may be a combination of all the theories.

Even if the toxic metabolite theory is true, it seems to me it might be very difficult to prevent with metabolic inhibitors. Most of these metabolites form through multiple enzymatic and some nonenzymatic pathways. The formation of DHMA has blood levels similar to MDMA and often higher within the first hour or two after dosing.

 

[MBaggott]

My friend has ventured to do his last weekend and he said it immediately terminated the high after he took celexa at 4 hours. However he had no hangover and no problem functioning immediately after, which leads me to believe this could prevent a lot of damage since after the 3-4 hour mark is when the neurotoxicity happens.

This. This should be the takeaway for anyone reading this thread.

 

[MagickalKat777]

Celexa is a heavy hitter. But there is an inherent risk mixing these drugs. Just take your reasonable dose of MDMA and take your comedown. Using other substances can mess up transmission of other chemicals. The comedown is part of the experience.

 

[DrTechno]

Sorry for reviving an old thread. Was reading and want to help the person for future use if he/she was able to get their hands on some SSRIs. There are multiple studies showing significant and/or complete protection with Celexa(citalopram) from mdma damage.

As J. Schmidt et al. has pointed out in their 1987 study, MDMA has a biphasic stage of serotonin depletion. First phase reaches maximum depletion at around the 3hr mark, with serotonin levels returning back to normal in around 24hours, than the second phase of serotonin depletion starts. Aparrentely this second stage of serotonin depletion is cause by neurotoxicity and is why people are usually saying serotonin levels take a month etc etc to restore. Rats given both Citalopram and Fluoexetine(Prozac) have showed nearly or complete protection against neurotoxicity which was calculated by reduction in SERTS, Serotonin, and one of it's metabolites.

I can point you out to more studies.

If you don't have any reaction to the SSRIs there is nothing wrong with taking one. In my personal experience, the only thing that helped me whenever I took a huge MDMA abuse dose was taking an SSRI afterwards. End the high instantly, you can sleep better, no brainshocks, no weird dreams etc. And no, there shouldn't be any risk of serotonin syndrome with SSRIs and MDMA, but don't combine them with 5HTP.