[valec]

dosed reasonably (~125 mg with no redoses), ideally at lower ambient temperatures, and ideally with an SSRI at the end of perceptible effects to stop MDMA to keep circulating through the neuron and causing oxidative stress, you will quite literally see 0 axonal damage. maybe some neurotransmitter depletion, but this is only temporary.

PCA yes that is concerning but I would be extremely surprised if it ended up in the MDMA supply chain. MDMA is made cheaply at quantities several magnitudes higher than research chemicals. it's much more likely PCA will be sold as a cut for others RC's -- especially as a part of those dreadful cathinone soups labelled "3-mmc" these days

[Aurornis]

> you will quite literally see 0 axonal damage.

There is absolutely no scientific backing to support such an absolute claim.

The animal studies using SSRIs worked because they dosed the SSRIs before the MDMA. By occupying the serotonin transporter the MDMA is prevented from entering the neurons, which prevents the damage.

Taking an SSRI afterward might do something for the very tail end of the dose, but that's after most of the action and therefore most of the damage. You can't get all of the recreational effects, then block the transporter afterward and expect the same protection.

SSRIs are also potentially dangerous with MDMA due to the possibility of serotonin syndrome.

There have been numerous recipes floated around in drug circles for combating the neurotoxicity but they’re extrapolations and hypotheses, not firmly supported concepts.

[el_nahual]

What is the best resource for "safer" MDMA consumption? (Like, which SSRI to take and at what dosage).

Also, isn't mixing SSRIs and MDMA a huge no-no, given the potential for a serotonin storm/serotonin syndrome?

[cess11]

You should avoid SSRI:s adjacent to MDMA use. The hypothesis is that by blocking the serotonin transporter you'd avoid dopamine getting reabsorbed into serotonin vesicles, but there is very little evidence that this would work and there are obvious risks.

SSRI:s will give you a strong tolerance against serotonergic drugs and it will take a long time to lower that tolerance, months, maybe a year or two. As far as I know it hasn't been studied scientifically but I've seen people get quite uncomfortable experiences from MDMA and 5-HT2a-psychedelics (LSD, psilocybin, mescaline, those) after being off SSRI medication for several months, that I amateurishly attribute in part to downregulation of serotonin sensitivity.

A more acute risk is MAO inhibitors, which are sometimes prescribed as antidepressives. You're more likely to suffer acute damage or die from a combination of MDMA and an MAOI than with an SSRI, though neither is a good idea.

The Bluelight forums are a decent source of harm reduction advice, https://www.bluelight.org/community/forums/. Be aware that some participants in the discussions have problems with risky or abusive use, or give bad advice. Stickied guides tend to be of high quality, however.

[_bin_]

Nope. https://pubmed.ncbi.nlm.nih.gov/16472832/

2mg/kg dose, so ~160mg for an adult human. More importantly rat to human is usually a 6ish HED factor so that’d be <30mg. In reality metabolism, brain volume, etc all matter but this is not an even remotely safe drug.

Also taking SSRIs near MDMA administration is one of the worst pieces of what is doubtless intended as harm reduction advice I’ve ever seen. You don’t hand people a recipe for serotonin syndrome because of a small scale rat test or two.

[valec]

> Also taking SSRIs near MDMA administration is one of the worst pieces of what is doubtless intended as harm reduction advice I’ve ever seen. You don’t hand people a recipe for serotonin syndrome because of a small scale rat test or two.

you have a deep understanding of releaser pharmacology if you state this. don't take it from me though--matthew baggott, one of the leading researchers studying enactogen pharmacology recommends doing this exact thing

[_bin_]

Okay, I looked at Baggott's work a little more. Here are my primary concerns:

1. He's talking his book to a certain extent. This is his life's work and he runs a company in this space (though a B corp) so he will have a bias here. That's fine overall, as it may help balance people unfairly biased against psychedelics, but it's worth remembering. I'm not saying this to impugn his character so much as to point out everyone has biases, and someone in his position likely has strong ones, even if partially-founded.

2. He believes an SSRI alleviates negative symptoms, but we don't know it does more than alleviate the comedown. It appears his endpoint was cognitive performance post-use, not long-term damage that may appear once off the SSRI.

3. This doesn't touch the dopaminergic risks of amphetamines, which are substantial.

A few exploratory bits of research into one potential way to alleviate the acute effects post-administration don't translate to an established method to use this in a remotely-safe fashion.