Think of it like this, specifically for SSRIs and psychedelics: Different drugs will bind to receptors in the brain that would normally be triggered by serotonin. Psilocybin, DMT, serotonin, melatonin, etc, are all basically the same "shape" as tryptamine, a precursor to most of those. The effects of different chemicals finding a place in serotonin specific receptors that have the same shape can be wildly different than serotonin.

To use a car analogy, its like putting pure ethanol in your fuel tank instead of gasoline. They are both flammable liquids that you can pour into your car as fuel, but they burn at completely different rates and can alter performance significantly.

What this does as far as serotonin is concerned, is that serotonin is more widely available to the rest of your brain. In the case of antidepressants like SSRIs, they function the same way but only bind with specific receptors and don't cause you to get high and trip. This allows serotonin to be more evenly used across the brain, in a manner of speaking.

As far as tolerance is concerned, different drugs will bind to receptors in different ways. Once you have "saturated" a receptor, it takes a while for it to be ready for another round. Psilocybin and even ketamine are being shown to be hundreds of times more potent than common SSRIs (in some ways), so it takes a while for those affected neurons to "recover". It's not that you have depleted your serotonin, it's just that natural serotonin has fewer places to bind to.

It's very important to realize this distinction. Combining SSRIs with other drugs can cause an extreme excess of serotonin in your noggin. Serotonin has no place to go so it builds up and causes a condition called serotonin syndrome. It's not a good thing and can be fatal.

My explanation absolutely does not cover all the details. However, it is just supposed to be a shift in how you think about how these chemicals work.

[–] TWeaK@lemm.ee 2 points 1 year ago (1 children)

specifically for SSRIs and psychedelics

Would you group MDMA in this classification? I don't think MDMA is an SSRI.

"Psychedelic" is also a much more wide ranging classification. MDMA isn't really a psychedelic.

SSRI's directly affect the body's absorption of serotonin, meaning serotonin lingers around more. My hypothesis is that MDMA affects the release of serotonin, specifically it sustains the natural release for longer.

[–] remotelove@lemmy.ca 3 points 1 year ago* (last edited 1 year ago) (1 children)

MDMA is classified as an amphetamine. It has some characteristics of a psychedelic as it is similar, structurally, to mescaline. You get the speedy effects as well as trippy effects, basically. It has a more distributed effect on dopamine and serotonin receptors but the concept is basically the same as far as how neurons "interpret" drugs.

In the case of MDMA, it does increase serotonin, dopamine and noradrenaline levels. So, by using your gland analogy with MDMA makes more sense in that these chemicals will be depleted and can leave you feeling like garbage the next day. Combine that with how neurons "see" different drugs, and that is more of a complete picture. You can only force feed your brain so many neurotransmitters before it needs to recover.

Serotonin syndrome is also a risk with MDMA. Not only are your neurons making more serotonin, it may not have a place to go.

[–] TWeaK@lemm.ee 5 points 1 year ago (2 children)

Yes, MDMA is an amphetamine, as per the name. However it is significantly different to mescaline, which has an extra functional group off the carbon ring. In 2D the molecules look very similar, but in 3D they're very, very different, and as such their function differs also. Mescaline is hallucinogenic, MDMA is not particularly so.

I'd be hesitant to attribute speedy effects to MDMA, in particular with tablet form, in which various drugs tend to be mixed. MDMA in pure form has nowhere near the same stimulant effect as speed, or ecstacy pills laced with speed or whatever else.

I don't think MDMA alone is likely to cause serotonin syndrome, however mixing it with SSRI's most definitely would be a high risk. Rather, the common issue with MDMA, particularly with excessive use over time, is serotonin depletion.

[–] remotelove@lemmy.ca 4 points 1 year ago

Chemical discussions aside, MDMA cut with other drugs is nasty. The hangovers from mixed MDMA are horrid, to say the least. More days of my youth than I would like to admit were spent in bed because of that trash.

Risk is risk. I hope that someone reads our discussion to be more familiar with those risks, TBH. Drugs are drugs, and drugs affect people in different ways.

But sorry if I got distracted with psychedelics rather than MDMA. I haven't read into MDMA in a while. I have been so entrenched in the mushroom world for a bit that everything reads like a conversation about psychedelics. (That spawned a yet another hobby of growing gourmet and medicinal mushrooms, but I digress.)

[–] lolcatnip@reddthat.com 2 points 1 year ago* (last edited 1 year ago) (1 children)

I've done MDMA many times, and unless I got it contaminated the same way every time, it definitely has a strong stimulant effect.

I should probably note that I did a reagent test on many of the batches I got, so I'm fairly confident it was the real thing.

[–] TWeaK@lemm.ee 1 points 1 year ago (1 children)

It has some stimulant effects, yes, but it's not as strong as speed and relatively weak compared to other amphetamines.

[–] lolcatnip@reddthat.com 1 points 1 year ago

Not as long lasting. "Not as strong" really depends on the dose. I take Adderall now and it's a lot milder than when I did MDMA.