Sensitivity developing with time?

[Espiritus]

Has anyone noticed an increased sensitivity to MDMA over time? Like you find the standard dose too much so you start taking only 70mg. Also you start getting more come up anxiety. If so, what is the reason for this?

Also, it seems that a person can no longer react well to the drug after some time despite having no issues for a long time. I knew someone who used to be able to roll normally and she wasn't abusing it. But eventually, just started vomiting every time she took it. She said she was getting too old for it maybe. Could that really be the reason though? Man I hope I can enjoy rolling for a while longer without developing nasty problems. I'm already worried noticing my increased sensitivity and anxiety on the come up.

 

[LabRat74]

Its a common phenomena actually i know several people who for one reason or another have had this happen. There's possibly a correlation with age and the brains capacity to handle that level of NT, or maybe something glutamate related.

I have a friend who gets psychosis *every single time* he takes mdma now after previously abusing that and ketamine a lot. Nmda antagonists reverse tolerance for many other drugs including amphetamines so his ket abuse may have played a factor, but we believe it was (to be pretty unscientific) just largely his body having had enough of the shit lol.

Another friend was completely resensitised to mdma and in fact almost all drugs (particularly cannabis which later induced a 6 month bout of agoraphobia which persisted even when he stopped smoking, he was a heavy smoker before and is again) after an incident whereby he siezed on ecstasy. He can still take mdma but in much lower doses now. He gets bad paranoid rage and anxiety on too much now.

Yet another friend of mine siezed after an incident presumably induced by a drop in temperature. It's cold outside in Scotland but hot and sweaty in clubs. He had a whole.pill when it was wise to take half. Totally fine all night. Came out and the drop in temperature caused a seizure which for the record is always a possibility as it increases brain heat and speed of neurotransmission and for analogy if the temp suddenly drops then the engine stalls. He ended up getting pneumonia in hospital later. After the incident he was anxiety ridden and all drugs, again particularly cannabis, had a very pronounced effect on him and induced extremely anxiogenic thought patterns.

The last individuals state that the anxiety is very much centric round the thought of the siezure coming on again and it seems that harsh or pronounced physiological/psychological changes are enough to invoke this fear. It's worth noting that it's similar to how.my first friend experiences the psychosis, it's the initial fear that he might loop that seems to trigger the first loop. We did a not so safe experiment to find out what the threshold for the loops was (turns out it was 30mg lol) and at that point he was aware enough to know he was becoming paranoid and not go delusional but still starting to get the niggle.

So on a lesser level / for those not being hospitalised or going psychotic, it's probably more than possible that the condition reflex is being triggered by a negative experience not just a neural or physical change.

However, if people are inducing brain damage/neurotoxicity then this triggers a glutamate release in the brain and in the case of traumatic injury or *possibly something like a drug induced siezure* it gets dumped en masse. Lots of glutamate is not good for you and as noted above it increases sensitivity to other substances by increasing excitatory response. This in itself is neurotoxic.

 

[Swim15]

I’d bet money that it’s related to changes in 5HT synthesis, transport, and kinetics.

All of this stuff - especially 5HT related - is closely tied to our guts/gut health and we’re learning even more about how microbiota impact kinetics of serotonin.

Using MDMA, as well as environmental factors, causes changes in the brain and gut so we are not the same after MDMA as we were before.

The vomiting is likely related as well since antagonism of the 5HT3 receptor is the mechanism for anti-nausea drugs. Lotta interaction with the vagus nerve via multiple pathways

 

[Espiritus]

Wow! I didn't know the seizure in colder temperature thing! I'll have to keep that in mind. I have to research more about glutamate and 5HT synthesis.

 

[Hilopsilo]

Yep, been taking MDMA for ~10 years now, I've only ever taken 100mg in a single dose in a night, and often times I get this feeling especially during the comeup that its too intense and im literally going to OD/drop dead. Every damn time during the comeup I swear next time I'll try just 75mg, but everything ends up swell so I suck it up and take 100mg. I think part of this is that I take drugs on average less and less as time goes on, less time to party, more time spent being a civilized member of society, I get less used to the state of being loose as fuck in general, so when it does happen I feel less prepared for it than I used to. I can't imagine increasing the dose, if I took a cap and my friend then said "oh oops I gave you mine thats 150-200mg", I'd be in the bathroom trying to puke it up so fucking fast, I swear I'd actually die

I'm probably about 65kg, have been since I ever started taking MDMA