Study shows that "MDMA-induced neurotoxicity was dose dependently increased by LSD." Can anyone comment with more information?

What a half-assed study! What were the body temperatures of the groups?

This makes sense, though. LSD is a 5-HT2*_a/b/c_* agonist. If you agonize 5-HT2*_c_*, your body temperature is going to rise. Remember all my ranting about body temperature and MDMA induced neurotoxicity? Higher body temps lead to higher 5-HT system damage. Hydroxyl radicals are the cause of the 5-HT system damage, but body temperature plays a huge role in how bad that damage is.

So yes, LSD can exacerbate MDMA induced 5-HT system toxicity by agonizing the 5-HT2c receptors, consequently leading to increased body temperature, overwhelming your antioxidant systems. This study starts going off on a tangent about how since fluoxetine blocked 5-HT system damage even though temperatures rose, that means that temperature is not the cause. No shit dumbasses! Temperature is a mediating factor, not the cause. Alpha lipoic acid (a potent CNS antioxidant) also blocks 5-HT system damage even though temperature stays high. That does not mean your little experiment was a result of another mechanism surrounding 5-HT2*_a_*. MDL is a 5-HT2*_c_* antagonist as well, so it blocking the toxicity fits perfect with temperature rise being the factor here. They could have isolated that by taking body temp readings.

Most of their postulations in the discussion are flawed. I've read most of the studies they cite. There are some flaws in those studies as well, but it's mostly their interpretation of the studies that is the issue. I would be willing to bet that it was LSD's 5-HT2*_c_* agonism that led to a temperature increase, which exacerbated the MDMA induced toxicity by overwhelming the body's antioxidant system. It's not 5-HT2*_a_* agonism, it's the temperature increase.

The two MDMA metabolites, 2,5-Bis-(glutathion-S-yl)-alpha-methyldopamine and 2,4,5-trihydroxyamphetamine, are to blame for the actual damage. Alpha lipoic acid binds to both and protects the axons from being damaged. Fluoxetine blocks the SERT, preventing the hydroxyl radicals from entering the neuron. It also happens to inhibit CYP3A4, preventing the metabolism to MDA in the first place. Both of those block 5-HT system damage, while body temperatures are still high. THC lowers MDMA induced 5-HT system toxicity as well, by lowering body temperature. It does not prevent metabolism, nor does it block the SERT. However, the lowering of body temperature allows the body's natural antioxidant systems to remain efficient. However, if you block the metabolism, you block the whole cause of the 5-HT system damage to begin with. THA and the gluthathione conjugate of alphamethyldopamine are the real assholes.

So protecting from this is a threefold affair. One, block the metabolites by inhibiting CYP3A4. Two, keep your body temperature down. THC is good for this. Three, block your SERT at the end of your roll. Fluoxetine works well for this, as well as providing more CYP3A4 inhibition.

So redo the study, but have the rats smoke some marijuana and see if the 5-HT system damage still goes up. Or they could have just measured body temps to begin with...