Seems like a very useful animal study would be to compare high-dose or rapidly-repeated-low-dose MDMA with and without various common mitigations and supplements, and look at autopsied brain damage—I assume none of these have been done yet?
I asked Claude to research it and looked at some of the studies it turned up.
Ma et al administer (nothing, MDMA, DXM 5 minutes before MDMA) to 3 monkeys each and use radioisotopes to look for sertonergic abnormality 24 and 30 months after administration. The DXM sure looks like it helps but also there are literally just three monkeys in this image, maybe the middle guy just didn’t have very many serotonin transporters to start with?? Maybe I can email the authors and get the raw data.
(Also they give these monkeys a lot of DXM—these are not cough suppressant dosages, the monkeys are probably tripping balls even without the MDMA. And DXM+MDMA is generally considered a dangerous combination—if you look up trip reports on Erowid they reliably describe having a bad time that lasts for days—so I would not try this on humans.)
Malberg et al find that after giving rats high-dose MDMA (recreational dose would be like 1mg/kg and they do 20 or 40) and autopsying brains 2 weeks later, serotonin levels were much lower on the rats who spent their MDMA trip in a high-temperature room than in a low-temperature room. 8 rats for each of the 18 experimental conditions.
Aguirre et al find that alpha-lipolic acid cuts serotonin decrease in half a week after administration, though they used a temperature-controlled room at 22ºC which the above study claims doesn’t decrease serotonin, so idk. They also use 8 rats per experimental condition, but they only have 4 such conditions so I trust them a bit less.
Shankaran et al find that vitamin C substantially decreases 2,3-DHBA during the trip but don’t look at effects afterwards.
As far as Claude could tell, no one’s ever done human RCTs for MDMA mitigations and looked at cognitive or neurochemical effects afterwards.
Before trusting the rat data, I’d want to investigate how similar their reaction to MDMA is to humans. When I did the comparison with ketamine I found out there is no known anesthetic dose of ketamine in mice and rats, you always combine it with another drug, which makes me think rats+mice are not useful models of ketamine’s effects in humans.
Seems like a very useful animal study would be to compare high-dose or rapidly-repeated-low-dose MDMA with and without various common mitigations and supplements, and look at autopsied brain damage—I assume none of these have been done yet?
Not that I found in 2018, at least.
I asked Claude to research it and looked at some of the studies it turned up.
Ma et al administer (nothing, MDMA, DXM 5 minutes before MDMA) to 3 monkeys each and use radioisotopes to look for sertonergic abnormality 24 and 30 months after administration. The DXM sure looks like it helps but also there are literally just three monkeys in this image, maybe the middle guy just didn’t have very many serotonin transporters to start with?? Maybe I can email the authors and get the raw data.
(Also they give these monkeys a lot of DXM—these are not cough suppressant dosages, the monkeys are probably tripping balls even without the MDMA. And DXM+MDMA is generally considered a dangerous combination—if you look up trip reports on Erowid they reliably describe having a bad time that lasts for days—so I would not try this on humans.)
Malberg et al find that after giving rats high-dose MDMA (recreational dose would be like 1mg/kg and they do 20 or 40) and autopsying brains 2 weeks later, serotonin levels were much lower on the rats who spent their MDMA trip in a high-temperature room than in a low-temperature room. 8 rats for each of the 18 experimental conditions.
Aguirre et al find that alpha-lipolic acid cuts serotonin decrease in half a week after administration, though they used a temperature-controlled room at 22ºC which the above study claims doesn’t decrease serotonin, so idk. They also use 8 rats per experimental condition, but they only have 4 such conditions so I trust them a bit less.
Shankaran et al find that vitamin C substantially decreases 2,3-DHBA during the trip but don’t look at effects afterwards.
As far as Claude could tell, no one’s ever done human RCTs for MDMA mitigations and looked at cognitive or neurochemical effects afterwards.
Before trusting the rat data, I’d want to investigate how similar their reaction to MDMA is to humans. When I did the comparison with ketamine I found out there is no known anesthetic dose of ketamine in mice and rats, you always combine it with another drug, which makes me think rats+mice are not useful models of ketamine’s effects in humans.