Reversing tolerance with psychedelics/MDMA?

[Tussmann]

The dopamine theory has been largely discredited, and the oxidative stress theory which sekio mentioned is currently in vogue. However with MDMA induced neurotoxicity there is more going on than simple oxidative stress, including events in which the main endogenous antioxidant, glutathione, may actually be required for MDMA to damage neurons.

But then how do supplements that aid glutathione production such as NAC and ALA have a protective effect on MDMA related damage.

 

[Epsilon Alpha]

But then how do supplements that aid glutathione production such as NAC and ALA have a protective effect on MDMA related damage.

Well its a multifaceted issue, oxidative stress does play a large role in apoptosis however its by no means the only thing going on in a 5HT neuron exposed to MDMA. Its kind of like a bunch of additive factors leading to the cell's death, and suppressing a few of those factors may lead it to try to repair itself rather than self destruct.

I'm very interested to hear what you think about MIN and its relation to (meth)amph toxicity. What's your take on how exactly the glutathione alpha-methyldopamine conjugates cause MDMA-like damage? Do you think it fits in the transporter? I would be surprised, but I don't see it causing that much damage outside the cell... Amino acid transporters maybe?

Well I haven't seen any studies detailing the exact mechanisms they undergo, but a pet theory is that it ends up binding to a very unexpected receptor like Fas or triggering some novel allosteric site on another receptor triggering that extremely difficult to prevent post exposure toxicity. It also might be a case of immune modulation as I'm starting to believe it is for methamphetamine as well, though I don't have any direct studies to support that conclusion.

I actually wouldn't be surprised if it was taken up by a transporter ala bromo-benzene after being conjugated. Transporters are weird like that, in fact the conformation favored by the transporter plays a retardedly large role in how a drug is "felt" (see modafinil vs cocaine at the DAT) but thats off topic.

 

[DeathDomokun]

Drugs, as I'm sure you are aware, don't usually induce the best survival traits.

Actually no, I am aware of quite the opposite. Something like McKenna's theory on psilocybin and evolution..

 

[jobe28]

It's just the brain trying to maintain homeostasis. We behave the way we do for a reason: it's been successful at keeping us alive and getting us successful offspring. So, the brain has been programmed to try to maintain those normal behaviors. Drugs, as I'm sure you are aware, don't usually induce the best survival traits.

Actually no, I am aware of quite the opposite. Something like McKenna's theory on psilocybin and evolution..

I don't understand what either of you are saying. What do you mean by 'survival traits'. Overall I would say it has no effect on your ability to survive.

 

[atrollappears]

lol I'm not familiar with McKenna but it's rather clear to me that, if our baseline behavior was similar to that when on psilocin or MDMA, we would not have survived long in the wild. Perhaps McKenna was talking about the potential for temporary changes in state to facilitate insight that becomes useful in one's normal state?

Edit: Having read wikipedia's article on McKenna's theory, I think he needed a lesson in natural selection... hahaha

I don't understand what either of you are saying. What do you mean by 'survival traits'. Overall I would say it has no effect on your ability to survive.

Perhaps in our, recently developed, highly forgiving environment :/

 

[DeathDomokun]

Do you honestly expect me to argue with your ridiculous claims when your name is "atrollappears"?
I'm not insinuating our baseline perception being similar to tripping balls and you know it.
Learn more

 

[MeDieViL]

A few anecdotes indicate that high doses of st johns worth for 2 weeks restores the magic; look for that thread on the forum where everyone loves to take a swim after they smoked some crack with their cat.

 

[atrollappears]

Do you honestly expect me to argue with your ridiculous claims when your name is "atrollappears"?
I'm not insinuating our baseline perception being similar to tripping balls and you know it.
Learn more

Hey I didn't mean to be offensive, but his theory just didn't make much sense to me on a few counts. If you would like to discuss it I would be happy to do so over private messages.
Yes, I'm sure McKenna was aware that if we were tripping balls all the time that would not be good for our survival, but if you look back to what started this conversation you will see that that's the only point I was trying to make, one about homeostasis.

A few anecdotes indicate that high doses of st johns worth for 2 weeks restores the magic; look for that thread on the forum where everyone loves to take a swim after they smoked some crack with their cat.

Really? Strange. But then again hyperforin is a strange chemical. Could you possibly link to this thread? (also I laughed at your description of that forum)