THC Prevents MDMA Neurotoxicity in Mice

[steppa]

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg ×4) were pretreated with THC (3 mg/kg ×4) at room (21°C) and at warm (26°C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB1 receptor antagonist AM251 and the CB2 receptor antagonist AM630, as well as in CB1, CB2 and CB1/CB2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB1 receptor antagonist AM251, neither in CB1 and CB1/CB2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB2 cannabinoid antagonist and in CB2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB1 receptor, although CB2 receptors may also contribute to attenuate neuroinflammation in this process.

THC Prevents MDMA Neurotoxicity in Mice (2010)

 

[Leithen]

Wow very interesting. Thanks for sharing! :d

 

[Nathanial.Dread]

Typical human doses of MDMA are 1-2 mg/kg, and *most* people don't use multiple times per night, certainly not over the course of 8 hours. Sure some do, but that's not a representative sample.

Consequently, these mice were getting 40-80x more MDMA than the average user will get. While certainly an interesting result, anyone who tries to generalize this to humans is making a few leaps of logic too many to be taken seriously.

Blessings
~ND

 

[null24]

Typical human doses of MDMA are 1-2 mg/kg, and *most* people don't use multiple times per night, certainly not over the course of 8 hours. Sure some do, but that's not a representative sample.

Consequently, these mice were getting 40-80x more MDMA than the average user will get. While certainly an interesting result, anyone who tries to generalize this to humans is making a few leaps of logic too many to be taken seriously.

Blessings
~ND

Forgive my medical ignorance, Natty, but would not the effects seen at large doses be reflected in smaller ones ? I'll agree this all sounds very suspect to me; when I used to do lots of XTC, I would also get stoned and would still suffer the effects afterwards, That's why I quit and won't do it now.

Can you maybe clarify for the denser brained among us what you mean?

 

[Nathanial.Dread]

but would not the effects seen at large doses be reflected in smaller ones

That depends on a lot of factors. Some drugs will display a certain effect at one dose, and then a completely different effect at another (apomorphine being one example, ketamine, which is stimulating at low doses is another), and so they can't always be sure that the effect they're seeing is one that any recreational user would ever experience.

It's also intellectually dishonest, in my opinion. All of this research on MDMA is, ostensibly, so that we can learn about how this drug interacts with humans, so we can make informed policy choices and make appropriate treatment decisions. No one is taking MDMA like this (it would be like taking multiple grams over the course of a night), but, when the time comes to make choices, this kind of thing is what will be cited as evidence in the discussions.

We've already seen the damage of this - back in the 80s and 90s, a lot of the studies that laid the groundwork for the MDMA/Neurotoxicity belief were completed in monkeys who where injected with absurdly high doses of MDMA a ridiculous number of times. It's not surprising that some toxic effects were found, at a certain dose, every drug becomes a poison. If I did the same thing with Tylenol, you'd also see terrible hepatic damage. Does that mean that we ban Tylenol because it's hepatotoxic? No, we just control the dose.

Blessings
~ND

Blessings
~ND

 

[null24]

Thanks. Of course I understand that the psychoactive effects of drugs are those deep in that often, and as you pointed out sometimes lower doses can have significantly alter the books that higher ones, stimulants becoming depressive etc. I guess this extends to any other type of activity as well such is that mentioned in the article.

Your point well made and taken.

 

[downwardsfromzero]

[...]
We've already seen the damage of this - back in the 80s and 90s, a lot of the studies that laid the groundwork for the MDMA/Neurotoxicity belief were completed in monkeys who where injected with absurdly high doses of MDMA a ridiculous number of times. It's not surprising that some toxic effects were found, at a certain dose, every drug becomes a poison. If I did the same thing with Tylenol, you'd also see terrible hepatic damage. Does that mean that we ban Tylenol because it's hepatotoxic? No, we just control the dose.
Blessings
~ND

That Ricaurte study didn't even use MDMA, somehow they 'accidentally' used meth :? The eventual retraction is quite famous for how it totally failed to be splashed across the media the way the original "study" results were.