Methylone and Mephedrones' long-term cognitive and neurochemical effects

[Folley]

I thought this was worthy of a re-post over here in ED where the people who use these chemicals can see it.

Abstract

INTRODUCTION/AIMS:
The use of cathinone-derivative designer drugs methylone and mephedrone has increased rapidly in recent years. Our aim was to investigate the possible long-term effects of these drugs on a range of behavioral tests in mice. Further, we investigated the long-term effects of these drugs on brain neurochemistry in both rats and mice.

METHODS:
We treated animals with a binge-like regimen of methylone or mephedrone (30mg/kg, twice daily for 4days) and, starting 2weeks later, we performed behavioral tests of memory, anxiety and depression and measured brain levels of dopamine (DA), serotonin (5-HT), their metabolites and norepinephrine (NE). 5-HT and DA transporter (5-HTT and DAT) levels were also measured in rats by [(3)H]paroxetine and [(3)H]mazindol binding.

RESULTS:
Mephedrone reduced working memory performance in the T-maze spontaneous alternation task but did not affect neurotransmitter levels aside from a 22% decrease in striatal homovanillic acid (HVA) levels in mice. Methylone had little effect on behavior or neurotransmitter levels in mice but produced a widespread depletion of 5-HT and 5-HTT levels in rats.

CONCLUSIONS:
Both methylone and mephedrone appeared to have a long-term effect on either behavioral or biochemical gauges of neurotoxicity in rodents.

http://www.ncbi.nlm.nih.gov/pubmed/23099177

 

[Renz Envy]

Why don't they also put an easy frame of reference in the study like "MDMA" or "Methamphetamine" so it's easier to gauge neurotoxicity? I also feel like MDPV would be quite interesting. I see MDPV as being quite possibly the most frightening abused designer drug of the decade. Sadly most people just know "bathsalts".

If nothing constructive comes of ED, I'll move it to ADD for the scientists to nitpick at.

 

[thabart]

Why do they use such ridiculous amounts in their studies? An average 80kg person would have to consume 2.4g twice a day, so almost 5g/d for 4 days. WHO consumes 20g in under a week? Of course they're gonna find some behavioural changes.

 

[JWills20]

Yeah I agree that the doses they administered are ridiculous and I don't see how they can rationalise testing such doses as only a minority would even consider administering that much, let alone actually do it. What's the point in this study really? I mean - brilliant - taking ridiculously large doses of serotonergic stimulants on consecutive days fucks up your cognition. Great, lets apply these results when stressing the dangers of 'bath salt' recreational drug use whereby doses are much, much lower and use is substantially less frequent. Just seems like the researchers are biased from the offset looking for adverse effects by administering far-fetched doses.

I'd much rather read a journal where they administer a standard recreational dose once or twice a week and then report there findings. I'd still regard this as abuse, but realistic abuse that could be applied to the real world and we could then stress the actual dangers of regular drug abuse.

 

[Heroic]

I'm surprised the rats survived.

 

[Dmytry]

I'm surprised the rats survived.

same, that much methylone would have caused my heart to explode

 

[Folley]

If nothing constructive comes of ED, I'll move it to ADD for the scientists to nitpick at.

It's already been posted in Drugs In The Media, so that's not really necessary



if they were giving normal doses though, they wouldn't be able to see any changes. They would be there, don't get me wrong, but I don't believe they have equipment sensitive enough to tell the kind of change that occurs after one 100mg dose... they need to basically blitzkrieg the receptors with neurotoxins to be able to tell where the damage is caused. You scale back that damage ratio wise depending on how much people are actually taking, and at the least you know what receptors and other areas of the brain are being damaged by abuse of these drugs.


20g in a week might seem a bit crazy to some, but let's not forget that some people are going multiple grams of mephedrone a day, or eating through giant packages of methylone every week. It's not really that out there for heavy abusers

 

[JWills20]

It's already been posted in Drugs In The Media, so that's not really necessary



if they were giving normal doses though, they wouldn't be able to see any changes. They would be there, don't get me wrong, but I don't believe they have equipment sensitive enough to tell the kind of change that occurs after one 100mg dose... they need to basically blitzkrieg the receptors with neurotoxins to be able to tell where the damage is caused. You scale back that damage ratio wise depending on how much people are actually taking, and at the least you know what receptors and other areas of the brain are being damaged by abuse of these drugs.


20g in a week might seem a bit crazy to some, but let's not forget that some people are going multiple grams of mephedrone a day, or eating through giant packages of methylone every week. It's not really that out there for heavy abusers

That could be a potential reason why they administer such large doses. However, surely that just suggests that recreational use doesn't significantly effect cognition and is therefore safe. It's almost as if they're looking to find negative effects by administering blitzkrieg doses. But at least its useful for determining the sites and receptors for damage and whatnot. I'd like to read the journal to see there rational behind such doses and what practical implications they suggested.

 

[Folley]

You're right. With one responsible dose, there is no measurable change... but we KNOW there is a change when abuse occurs, so they need to come up with certain models that can represent this abuse, but take place in a matter of weeks and not years.


It's just simply too time consuming to try and dose a group of mice every week, it would exponentially increase the costs of the study.

 

[franksidebottom]

Interesting what isn't depleted after four days of eating the equivalent of 5g/day... I'd expect my brain to be porridge 2 weeks after that kind of binge.