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Discussion => Drug safety => Topic started by: simantecort on September 21, 2012, 04:21 am

Title: New study shows serotonin and recognition damage following Mephedrone use
Post by: simantecort on September 21, 2012, 04:21 am
It seems, based on a few recently conducted studies, that mephedrone causes permanent recognition impairment in rats and temporary serotonin depletion (<10 days)

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045473
5-HT = Serotonin

Repeated high doses of MMC (4×10 or 4×25 mg/kg, I.P., once every 2 h), paired with elevated ambient temperatures (≥27°C), depleted 5-HT when measured 7 days later in rats [10]. This is an effect reminiscent of that seen with high doses of MDMA in laboratory animals [25], [26], [27], [28], although controversy continues as to the significance of such effects for humans [12], [29]. It is unknown whether the 5-HT depletion reported in rats following binge dosing with MMC is permanent. Secondly, recently published work by Freeman et al. [30] is suggestive of lasting cognitive impairment (as measured by a prose recall task) in human MMC users.

In the present study we therefore sought to clarify whether lasting decreases in regional levels of 5-HT or DA occurred following exposure to MMC in rats and to investigate the possibility that this treatment may induce lasting cognitive impairment. Our previous research has documented cognitive and social impairment in rats weeks or months after relatively brief exposure to drugs such as MDMA and METH [25], [27], [28], [31], [32], [33]. These effects are consistent with reports from other groups [34], [35], [36], [37].

In summary, our data confirm powerful acute effects of MMC on monoaminergic neurotransmitter systems. However, 10 days of chronic MMC did not appear to induce any overt injury or lasting alteration in DA or 5-HT systems. Despite this, the impairment of recognition memory observed in high-dose animals more than a month after the cessation of drug provides reason to suspect that MMC may still induce major neuroadaptations, albeit of a subtle nature not detected in the current study. Confirming this finding via replication and pursuing a mechanistic explanation for the observed impairment are obvious priorities for future studies.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Janus on September 21, 2012, 05:01 am
Yeah I guess I would immediately assume that when you induce these sort of conditions a priori. You're going to have increased expression of monoamine oxidase. The 5-HT receptor is going to be polyubiquinated and targeted for proteasome degradation as it's constitutively activated. And, over a long enough period induce alterations at the genetic level. However, you know there could always be some other physiology at play here than the horrid "brain damage". For instance say, these rats were developing an immune reaction to the substance over this sort of long period of abuse. They would of course become indolent as they did and as they did less social.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Novartis on September 21, 2012, 05:13 am
Is mephedrone the same as "bath salts?" If so I saw a documentary about this dude hooked on bath salts for about 6 months who developed permanent schizoaffective disorder and had to be confined to an institution.... there was also a news story I read about a homeless guy eating another homeless guy's face off while high on bath salts. That shit was legal at head shops up until a little while ago. Sad as hell if you ask me - I remember seeing kids fucking around with that shit bought legally from the shops.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: simantecort on September 21, 2012, 05:23 am
janus: indeed the conditions of the study seem rather sketchy when you consider that human mephedrone use is hardly similar to the administration performed in this study. i couldn't even fathom the idea of intravenous administration every 2 hours in a human, though similar studies conducted with other chemicals did not produce genetic changes like those seen here. and i agree that it is hard to pinpoint whether the social response was due to the vague colloquialism "brain damage" or due to some unseen force. in the end, however, the method of action is perhaps not as significant as the end result anyway; that is, after reading this, i don't care whether it induces chemically significant changes to my serotonin receptors, because the rat study reaffirms fears that mephedrone has permanent personality altering effects. i mean, come on, a dude ate another guy's face off. i certainly won't be trying it out!

sawyer
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Limetless on September 21, 2012, 07:04 am
Oh well I'm fucked then.  ::)
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: sniper123 on October 03, 2012, 01:23 am
Oh well I'm fucked then.  ::)
What about the lab rats using mdpv, meph, and meth on the weekends? I would immaine something along the lines of a nuke in the brain?
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: billybigbuds on October 03, 2012, 07:57 am
Yes, its well known that if you consume a LOT of anything it might have repercussions.

Methedrone, I know people who used 'normal amounts' and who seem to be fine.

Using too much of anytthing is bad for you. Even too much sex. Or alcohol, food, too much oxygen, too much salt, too much butter, beef, red meat, chicken and fish.

The moral of the tale is don't do a lot of anything until you know you won't drop dead.

 ;D

Good morining to fellow UK workers!
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: synikal12 on October 03, 2012, 01:04 pm
Yes, its well known that if you consume a LOT of anything it might have repercussions.

Methedrone, I know people who used 'normal amounts' and who seem to be fine.

Using too much of anytthing is bad for you. Even too much sex. Or alcohol, food, too much oxygen, too much salt, too much butter, beef, red meat, chicken and fish.

The moral of the tale is don't do a lot of anything until you know you won't drop dead.

 ;D

Good morining to fellow UK workers!
Except smoking pot. I'm at about a quad-half oz a day and I see very little repercussions. Hell I can stop smoking pot tomorrow and i'll be damn near the same person I was before  :P
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: JForce on October 03, 2012, 01:20 pm
I've heard that mephedrone is also 2-3 times more corrosive on the nose than cocaine.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: fuckoffehbuddy on October 03, 2012, 01:30 pm
Except smoking pot. I'm at about a quad-half oz a day and I see very little repercussions. Hell I can stop smoking pot tomorrow and i'll be damn near the same person I was before  :P
[/quote]
yeah i agree i'm about the same amount wise
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Limetless on October 03, 2012, 03:07 pm
I've heard that mephedrone is also 2-3 times more corrosive on the nose than cocaine.

Yeah that's about right too lol.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: painbow on October 03, 2012, 03:21 pm
uh oh spaghettio
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Niriane on October 03, 2012, 09:43 pm
I've heard that mephedrone is also 2-3 times more corrosive on the nose than cocaine.

Yeah that's about right too lol.

Any way to combat this? I've heard that some use a wet tissue to clean their noses, and others wash out their noses after snorting.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: b999 on February 20, 2013, 10:57 am
What about very occasional use, say once a month or something...  Does it screw up your sleep if you take it in the morning to have a roaring day?
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Macmeth on February 26, 2013, 02:01 pm
Have only had mephedrone 5 times, 1st time i was'nt well researched and thought about a 1/10 of a g would be right, went a bit harder and snorted it, ended up rushing and puking violently while the buzz got stronger, got to say about the worst reaction i have had to a drug. Took it 3 more times in caps and it was ok. Then took the last biggest cap tonight, have been on the meth pipe for 4 days. As it started to come on i got so fukin sick, worst i have felt nearly ever, the pain getting stronger and stronger due to the drug comming on. Ended up with a cvouple of painfull pukes and some violent stink arse shit. In the puke bowl was a pile of bloody, pulpy stuff. Still dont know if it was blood or some undigested food. There are many chems, over the counter meds that cause spontaneous bleeding so i dont know.
Slowed me up a bit got me thinking about retiring.

Oh and there was some bullshit article about a man eating some one on this stuff.
People with bad, anti social personalities do bad shit, on drugs they do badder shit
people with good manners and social concience get high, it does'nt change them into monsters.
The media, government agencys and the ever powerfull booze lobby groups put that shit out for the sheep to read. Dont believe anything that is published by a group with a vested interest unless you know it to be true
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: connoisseur on February 26, 2013, 05:18 pm
It seems, based on a few recently conducted studies, that mephedrone causes permanent recognition impairment in rats and temporary serotonin depletion (<10 days)

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045473
5-HT = Serotonin

Repeated high doses of MMC (4×10 or 4×25 mg/kg, I.P., once every 2 h), paired with elevated ambient temperatures (≥27°C), depleted 5-HT when measured 7 days later in rats...
That's as crazy as the 1970s study that tried to prove that cannabis is lethal by exposing mice to so much smoke that they died from a lack of air.

4x25 mg/kg means 7 grams of Mephedrone for a 70 kilo person taken within 8 hours. I have yet to come across a roller taking so much in one session.
Conclusion: This is absolute bullshit.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Limetless on March 05, 2013, 06:12 am
over 24 hours maybe lol.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: gtgeorgz on March 06, 2013, 12:47 am
I know of people that have gone through 6/7g's of Mephedrone in a day for repeated days as well (could be 4MEC though, or whatever they cut it with on the streets nowadays). But they have heart/circulation problems now.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Limetless on March 06, 2013, 01:13 am
I know of people that have gone through 6/7g's of Mephedrone in a day for repeated days as well (could be 4MEC though, or whatever they cut it with on the streets nowadays). But they have heart/circulation problems now.

Yeah been there done that, had to stop using it for bout a year for it to get to ok.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: gtgeorgz on March 06, 2013, 12:47 pm
Shit man, glad you're ok now though.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: DrugBuddy on March 06, 2013, 12:51 pm
Yeah been there done that, had to stop using it for bout a year for it to get to ok.

Wow hope you are ok Lim. What were the long term effects for you? Low mood? Skin or digestive problems? Mephedrone is so new it's not well understood yet. The study is flawed, but still insightful and we need more.

How do you find it now going back? I imagine you don't binge anymore.

Your DrugBuddy.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: kmfkewm on March 07, 2013, 08:49 am
imo mephedrone is absolute toxic shit. That said...

Claim:

Quote
Secondly, recently published work by Freeman et al. [30] is suggestive of lasting cognitive impairment (as measured by a prose recall task) in human MMC users.

Abstract of citation:

Quote
Design  A mixed within- and between-subjects design compared 20 mephedrone users, first while intoxicated (T1) and secondly drug free (T2); and 20 controls twice when drug free (T1 and T2).

Settings  Participants' own homes.

Participants  Healthy adults recruited from the community.

Measurements  Subjective effects, episodic and working memory, phonological and semantic fluency, psychomotor speed and executive control at were assessed at T1 and T2. Trait schizotypy, depression, changes in mephedrone use since the ban and attitudes influencing use of a hypothetical new legal high were indexed at T2 only.

Findings  Compared with controls, mephedrone users had generally impaired prose recall (P = 0.037) and higher scores in schizotypy (P < 0.001) and depression (P = 0.01). Mephedrone acutely primed a marked ‘wanting’ for the drug (P < 0.001), induced stimulant-like effects, impaired working memory (P < 0.001) and enhanced psychomotor speed (P = 0.024). Impulsivity in mephedrone users correlated with the number of hours in an average (nearly 8 hour) mephedrone session (r = 0.6). Users would be drawn to use a new legal high if it were pure, had no long/short term harms, and was positively rated by friends or on the internet.

Conclusions  Mephedrone impairs working memory acutely, induces stimulant-like effects in users and is associated with binge use. Factors that influence users' attitudes to new drugs might help to predict future trends in use of the many new psychoactive substances emerging on the internet.

They apparently tested the mephedrone users while high and then some unknown amount of time later while they were no longer intoxicated. The only conclusion they came to was that it caused an acute impairment in working memory.

In summary

Quote
Secondly, recently published work by Freeman et al. [30] is suggestive of lasting cognitive impairment (as measured by a prose recall task) in human MMC users.

versus

Quote
Conclusions  Mephedrone impairs working memory acutely, induces stimulant-like effects in users and is associated with binge use. Factors that influence users' attitudes to new drugs might help to predict future trends in use of the many new psychoactive substances emerging on the internet.

Unless the cited study goes into more detail than the conclusion of the abstract, the claim of lasting rather than acute cognitive impairment is not an accurate summary of the citation provided. At least if you take the word 'lasting' to be different from 'acute', which I certainly do.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Limetless on March 07, 2013, 11:17 am
Yeah been there done that, had to stop using it for bout a year for it to get to ok.

Wow hope you are ok Lim. What were the long term effects for you? Low mood? Skin or digestive problems? Mephedrone is so new it's not well understood yet. The study is flawed, but still insightful and we need more.

How do you find it now going back? I imagine you don't binge anymore.

Your DrugBuddy.

Nah I never got any Mephpression or anything like that. I just got a tweaky heart when using stims and some skin issues. And I binge yeah but just not as often as I did.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: Limetless on March 07, 2013, 11:19 am
Although having said that, I haven't had any issues from using my UC. Was only from the way-back-when shit.
Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: chil on March 07, 2013, 12:34 pm
imo mephedrone is absolute toxic shit. That said...

Claim:

Quote
Secondly, recently published work by Freeman et al. [30] is suggestive of lasting cognitive impairment (as measured by a prose recall task) in human MMC users.

Abstract of citation:

Quote
Design  A mixed within- and between-subjects design compared 20 mephedrone users, first while intoxicated (T1) and secondly drug free (T2); and 20 controls twice when drug free (T1 and T2).

Settings  Participants' own homes.

Participants  Healthy adults recruited from the community.

Measurements  Subjective effects, episodic and working memory, phonological and semantic fluency, psychomotor speed and executive control at were assessed at T1 and T2. Trait schizotypy, depression, changes in mephedrone use since the ban and attitudes influencing use of a hypothetical new legal high were indexed at T2 only.

Findings  Compared with controls, mephedrone users had generally impaired prose recall (P = 0.037) and higher scores in schizotypy (P < 0.001) and depression (P = 0.01). Mephedrone acutely primed a marked ‘wanting’ for the drug (P < 0.001), induced stimulant-like effects, impaired working memory (P < 0.001) and enhanced psychomotor speed (P = 0.024). Impulsivity in mephedrone users correlated with the number of hours in an average (nearly 8 hour) mephedrone session (r = 0.6). Users would be drawn to use a new legal high if it were pure, had no long/short term harms, and was positively rated by friends or on the internet.

Conclusions  Mephedrone impairs working memory acutely, induces stimulant-like effects in users and is associated with binge use. Factors that influence users' attitudes to new drugs might help to predict future trends in use of the many new psychoactive substances emerging on the internet.

They apparently tested the mephedrone users while high and then some unknown amount of time later while they were no longer intoxicated. The only conclusion they came to was that it caused an acute impairment in working memory.

In summary

Quote
Secondly, recently published work by Freeman et al. [30] is suggestive of lasting cognitive impairment (as measured by a prose recall task) in human MMC users.

versus

Quote
Conclusions  Mephedrone impairs working memory acutely, induces stimulant-like effects in users and is associated with binge use. Factors that influence users' attitudes to new drugs might help to predict future trends in use of the many new psychoactive substances emerging on the internet.

Unless the cited study goes into more detail than the conclusion of the abstract, the claim of lasting rather than acute cognitive impairment is not an accurate summary of the citation provided. At least if you take the word 'lasting' to be different from 'acute', which I certainly do.

This study (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045473)  says that :

Quote
However, no residual changes in 5-HT or DA tissue levels were observed at 7 weeks post-treatment. Overall these results show that MMC causes acute but not lasting changes in DA and 5-HT tissue concentrations. MMC can also cause long-term memory impairment. Future studies of cognitive function in MMC users are clearly warranted.

Title: Re: New study shows serotonin and recognition damage following Mephedrone use
Post by: chil on March 07, 2013, 12:48 pm
Here's an interview I've found from the guy who led the above-posted study, in which he explains in simple terms Mephedrone effects on the brain:

http://www.news-medical.net/news/20121016/Mephedrone-and-memory-loss-an-interview-with-Craig-Motbey.aspx

Quote
However, when we looked at the brains of the memory-impaired rats, we didn’t find any long-term changes in their neurochemistry: their dopamine and serotonin levels were the same as the control rats who hadn’t had any drugs. So, whatever it is that is driving the memory impairment it is not something as simple and as obvious as too much serotonin, for example. That’s the next big thing: working out the physical mechanism of the interaction of mephedrone and memory.

Quote
Q: Did your research show a correlation between the amount of mephedrone taken and the level of memory loss?

A: Correlation is too strong a word for it, but the memory impairment was only found with the highest dose used. The two lower dose groups did not show any memory impairment.