How toxic is Mephedrone?

[Josama]

Well,thought it would be good too also add my experiences with meph.I used it 3 Weekends in a row.Thought that it wasn't meph alone,it were caps containing a mix of 125 mg meph and 125 methylone.

The first night I took one pill and drank one vodka redbull(red vodka).The first thing that I noticed whas that the crown of my head was cribbling,while on it,feeled like someone was massaging head.(this happened every time)
The day after I only had a slight comedown(I never did any drug expect Cansbis before that).
The first 4 days after I noticed an increase in concentration,calmness and engery.(good,not nervous)
On the 4 day I had sports in school and noticed that my at the place of my head where I got that cribbeling It hurt(well it did't really hurt,felt like somebody would pick you with a pencil) when running around,but faded after 2 hours of sports(I think this is actually from the methylone?).The same afternoon I noticed some moprphing of the lanscape when watching in the same place for serveral seconds(this was gone the next day and didn't come back)From the 4 day onwards I began feeling nervous,but in a good way.

The second Time effects seemed too be a litte decreased at the same dose.
The second time I only drank coca cola.Effects dured not quite as long as first Time and the comedown was also worse.
The second day after taking it,I feeled for the first time a real side effect,suddenly while sitting in class I became pretty hot and started sweating,the sweat smelled like mephedrone.Luckily it only dured less than a minute and felt noticebly better after.This time also while doing sports my head hurt.

The third time I took 2 caps at once so a mix of 250 mg methylone 250 mg mephedrone.The only it time I had jaw clenching,but only for half an hour or even less.Drank only coca cola again,had the worst comedown yet the day after,also craving,but countered that with canabis.
2 days after I felt tired and had nomotivation but wrote 52/60 points in my history test(I never had on above 50 since primary school)On the End of the test I began feeling somewhat ill,after the test in the next lesson I felt asleep and after waking up I again became hot and began sweating for less than a minute,this time sweat didn't reek like meph thought.I decided to go home and after I stood up I felt dizzy for a few seconds, again I began sweating a little but faded again after less than a minute.When I arrived at my home I took one rathiopharm grippal C+,eat something a slept for an hour,after waking up took another RG C+ and an hour later felt complety fine again.

Also note that the first and the third time I danced like crazy while the second I was for the most part writing messages with my phone.
The tree times,I never feeled the slightest increase in heart rate as when to compared when I drink a cup of coffee my heart feels like it has doubled it's speed.Also I have ADD.And I smoke 25 cigarettes day(if that is relevant)

So,hope this helps a little


PS: I wrote this while complety sober

 

[4-OH]

^

Sorry Jo, but it's really hard to read if it's one block of text, could you separate it into paragraphs so I can read it and respond

 

[Josama]

Divided in 3 paragraphes,hope that's better.

 

[vecktor]

can people stop posting inane mephedrone trip reports in this thread, unless your trip report specifically refers to the thread topic which is How toxic is mephedrone. there is a whole sub forum helpfully called trip reports to post this useless shite in.

the signal to noise in this thread is becoming abysmal.

 

[Josama]

Well,sorry,I had no intention of making a trip report out of it, I just wanted to point the out the side effects so that people can use it as a hint on concluding how toxic it is. I just wanted to write it as a whole so that it makes sense.

If it's useless than I'm very sorry, I just wanted to help.

 

[pk5000]

Seems like this guy says it's safe http://www.psych.usyd.edu.au/staff/iain/

"Professor Iain McGregor was quoted as saying that there was nothing wrong with the 'designer drug' Mephedrone. A synthetic compound which is marketed widely on the Internet under an assortment of names which include 'MM-Cat', '4-MMC' and 'Plant Food Meow'.

Mephedrone, which is banned in Finland, Israel, Sweden and Denmark, comes in either powder or pill form and is derived from the khat plant.
Khat is a legal stimulant normally consumed by chewing, which is widely available on UK high streets in communities with large ethnic minorities originating from Somalia, Ethiopia and the Sudan.

Professor McGregor, director of Sydney University's Psychopharmacology Laboratory, was quoted as saying that there was nothing wrong with the drug.

"Unfortunately for people like myself ... who [is] here to tell people drugs are bad, there doesn't appear to be a whole lot that is bad about it," Professor McGregor said."

now if he would only detail the reasons or tests behind why he feels that way.....I think a lot of people would be interested...

 

[nuke]

Seems like this guy says it's safe http://www.psych.usyd.edu.au/staff/iain/

Seems like that guy's comment was taken completely out of context:

Iain McGregor's reply to the fairly long e-mail I sent him about his statements about mephedrone in that article...

hi (Riklet),

that article was one of the worst pieces of journalism i have ever read, and completely misrepresented my views.

i had a long conversation with the journalist and assisted her in every way possible to access further information about mephadrone.

my viewpoint was that there was hardly any systematic research on mephadrone and as such we were unaware of its toxicity.

if was a "don't know" rather than a green light to use the drug.

i think what she wrote was almost criminally irresponsible as well as an abuse of the courtesy i showed her in discussing the topic in depth.

i have made this clear to her in an email sent today. i guess i should learn to expect this from murdoch press journos - sigh!

thank you for your thoughts on the matter. i would be grateful if you would also forward your views to the journalist involved:

Marnie O'Neill <[email protected]>

best wishes, iain

http://www.bluelight.ru/vb/showpost.php?p=7742262&postcount=119

 

[Annapurna]

Since there do seem to be dangers in taking mephedrone and so many of these new designer drugs, what are the alternatives, or at the very least, which of these legal highs is the safest but with a decent high?

 

[pk5000]

thanks for following up Nuke....great post....and I figured something was off about the story....

 

[nuke]

Since there do seem to be dangers in taking mephedrone and so many of these new designer drugs, what are the alternatives, or at the very least, which of these legal highs is the safest but with a decent high?

The 3-Fluoromethcathinone that's going around right now apparently is probably at least a little bit safer, I would guess. It should be selective for dopamine and norepinephrine, so it would at least be less neurotoxic (or not neurotoxic) because it's less serotonin releasing. It's probably a much cleaner feeling stimulant too, should be similar to amphetamine or methcathinone. MDPV is also probably fairly innocuous, but no one can say what the long term effects would be.

 

[7zark7]

The 3-Fluoromethcathinone that's going around right now apparently is probably at least a little bit safer, I would guess.

Sorry to go slightly OT, but is that the same or similar to Flephedrone (4-Fluoromethcathinone)?

 

[nuke]

Oh, that was my mistake, sorry. The stuff that's going around now is 4-Fluoromethcathinone I guess (Flephedrone? What a bizarre name...) 3-Fluoro will probably prove to be the better and more clean stimulant if I had to guess. I had thought 3-F-MCAT had made rounds too but I don't know. I don't have a ton of interest in these weird cathinones.

edit: No, I was right: http://www.bluelight.ru/vb/showthread.php?t=458536

 

[nuke]

Okay, good news as to the toxicology of 4-Methylamphetamine:

p-Bromoamphetamine 27 and p-bromomethamphetamine 2R, 29 lower brain
serotonin to an extent comparable to the reduction caused by the corresponding
p-chloro compounds. pFluoroamphetamine decreases serotonin levels, but its
effects do not persist to the same degree as those of p-CA.27s 30 Other parasubstituted
amphetamines have less activity (trifluoromethyl, phenoxy) or no
activity (methyl, methoxy ) as serotonin depletors.20
Norfenfluramine is an analog of p-CA that bears an m-trifluoromethyl substituent
instead of a p-chloro substituent on the ring. Norfenfluramine and
fenfluramine (the N-ethyl compound) lower serotonin in rat brain for a very
long time, though they are slightly less active than p-CA.3*-34 Although Costa
and Revuelta 32 have reported that norfenfluramine increases serotonin turnover
instead of decreasing it, as p-CA does, we find that norfenfluramine causes a
rapid reduction of tryptophan hydroxylase accompanying the decline in serotonin,
just as p-CA does (TABL3E) . Sanders-Bush et al. have reported shortand
long-term depletion of serotonin and tryptophan hydroxylase in rat brain
after injection of fenfluramine.'? In general, the actions of norfenfluramine and
fenfluramine on brain serotonin neurons may be very similar to those of p-CA
and other chlorinated amphetamines.

Ray W. Fuller, "STRUCTURE-ACTIVITY RELATIONSHIPS AMONG THE HALOGENATED AMPHETAMINES" Annals New York Academy of Sciences 1978

So despite the large amount of 5HT release, no 5HT neuronal toxicity (or at least no permanent decreases in 5HT) seems to be apparent with 4-MA. This is interesting, but it still doesn't necessarily mean that 4-MMC is safe in terms of neurotoxicity in terms of both dopamine neurons and 5HT neurons.

 

[MeDieViL]

Interesting, great post nuke.

 

[Unbreakable]

What is wierd is that those people who have reported severe reactions had taken it previously at high doses without adverse effects. which inspiredme to look into the likely metabolites

We know little about the metabolism of 4-mmc, I would expect that the metabolites will be the betahydroxy compound (paramethyl ephedrine) the N-demethylated betahydroxy compound (paramethylnorephedrine) more on these later...
and to a lesser extent the metabolites from P450 oxidation of the 4-methyl position;- the hydroxymethyl (benzyl alcohol) and the carboxylic acid this seems more common with the more lipophillic cathinones. all water soluble and so elimination is going to be renal, with limited amounts in other fluids.

I think that the metabolites rather than the drug itself will provide the answer to the toxicity.
the betahydroxy compounds are almost certainly the primary metabolites of mephedrone, and these are known compounds with toxicity data:
ed betahydroxy compound (paramethylnorephedrine) more on these later...
and to a lesser extent the metabolites from P450 oxidation of the 4-methyl position;- the hydroxymethyl (benzyl alcohol) and the carboxylic acid. all water soluble and so elimination is going to be renal, with limited amounts in other fluids.

I think that the metabolites rather than the drug itself will provide the answer to the toxicity.
the betahydroxy compounds are almost certainly the primary metabolites of mephedrone, and these are known compounds with toxicity data:

the primary metabolite paramethyl ephedrine is compound II in the paper below and is 3.4x more toxic than ephedrine in guinea pigs or 2.27 x more toxic than ephedrine in rabbits

AMINO-ALCOHOLS. II. HOMOLOGS AND ANALOGS OF PHENYLPROPANOLAMINE
Walter H. Hartung, James C. Munch, W. Allan Deckert, Frank Crossley
J. Am. Chem. Soc., 1930, 52 (8), pp 3317–3322
DOI: 10.1021/ja01371a046

asuming that this metabolite s the primary metabolite,
working from the sc guinea pig LD50 of 175mg/kg using the standard conversion of divide mg/kg by 4 to go from guinea pig to human gives 44mg/kg for this metabolite as the LD50 for humans. an estimate of around 3.3 g for 75kg body weight. people with idiosyncratic metabolism or are taking caffeine as well will die at lower doses.

we know that vanilla cathinone has central half life of 1.5 hrs or so, and that the beta hydroxy compound cathine has a much longer half life 5 hrs or so , extrapolating this to 4-mmc would seem to suggest that repeated redosing of 4-mmc raises the levels of the betahydroxy metabolite, even though plasma levels of 4-mmc do not significantly rise above the initial peak. the longer the redosing continues the more this metabolite accumulates.

4-mmc is also a chiral molecule, unlike ordinary methcathinone it is a mixture of enantiomers, as it is made from 4-methylpropiophenone rather than a chiral precusor. with other cathinones both enantiomers have cardiac activity but only one has significant mental effects. the other enantiomer in 4-mmc is not contributing to the central effects but it is causing cardiovascular effects.

http://www.pubmedcentral.nih.gov/art...?artid=1884326

people are taking grams of a drug that metabolises to an ephedrine like compound, a compound that is considerably more toxic than ephedrine in animal models and a metabolite which likely has a much longer half life than 4-mmc, and we wonder why there are problems. the interesting thing is not that there are problems is that they are relatively infequent.

the vendors should have pulled this stuff when adverse effects were first apparent, but they don't give a fuck as long as the money rolls in.

they should also do their homework properly, I got all this with an hour of googling.
I should be a due diligence consultant, my standard rate is 2K USD per day

please be careful with this stuff, used in moderation it is probably reasonably safe perhaps no worse than methcathinone itself.

repost of earlier post, not new

 

[Rectify]

The human body's detoxification metabolic pathways oxidize toxins, not reduce them. Therefore, 4-methyl(pseudo)ephedrine from mephrone has slim to no chance of being a metabolite in this instance.

 

[nuke]

Cathinone is reduced to both (-)-norephedrine and (-)-norpseudoephedrine in plants and in mammals by stereospecific keto-reductions, which makes sense because they're more polar and therefore more easily excreted. I would wager mucho on a beta-hydroxylated 4-MMC metabolite. I mean, it's even called (-)-cathinone reductase, the enzyme that executes the reaction in khat.

The opposite reaction, the oxidation of the alcohol to the ketone, has pretty much no chance of happening and indeed doesn't happen if you look at metabolic data in mammals.

 

[Rectify]

That's interesting to hear and also a bit odd.

Most metabolic chemical transformations involve oxidation (chemically burning) of the drug.

You're also right that benzylic oxidation in vivo certainly doesn't occur with ephedrine et al.

 

[nuke]

It's possibly good news, but the problem is that the compound wasn't evaluated for DA/NE neuron neurotoxicity as well. Both cathinone and amphetamine are neurotoxic to dopamine neurons in high enough doses.

Drug Alcohol Depend. 1982 Aug;9(4):279-84.
Neurochemical similarities between d,l-cathinone and d-amphetamine.
Wagner GC, Preston K, Ricaurte GA, Schuster CR, Seiden LS.

Cathinone, the principal alkaloid of Khat, was compared to the psychomotor stimulant d-amphetamine on a number of neurochemical measures. Like d-amphetamine, d,l-cathinone released and blocked the uptake of tritiated dopamine (DA) in synaptosomal preparations. In addition, repeated high doses of d,l-cathinone produced long-lasting DA depletions in various rat brain regions and decreased the number of synaptosomal DA uptake sites in a manner similar to that seen after repeated d-amphetamine administration. Importantly, this DA neurotoxic effect of d,l-cathinone, like that of d-amphetamine, is selective since regional brain levels of norepinephrine (NE) or serotonin (5-HT) are not altered on a long-term basis by repeated administration of d,l-cathinone. These findings are discussed with reference to the current practice of Khat leaf chewing by people in north-eastern Africa.

However when you n-methylate them to become methcathinone and methamphetamine, the drugs become both potent dopaminergic and serotonergic neurotoxins. It's thought that the secondary amine facilitates greater release of monoamines while enhancing the potency of serotonin release.

The possibility thus remains that the drug could still be toxic -- but we'll have to wait and see for some actual scientific results on the compound itself. Until then, caveat emptor.

 

[hugo24]

PMA no serotonin depleter either,good I can take massive amounts now