ebola?
Bluelight Crew
Intriguing. Which SSRIs do not?
-
N&PD Moderators: Skorpio
How toxic is Mephedrone?
- Thread starter Giovanni
- Start date
Intriguing. Which SSRIs do not? 
I will attempt to meet some of your requests, if only to try and reverse some of the misrepresentation I am attracting. Please note that while I find your hypocrisy wildly entertaining, it worries me a little that you are a moderator on a thread dedicating itself to advanced drug discussion at all.
1) You really ought to know this one. MDMA releases serotonin. Taken from http://www.psychotropical.com/CNS_stimulants_with_MAOIs.shtml
Large doses of MDMA cause a rapid release of endogenous serotonin from the stores in the presynaptic nerves; so much so that a substantial MDMA dose will deplete about eighty percent of the serotonin stores
Please look literally anywhere for scientific literature supporting this claim.
Being new to the board, I have never heard of Nuke, so sorry, no.
2) Friend, it would appear YOU are the one who hasn't read the paper. You've TWICE failed to grasp either of the two conclusions the author(s) made:
a) Those being that methcat is a substrate inhibitor (IT'S IN THE TITLE)
(from the paper discussed)
"We previously reported that the psychostimulant drug methcathinone inhibits serotonin accumulation via the plasma membrane serotonin uptake transporter."
b) And that a superfusion of the drug causes efflux/release of serotonin
"Supporting the hypothesis, superfusion of [3H]5-HT-containing platelets with methcathinone or with para-methylthioamphetamine produced a large increase in tritium efflux. The efflux declined when the drugs were removed."
and also "...Under superfusion conditions, transporter substrates will evoke an increase in released [3H]5-HT through a carrier-mediated exchange process."
By the by, I understand the correct use of former and latter. I happened to write the post on 2 hours of rough sleep spent in questionable comfort, so I assume you'll overlook a simple human error anyone of us could have made. Now hold on, you'd know about those...
Again, from http://www.psychotropical.com/CNS_stimulants_with_MAOIs.shtml
MDMA, ecstasy (3,4-methylenedioxymethamphetamine) acts like tyramine, but seemingly more as a releaser of serotonin than noradrenaline, and its serotonergic action is blocked by serotonin reuptake inhibitors [14].
Let's take citlopram for example. The 'purest' SSRI (bar escitalopram, its isometrically cleaved relative)
http://www.nature.com/npp/journal/v22/n5/full/1395472a.html
"The main result of this study is that the psychoactive effects of 1.5 mg/kg MDMA were substantially attenuated by pretreatment with the SSRI citalopram (40 mg iv)."
Note an earlier Ricaurte study of showed pretreatment of fluoxetine 20mg failed to attenuate serotonin release in rats dosed with mdma, the author suggesting a possible discrepancy in relative ability to block uptake of 5-HT between citalopram 40mg and fluoxetine 20mg as the cause. I suggest other factors relating to errors in the experiment, probably that the wrong test compound was used in the first place, if it forms part of a series relating to his other studies on mdma. The report below contradicts Ricaurte's findings and, if correct proves SRRIs PREVENT MDMA FROM WORKING. PLEASE PROVE OTHERWISE.
Fluoxetine: arguably the'dirtiest' SSRI in vivo (sertraline being a significant DRI in vitro) which despite being the first SSRI to be heavily marketed as such, is, in its ability to block 5HT-2C receptors, atypical of its class. Malonate is used in the study as a catalyst to mdma-induced neurotoxicity via 5-HT release. From http://jop.sagepub.com/cgi/content/abstract/20/2/245
"in this study we sought to determine whether pharmacological blockade of MDMA- and/or malonateinduced dopamine release prevents neurotoxicity. Fluoxetine, given 30 min prior to the malonate/MDMA combination, afforded complete protection against 5-HT depletion and reversed MDMA-induced exacerbation of dopamine toxicity found in the malonate/MDMA treated rats."
3) "Serotonin syndrome is not an inevitable consequence of mixing a SE releaser and a SSRI"
Well...um, duh. Why, if you know what you're talking about, would you even make such an obvious statement. Serotonin syndrome is AVERTED by taking an SSRI since, as I have made clear, it attenuates 99% of MDMAs ability to release 5-HT.
Are your terms met? Are you satisfied. I hope so.Last edited:
You were talking about 4-MMC and Methcathinone, so how is MDMA being a SE releaser supporting what you are saying, perhaps you should randomly mention fenfluramine or PCA as being SE releasers too? you couold even post literature refs.
Sorry. I was under the impression you were ignorant of that. Obviously not.
Since we know it is vasoconstrictive and perhaps cardiotoxic, now we can continue with the discussion of the drug. Proposing potential mechanisms of action and how this relates to (neuro) toxicity or lack thereof
what is your obsession with neurotoxicity?
who gives a fuck if it is neurotoxic or not if it is toxic in other ways and kills or severely damages people.
as I said earlier neurotoxicity is a minor concern, I think I said it was a red herring, the amount of neurotoxic damage required before anyone notices impacts on their everyday normal functioning is huge.
I don't know whether 4-MMC is neurotoxic or not, neither do you.
I would be much more interested in discussing the blue knee phenomenon.
Urm, anyone who cares about their mental health, retaining their personality, memory, cognitive/executive functioning
Anyone who isn't already emotionally retarded from mashing their brains on pills and speed and god knows what else.
The safety margin appears to be relatively high . At <1.5g the majority will not experience any troubling side effects such as those described.Last edited:
pofacedhoe
Bluelight Crew
^^neurotoxicity is very small amount of damage, having a stroke is a large amount of brain damage. would you say that vasoconstrictive tendencies would heighten the chance of having a stroke? if so then this is toxicity that would encompase a lot of neurons.
what about stokes then^?
pofacedhoe
Bluelight Crew
very true but on the subject of stimulant abuse and heart problems-my friend who has for a number of years been a heavy (2grams a night on average) user of cocaine (a drug with SRI effects that are strong) and thought he was having heart problems. after extensive medical tests and him admitting to them his use of xanax and alcohol the hospital came to the conclusion that he was suffering from anxiety and panic attacks (as his heart was indeed in okay shape). now what i am saying is that the lowering of serotonin in a person due to downregulating as a result of abusing the serotonin system (with stimulant drugs affecting said neurotransmitter) could appear just like mdma users who get panic attacks after they stop using the drug, i also found these effects to happen after discontinuing SSRI antidepressants.
of all the neurotransmitters to mess with serotonin has a very important inhibitory effect on behaviour and is therefore not something to mess with unless we want all our future choices to be affected. Altering long term capacity for judgement is not so clever.
Agreed
So irreversible brain damage from substance use is bad? But strokes are worse? Then yes ok.
What is the likelihood of stroke on a scale of say 1-10 at the aforementioned dose, spaced out over 12 hours..
Hammilton
Bluelighter
- Joined
- Sep 2, 2008
- Messages
- 3,435
You're not all that bright. You were 'under the impression'? Do some thinking.
I agree completely, neurotoxicity is a red herring. There are far bigger concerns.
You really don't know what you're talking about. Yeah, it's almost certainly neurotoxic. Does it matter much? No.
We're talking about very small changes that don't have any practical impact on daily functioning or even the ability to take tests.
And it's unlikely to even be irreversible. Your brain can easily compensate for any changes that occur, and often within just a few days. The changes themselves may indeed revert back, but even if they don't, most likely the changes will have no effect. fMRI and PET scans show changes in the brain after various drug use, but tests of functioning show minor alterations in memory, cognition, intellect, etc.
Why call it neurotoxicity if there's no impact on functioning or even test scores?
Vasoconstriction is a much more worrying issue.
The question in my opinion is, how much worse Mephedrone is as a vasconstrictor than similar substances.
I just checked Wikipedia and basically all stimulants and even some psychedelics act as a vasconstrictor.
On drug-forums (http://www.drugs-forum.com/forum/showthread.php?t=89052&page=2) user rb10101 posted that he got purple knee side effects from mephedrone use, but also mentions that he got the same side effects from methylone use.
The thing is just that people tend to abuse Mephedrone much more than for example Methylone, which makes it obvious that much more side effects are reported from Mephedrone use than from Methylone use.
However at least based on this post, Methylone also seems to be able to cause these problems...
pofacedhoe
Bluelight Crew
strokes are irreversible brain damage, neurotoxicity pales in comparrison to the scale on which a stroke will affect you
Mugz
Bluelighter
saw a mention of l-arginine earlier in the thread mentioning that it may help the short term effects of vasoconstriction, but there wasnt really any further discussion into it.
Would this supplement be worth taking just in case??
flacky
Bluelighter
Here was the theory that I posed:
pofacedhoe
Bluelight Crew
LOL i really dont want to get "brutal nausea" !Got the name all wrong - Stugeron - I think it's sold mostly as a motion-sickness OTC in the UK
It's an antihistamine which somehow (no clue) blocks the messages being sent to the 'vomit centre' of the brain in motion sickness, thus preventing vomming. BUT It also inhibits the contraction of vascular smooth muscle cells -by blocking calcium channels- and reduces blood viscosity (http://home.intekom.com/pharm/janssen/stugeron.html)
Dead man's knees no more?closedeyevision
Bluelighter
- Joined
- Aug 14, 2007
- Messages
- 101
to go back to topic- mephedrone can = methemoglobinemia, anyone?
this haapens with some of the substituted amphetamines and a lot of the anecdotes of people turning blue etc sound a lot like it.
indeed here in scotland, two people were hospitalised with the condition after comsuming what they said was cocaine. A warning went out suggesting a contaminated batch of C, could it be they were hoofing mephedrone instead?