N&PD Moderators: Skorpio
Mephedrone science
as the original post says the purpose of this thread was to have a place where scientific data regarding mephedrone could be posted free from the drivel that all other mephedrone threads become infested with.
all posts that don't meet the requirements will be deleted.
start a new thread, and include some research or some ideas and you will get a response.
this thread is a clearing house for scientific data relating to mephedrone.
I'm resurecting this post from the dead. I used to work when I got out of college in a very prominent research lab involved in looking at DA and its role in reinforcement from drugs. In other other facility we were looking at drugs that increase 5-HT availability. Both in animal models. The latter was trying to use 5-HT agonists to produce models of schizophrenia- atypical schizophrenia (DOI was one of our drugs of choice- because it was unsecheduled back then but we tested MDMA and its racemic form and its enatiomers, psylocybin, even non 5-HT specific drugs like PCP/ amphetamine enatimeros for shits and giggles.) In the other lab lots of different studies were taking place utulizing cocaine, amphetamines, methamphetamine, heroin, morphine (its an interesting feeling being alone in a room with a 20 G jar of heroin (I think produced by sigma back then ) and being dope sick. Anyway, my indescriminate use of heroin, meth, and other drugs made me a liability- they didn't have proof but let me quitely go- but I never stuck my hand in the cookie jar case you were wondering. My undergrad degree was biochem/ minor psych, went to a UC campus. Anyway I switched careers in the early part of this century to nursing but still have some, though outdated knowledge (augmented by a graduate corse in neurochemistry). Alot, I'm sure has change.
So what I have learned is that Mephedrone is postulated to have serotonin and DA stimulating activities. 5-HT has several receptor types and subtypes. I remember my PI saying that 5-HT was the most prevalent neurotransmiter in the nervous system (central and peripheral).
Now, a question, dose its empathogenic qualities build rapid tolerance with redosing? It would be interesting if not. Does it cause the anorgasmic effects associated with 5-HT agonists, our is it amphetamine like prosexual- i know alot of factors play into this so it probaly varies individually.
Now, In my line of work (nursing) I am interested in practical applications- harm reduction. It sounds like the adverse effect profile includes arrythmias, tachycardia (which interfers with repolarization), increased incidence of thrombosis/ hypercoagulability, peripheral vacular disease, probable neurotoxicity, adverse effects most likely compounded by redosing.
When a patient's BP tanks, you first give a fluid bolus (250cc IV)- even if they have a Hx of CHF- in which case give the bolus with caution and run by the doc in your emergency standing orders implementation call- you give a bolus with caution. Then you turn to vassopressors- DA and levophed (NE) infusions being the drugs of choice in the US. Ephredine IV push is the agent@ my institution is used to reverse anaesthesia induced hypotension. After a 250 cc fluid bolus you give 5 mg IV, then if this is not effective 10 mg, why it is used preferentially to other vassopressors/sympathomimetic agents I haven't bothered to explore fully yet.
One expect the opposite. However, eleveated BP and if ones heart decides to go into Afib could cause a clot to be thrown resulting in a CVA (blood clot blocks the blood supply in one of the vessels of the brain. With amphetamines I remember experiening evidence of decreased blood supply to my extremities, even experiencing black almost purplish tinges of, especially when I was sitting in one place doing some repatative task for a long time.
So off the top of my head this drug should be avoided by people with a history of hypertension, heart disease, palpitations, irregular EKGs, previous heart attacks (MIs) or stroke, Heart Failure, kidney disease, hep C or liver disease, disorders of the blood (anemia, blood clotting disorders) peripheral vascular disease (very imprtant), diabetes.
I'm no doctor, but I would sugesting staying well hydrated (but dont over do it- don't want hypo natremia or kalemia, calacemia, magnesemia. If this has both alpha and beta blocking effects one could theoretically use a beta blocker (metoprolol 12.5 mg, more in individuals with higher blood pressure or that insist on taking this drug despite above mentioned conditions prophylatically. If it has alpha blocking effects- clonidine 0.1 mg might help but be aware that taking this drug if one dosen't take it routinely or is an opiate addict in withdrawl runs the risk of precipitating a hypotensive episode plus it isn't a competative a inhibitor- it binds to a2 autoreceptors prsynaptically reducing the release of catacholamines in a fibers. Taking enteric coated aspirin might decrease the risk of thrombosis by inhibiting platelet agreggation. You could take this at 81-325 mg with a acid reducer (just avoid cimetidine/tagument because it might effect is metabolism leading to toxic levels- don't know about its metabolic pathway.
As for nerotoxicity, they use to recommend taking antidepressants that block the reuptake right before baseline(rationale was that the toxic mediators would be blocked from being absorbed pre synaptically. But with SSRIs you run the risk of blocking its 5-HT effects esspecially if you decide to redose but more dangerously run the risk of precipitating a serotonin syndrome- pretty fucking life threatening stuff. Vit C and Vit E in high doses might be a good idea but I don't know if they are really effective in preventing free radical associated neurotoxicity.
The bottom line is, my non medical but somewhat informed 2 cents is don't take this stuff until more is known. Unless you feel compeled to further the understanding of human drug research as a human guinea pig.
But if you insist on taking this- get a full physical first especially if you are over the age of 30. My gut tells me that the side effect profile is less than other drugs in common use therapeutically (warfarin, ect...) Especially given that most users probably have youth on their side. But this would be a bad way to find out prexisting conditiona: about a congential heart deffect, seizure disorder, among a myriad of other things.
So to sum my arguments- Don't do it until more is known.
If you insist on using it- drink plenty of fuids but don't over do it say 1-3 L max over a 12 hour period. And make sure you pee during this time.
Staying in motion will help relieve some of the decreased blood flow to the extrmities.
With the alpha/beta blockers- if your normal blood pressure runs bellow 100 or your maybe an althlete whose HR is bellow 60. Beta blockers are a bad idea in this case- this is all speculative so the meds IV mentioned could do more harm than good. So I would avoid these as prophylaxis.
If your heart is racing, feels like its gonna come out of your chest, your short of breath, dizzy, or have chest pain- I would consider seeking immediate medical attention. sweating profusely (if the 5-HT effects don't inhibit this), your toes or fingers take on a dark tinge, I would watch closely, apply heat, and seek medical attention if your circulation seems to get worse.
81 mg of enteric coated aspirin wouldn't hurt unless you have anemia or some kind of other bleeding disorder.
If you start spiking a fever stay hydrated but the more imporatant first step is Ice packs under your armpits and on the back of your neck, especially if your flushed and not sweating. Seek immediate medical attention- 5-HT syndrome or malignant hyperthermia/seizures might be right around the corner. The problem with serotonin syndrome is that that early symptoms of the disease mimic the normal side effects of the drug. A dramatic temp spike ( I would worry about anything above 101.5 which is in the 38.3 or .4 cesius range, I think, is an ominous sign. Rest cool off and leave the party- use cooling measures and take your temp often
Absolutely avoid if you have taken an MAOI within 2 weeks. Avoid combing with ayahuasca, harmine, harmaline.
ps- if the rate is supper high a calcium channel clocker like diltiazem/ cardizem is probably the drug of choice but in this case HR>150 sustained (take your pulse for 15 minutes and multiply by 4) especially if you start feeling missed beats is time to go to the hospital- you should be on continuous EKG and they might Rx a dilt drip and maybe benzos for agitation.
Now that I scarred you, panic attacks could possibly mimic some of these symptoms so don't be overly concerned- I think if you insist on using- redosing is your worse enemy.
disclaimer: Don't take this as medical advice unless you consult a physician. I am just floating some of these ideas as possible harm reduction measures in people that use Mephedrone and soliciting other ADD expert imput. Best potenially safe harm reduction is don't redose (keep limited supply on hand), maybe aspirin, don't mix with alcohol, and stay adequately (but not overhydrated). Take warnings seriously so your alert to potential complications.
Again aviod until we know more about- use E instead, amybe even speed or meth (again try to keep moderate amounts on hand)- redoucing will fuck you up. Don't use every weeked if you must or more frequently than once every month or two at most.
My objective for writting this is to get input from BLers with knowledge of advanced drug science, theoretical and applied so we can get preliminary info on a harm reduction statement about this drug in keeping with our mandateso I would appreciate informed input and critique to help put out a simple harm reduction statement on this drug that little seems known about presently compared to ther drugs with abuse potentials. Maybe we can come up with a unified and coherent statement and add it to the FAQ that I belive is floating somewhere on BL. The pharmacological prophylaxis is speculative and probably not material for the FAQ or maybe another HR document but the low dose aspirin might be beneficial because its OTC and realatively free from side effects unless the user is under 12 and at risk for Ryees syndrome in which case they absolutely shouldn't be anywhere near doing this drug. But realistically I started drinking when I was 11 and would have done coke when I was 12 but luckily I didn't have a connection.
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By the way, in the old days we used to use radigraphic receptor binding studies in animal models to elucidate which receptors or parts of the brain the drugs bound to. Bheavioral experiments measuring changes in behavior analogous to the effects of well studied drugs was another technique. Another one was sticking a canula in the rats brain and measuring metabolites of neurotransmiters using HPLC- but that assay was problematic.
The other way was puting cell free extracts containing receptors and seeing which targets or determinates the drug bound to by coupling the molecule with luciferase. Then it was put in cells systems and functional assays were carried out to determine its affinity, and whether or not its an agonist, antagonist, reverse agonist, agonist/antagonsit, or partial agonists. Then came animal models, human trails, ect... combinatorial chemistry combined with rational drug design and high throughput screening was supposed to speed up the drug discovery process. Don't know how it panned out but bench science was funner.
Sturnam
Bluelighter
I recently came across a new article dealing with mephedrone's effects on 5-HT and DA in the nucleus accumbens.
Here's the article:
J. Kehra,b*, F. Ichinoseb, S. Yoshitakeb, M. Goinya,b, T. Sievertssonb, F. Nybergc and T. Yoshitakea. Mephedrone, compared to MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and serotonin levels in nucleus accumbens of awake rats. British Journal of Pharmacology April 2011
I have the full article if anyone wants it, and if anyone from the other BL wants me to, I can post it over there as well.
sackynut
Bluelighter
^awesome post its good to see another study on 4mmc especially one on its binding and monoamine properties.
ebola?
Bluelight Crew
Holy shit on these data! Neat.
Now, how should we interpret measures of intercellular monoamine concentrations at ceiling (I assume that's what this is, a la whatever study found methamphetamine to increase intercellular DA to 100%?)? What is their measure of basal intercellular monoamine levels? A rat in its typical environment sans structured activity? a rat fucking another rat? 
Anyway, doesn't matter...
How does this measure relate to conditions where human users adjust dosages to yield desired effects?
Relatedly, what do these measures indicate when we ask what happens when dosage levels are equipotent for release of a given neurotransmitter or effects-set? Might not matter much, as meph users so often take higher doses with greater frequency than those who choose d-amp or mdma. However, maybe obviously, your typical mdma user won't dose with level and frequency typical of attempts to chase DA fx, while amp and meph users will, and meph users will experience compulsory severe 5ht release.
And then there's the question of generalizing from high doses given to rats to lower doses that humans take. For example, they administered amp at a dose high enough to cause 5ht release, a dosage level that humans rarely reach. At high dosage levels of d-amp, moderate neurotoxicity manifests, while at low dosages, neurotoxicity is modest/mild.
ebola
ebola?
Bluelight Crew
Also, generalizing from 4-meth-amp's neurotoxicity, it seems that relatively a 'balanced' ratio of DA to 5ht efflux is a bad thing.
ebola
Sturnam
Bluelighter
Holy shit on these data! Neat.
Now, how should we interpret measures of intercellular monoamine concentrations at ceiling (I assume that's what this is, a la whatever study found methamphetamine to increase intercellular DA to 100%?)? What is their measure of basal intercellular monoamine levels? A rat in its typical environment sans structured activity? a rat fucking another rat? Anyway, doesn't matter...
How does this measure relate to conditions where human users adjust dosages to yield desired effects?
Relatedly, what do these measures indicate when we ask what happens when dosage levels are equipotent for release of a given neurotransmitter or effects-set? Might not matter much, as meph users so often take higher doses with greater frequency than those who choose d-amp or mdma. However, maybe obviously, your typical mdma user won't dose with level and frequency typical of attempts to chase DA fx, while amp and meph users will, and meph users will experience compulsory severe 5ht release.
And then there's the question of generalizing from high doses given to rats to lower doses that humans take. For example, they administered amp at a dose high enough to cause 5ht release, a dosage level that humans rarely reach. At high dosage levels of d-amp, moderate neurotoxicity manifests, while at low dosages, neurotoxicity is modest/mild.
ebola
I'll try and answer some of these questions.
For basal levels, each rat's 3 baseline collections are analyzed, and the mean is 100%. Note that you have to normalize each rat to 100% because of the wide variation in catecholamine levels.
Also, you mentioned that the amphetamine dose released 5-HT. Well, this is true (165% ), but the authors note that it is not statistically significant. Also, their MDMA and amphetamine doses aren't that high. I'm pretty sure I remember a lot of MDMA research in rats using 20 mg/kg, especially the ones showing neurotoxicity.
As for how relevant it is, I believe it's petty good as far as dosing. Human doses are usually 1/7th (I believe...) on a mg/kg basis compared to rats. So, even if you take the highest dose of mephedrone, 3 mg/kg, and don't do the species conversion, it makes 177 mg for a 59 kg (130 pound) person. And I don't know if anyone who does mephedrone ever sticks with that amount.
Of course, it could also be that humans need more before effects manifest themselves....
