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MDPV Megathread 11: Still sorting all the porn.

Interesting article recently published in the Journal of Neurochemistry:

"3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter"

Abstract

Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of ‘bath salts’ and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classifed chemically as b-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neuro-chemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS.

Unlike methamphetamine, the b-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to signifcantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings.

The b-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that b-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity.

Keywords: dopamine nerve ending, dopamine transporter, neurotoxic amphetamines, neurotoxicity, b-ketoamphetamines.
J. Neurochem. (2015) 133, 211–222.

I haven't read the article yet but it looks as if it not only supports the theory that MDPV is non neurotoxic but actually acts to protect against the neurotoxic effects of other damaging drugs. It's great that this kind of research is being done but in a less fucked up world such results would have been established long ago.
 
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=D

QFT!

I'd say as long as those Guys don't show up, there's no reason to Freak out!
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Howard the Duck!

Also, that's really interesting stuff, Bulon!
 
I hope I'm not breaking too many rules by reproducing part of the discussion section of the above mentioned article but this is information that needs to be disseminated one way or another:

"3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter"

John H Anneken, Mariana Angoa-Perez and Donald M Kuhn JOURNAL OF NEUROCHEMISTRY | 2015 | 133 | 211–222

Mephedrone and methylone, like methamphetamine, are substrates for DAT-mediated uptake and they cause release of DA via carrier-mediated exchange (Baumann et al. 2012; Cameron et al. 2013a,b; Eshleman et al. 2013). MDPV is not a substrate for transport and interacts with the DAT strictly as a blocker, like cocaine (Baumann et al. 2013; Cameron et al. 2013a,b; Eshleman et al. 2013; Kolanos et al. 2013; Simmler et al. 2013a). This dichotomy of interaction with the DAT by mephedrone and methylone on one hand and by MDPV on the other can explain their opposing effects on methamphetamine-induced neurotoxicity. Mephedrone and methylone enhance the effects of methamphetamine, most likely by increasing the release of DA above that caused by either drug alone. This possibility has not yet been tested but is supported by prior results showing that treatments resulting in an increase in the
releasable pool of DA significantly accentuate methamphetamine-induced damage in DA nerve endings (Thomas et al. 2008, 2009).

MDPV has an effect that is similar to more classical DAT blockers and protects against methamphetamine-induced neurotoxicity. Compared to amfonelic acid (Schmidt and Gibb 1985; Pu et al. 1994) and nomifensine (Angoa-Perez et al. 2013), which provide partial but significant protection, MDPV completely prevents the damaging effects of methamphetamine on DA nerve endings. By blocking DAT-mediated transport (inward or outward), MDPV blocks methamphetamine-induced efflux of DA (Simmler et al. 2013b). This property alone represents an important mechanism by which it protects against DA nerve ending damage caused by drugs that depend on inward DAT transport to exert their toxicity to include the neurotoxic amphetamines and MPTP (i.e., MPP+). MDPV may be one of the most powerful blockers of the DAT yet described (Baumann et al. 2013; Eshleman et al. 2013; Simmler et al. 2013a). It is also more effective than bupropion or methylphenidate in blocking methamphetamine-induced DA release (Simmler et al. 2013b) and is the most potent drug identified to date for protecting against methamphetamine-induced damage to DA nerve endings.

Methamphetamine is probably the prototypical neurotoxic amphetamine. Its ability to flood the synapse with DA, especially after binge administration (O’Dell et al. 1993), is thought to be the first step in a cascade that leads rapidly to mitochondrial dysfunction, enhanced excitatory neurotransmission, increases in glial reactivity and oxidative stress, nerve ending damage, and apoptosis (Halpin et al. 2014). The numerous facets of methamphetamine-induced neurotoxicity have been studied in great detail over the past three decades, whereas the dangers associated with bath salts have emerged only recently. However, the b-ketoamphetamines
should offer new possibilities for achieving a better understanding of the mechanisms by which methamphetamine, amphetamine, and MDMA cause damage to monoamine nerve endings. Mephedrone and methylone cause little or no neurotoxicity yet they cause significant efflux of DA and inhibit its re-uptake through their interactions with the DAT. The interactions of mephedrone and methylone with the DAT are very similar to those of methamphetamine and this leaves unanswered the question posed above of why they enhance the neurotoxicity of the amphetamines as opposed to offering protection. It could be predicted that mephedrone
and methylone would dilute the effects of methamphetamine on DA release by substituting less toxic DAT substrates for a
more toxic one. This does not appear to be the case. Several other possibilities offer sources for speculation regarding enhanced neurotoxicity when mephedrone or methylone are combined with methamphetamine and include the following points. First, the b-ketoamphetamines could alter the pharmacokinetics or metabolism of methamphetamine such that blood and brain drug levels are increased in amount and/or for longer periods of time over those seen
after methamphetamine alone. The b-keto group increases the polarity of mephedrone and methylone and reduces their relative penetration into the brain (Hill and Thomas 2011). It is therefore possible that methamphetamine-induced alteration in the integrity of the blood–brain barrier (Northrop and Yamamoto 2012) could make it more permeable to the b-ketoamphetamines. The net result of these possible effects would be similar to treatment with higher doses of both drugs. Second, at the level of the DA nerve ending, it is possible that the bath salts enhance methamphetamine toxicity because of increased release of DA over that seen after either drug alone. Methamphetamine collapses the pH gradient across the synaptic vesicle membrane, allowing DA leakage into the cytoplasm and subsequent efflux via reverse transport (Sulzer et al. 2005). Methylone and mephedrone release cytoplasmic DA via reverse transport through the DAT, but they differ significantly from methamphetamine in that they have little if any affinity for the vesicle monoamine transporter and thus their inhibition of uptake and stimulation of release from synaptic vesicles is far lower than that of methamphetamine (Eshleman et al. 2013). Because methylone and mephedrone do not likely release DA from synaptic vesicles, combined treatment with either mephedrone or methylone + methamphetamine could recruit greater numbers of DAT molecules to result in heightened DA eflux into the synapse because amphetamine-induced release is greater when originating from both synaptic vesicle and cytoplasmic stores versus cytoplasmic stores only (Pifi et al. 1995). Third, mephedrone and methylone could enhance methamphetamine toxicity by inhibiting monoamine oxidase A. We have shown previously that the monoamine oxidase A inhibitor clorgyline significantly increases methamphetamine-induced depletion of DA (Thomas et al. 2008 ) but it is not known if the bath salts inhibit monoamine oxidase.

Ongoing studies in our laboratory are directed at achieving a better understanding of these possible mechanisms by which the b-ketoamphetamines accentuate methamphetamine-induced neurotoxicity. From a strictly pre-clinical, mechanistic perspective, MDPV has the potential to be an effective neuroprotectant in drug-induced neurotoxicity and in neurodegenerative conditions such as Parkinson’s disease, or for treatment of stimulant dependence. MDPV is not neurotoxic and is far more potent in preventing methamphetamine-induced DA release than bupropion or methylphenidate as mentioned above (Simmler et al. 2013b). The latter two drugs have been tested as treatments for stimulant dependence (Tiihonen et al. 2007; Elkashef et al. 2008 ; Shoptaw et al. 2008 ) with mixed outcomes so far. However, as a powerful DAT antagonist, the abuse potential of MDPV is high in humans (Coppola and Mondola 2012) as well as in animal models of addiction (Watterson et al. 2012; Aarde et al. 2013b; Bonano et al. 2014; Karlsson et al. 2014) and this property alone would limit its use as a therapeutic agent. Despite its abuse potential in the illicit market, MDPV or a structural variant with lower abuse potential could have clinical effectiveness in treating substance abuse disorders as do methadone and buprenorphine, drugs that also possess high abuse potential in humans.
 
Thanks Shambles! I will have a story to tell one way or another after May 23. Curiously, I don’t feel bad about my current decision to indulge in a day’s binge. Rest assured I will do the weighing (and flushing) days before I actually come to use it :)

The thing about addictive drugs is that these cravings are truly unique to a handful of people who seem to enjoy MDPV. I mean, I enjoyed IV coke as much as anyone and more than some, but I don’t feel the slightest urge to have a binge on it these days.
 
So, to sketch out what happened: one day after many years free from the grip of MDPV, I developed a sudden all-consuming desire to spend a day vaporizing doses of MDPV off foil and looking at porn. Mind you, it was as surprising and unexpected as it was powerful — after a few days of thinking about it pretty much every waking moment I had no doubt, none whatsoever, that I could abstain from a much-craved relapse.

I mean, I had it all in life and I nearly lost it all and I won it all back again, and here’s me years down the line, just wanting to pull on that lever, dive headfirst into the short-lived bliss of dopamine release. I would gaze off in a reverie, imagining in every tantalizing detail how I would go about freebasing 20mg, cut off a longish straw, put a lighter on minimum, and position it under the foil. How it would hiss and bubble a little at first, for maybe 1/5th of a second, and then rise up in a stream of yellowish smoke that would be sucked into the straw and into my lungs. How I would hold it in and feel my heart beating faster and faster, and then I would exhale, and still have about 9 similar doses left.

In fact, just thinking about this ritual had my heart pumping excitedly. And I would like to stress this part, I have been clean for close to 5 years, and the cravings just came out of nowhere. Funny how it rewires the brain, eh?

My best hope to come through it in one piece and not a total wreck was to try and do it somewhat responsibly, i.e. set myself up with a small amount (I was thinking 200mg) and only use for a day and then spend a few days recovering. I resolved myself to this fate and went and put in an order for a gram of the stuff. A small part of me wanted to resist so desperately, but a much bigger part of me was having none of it.

While I was at it, I also picked up a gram of K, and it arrived much sooner than the MDPV would (it’s still en route). Long story short, after two nights in the K space I feel back to normal (and the gram is gone :)). My brain is reset. The incredibly powerful cravings are gone. My rational mind is back in charge again. I am able to reason sensibly and realize why a normal life and health are worth more than a few hours of wild wanton pleasure at the cost of upsetting the fine (and already once-shattered) neurotransmitter balance — I still think I would’ve been fine physically, but my sensitivity to sounds would’ve skyrocketed to painful levels, and the self-loathing could persist for long weeks (and I’ve grown to rather like what I’ve become in recent years).

When I think about inhaling a lungful of sublimated PV, I feel a distant interest rather than a placebo rush and a barely controllable desire to indulge right here and now. When that envelope comes next week, I’ll know what to do :) Oh also posting here is a great therapeutic tool, even if few read this/reply.

tl;dr: recovering MDPV addicts may find that K helps curb cravings. Hole liberally, your brain needs that reset (plus it’s fun)!
 
pv is the devils work the smell alone has got me kicked out of home etc, never had such problems with meth, yeah crystal meth and mdpv beats that for price/paranoia, the come down seems to get more brutal i have 200mg of diacz (the legal ones) around for my last 1g and still felt like shit
 
a up yoyo50 good to see your still alive and kicking

and never a truer word said its evil put me in the garden of eden instead of hell and we aint meant to be in there

now mxe that landed me in hell then let me out :)
 
mxe was good until i was doing 5g a week, wasn't getting any effects just had to do it to feel normal wasn't holing anymore etc, can still get it but choose not too, gotta find my own place to live now which will prob be with some shared place with people taking worse stuff than mxe x/
 
all the best finding some where mate yeah i am now with 5g bags now and only just hitting real holes for the first time , what ive done before i believed were but now i know

mdpv though has lost all its appeal of late i can get cheap as well but it just doesn't do it for me now
 
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Played with zum mpa the other day along with zum Mxp (never again mxp. crappy drug, mxe next time, big luv for mxe). But man had not had ztimz in long time (my button iz broke zo I uze Z inztead, lookz ztupid haha i know) but man it could not juzt cut it that mpa. got me thinkin of mdpv or even a-pvp and get that horny crazy feeling & get into maniac-land again trickerz me a little. But dno, not had any for agez it feelz. Hope ya all good my fellow fiendz <3 <3
 
waiting on 7g of mpa in the morning and some other thing as well got to doc tabs sat here calling to me :)

could get some mdpv but like ive said that its a spent force with me now
 
So it happened. Nick ordered 500mg of PV. After a very long break. Wow I don't know why. Guess because I saw the message on the vendor, and had to choose MDPV or MXE (my beloved chems) and low on cash so ended on PV. Can't wait and in a way I can.
 
lucky children. enjoy while the rest of us languish in mediocrity.
 
Posting this as a heads up for you PV heads out there.
Recently received an order of 4 grams MDPV from a quasi-reputable source (they have always been on point for me, not so much for others on occasion.)

Tan/grey/off-white color. Not nearly as wet and sticky as the white MDPV I love so much. No visible crystals, not extremely clumpy either.

Not much odor to speak of, although it faintly smells of cardboard.
Vaped with Al Foil and a glass rose pipe.
When vaped:
- burns up extremely quickly
- when vaped slow, forms an orange/red liquid.
- tastes nothing at all like other PVs I am used to (white MDPV, apvp, aphp)
- tastes like dried ass mixed with cardboard and soil.
- extremely mild stimulatory effects
- sexual enhancement present, however getting erect is a pain in the ass, which is not what I am used to.
- would be 100% okay with not masturbating/having sex
- head foggy, super foggy. typing is a bitch.


did some more doses.... got a killer headache and tachycardia. Fuck this batch....whatever it is.

It tastes/burns like, and its effects are similar to a batch of MD-PHP (md version of a-php) that I got about 6 months ago. Seriously don't waste your time, if your vendor has tan/off white MDPV from china, its bunk.

Further re-dosing lead to mild increase in sex drive, extreme headache, throat pains.

Snorting it reveals a strong odor of solvent, ethanol/acetone from the scent of things. Snorting actually produced a minor rush and some very mild euphoria, accompanied by more headache.

Ill try and post a picture of what I received soon.
Anyone with similar experience(s)?
 
why not have it tested ? Contact your vendor and tell then not what you ordered - they may have bought a dirty batch.

Tell them your having it tested and then let them know the findings
 
why not have it tested ? Contact your vendor and tell then not what you ordered - they may have bought a dirty batch.

Tell them your having it tested and then let them know the findings

Indeed this is exactly what I plan on doing. Ill report back when I get the findings.
Update on my grey/off white tan batch:
Its definitely a PV derivative..... after further testing most likely impure/poorly washed mdpv.
Having already dosed, and no benzos on hand, I was in a bit of a pickle. The effects profile of this batch vaped was so overwhelmingly negative that the urge to redose did not come upon me until about 2 hours after the last dose. However I knew better than to vape it again and feel shittier/risk my air ways closing up.

Ended up doing 5-6 10mg rails over the course of the night. Burned like holy fucking hell. The nasal side effects and the burn greatly resembled a-pvp.

Effects-wise, I got a nice solid PV rush and PV high. My throat felt like it was about to close up and as if someone had been stabbing at it with a knife the day prior. Eerily similar to a-pvp crystal snorted, but not quite the same. I also took a small amount and made freebase with it, ONLY to check how much yellow base oil I could get from 100mg of powder. Discarded all of that once I verified. Base oil looks and acts the same as MDPV, however there was significantly less oil produced than past batches run through the same process.

Still wouldnt spend my money on this batch given prior knowledge, but at least nasally it does have some minor pv magic. Also.... nasally this stuff RIPS my septum up just the same as apvp... watch yourself.

Will report back with test results when those come in.
 
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