Can you give a layman's run down on the MDMA neurotoxicity issue? What sort of effects are noticed in users who have done too much too often for too long and in the wrong combinations? That's a topic I was unfamiliar with and it seems pretty complicated on the actual research side of things.
acidfly summed it up pretty well -
It takes about a month to generate the serotonin your brain dumps, so there's a loss in emotional quota for a period after consumption (after the high). The up has a down cost. Taken too often, or too frequently, and your receptors effectively become damaged (from the serotonin flooding which causes the receptors to retract, and subsequent lack of serotonin), and aren't as capable of serotonin uptake. This can have lifelong implications, like lack of emotion, or emotional response. Anxiety is a huge one, because if there's no "happiness", it's a dull, panic state. Not sure how to best describe that last part, but that's how it feels. Everyone I knew, knew to take it only once a month. Longer periods between (6+ weeks) to experience similar highs.
If you want my massive rambling version instead -most stimulants work by either releasing, or inhibiting the reuptake of, 3 chemicals in your brain: serotonin, dopamine and epinephrine/adrenaline (and drugs like MDMA which aren't really stimulants in the traditional sense but have the same mode of action - here in Aus they're all categorized under ATS: Amphetamine Type Stimulants, although they sometimes include coke in this category, which has a similar effect but works but inhibiting reuptake, not stimulating release).
Serotonin is your basic mood regulator. You know when you're having just a good day, everything is going well, you're happy and content, and all this flows into putting you into a good mood where you feel happy about your life, you feel close to the people around you, and just generally feel contented and good with yourself? That's serotonin at work, which is why so many antidepressant drugs are drugs which are supposed to make you happier by increasing your levels of serotonin (also why you can't get high on MDMA when you're on these SSRI's). Psychedelics also act on serotonin, but they don't directly release it - I'm a bit iffy on the specific mechanic of it since I've always preferred dissociatives.
Dopamine is the "reward" chemical which gets a lot of talk (and is wrongly attributed to being the chemical released by opiates, which function by releasing endorphines - literally "endogenous morphine," there is some secondary dopamine release because anything which feels good, especially anything tied into a repetitive cycle of behavior, is gonna release dopamine, but dopamine isn't directly released by opioids that I know of, and isn't the primary cause of the high). This is when you pull something off - you finish something you trained really hard for and you kick ass and win and everyone is cheering, you go up to that hot girl at the bar and she's really into you and you hook up, or you go to work and finish some major project and it does really well and you get a ton of praise from everyone and a raise from your boss. You feel great, on top of the world, you're the fucking man, like you can take on the universe. That's dopamine. But because it's the chemical your brain pumps out as a reward for doing things you're supposed to do (even just eating, drinking, sex, exercise, etc), you're naturally designed to crave it, so drugs like meth and coke which increase it's levels in a big burst become really addictive - your brain becomes programmed to think that snorting that white powder or hitting that glass pipe is something which it's supposed to do to feel good - it's kind of fucked up because even though I was far more addicted to opiates than meth and given a choice would spend a day high on heroin over meth any day, it's meth that I mostly dream about at night and wake up sweaty and heart pounding, your whole mesolimbic pathway - that reward system - just gets hijacked by the drug).
Adrenaline I figure you know, so I'm not gonna go into it, but the degree to which the drug increases it is responsible for the peripheral nervous system effects - the sweating, shakiness, pounding heart, the physically "amped up" side of the effects, and the edgy anxiety side of the high.
Your serotonin receptors are also really sensitive compared to the dopamine receptors (the main ones involved in coke, amphetamine, and meth - although meth releases slightly more serotonin at first, which is why it feels so amazing and somewhat unique the first few times and probably plays a role in the neurotoxicity and addictiveness), and your serotonin doesn't replenish quickly the way dopamine/adrenaline do.
Basically the ratio at which these receptors are affected are what determines the drug's effect. So something like MDMA (high serotonin, low dopamine and adrenaline) will make you feel amazing and loved up, music feels awesome, just touch and sensation feels awesome, you're emotionally open, talkative, everyone feels like your new best friend (it's sometimes classes as an empathogenic drug). It can be a very strong emotional bonding/cleansing experience in the right context (which is why they're experimenting with using it in marriage counseling and PTSD therapy - it opens you up and connects you to other people), but it can also just result in you having deep and meaningful conversations with someone you met 5 minutes ago on the dancefloor and will never see again. But it's not very stimulating and energetic, often it takes a conscious effort to get up and dance for extended periods of time - although it feels amazing when you do - you just want to sit there and feel amazing. But without the huge dopamine hit, it isn't very addictive, and without the huge adrenaline release, it doesn't get you really amped up (which is why a lot of ecstasy pill makers include a bit of meth, or caffeine or some other stimulant), and you can sleep more or less directly after it wears off.
Then you've got something like cocaine, which is in many ways an opposite (low serotonin, high dopamine, moderate adrenaline). You get the egotistical, manic, 'top of the world' high (which is why the stereotype of the douchy cokehead exists). Because it releases more adrenaline, you get more of the straight stimulant effects - energetic, can't sleep, bouncing around, twitchy, heart rate and blood pressure go up, and so on.
Meth is similar to coke, except it also has a bit of a serotonergic effect (moderate serotonin, high dopamine, moderate - but lower than regular amphetamine sulphate - adrenaline), which is why the first few times you use it you get a good dose of that magnanimous, open, glowing feeling the serotonin gives you. But because the serotonin is quickly depleted and the receptors are sensitive, this doesn't last long, and after a few times it turns into the aforementioned regular stimulant high. There's also a direct correlation between how you dose the drug and how addictive it is - this is because the faster the drug kicks in, the stronger the association your mesolimbic pathway, the reward system dopamine acts on, builds with that method of dosing. If you suck on a pipe and you're suddenly feeling amazing even while you're still pulling in the vapor, of course then that's a stronger association than snorting a line and slowly feeling the high kick in over 2 or 3 minutes, which of course is still a much stronger association than eating a pill and then having the high kick in 20 or 30 minutes later. And of course pressing a plunger on a syringe which pumps the whole dose into your bloodstream at once is the ultimate instant gratification cause the whole thing whacks (heh - I originally typed "smacks," realized it might seem like I was making a pun, and replaced it with another unintentional pun) you in the gut at once while you're pulling the needle out of your arm.
Anyway the reason I'm off on this tangent is this association between ROA and addiction rate is a huge part of the problem with meth in Australia. Unlike coke, which cannot be taken orally and has to be cooked into crack through junkie science to smoke, meth can be eaten, snorted, smoked and injected (also plugged aka. up the poophole, but that's not a popular option for meth - although surprisingly popular for MDMA), each experience subsequently stronger and more addictive. So it's easy to start out taking a dab of gas/speed (cheap, shitty, damp powder meth, often racemic instead of purely dextrorary, which is sold for about 1/3 the price of regular crystallized meth) at a festival, or from a mate at work, for an energy boost, then stepping up to snorting it in the bathroom with your pills at a club instead, then you're in the carpark or at a house party and someone offers you a pipe and it gets you a faster, stronger, smoother high for less money, so next time you hit up your dealer you ask for shard/shabs/ice (crystal meth) instead.
Then after a while smoking you've stopped going out to parties because that's a waste of money you could spend on more meth, and you've got a tolerance, and the pipe isn't doing it for you, and you can't get the same rush you used to no matter how huge a toke you take, and you start wondering whether needles are that scary after all. So there's a huge spread from functional, casual use to frequent, recreational use to constant, addictive use, just as there's a huge spread of the drug across the socio-economic spectrum and geography of the country at the moment. The media are losing their shit because the city markets have peaked for a while now, so there's allegedly, can never tell with the media, a huge surge of rural meth from all the spillover, bikies taking out what they couldn't sell in the city, etc. - where prices are actually falling for the first time in years due to oversaturation, which is making it hard for the low level dealers. Unlike the heroin problem we had in the 80's and 90's, there's no strict "they're the junkies we gotta deal with," no "society v. the druggies," because the same kids who'd "never smoke ice" are taking dabs of powder meth on the weekend (I mentioned my highschool dealer who sold ice as MDMA - he also used to mix it in with the bags of pills he sold - I had no idea until I bought some myself for the first time and was like "hey I know that smell") and just slowly get pulled in by the gravitational effect of it all, that hijacking of the dopamine system. It's pretty much the ultimate drug to ruin a whole bunch of lives with.
So ok after that massive tangent about Australia's meth problem and how stimulants work, back to the actual question you asked about MDMA neurotoxicity.
As far as actual effects, the first quick point to make is that it's hard to say precisely, because a lot of what is sold as MDMA is either adulterated with other drugs, or just not MDMA at all. Before research chemicals became available, one of the famous pill pressers - Carl Williams, they made a TV series about the dude - used to press pills with meth and ketamine in them, figuring a lot of people wouldn't know/care about the difference. And he got rich, so obviously a lot of them didn't (although I know some people who used to buy them intentionally for the ketamine content - K doesn't metabolize well orally, so each individual pill would have needed a huge dose to vaguely simulate the weird stimulated-sedation thing MDMA does, but crush and snort them, and you've got yourself some cheap K with a bit of speed thrown in). And of course anyone who takes MDMA probably has a history of using other drugs as well, even if it's just weed and booze, it's enough to make precise studies difficult.
These days it's even more random, with all the new RC's out there (some of which aren't actually neurotoxic - such as 4mmc aka. mephedrone, although it's hell for your circulation system - even worse than coke, funnily, when it was legal in the UK for a year or so and everyone took it instead of MDMA/coke, the number of deaths from these drugs went down by 30% or so because people weren't getting toxic pills and mephedrone doesn't have the same propensity to trigger random strokes/heart attacks as cocaine). That said, generally speaking, the effects take place on both a cognitive and emotional level. The cognitive effects aren't as noticeable, as apparently the brain has an easier time healing around the damage and forming new pathways, but they've done studies testing people who used to take MDMA frequently in their youth but have since stopped for several years, and found that they scored lower on a bunch of things I don't remember (I could try find the actual studies, but if you just type in "MDMA neurotoxic" or similar in pubmed you can find summaries of a lot of studies). Memory was a big one, and problem solving, iirc, but the difference was statistically significant but not exactly crippling.
The emotional stuff is a lot more insidious. Like I mentioned before, a ton of people I used to party, especially those who took pills way more often than I did (I made at least a solid effort to spread it out to once a month) are now emotionally damaged in some way, on anti-depressants and tranquilizers (including yours truly), a lot of anxiety and depression. Even the ones who haven't been diagnosed (that I know of) I've seen the changes in over the years, they just lose some of their spark and enthusiasm for life, Acidfly summed it up pretty well:
like lack of emotion, or emotional response. Anxiety is a huge one, because if there's no "happiness", it's a dull, panic state.
They walk around like they're just living life by rote, not really feeling anything about anything. Flat. The worst cases, the ones who'd eat pills every week or two for years on end, just end up kind of deadeyed. Uncomfortable to be around. A lot of them don't do much but go to their deadend job, come home, smoke weed and drink. No ambition, no passion, no connection to anything. It's really fucked up to see.
The reason this happens with MDMA more than most other drugs is that, as has been mentioned, the serotonin receptors are really sensitive, and serotonin takes a while to replenish (which is why you can't binge on MDMA, and taking it two night in a row will make you suicidally depressed). Dopamine is produced fast enough that you can keep it pumping as long as you have more coke/meth/whatever, and the dopamine receptors are hardier, although not immune, meth use is neurotoxic to the dopamine receptors as well, although the effects tend to not be as severe unless you go absurdly hard, for years on end. the mental health effects on the other hand, tend to be more dramatic, depending on lifestyle - lack of sleep/good food is a huge contribution to a lot of meth addicts flipping out, those who keep a nutritious diet, drink plenty of water and don't skip multiple nights of sleep in a row for extended periods tend to not be the ones who go psychotic and paranoid, even if they're using daily, although it can still happen). Then there's the
There are a lot of plans and theories for avoiding the neurotoxic effects of MDMA out there (although many of them are just focused around not losing the effects of the high, instead of preserving long term mental health, and few of them make any difference, some are counterproductive - I experimented with a lot of them back in the day). People talk about pre-loading with various supplements (some specifically made for that purpose and sold online/at head shops) to make the high better, or post-loading to make the comedown easier/abate the neurotoxicity, and all sorts of crazy spacing out schedules. Generally it's agreed once a month is the maximum if you wanna stay safe and keep enjoying the drug, once every 2 months is better, and sticking to 2 - 4 times a year is ideal. Of course this is usually a case of "do as I say, not as I do," which is common in harm reduction circles - it's easy to talk about moderation and safety, not so easy to stick to it in the thick of the moment, and I sometimes worry that people use the fact that they follow some basic HR tenets to justify other risky behavior to themselves - but it's just a hunch. I do know that one of the unintended side effects of the internet harm reduction scene is it becomes a place where you hear about all these cool new drugs you would probably never have known about otherwise - especially big problem now that new Research Chemicals are coming out every week. Harm reduction websites often walk a fine line between providing a space for people to help eachother use these drugs safely and providing people a space in which they end up advertising or reviewing them. But overall I think the benefits outweigh the suspected risks.
But when it comes to MDMA safety, the basics are best. Buy your drugs beforehand, test them with a kit beforehand to make sure they're actually MDMA. Don't take them if they're contaminated with meth/amphetamine (it'll show up on the test kit), as that will enhance the neurotoxicity and the comedown specifically. Start small with each new batch - pill potency varies absurdly, now more than ever. There are pills sold in Europe with up to 270mg of MDMA in them (the recommended dose for an adult male is 80 - 120mg), but also pills sold with 20 - 30mg. You can see how that could be a problem. And capsules/powder has god knows what purity. Best way is to eat a half, maximum (1/4 for first timers, really small chicks and untested pills), wait until you come up on it, then if it's been an hour or so and you're not quite where you want to be, gauge the effects and snort a bit more, as that will kick in faster to top up your high. You can always take more, but you can't untake ending up in a coma because you decided to YOLO it and double dropped 2x 250mg pills. Stay hydrated (but don't overdrink water - a bottle/hour if dancing, half a bottle if not, hyponatremia is an ugly way to die, and a few people got hit with it in the 90's because the extent of harm reduction was "drink water so you don't overheat," and so water became some kind of MDMA panacea for idiot teenage girls). If someone feels a bit unwell, get them some fresh air. If some fresh air and calm and a few sips of water don't settle things down, then seek medical attention. Better that they're embarrassed than dead. Personally, I'd say if you like your brain, maximum of 4 times a year and 6 week break between each is a good limit. There are always more pills and parties, there aren't always more braincells.
I was wondering because he mentioned being a weekend warrior too and the comedowns from MDMA and "suicide Tuesday" and earlier doing heroin all weekend then needing to get through Sunday before he could switch back to suboxone. Just seems coming down off binges like that would make work seem impossible.
Short answer:
Having a job means more drugs.
Long answer: On and off. For the first 6ish months after I first tried and fell in love with MDMA I was still in highschool, living off WoW accounts (not a full time business, although I got an impressive amount for my main pre-BC when I quit the game for the first time, but enough to scrape together cash for a couple pills here and there). Then I spent a year studying and working a shitty fast food job. I put my degree on hold after a year (celebrated by candyflipping at a rave), during which I traded in my fast food job for a sales job. Up to this point I'd usually kept by partying to a max of a single night on the weekend, occasionally a back to back.
That changed when I started sales. It was way better money, but the hours were intense and the commission system meant there was a lot of stress, so on the day and a half I had off as my weekend, I would get stuck into it. And then I'd need a morning pick me up on Monday, which was either whatever was left of my stash or an insane amount of caffeine. A ton of my co-workers also partied heavily (and all of them lived on energy drinks), although we mostly traded stories on Monday morning more than actually getting high together, except for the occasional line at work to keep going or joint afterwards, since we all hung out in different scenes - one amazingly hot girl was a meth addict with a dealer boyfriend in jail, fresh out of what I presume was only her first stint in rehab, my team leader and a bunch of the others would eat pills and drink a ton at mainstream electro clubs, and we had a few gay guys come and go. I'm pretty sure my GF was the only person there not getting fucked up, and that's cause I kept her away from it as much as I could, she was messed up enough and would have gone downhill like a fucking boulder pushed off a cliff - but I was 19 and she was fun to hang out with (when we weren't fighting or breaking up) and amazing in bed (her being a squirter and me being unable to cum because I was on meth ruined a few mattresses), so it was a relationship built mostly on weeknights and Sunday afternoons spent in bed or watching movies (having a cute naked girl with you in bed eases the comedown considerably), occasionally we'd go straight from work to a movie or a dinner date, but that's about it.
After that I was unemployed for 9 months because my health went to shit. I got hit with glandular fever and it wiped me out for 9 months. Literally asleep 14+ hours a day, every day (part of it was probably just recovering from the months of a lifestyle fueled by fast food, caffeine and meth, in hindsight). This is when I first got into opiates, because either as a result of the virus (apparently pain after viruses is a thing that happens, something about nerve? fuck if I know) or of being in bed 14+ hours a day for months on end, my back started killing me. You know the way your bones ache when you have a really bad flu or whatever? I had that during the acute phase of the virus, and it's like it faded from the rest of the body but just piled up and amplified in my upper back. So I started taking a lot of pills, at first just non-narcotic painkillers, then low dose OTC codeine, then high dose codeine extracted from the pills, which started about 3 months into this phase and was where the opiate thing kicked off. When you're awake only 10 hours a day and you spend it feeling like your back has gravel lodged between the joints and muscles, you'll take whatever relief you can get. If that relief also allows you to catch a buzz, that's good to (I remember actually writing about my experiments with the codeine extractions in the drug thread back on FOH).
Eventually my energy levels came back and I went and got a job at a sandwich place down the road. It was a pretty shitty job, but it paid ok and was within walking distance. Hunching over making sandwiches for hours a week did't do my back any wonders though, and I'd frequently stop off at one of the chemists to grab a pack of codeine pills. One dose to chill out when I got home, watch a movie or do some gaming, then redose and go to bed. Also around this time that I found harder opiates. I'd been poking around my old contacts trying to find something ever since I'd started working again, but it took a month or so for a friend to come through with a fentanyl patch, an oc20 and 10mg of morphine. I tried the fentanyl patch (a small strip cut off and applied to the gums), but took a bit too much and it just made me really sick (and like I've said, Fentanyl isn't too euphoric to begin with). It was that weekend that I ate the oc20 and the 10mg of morphine in one go and holy shit I was in love. I'm not going to wax poetic about the opiate high here, but going from codeine to oxy/morphine was kind of like going from getting a toothy BJ from the chubby chick in your English class to mind blowing sex with your hot celebrity of choice (Alison Brie for me, thanks). I mean relatively speaking, they're similar experiences (a woman stimulating your genitals, or a drug stimulating your opioid receptors), but it was just a whole other level of pleasure. If MDMA was the "holy shit are the other ones this good?" then the oxy/morphine combo was "holy shit I want to feel like this for literally the rest of my life."
Anyway I stuck it out with this job, and went back to study the next year. This was in the middle of the MDMA drought, and all the ketamine flowing into my city had been cut off, so after the brief summer where Mephedrone was freely available, the only party drug left was meth. So I was studying part time, going out most weekends smoking meth and working 25 - 30 hours to fund it all (often keeping myself going with leftovers from my weekend stash - I know pharmaceutical amphetamines are popular for study in the US, but meth does the trick just as well, and my grades were a lot better this time around... first semester anyway).
Of course something had to give, and I started to wig out. Combined with some drama involving money and missing drugs and bikies, sleep deprivation and the amount of pressure I was under from my combined work/study schedule, I started getting paranoid and edgy, terrible comedowns, losing a lot of sleep even when sober, when I went out I spent as much time in the carpark with the pipe as did in the club (I wasn't the only one, the MDMA drought created a lot of meth addicts - people are always going to want more than booze to keep them dancing all night).
For a while I handled this with alcohol and my new BFF, oxycontin, but eventually something just snapped. Every time I smoked meth my chest would squeeze and my heart would pound away like it was trying to explode out of my ribcage. There were also some more subtle weirdness that manifested at the time which I only recognized in hindsight. I'd be paranoid that customers who lingered in the store too long were actually bikies here to get money out of me, I'd sometimes find myself in lectures confused about whether it was my first (that is, the first year which took place 3 years earlier) or second year of Uni, I'd get panic attacks (although I didn't recognize them as such, I just figured my heart was giving out under all the meth and caffeine - the store gave us 50c cups of coffee) and weird periods of dissociation, which is really unpleasant when it's not drug induced.
After a stupid 4 day binge I gave up on meth for the most part and swapped to oxy fulltime. It was about 50/50 at that stage anyway, even on the weekends often I'd start mixing the oxy with the meth as soon as we left the actual club (which felt amazing and really cushioned the crash) - one of my dealers was a professional photographer who covered most of the gigs I attended, and most of my party friends weren't into opiates, so I didn't have to share. I still used to get stupid when I drank too much and run to the closest dealer occasionally, but it always ended badly and after a few months I mostly gave up on the prospect and it became a drug I'd use once every month or three. Barring a brief stage after I got onto suboxone, I've used it less and less over the years (before 2 weeks ago, I had gone over 2 years without it).
Oxy felt just as good as meth (and no comedown!), got rid of the knots in my shoulderblades and didn't fuck with my head (which mostly straightened out, I never went psychotic or anything, thank God, seen enough of that in other people) or put the same strain on my body, while still giving me a motivating buzz at the right dose which kept me going through work - if not study. By second semester 2010 I was neglecting study for work, where I made the money to buy oxy, although I didn't actually develop a habit for another 3 or 4 months. The first time I noticed getting sick (other than a bit of discomfort when I went through a phase of taking the codeine extractions 3 times a day for a month) was after a 5 day binge. Went to an interstate festival with 20 or 30 oc80's, since the prospect of dealing with all that tweaker bullshit didn't seem like it would make for a fun weekend with friends I don't see often. Started snorting oxy in the bathroom at the airport before our flight and didn't stop until 2 days after I got home (although I did manage another class act, getting kicked out of a festival an hour before the end after vomiting on a tree from a combo of oxy and GHB (G on an empty stomach has without fail made me throw up every time), but we had a brilliant weekend just chilling in our hotel room or wandering the city and the harbor, all completely out of it on oxy. One of the best times before it went shit. Some of the others were taking an obscure psychedelic - 2CT7 I think? - and ended up ordering the same movie 3 times on the hotel room TV, and another mate made a ghetto-crackpipe out of a pen and a wine bottle lid, and was smoking MDPV out of it (a dopamine reuptake inhibitor, kinda like coke, was very popular in Europe for a while).
Anyway After 5 days of heavy consumption, I went to work and noticed I felt like ass. No Trainspotting type shit, but I was aching in everywhere instead of just my shoulderblades, getting hit by cold shivering and depressed as fuck. I ate some codeine when I got home and felt better, repeated the same process the next day, then the day after I woke up to a message from a friend saying he had 5 fentanyl patches he was looking to sell. Making sandwiches all day paled in appeal to enough of even my least favorite opioid to keep me nodding for a week or two, so that was that.
Since then my only gainful employment was two months stacking shelves an an upmarket fresh food store (conveniently within walking distance of a close friend who was also a heavy user). The first month went surprisingly fine (extra money meant worst case scenario I could stay well with codeine if I had a shift, although keeping me well is all it did, stupid tolerance), despite longer and more frequent bathroom trips than most employees require (and once having to cut off a conversation with the manager to run out the back door and throw up because I'd forgotten to take my phenergan, but I managed to talk my way out of that one). Unfortunately my month there was a training period for the new store they were opening in another suburb, and the woman they chose to manage there was far more switched on to my droopy eyes, tiny pupils and excess bathroom trips, and I got fired. Can't blame her really, I was hardly employer of the year (although I got no complaints at the first store, luckily the uniform involved long sleeves) but that was that.
I went onto suboxone a month or two later, and then went back to Uni, which worked for a semester, then I started skipping suboxone to get high (that particular weekend you're mentioning happened during the mid-semester break here - iirc. I went Tues - Fri getting high, got ripped off with the H on Saturday then spent Sunday waiting out the 24 hours before I could take my suboxone again) then put my degree back on hold so I could sort myself out, which kind of worked. I finally stopped using opiates, but I spent most of that year eating benzos (especially xanax) like candy and about 4 months injecting ketamine and MXE. I finally got sick of that (MXE comedowns are almost as bad as meth, and like meth, it does weird, weird things to your head - I can handle being a junkie, don't think I could handle being psychotic, I might not like reality, going off how much time I spent trying to escape it, but I do like being able to make reasonably logical sense of it) about 7 months ago. And since then I've been sober (discounting social drinking and that one bong), other than an indiscretion at a party a few weeks ago involving some GHB and meth.
Jesus this is turning a bit more autobiographical than I intended. Let me know if it's TMI and I'll reign in my rambling and sidetracks for shorter and more concise answers.
