blocking amphetamine (adderall, dexedrine) tolerance

well swim tried potentiating it with tums but the difference is subtle at best, so swim thought he would ask if there's anything he can take to block amphetamine tolerance, in the same way that say, dxm blocks opiate tolerance?

 

Amphetamine has almost the same mechanism of tolerance as opiates. It involves the gated Ca++ channels in the brain. DXM will also inhibit amphetamine tolerance, but its a pretty shitty way to do it. A far better susbstance to use is magnesium. Magnesium will even reverse the tolerance you already have over time. I'd reccomend a 250mg magnesium suppliment daily. Thats what I use and it works phenominaly.

 

Daedalus, would you explain this alittle more please? you seem to keep yourself well informed, thank you,D

 

This is one of the better explanations I've found on the subject, written by DAG:

Amphetamine tolerance is caused by excess Ca++ influx through the NMDA receptor gated calcium channels on the outer membranes of the dopamine cells bodies in the ventral tegental area, one of two areas in the brain with concentrations of dopamine producing neurons.
As alluded to above, taking an appropriate NMDA (partial) antagonist will prevent the development of a tolerance for the effects of an amphetamine or amphetamine-like stimulant. Also, by preventing excess Ca++ influx into the neuron, an NMDA antagonist will prevent associated brain alterations and damage (excitotoxicity).

Studies have indicated that amphetamine tolerance is prevented by exogenous or endogenous agents that are able to inhibit excess Ca++ influx into the neuron through the gated calcium channels on the neuronal membrane that have NMDA subtype glutamate receptors.Glutamate , the body’s major excitatory neurotransmitter, opens the gated calcium ion channels upon attaching to the NMDA receptor. A number of other receptors are also expressed on these calcium channels, which, when stimulated, either facilitate or inhibit glutamate’s action.

It is also important that agents that inhibit calcium channel activity not also cause deficient Ca++ influx. For example, ketamine is a full NMDA receptor antagonist, that prevents excess Ca++ influx and amphetamine tolerance. But being a full NMDA antagonist, ketamine in excessive doses results in deficient Ca++ influx. This could be one of the reasons it leaves K-user in a state of disassociation.

So basically we have following NDMA antagonists:
1. Memantine (Akatinol/Axura)
2. Acamprosate (Campral)
3. Amantadine (Symmetrel/Amantix)
4. Magnesium (supplement)
5. Dextrometorphan/DXM
6. Ketamine
7. PCP
(funny that 5,6,7 are recreational drugs)

Two of them have minimal (or none) side effects and have been identified (and verified by one anecdotal person, which has been taking amphetamine-type stimulants and NDMA antagonist with same beneficial effects for a period of 2 years) as preventing amphetamine tolerance: 1) Memantine and 2) Acamprosate.

1) Memantine is a partial NMDA antagonist that effectively puts an upper limit on Ca++ influx without compromising healthy levels of Ca++ influx. Memantine is not available in the US at this time. It is in stage 3 trials for Alzheimer’s disease. US approval may come within the next 2 years. Memantine is now approved in the European Union for the treatment of Alzheimer’s. It has been marketed in Germany since 1978 for the treatment of dementia and other cognitive disorders. It comes in 10mg tablets. One or two tablets/day are sufficient to prevent amphetamine tolerance, overactivity of the NMDA receptor and consequent free radical stress inside the neuron. The most expensive option though.

2) Acamprosate (n-acetyl-homo-taurine) analogue of the amino acid taurine. Alternatively, it may be termed as a carrier molecule for taurine, that allows taurine to readily cross the blood brain barrier, unlike taurine itself. Taurine is a NMDA receptor antagonist. Acamprosate is an investigational drug in the US, undergoing stage 2 (?) trials for the treatment of alcoholics. It is available in most European countries as a treatment for alcoholism, with great efficiacy. Cheaper than memantine, however efficiacy should be the same.

3) Amantadine, originally used in the treatment and prophylaxis of influenza infection and drug-induced Parkinsonism, also blocks NMDA receptors. Besides it is beneficial in traumatic head injury, dementia, multiple sclerosis,cocaine withdrawal and depression. Amantadine appears to act through several pharmacological mechanisms, none of which have been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. I couldn't find what amount of the drug should be used to block NDMA. Cheaper than Acamprosate. No one has tested it yet, but I think it would be a good choice.

4) Magnesium is also an NMDA antagonist. Most people are deficient in magnesium, and stress reduces magnesium levels. Whether or not one takes amphetamines, magnesium supplementation is very important for mood, general well-being and keeping stress levels under control. It is also important to take magnesium in efficient form, with adequate bioavailability. The best type is magnesium glycinate (chelated) with bioavailability at around 80%. Second best is magnesium carbonate with (I don't remember exactly) bioavailability at little above 30%. Supplemented magnesium should be at 500 mg/day level. Also there is a study which shows that children who use amphetamine-type stimulants have bad magnesium/calcium balance. Calcium levels stay the same with amphetamine usage, but magnesium levels drop.

5) DXM - definitely the cheapest option of all NDMA antagonists, but I'd rather use Memantine or Acamprosate. Although, I've heard anecdotes that doses as low as 70 mg/day are enough to block NDMA - I couldn't find those amounts in abstracts/studies.

6) and 7) I wouldn't use as an amphetamine tolerance prevention. Ketamine for its known effects (you wouldn't want to be in a K-hole during the tweak just for the sake of prevention tolerance)
PCP - this one doesn't need explanation. It has nasty side-effects and I've mentioned it just because it is a NDMA antagonist. I wouldn't touch it even if it was dirt cheap.


So basically combination of partial NDMA antagonist and amphetamines should prevent tolerance. But I'm curious whether NDMA antagonists are able to *reduce* amphetamine tolerance. If yes then my goal would be to reduce it as far as to the point of first speed experience :] Right now, I have high amphetamine tolerance (too much tweaking during short time in the summer) so I will be using Acamprosate to try and reduce my tolerance. I'll post my results here.
And sorry for the length of the post - but I just wanted to write down everything I researched during last few days (I skipped PubMed abstracts).
Take care.

 

• Thank you!! ok, so if you like having your brain picked, i have so much i could ask, ill just ask you this (for now ) being on adderall 15 years i have had many increasings, my script allows 90mg. well , you know as well as i , the way the body breaks up and time, leads to tolerance. so 5oomg of the magnesium a day, just plain over the counter magnesium carbonate 500mg? or 250mg? also if over time it reduces the tolerance, what would you think the down-size amount and how often could start ? im aware you're not a Dr. but you clearly know this stuff. Sadly DR. TODAY RELY ON THE SALES REPS, AND THE SALES REP JUST PUSH. im starting to think pharmacists may be falling into the hands of the pharmacutical co. I cant thank you enough for your info,but for the time you took to reply and write back. peace to you, dierdre

 

1. I've been prescribed adderall for many years now. Schemed it from the start. At the beginning I would go on several short binges and my supply would last a few weeks. By the time I found out about this method of tolerance reduction/inhibition it was not abnormal for me to start a binge with a dose of 160+mgs with 600mgs being consumed in 2-3 days easy. This is when the doctor shopping started but that’s another story for another thread. When I found out about this I began taking 250mg magnesium daily when I wasn't tweeking and up to a gram daily when I was tweeking (just for good measure ). After 2 months of this "therapy" I noticed that my supply started lasting 2-3 times as long and I got much better effects. The euphoria finally came back after being gone for years. After probably 6-8 months on this regimen I can take a starting dose of 60mg and be flyin high.

2. I choose to take 250mg daily as it seems to provide the desired effects. A hardcore (crystal daily) tweeker will be better suited at 500mg daily.

3. Don't expect to take it for a week and have your tolerance disappear. The only thing it will do at first is prevent your tolerance from getting any worse. It will take months before it reduces your current tolerance but if you stick with it you will notice a decreased tolerance.

4. A strong medical benefit from this is that your dosage won't need frequent adjustment. The less you need to take to achieve the desired theraputic effect the better. Amphetamines over time can do some serious damage to the brain.


If you've got any more questions I'd be more than happy to answer them.






Edit: Also, I'm a bit twacked at the moment so some of this may seem a bit rambly (is that even a word?) but after i get some sleep I'll look it over and see if there is anything i need to make more clear . . .

 

i cant tell you how much this has helped.i do read and search this all the time, but i must have not tuned in on this. is this even been given any case study? well, i bet not, being that it counters the dosing in time. why would shire want to, if it takes away from the all mighty dollar. i am starting the mag. today. Dr. shopping, geesh , been there,due to the crack downs in the last 2 years, and my own entanglements << ha i would tell anyone,don't do it.its not worth it. anyway, you have given me hope, thank you. peace to you, dierdre

 

hey thanks for the very informative response daedelus . wow i feel like an amateur, never had more than 90mgs in a day, and i've gradually upped my standard dose from 30mgs to 45mgs, and i'd rather not go far beyond that (wary of health repercussions), so i think i'll try the magnesium as well.

 

As you should be (wary of health issues), this is the smart way to go. Even though it is rather difficult to actually OD on amphetamines, provided that you are otherwise healthy, it's still rather taxing on your heart, circulatory system and brain to take large amounts of amphetamines. Go to a pharmacy with a BP machine sometime while your tweeking and see how high your blood pressure gets . . .

 

i know they say it can up your blood pressure, but i make a point to extra coffee and at times the added dose before i go to the Dr. just to see if it has any effect. i hit the below to normal range. how could this be?

 

At a recommended dose its hit or miss really on the BP. Some people have it skyrocket and some don't change at all. When you get into higher than normal doses though its pretty much guaranteed to raise your BP.

 

Yo everyone,

I just received a prescription for ADD (who knows if it's a real organic brain disorder or not) and have been doing extensive research on how to minimize my tolerance - after only 8 straight days I'm up to 60 mg twice daily to get me to my own personal "happy place" :=) I'll be running out far before my next script fill at this pace, no bueno!

So, as a result of research I came across NMDA partial antagonists - I've been trying to grasp the biochemistry (as best as I can understand, only took a few chemistry classes in college) of NMDA partial antagonists and how/if they can truly prevent (or some may even reverse) amphetamine tolerance, as MANY in other forums have claimed they can from personal experience. The most promising (and healthiest, most others are strong drug) appears to be magnesium taurate/taurinate (but some say magnesium glycinate) but the the former was used in a dperession study and was considered a better form (don't ask me why).

I know Daedalus who commented previously in this thread a few months ago had great success with drastically reducing his tolerance to Adderall by using magnesium, but he didn't specify which form he was using. Bro, Daedalus! Are you still out there? If you happen to read this will you inform me of the kind of magnesium you are/were using and if it's still keeping your tolerance at a standstill or even reducing it further? I tried to PM you but I'm to new to the forum I guess and can't yet.

Anyone else had success with other NMDA partial antagonists? If so please for the love of all us fellow euphoria chasers, share your experience in detail! For example, which NMDA antagonist do you use, each dosage amount you, how many times you dose with the NMDA antagonist in a day, how long until you observed a reduction in your amphetamine tolerance, etc.

Hopefully there's some success stories out there! I'm starting magnesium tomorrow after taking a weekend "drug holiday" from my Adderall. I'll be checking back soon, but in the meantime, take it light my friends . . . Robert

 

ok just so im not confused... i should go to the store and buy magnesium pills to help reduce tolerance?

 

I just use regular old magnesium oxide lately. It has a pretty low bioavailability but its cheapest and easiest to find. The best though is the chelated form. Its hard to find in stores (at least in my area) but it can be had here: http://www.vitaminshoppe.com/store/...t=cs&source=FG&ci_src=14110944&ci_sku=SL-1088

I'd recommend using that first to do the big work, and then you can switch to the cheaper and easier to find magnesium oxide as a maintenance type dose when your tolerance has been reduced.

 

Daedalus,

Hey man - I really appreciate the rapid response! That post by DAG on bluelight a couple years back concerning Ca++ channel blocking & tolerance development is infamous throughout the internet!

I was skeptical though, until I began to read several people's experiences such as yours - such anecdotal evidence caught my attention and I began to consider that maybe that guy's research on the tolerance problem was accurate! I finally read enough reports on various forums from people who tried the different NDMA antagonists, claiming they had actually halted amphetamine tolerance, that I became pretty convinced there was some truth to this theory (your one of only a few I've found who have successfully reversed their tolerance!) - so I decided to put on my white lab coat, grab a clipboard, and proceed with my own personal empirical study.

I actually went to the vitamin shoppe this morning and picked up some magnesium (unthinkingly assuming it was the "glycinate" chelated form) while in a rush on the way to class, but tonight I realized my stupid ass bought the "citrate" form (sounded like "glycinate" at the time!) which is not chelated - I haven't even read of anyone that's used that form, so man was I pissed off! No wonder it was so dam cheap! lol

Anyways, I've been downing 60mg DXM syrup the last couple days, dosing twice a day (CVS brand, contains ONLY DXM 15mg per tsp). I only started Adderall less than 2 weeks ago, and already it takes about 65-70mg per single dose to give me a decent stimulant buzz! Although, I did begin taking more than I was prescribed from day 1, but still, dam! I have drank Starbuck's coffee for YEARS on a daily basis (recently quit after I started Adderall) and every friggin' morning got the same or similar stimulant buzz from a single 16oz cup, and would often drink more at night and get a mild stim buzz again! I just don't begin to grasp the biochemistry of why the body adapts to certain drugs so dam fast (Adderall in a week), while others (caffeine for me) it seems to hardly even adapt to even over a period of years - total mystery to me.

My experience of minimal caffeine tolerance after daily use for years was part of the reason I was utterly astounded how quickly my tolerance built to Adderall. Man, I was so disappointed - more like COMPLETELY HEARTBROKEN, it was as if some incredibly beautiful "natural blonde" with sky blue eyes, somewhat tall with a slender hourglass figure (my physical ideal) - who possessed every single personality trait I've always preferred (witty, highly intelligent, adventurous, etc) just abruptly approached me and asked me out! So we go out and for a week there's sparks & fireworks all over the place because the chemistry between us is so powerful & perfect!! Then, out of nowhere, after a week she just stops returning my phone calls and changes her number and moves out of town! Well, I'm sure you get the analogy - that's EXACTLY (well maybe not exactly, but close!) the sense of betrayal you feel from Adderall after this completely unexpected tolerance it produces sucker punches you in the nuts, just when you least expect it! All due to some quirk in its chemical design!

Adderall teases you for about a week when you first begin taking it by providing you endless waves of soothing euphoria that feels so blissfully normal that it even permits you to live a normal life (unlike taking extasy, which feels wonderful, but look in the mirror when your on it, you sure don't look wonderful!) - day after day Adderall soothes your soul with comfort and boundless contentment, UNTIL, it decides to abruptly slam the pleasure door right in your face and then proceeds to put timed locks with bolts so you can't back in until you've waited a certain length of time (days).

Whatever, sorry for being melodramatic, but seriously, unless this NDMA antagonist Ca++ channel blocker biochemical theory works for me, I'll be forced to only use my Adderall a few times a week, and that will not be acceptable, because somedays I'll feel like a super mac daddy ready to aggressively attain every goal I've ever conceived of and then make new ones, but then the days off Adderall I'll be content just surfing the net diverting myself and thinking what could have been - I believe my dopaminergic reward system/limbic system pathways are that screwed up.

I took this last weekend off, a total "drug holiday", and was rewarded with a "little" tolerance reduction, from 70mg to get buzzed down to 50mg on Monday to get me about as blissfully wired as the 3rd or 4th time I took Adderall, but then guess what, yesterday I downed the same 50mg twice (Tuesday) and didn't notice a dam thing! Nada! Nothing!

Tell me, how in the hell can the same dose change so dramatically in its effects in barely 24 hours??!! In other words, just 14 hours later the same 50mg dose provided zero effect, when just hours before the same dose caused a nice "long lasting" euphoria!! Just thinking about it makes me need to exhale a big long Sigh . . . does there happen to be a neuropharmacologist reading this rant that can explain how this shit happens? What's up with this process!!

Well, I'm not playing games anymore - I'm going to the Vitamin Shoppe again today & grabbing the right magnesium this time, and just because I'm desperate right now (It also happens to be finals week at my university - I'm in a rigorous academic program and can't concentrate worth a shit right now), I'm going to continue gulping down 80mg of that nasty ass DXM crap too - although I've felt kind of like a middle-class junkie packing a big ass bottle of cough syrup around with me in my backpack during the day just to try and fend off a tolerance to amphetamines (if some people only knew!).

Ok, I just have two more questions to ask you daedalus, because I really need get this "method" to kick into gear somehow/someway, or, for now at least, inhibit my present tolerance from growing - so hopefully you won't be bothered by my inquires too much, due to my story evoking some empathy (or pity, whichever sentiment strikes you first!).

Have you ever tried the "taurate" form of magnesium, and if not, have you read/heard any reports about whether it's effective or not at reversing AMP tolerance? I've been reading around how it's allegedly the most superior form (even read a scientific journal article describing magnesium taurate, but they were using it to cure depression in that study, so who knows how/if that applies regarding our purposes, and I don't begin tov have the time to go reading Pub Med pharmacology journals in an attempt to verify this magnesium/calcium biochemistry neuron trick (I couldn't even if I had the time, I've only taken 2 chemistry classes in my life!).

I'd almost be content achieving half the success you have Daedalus! Hey man, can I ask you this much, is the Magnesium (including all the various forms you've used) still working for you with the same effectiveness it did when you first began supplementing with it? Which form do you think drop-kicked your AMP tolerance the best out of them all?

Lastly, what is a necessary "initial starting dose" for you to get "good effects" from your Adderall these days? Has the magnesium ever lost any effectiveness over time after you experienced an initial big drop in your tolerance?

Ok, I'm done, really I am - sorry for 50 questions, I just need to get this chemical configuration solved ASAP so I can get my mind buzz back and actually be productive again like I was for a week straight, which for me WAS A BIG DEAL, given the listless state I can sometimes find myself in.

I was actually diagnosed with so called "ADD" by my psychiatrist recently (who knows if it's a real organic frontal lobe brain disorder as purported - perhaps it is, but I don't have time to look into it presently) and within 2 hours from the start of our session, I was walking out of a pharmacy with a bottle full of little blue pills in my hand! I don't even think I made it to the front door before I had chewed up several 10mg pills swirled around with a dash of cold green tea!! Ahhh, the memories . . .

It was the psych doc that offered me a totally unsolicited powerful stimulant without me even "hinting" that's what I wanted!! I never thought in a gazillion years a doctor would ever prescribe me Adderall (believe me, thought about trying many times, but I'm not a good actor) and I never had the sack to go and ask a doctor for it thinking he/she would see right through to my true motive, to get my little hands on a pharmaceutical grade euphoria producing chemical! Also, I always assumed you had to have been diagnosed with ADHD when you were a kid for the diagnosis to be legitimate.

I originally went to see my psych doctor to get on one of the new wave of anti-depressants (like that way cool sounding selegiline skin patch called "EMSAM" - it causes more dopamine to float around in your brain by completely blocking the enzyme that disassembles it in the neuronal synaptic gaps - more cerebral dopamine=paradise found!). Alright, wish me luck on my quest and hopefully you'll have time to respond to this verbose ramble of a post (or anyone else who has succeeded in controlling their stimulant tolerance) - thank you for reading if you made it this far . . .

Robert E.

 

just one question

after looking into the magnesium debate and even trying dosing everyday along with my Dexedrine i see that it does work moderately well. After looking it up i see that it is a alkalizing agent which is supposed to increase the absorption rate of amphetamines already. Could this be why people see it as a decrease in tolerance and it might just fuck you over in the end.

just curious on your thoughts of this.

 

wow, bump for a really good read.

today i took a total of 50mg of Adderall XR and was feeling AWESOME. I initially was going to stop at 40mg because the waves were feeling perfect, but decided to take another 10mg. I'm going to keep it at 40mg, hopefully I won't build up a tolerance too high. I couldn't believe how great Adderall really worked for me. I honestly might have some mild-ADD/ADHD. The focus I got in classes today was just unreal. School today just went by a breeze. I was tuned in all day, it was awesome. After this experience, I might try and have my doctor prescribe me some Adderall but in a higher dosage, 20mg would be perfect and preferably IR.

BTW, does anyone know if on your insurance billing, the kinds of medication come up listed? I would rather not have my mom know I was on Adderall, having ADD/ADHD or not.

 

Hey, I got myself magnesium oxyde (half immediate release half time release 300mg) + B6 + B9 and taurine for an amount of money I consider ridiculously high (local pharmacy).

It is kind of bioavailable/usefull?

 

And I just noticed this post is kind of hugely outdated. Sorry...

 

After getting off opiates 2 years ago this month, I have been taking 250mg of Mag just to see if I could get my tolerance down over a period of time if I ever needed pain relief in the ER, I wouldn't need double and triple doses to fell any relief. During my opiate use I had a colonoscopy and when they though I was sedated enough I was quick to inform them that it simply wasn't the case when I came right up off the table. They immediately doubled up the dose once I told them I was a pain patient. Two weeks ago I had to go to ER late at night for an abscess tooth, the pain worst than either of the kidney stones I've experienced before, I received about half a dose via needle compared to a Demerol shot I had been given for a kidney stone once and was relieved to notice I had been reduced to a blubbering Idiot! So currently, I don't have much of a tolerance for pain relief. I've been on Adderall for about 18 months, starting out at 60mg/day, but I never made it that high, normally taking 30, sometimes 45mg/day.