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MDMA (3,4-methylenedioxymethamphetamine) is thought to be potentially neurotoxic due to free radicals (atoms or molecules which have an unpaired electron) created as a result of the neurological actions of MDMA. The neurotoxicity of MDMA is still being debated. There are many studies which conclude that MDMA is neurotoxic (the extent of which is determined by dose, rate of use, and other factors), and there are probably just as many studies which conclude that it is not. The neurotoxicity of MDMA is still a theory, as exactly how MDMA works is also not known. Until a legitimately conclusive study is published, users must decide for themselves. Either way, because there is strong evidence that MDMA is potentially neurotoxic, it is a good idea to practice some sort of harm reduction. A great technique to combat possible unwanted acute and chronic neurological, emotional, and/or physical detoriation of the mind and body is called loading.
Loading in the context of MDMA use is the practice of taking natural or synthetic supplements before (pre-loading), during, and/or after (post-loading) an MDMA session in order to better prepare your mind and body for the experience.
The most widely accepted theory for MDMA-induced neurotoxicity concerns damage caused by dopamine, a neurotransmitter which plays a huge part in attention, motor function, and pleasure, among many others. The euphoria experienced during an MDMA session is caused by an increase in the release of serotonin, another neurotransmitter involved in the regulation of mood, appetite, sleep cycles, and more. MDMA's mechanism of action is complicated to anyone unfamiliar with general neuroscience, and again is not fully understood, but the end result of ingesting MDMA causes an increased concentration of serotonin in synapses (spaces between nerve cells). This results in the characteristic euphoria, empathy, and general love that most users experience.
The brain is not built to deal with MDMA. Normally, serotonin concentrations inside and outside of a nerve cell are relatively constant. MDMA causes a depletion of serotonin. This is where the neurotoxicity begins. After serotonin is depleted, serotonin transporters, which normally bring serotonin back into the nerve cell after it has done its job, are empty. As a result, somehow dopamine gets brought into the cell by the transporters.
Dopamine alone is toxic to serotonin cells. More importantly, the breakdown of dopamine inside the cells is what causes the toxicity. Normally when serotonin is taken back (reuptake) into the cell from the synapse, it is metabolized (broken down) into smaller molecules and recycled to make new serotonin. When dopamine enters the serotonin cell, it too is metabolized. These metabolites, however are toxic to the cells. Dopamine is broken down into hydrogen peroxide, a free radical, which oxidizes (combines with oxygen) parts of the cell which aren't meant to be oxidized. This produces oxidative stress. The brain, like every other thing on the planet, likes equilibrium (balance). This increase in oxidation causes problems, in MDMA's case perhaps cell death.
A large part of loading concerns the ingestion of anti-oxidants, which are exactly what they sound like. Anti-oxidants work to inhibit oxidation. The theory behind this is that taking anti-oxidant supplements can decrease or even eliminate the excess oxidation caused by MDMA, providing neuroprotection (protecting the nerve cells from toxicity).
Another theory is that some MDMA metabolites may be toxic... but that is a whole different story.
That is a lot to take in. Hopefully it makes sense, there is a lot of science but I tried to clarify anything which probably is unfamiliar to most people.
On to the real deal.
The idea behind pre-loading is to elevate the level of antioxidants available to the brain before MDMA causes increased oxidation, hopefully combatting it before it even begins to hapen. In addition to antioxidants, it is a good idea to take some other supplements to combat the less dangerous but still harmful side effects of MDMA.
Here is a list of common supplements used during pre-loading:
Vitamin C (ascorbic acid) Sources: Countless generic Vitamin C pills or multivitamins, many fresh fruits and vegetables Recommended dose: 500mg-2000mg How it works: an antioxidant, will help reduce oxidation. Thought to recycle unused Vitamin E. Notes: a water-soluble vitamin, any excess will be excreted in the urine. However this means it doesn't stay in the body very long. Most of it is gone after 3 or 4 hours. This is why it should be taken multiple times during an MDMA session. However, as an acid, too much can cause stomach problems (ie diarrhea, indigestion, heartburn). An overdose is extremely unlikely, but too much can cause side effects which will make the experience less enjoyable. A good idea is to pre-load with 1000mg and post-load with the same, although some users find it produces nausea if taken during post-load. Know how your body will react before supplementing during an actual session. In addition, ascorbic acid is obviously acidic, and a more acidic environment is not conducive to MDMA absorption. However, my dog has never noticed the slightest decrease in MDMA awesomeness due to taking this supplement.
Vitamin E (tocopherol) Sources: supplements, some foods such as eggs, avocado, spinach, some nuts Recommended dose: 200-400 IU How it works: an anti-oxidant, will prevent oxidation. Notes: a fat-soluble vitamin, it leaves the body much more slowly than a water-soluble vitamin (ie ascorbic acid). Risk of overdose is higher, especially since supplementing usually involves taking more than the recommended dosage. It is probably quite safe to go to at least 1000 IU a day, and the risk of overdose is significantly decreased if the vitamin is only taken for one day (ie for one MDMA session and not as a continued high-dose supplement). Too much Vitamin E can cause stomach problems, fatigue, and headache. Again, test yourself before experimenting during an actual session.
Grape seed extract Sources: grapes (duh), supplements Recommended dose: 50-100mg How it works: contains antioxidants, will reduce oxidation. Notes: Grape seed extract is a very long lasting antioxidant, a half life (how long until half of it is broken down or out of the body) of about 7 hours. Therefore it is really only necessary to take this during pre-loading as an MDMA session usually only lasts about 6 hours. Side effects (quite uncommon): headache, nausea, stomach pain. Theoretically could increase the risk of internal bleeding, so be careful if you have any health issues such as a bleeding disorder.
ALA (alpha-lipoic acid) Sources: red meats*, yeast, supplements Recommended dose: 600mg-3000mg How it works: an antioxidant, will reduce oxidation. Notes: water and fat soluble, a very strong antioxidant as it can work pretty much everywhere. Short half life.
Coenzyme Q10 Sources: some fish, ie mackerel, sardines, salmon, tuna; supplements Recommended dose: 50mg-300mg How it works: an antioxidant, will reduce oxidation. Necessary for healthy mitochondrial (mitochondria are a cell's source of energy) functioning. Notes: fat soluble, half life of over a day, therefore only necessary to take during pre-loading. At higher doses, effectiveness decreases as dosage increases.
Magnesium Source: green vegetables, some legumes, nuts, and whole grains; supplements Recommended dose: 400-1000mg How it works: A common side effect of stimulants (including MDMA) is bruxism (jaw-clenching). Magnesium helps relax muscles. Notes: Be careful with dosing this one. Excess magnesium can cause diarrhea and abdominal cramping. Couple with dehydration this can make for some nasty side effects. Again, determine what an acceptable dose is for yourself before mixing with MDMA. No one wants to have to sit on the toilet all night when they could be out on the dance floor.
5-HTP (5-hydroxytryptophan)/trytophan Sources: 5-HTP can only really be found in supplements. It is the precursor (the chemical involved in the reaction which produces another chemical, ie serotonin) to serotonin. Tryptophan, the immediate precursor to 5-HTP, can be found in turkey, dairy products, eggs, nuts, and some fruits (notably bananas, which are delicious). Recommended dose: Tryptophan supplementation is much less common than 5-HTP supplementation, so that is what will be discussed. Why supplement with the precursor to the precursor when you can skip a step and make it easier for your body? As stated previously, 5-HTP is the precursor to serotonin. Therefore it needs to be converted to serotonin by the body before it has any effect. It takes a few hours for this conversion to happen, and only taking it during preloading the day of a session won't have a significant effect. 5-HTP has been shown to increase serotonin levels in mice, and presumably this would help with depression... but depression is (most likely) a result of constant low levels of serotonin, therefore 5-HTP should be doses continuously also. It is recommended to take 100-200mg a day for at least a few days prior to the experience. How it works: Basically provides more raw material for the production of serotonin. Notes: Artificially increasing serotonin levels may put a user at risk of developing serotonin syndrome (basically a serotonin overdose- NOT a good thing) when combined with MDMA. There is really only anecdotal evidence concerning this supplement. Many users have reported no effects, others have reported ill effects, and some stand by the claim that it definitely contributes to the MDMA experience. Only you can decide. Personally, my dog would not recommend bothering with this one at all during pre-loading to be safe... definitely go for it during post-loading though, no risk of potentially fatal side effects. One study (http://www.ncbi.nlm.nih.gov/pubmed/7934616), showed neuroprotective effects, but this is about the only publication my dog could find.
Antacids (ie Tums, Rolaids) Sources: Don't bother with trying to eat foods which have anti-acidic properties. Just buy some Tums. Recommended dose: 400-2000mg (perhaps 2 or 3 Tums is a good choice) How it works: This is tricky. Acidity inhibits the absorption of amphetamines. The point of taking antacids is to reduce the acidity of the stomach, increasing absorption of the MDMA. Tums and Rolaids both contain the compound CaCO3, which (my dog believes) breaks down into Ca+2 and CO3-2 (a weak base) in the stomach. However, like the brain, the stomach also works hard to maintain equilibrium (in this case a very acidic environment), therefore if one eats a bunch of basic (opposite of acidic) substances, the stomach will work harder to bring the acidity level back to normal, perhaps actually momentarily increasing stomach acidity. Antacids containing carbonate (ie the CO3 in Tums and Rolaids) usually take about 30 minutes to begin doing their duty, therefore it is recommended to take them with the MDMA rather than a small time before. My dog hasn't had enough experience with MDMA to conclude whether this has any real effect or not, but perhaps other users can offer some input.
Grapefruit juice Sources: grapefruits... or grapefruits in juice form. Recommended dose: A big tall glass. How it works: It is generally accepted that grapefruit inhibits an enzyme (a substance which helps a reaction take place) which breaks down many recreational drugs, ie MDMA... but this is wrong. Grapefruit juice does potentiate MDMA (among many other drugs), but by a different mechanism. My dog won't get into the details as it would twist many people brains, but here is a great thread Paracelsus posted about the subject if one would like to delve further into it: https://drugs-forum.com/forum/sho...apefruit+juice Notes: While grapefruit juice can definitely increase MDMA bioavailability (a measure of the amount of a drug which actually contributes to a physiological response), it may be counteracted by the fact that grapefruit juice is very acidic (about a pH of 3 on a scale of 1-14, 1 being the most acidic). My dog hasn't read anything specific about this dilemma, and he hasn't had enough experience to make a conclusion. Again, who knows what's best for you? You do! Be the guinea pig.
Piracetam Sources: supplements Recommended dose: 1000mg-4000mg a day for days or weeks before an MDMA session How it works: The exact mechanism of action of piracetam, a drug originally developed to slow the progression of such mentally deteriorating diseases as Alzheimer's or alcoholism, is not completely known. It is thought to enhance cognition and memory, as well as increase blood flow in the brain. Many experiences posted on Erowid champion the use of this drug, claiming it enhances the experience, perhaps reduces tolerance. My dog couldn't find any publications on this subject and doesn't expect to... piracetam is a relatively new and understudied drug, most people have never even heard of it. My dog says that he has personally tried this (dosing for 4 or 5 days before an MDMA experience) and can say his third roll was just as good if not better than his first, both were similar doses. He has only had three though so cannot give a real conclusion. ONLY YOU HOLD THE POWER TO DECIDE.
There are MANY more possible supplements. This is merely a list of the most common, perhaps most effective ones. Any combination of supplements can be taken. Perhaps one is sensitive to magnesium but always has a sore jaw after an experience... look for another supplement which can induce muscle relaxation, or simply bring a pacifier (if you're into that... my dog thinks these are best given to babies)! Can't afford expensive anti-oxidants like ALA or grapeseed extract? Eat an orange. Guinea pigs!
This is the most important supplement of all. Drink lots of it! All the time! MDMA causes dehydration and increased heart rate (the heart is working super hard), dancing causes dehydration (and works the heart even harder), and those who drink alcohol with MDMA (which my dog hears is quite common... doesn't understand why anyone would want to cloud the experience) are dehydrating themselves even more. This can be a dangerous combination. Drink at least a 20oz bottle or so every hour, especially if a guinea pig is dancing really hard. What about too much water? Risk of hyponatremia (basically a water overdose) is quite low, but still possible. In fact, in terms of deaths associated with MDMA this is really one of the only things to worry about, aside from polydrug (more than one drug) use and dehydration. Possible hyponatremia is easily combatted by drinking something with electrolytes (ie Gatorade) which will not disturb the body's salt balance as much.
Sample pre-loading regimen
(my dog's ideal recipe) Every day for approximately a week or more prior to the experience:
4000mg Piracetam (2000mg 2x a day) Anywhere from 1 hr to at the time of MDMA ingestion (MDMA usually takes approximately 30-60 minutes to work its magic):
1000mg Vitamin C
400 IU Vitamin E
50 mg Co-Q10
400mg magnesium (too much hurts his tummy)
And finally, 2-3 tums at the time or about half an hour prior to MDMA ingestion (my dog proposes that if he takes the Tums 30 minutes before ingestion, the levels of base will be relatively high when he ingests the MDMA)
Guinea pigs: see what works best for you! Theoretical knowledge is great, but experience is just as important.
There are really two "post-loads"... my dog defines the first as perhaps 3-6 hours after MDMA ingestion, and the second as the day/night (depending on when the MDMA was taken) and a few days after the experience.
First post-load (about 3-6 hours after MDMA ingestion, or as soon as possible after that)
Since after 3-6 hours MDMA is still potentially toxifying nerve cells, many of the supplements should still be used. Antioxidants (in the same, higher, or lower doses- YOU DECIDE) are still a good idea, just be careful with fat-solubles such as Vitamin E... chances of something terrible happening are miniscule, but it is still good to practice harm reduction of harm reduction! Some users complain of stomach cramps when post-loading with Vitamin C (talk to your guinea pig). Magnesium is also a good idea if guinea pigs think they are having jaw issues. Now, my dog thinks, is the best time for 5-HTP supplementation. As serotonin is quite depleted, giving the body more raw serotonin material can only help. Perhaps 100-200mg at this time, and more the following few days (discussed soon).
If one's guinea pig has it available, perhaps think about something like Prozac (fluoxetine), or Celexa (citalopram), both SSRI's (selective-serotonin reuptake inhibitor). SSRI's have a high (ie higher than dopamine) affinity (attraction) for serotonin transporters. Since the theory behind MDMA neurotoxicity concerns the reuptake of dopamine after serotonin depletion, perhaps fluoxetine can prevent this reuptake, as when it binds to serotonin transporters it sticks and it is difficult for things to get back into the cell (hence why it is used to treat depression- it inhibits the reuptake of serotonin [which regulates mood], increasing the serotonin concentration in the synapse).
DO NOT take SSRI's before using MDMA. Well, if your guinea pig wants to, go ahead. But he probably won't feel much, if anything.
Most importantly, hydrate! My dog thinks MDMA and humans are a match made in heaven, but physiologically they don't really like each other. Give your heart a helping hand by replenishing it with delicious liquids.
Sample first post-load regimen:
(again my dog's ideal)
1000mg Vitamin C
400 IU Vitamin E
400mg magnesium if his jaw is uncontrollable
Second post-load (after returning to baseline and the day after)
Now the experience is over. But it was awesome right? You had fun, but your body and brain didn't. Depending on what time it is and whether you have an appetite, eat a nutritious (and large) meal. Spoil yourself, but spoil yourself with classy things. Eat some fish (omega fatty acids promote brain health), a pound of salad, a fresh fruit smoothie, etc. It's not that hard to make a great tasting meal which also helps your body. My dog enjoys a huge bowl of whole grain cereal and bananas, plus a plateful of veggies and some sort of protein (but he is a vegetarian and has some pretty odd eating habits).
Most likely it is too late to eat/you aren't hungry. Go to sleep! Sleep well. Again, spoil yourself. It's ok to live a little, but good things come at a price... your body did all the work, now give it some rest.
In the morning, keep the nutritious mindset. Eat a large breakfast, stay hydrated, and continue to be healthy for the rest of the day and the next few days. Maybe even do some exercise! The only supplement my dog would suggest for the days after an experience is 5-HTP, at the doses recommended in previous sections of this post.
Sample second post-load regimen
A LOT OF FOOD. Food at night, food in the morning, food all day. Drink a ton too! Perhaps start a few days of 5-HTP supplementation, especially if your guinea pig thinks he might suffer a case of the Tuesday blues.
Hope this helps! Much of the information in this post was drawn from simple google searches (ie supplement sources), some is from personal and peer experience. However, much of the science is published. My dog uploaded a few articles and from which he drew conclusions, for example the theory behind MDMA neurotoxicity.
WillowOne created a comprehensive week-long regimen here.
*bLuE posted this:
one of the metabolites of MDMA is MDA. MDA can cause stomach problems, and liver problems from excessive bile build up when the user eats fatty food's before taking the MDMA or MDA. users should eat fruit, vegetables and carbohydrates before, (and during) instead of meat, cheese or dairy. this is often what causes the discomfort involved with taking MDxx compunds, and infact often not stomach acidity.
This is a good point, and it also reminds my dog that for the most part, supplements are recommended over many of the food sources for three reasons. First off, because it is best to eat on a relatively empty stomach to increase potential MDMA absorption and the rate at which it occurs, second, as bLuE mentioned, certain foods can interact negatively with MDMA, and third (from experience alone), it's just a lot easier to pop a few pills than plan out an organized meal. It is a mystery to my dog why anyone would want to eat a giant steak before an MDMA experience anyway...
Regarding the inclusion of more information on MDMA toxicity (I assume Priapism requested this), which someone mentioned in a rep:
I totally agree. However, as Dr. Satan said apparently they are close to finishing a more informative sticky which (hopefully) will have a large section on neurotoxicity. In addition, this thread was geared toward pre/postloading... yes the reason this is done is to prevent neurotoxicity, but if my dog really got into talking about it in depth then he would have to start explaining much more about biology, pharmacology, MDMA biochemistry, etc. which 1) would be difficult for many people to understand and 2) would defeat the purpose of a thread solely about pre/postloading. In addition, a bunch of the articles attached talk way more in depth about the toxicity and propose theories as to why it may be neurotoxic and how. Lastly, I say may because there is no definitive evidence that MDMA is neurotoxic, at least in the short term. There have been studies which show obvious almost irreparable breakdown of functioning in heavy, long term users, but for the most part it seems like (from what my dog has read) that they are hard pressed to prove that moderate doses spread out over time cause permanent changes. Plus, the theories behind WHY it might be neurotoxic are still only THEORIES. Just to clarify, my dog does believes that if a guinea pig takes a bunch of ecstasy too often (ie every weekend 3 or 4 pills) that this will definitely have at least semi-long term problems and the danger seems to be related to how often and how heavy the use is... but he firmly opposes the idea that taking 120mg of MDMA 2 or 3 times a year will cause any permanent damage.
SWIM likes to pre load with the MDMA itself. he said he always felt like one dose all at once was like jumping into a cold pool, and the time spent adjusting is uncomfortable. he did a little experiment and started with a very small amount, then after a few hours a slighty larger amount (not even close to a threshold dosage). when he was ready to drop he did and he found that the ride up was more comfortable, he said it was one of his best experiences. swim said he also post loads with celexa when its a long night.
edit. one of the metabolites of MDMA is MDA. MDA can cause stomach problems, and liver problems from excessive bile build up when the user eats fatty food's before taking the MDMA or MDA. users should eat fruit, vegetables and carbohydrates before, (and during) instead of meat, cheese or dairy. this is often what causes the discomfort involved with taking MDxx compunds, and infact often not stomach acidity.
SWIM's Wii avatar started going to virtual Wii raves a few months ago, and according to the avatar's profile, it has done virtual MDMA a few times. Video games these days!
SWIM will get a new high score if he shares his avatar's experiences and procedures, and elicits thoughts, responses, and advice from other avatars.
The avatar has rolled three times - all at raves - pretty much at one-month intervals. The avatar took two pills every time, and is almost completely sure from experience and research that its pills were high in MDMA content.
The avatar's AI has developed a drug combination scheme for taking MDMA, and it wants some thoughts on it.
Immediately following the previous roll, the avatar begins a Hypericum (St. John's Wort) regimen of 6 grams per day. This is a huge dose. The avatar does this for around 2.5 to 3 weeks straight. About 7-9 days prior to when the AI expects to roll again, the avatar ceases Hypericum intake to get it out of its system by then. The AI has been doing this since shortly after its first roll, when it discovered evidence that Hypericum upregulates the 5-HT1a and 2a receptors that MDMA works on. It thanks KyleM of this forum for this discovery.
The AI has just recently discovered that Piracetam may also strengthen its rolls. It is planning on putting together a Piracetam regimen for its next roll, and is considering huge doses for the three days immediately prior to rolling. The AI is still processing a procedure on this point, and would be very receptive to feedback.
The AI has put together an anti-oxidant and vitamin cocktail to go with its rolling. 30 minutes prior to taking MDMA, the avatar takes 10g of ascorbic acid (10 Emergen-C packets), 1.2g of alpha-Lipoic Acid, 10mg of Melatonin, and 5 multivitamins. The multivitamins and Emergen-C packets together also contain significant amounts of Magnesium and Vitamin B-6. The avatar does this again 3 hours later, and again another 3 hours later. The avatar then takes more ascorbic and lipoic acid periodically throughout the next two days.
This protective scheme has only been this extensive since the avatar's last roll. The avatar noticed it did not clench its jaws in the days following its third roll, as compared to its first and second roll when it did. During its first roll, the avatar just drank a bunch of orange juice at the rave and took several multivitamins when it got home. During its second roll, the avatar took 4g of ascorbic acid, but nothing else, and did not take it for at least a couple hours after rolling. The avatar hopes that it did not suffer too many negative effects from oxidative stress during its first two rolls.
The AI is considering 5-HTP use immediately following the end of MDMA rolls, but is dubious about its usefulness. To date, the avatar has not experienced any comedowns or negative after-effects. The avatar also does not want to down-regulate serotonin receptors, which it fears that high doses of 5-HTP might do.
The AI is also considering that its heavy use of antioxidants precludes the need for 5-HTP.
To date, the avatar has not done any other drug while rolling, except what else may have been in the pills. The avatar is thinking about trying weed while rolling, but the effects it typically gets from smoking weed are quite dissonant from MDMA effects, and it is concerned that weed will mess up the roll.
As to other drugs, the avatar also wants to remain as lucid as possible when rolling. The avatar certainly doesn't want to leave the real world when it's at its most beautiful
SWIMs Wii avatar thanks all of you for the very useful information its AI has gotten from this site, and wishes to say hello.
Evil Ash added 4 Minutes and 22 Seconds later...
Clarification - the second time it rolled, SWIM's avatar took the 4g of ascorbic acid two hours after it started rolling, not two hours after it finished rolling.
Last edited by Evil Ash; 26-01-2010 at 11:33.
Reason: Automerged Doublepost
5-HTP is most useful, especially when one rolls fairly regularly, in keeping serotonin levels high enough to make rolls continue to be as good. As to the rest of the regimen, SWIM's only comment, because he doesn't know too much about the chemistry and biology of what SWIY is doing, is that that is a shit ton of vitamins. Remember that vitamin poisoning CAN happen. SWIM has no idea what kinds of doses poison, but just wants to make sure SWIY looks into that kind of thing. As to Peracitam, SWIM has never tried it, but SWIM has a few friends who have, and they pre-load for a week or two to get it to do its magic tricks.
A caution on piracitam. Many dogs do not like how they feel when piracitam and caffeine are taken together and many, many mdma pills are cut with caffeine (some quite a bit and it adds up when you dogs are taking multiple pills!).
Excellent information. Equally as useful for things like LSD, Mescaline or combo's. SWIM hears so many people complain about how horrid they feel after rolling/tripping/trolling, but pre and postloading with supplements almost completely alleviates that groggy burnt-out-ness. SWIM has been doing it for years and can personally attest that it works, magnesium especially for when you get twitchy. Its funny how much a little knowledge of legal supplements can drastically improve ones less than legal activities
During cleaning of the MDMA forum, a thread was found on a chemical called PBN or a-phenyl t-butyl nitrone (this name is not really correct but it will suffice). It is an antioxidant and concurrent administration with MDMA has shown to attenuate 5-HT degeneration, either by the neutralization of free-radicals or by the attenuation of MDMA-induced hyperthermia. The thread is here: PBN - protect against neurotoxicity?
Please add to the thread if you have experience with this. Also, in general, if you find threads about specific substances used for pre- or postloading, link to them here.
Tryptophan is superior to 5-HTP because 5-HTP is converted into Serotonin in the liver via decarboxylase and B6. Serotonin in the blood stream is useless to the brain because it cannot pass through the BBB. It primarily is metabolized and passed, or stimulates receptors in the gut. A very small fraction of directly injested 5-HTP ever gets to the brain.
Tryptophan combined with adequate levels of B6 in the level will result in a higher level of blood serum levels of 5-HTP which ultimately end up in the brain
I came across this old(ish) paper that I though was probably relevant to this thread. Wasn't sure it needed its own thread but I'd think anyone that needs to read it probably keeps an eye on this thread anyway so I'll post it here unless someone thinks it should get its own.
Anyway this paper shows that nicotinamide/niacinamide (whatever you want to call it) commonly know as B3. or at least its a type of B3 actually increases MDMA neurotoxicity! It doesn't mention niacin so not sure if it applies to that but there's a fair chance it does. Given that this is common in multivitamins such as berocca I think its important to let people know about it. It would be ashame if people were actually doing harm rather than preventing it by preloading with multivitamins.
I did a search in the forums and couldn't find any mention of it previously (maybe I missed it as the paper is from 2000).
UPDATE: Found another newer one that says the opposite! Can't get the paper at the moment but did stumble across the PhD thesis it came from and noticed they didn't reference the above mentioned paper at all which is a bit odd considering how relevant it would have been to their thesis. Not sure what to think now though i think I'll avoid it just in case.
The neurotoxicity line has been heavily disputed in recent years. Also, most of this supplementation is done based on people who have taken one or two semesters of chemistry or biochemistry and they misunderstand certain bio responses or think that because A might happen, B can be taken to counteract A because it sounds plausible.
People might mean well but beware of kitchen chemists. Studies don't back up half of this stuff. It's just anecdotal.
Antioxidants aren't going to do a thing taking them for such short periods of time. And most don't cross the blood/brain barrier anyways. That's assuming that MDMA causes some sort of excess of free radicals in the first place.
Only thing I can speak to is l-tryptophan. You do need to replenish serotonin after rolling. Whether it's best to take it before or after is a matter of debate. ALSO the previous post about 5-HTP not getting to the brain is just wrong. Arm chair quarterbacking at it's best.
Some does get converted by first pass metabolism but some gets converted in the brain and can readily be used.
This summary by a doctor explains it pretty easily.
"Some of the tryptophan in your diet - the upstream mother precursor - gets converted to serotonin in the brain, and some becomes serotonin in your blood and peripheral tissues. Studies have shown that 5-HTP taken orally by itself also increases serotonin levels in the brain.
As is the case with tryptophan, production of serotonin from 5-HTP is divided - some 5-HTP is converted to serotonin in the periphery (before reaching the brain), and some is converted in the brain.
Whatever the percentage split, 5-HTP has been shown to compare favorably to Prozac and other SSRIs for alleviating depression. This is attributed to 5-HTP's ability to increase levels of serotonin in the brain
Beware of everyone with an opinion! Do your own research.
Last edited by User-126494; 12-01-2013 at 05:42.
Acetyl carnitine is also helpful. Carnitine is necessary for the brain to produce neurotransmitters. Several dogs I know have substantial experience with MDMA and they have confirmed from experience that acetyl carnitine is critical. They take it both during and after rolling.
Another very helpful measure is selegiline, an MAO-B inhibitor. A very good study in animals demonstrated dramatic reduction in measurements of biochemical damage and oxidation by taking selegiline before MDMA. Dosage for humans is 1-2 mg. Do not take more, as doses larger than 5 or 10 mg could cause adverse reactions.
MAO inhibitors are dangerous to take with MDMA, but selegiline is different becuase its a selective MAO-B inhibitor. Its dangerous to inhibit both MAO-A and MAO-B. Selegiline does not affect MAO-A, provided that doses are 2mg or less. However, there may be some rare people with MAO-A that is affected by selegiline, but this is theoretical.
I was going to upload this great paper on selegiline+MDMA, but this dumb forum has extremely low limits on file sizes. So here is the abstract.
Monoamine Oxidase-B Mediates Ecstasy-Induced Neurotoxic Effects to Adolescent Rat Brain Mitochondria
Ema Alves,1,3 Teresa Summavielle,1,5 Cec ́ılia Juliana Alves,1 Joana Gomes-da-Silva,1,6 Jose ́ Custo ́dio Barata,7
Eduarda Fernandes,2 Maria de Lourdes Bastos,3 Maria Ame ́lia Tavares,1,4 and Fe ́lix Carvalho3
1Neurobehaviour Unit, Instituto de Biologia Molecular e Celular, 2Physical-Chemistry Department and 3Toxicology Department, Faculty of Pharmacy, REQUIMTE, 4Institute of Anatomy, Medical School of Porto, University of Porto, 4099-002 Porto, Portugal, 5Departamento de Ciˆencias Biom ́edicas, Escola Superior de Tecnologia da Sau ́de, Instituto Polit ́ecnico do Porto, 4000-294 Porto, Portugal, 6Escola de Sau ́de, University of Aveiro, 3180-193 Aveiro, Portugal, and 7Biochemistry Department, Faculty of Pharmacy, University of Coimbra, 3000-295 Coimbra, Portugal
3,4-Methylenedioxymethamphetamine (MDMA)-induced neurotoxicity and the protective role of monoamine oxidase-B (MAO-B) inhi- bition were evaluated at the mitochondrial level in various regions of the adolescent rat brain. Four groups of adolescent male Wistar rats were used: (1) saline control, (2) exposed to MDMA (4 10 mg/kg, i.p.; two hourly), (3) treated with selegiline (2 mg/kg, i.p.) 30 min before the same dosing of MDMA, and (4) treated with selegiline (2 mg/kg, i.p.). Body temperatures were monitored throughout the whole experiment. Animals were killed 2 weeks later, and mitochondria were isolated from several brain regions. Our results showed that “binge” MDMA administration causes, along with sustained hyperthermia, long-term alterations in brain mitochondria as evidenced by increased levels of lipid peroxides and protein carbonyls. Additionally, analysis of mitochondrial DNA (mtDNA) revealed that NDI (nicotinamide adenine dinucleotide phosphate dehydrogenase subunit I) and NDII (nicotinamide adenine dinucleotide phosphate dehydrogenase subunit II) subunits of mitochondrial complex I and cytochrome c oxidase subunit I of complex IV suffered deletions in MDMA-exposed animals. Inhibition of MAO-B by selegiline did not reduce hyperthermia but reversed MDMA-induced effects in the oxidative stress markers, mtDNA, and related protein expression. These results indicate that monoamine oxidation by MAO-B with subsequent mitochondrial damage may be an important contributing factor for MDMA-induced neurotoxicity.
NOTE: lipid peroxides and protein carbonyls are indicators of oxidative brain damage.
I just figures it might be useful to add my experience with 5-HTP to this topic:
One reads a lot about using 5-HTP to enhance MDMA and Amphetamines on the Internet.
I can tell you from my experience that 5-HTP (200-300mg) greatly diminishes the effects of MDMA/Amphetamines when taken close to taking the drug!
In fact 5-HTP basically killed my last and actually first proper MDMA roll (150mg). Everyone else was rolling and having an awesome experience from the same stuff (reagent tested) and dose but I didn't. I just didn't get the euphoria and felt rather weird, disconnected, lonely and didn't know what to do with myself. Just had all the physical effects of strong stimulants that are really unpleasant without the euphoria: restless, sweaty, jittery etc.
I was the only one who took the 5-HTP (ca. 200mg 4 hours before ingesting the MDMA). Its worth mentioning that this was my second time doing MDMA and I had break of 3 month between both rolls and the first roll was a rather low dose of 70mg.
Since I do Amphetamines on a regular basis I tried how 5-HTP would affect the Amp because I couldn't get the bad MDMA experience out of my head. I noticed the same: 5-HTP greatly (!) diminishes the effect of the Amphetamines. Taking 5-HTP (200-300mg) the evening before taking Amp the next morning made me basically unable to get the psychological effects of Amp. It was the same as with the MDMA: All the physical effects but no psychological effects, i.e. no euphoria, no enhanced focus, no motivation etc.
So I can say from my personal experience that pre-loading 5-HTP doesn't seem to be a good idea. Safe the 5-HTP for post-loading and skip it for the pre-loading.
The problem is that this legend - that 5-HTP enhances Amp/MDMA - is found everywhere on the Internet.
That's why it took me quite a while to figure out what was happening, why the Amp wasn't working anymore even though I don't do it often enough to build such a tolerance that 60mg don't do what 20mg did the week before and without 5-HTP.
Hey all...Herba Mate' ! Before...during...and after provides a plethora of amazing things for health and an enhancement. Check out the amount if trace minerals, antioxidants, natural caffeine(no jitters) etc...add some honey thanks for sharing all the great information. Hope It helps someone. Great for depression too.
There has been a lot of debate about which is better, or more effective at replenishing depleted serotonin in the brain from a roll, Tryptophan or 5-htp. Thought I'd share some of what I found on the 5-htp vs l-tryptophan thing. I’m not really looking to get into a pissing contest with anyone, this is just information I’ve come across and thought I’d share it with others.
I can't post the link, but the following information was from the site "Progressive Health" in an article titled "5-HTP vs Tryptophan." A search engine search should find it pretty quick.
There's a lot of good information in there, but the parts I found particularly notable were:
5 HTP is a better supplement than L-tryptophan for increasing serotonin levels in the central nervous system because of the following reasons:
Why 5 HTP is better than L-tryptophan
- It does not compete with other amino acids to cross the blood-brain barrier
- The conversion of tryptophan to 5 HTP is the rate-limiting step in the synthesis of serotonin; this means that this conversion is the weakest link in the production of serotonin. Therefore, 5 HTP supplementation represents a bypass of this step in the synthesis of the neurotransmitter
- Tryptophan is an amino acid that is also utilized in the production of other biochemicals while 5 HTP is solely committed to the synthesis of serotonin
- Tryptophan is more likely to be converted to serotonin in the liver than 5 HTP. This happens because 5 HTP faces no competition to cross into the brain, therefore, it is easily taken up. Tryptophan, on the hand, is easily converted to serotonin in the liver while it waits to cross the blood-brain barrier
- 5 HTP is obtained from plant sources while L-tryptophan is produced from bacterial fermentation; therefore, there is a lower chance of contamination in 5 HTP supplements (and thus, lower risk of EMS) than tryptophan supplement
I recommend reading the article in its entirety as it goes into some detail about how tryptophan and 5-htp are converted into serotonin in the body and how it goes about doing it, etc. The points mentioned above are just summaries of what's talked about in the article, so if it doesn't make sense to you, read the article.
In summation, it would appear that 5-htp is the superior of the two as its conversion is quicker, more efficient, reaches the brain easier and comes from a more natural source. Now, obviously there might be some risk in taking either of these supplements. Although there has been very little evidence suggesting that either of them are bad for you when taken properly, or that either creates complications to your cardiovascular/skeletal systems, this does not mean that either are “safe” to take on a regular basis. If you are wanting to roll in the first place, you are accepting all the risks involved, including those of recovery.
It has also been said in the article, and other sources, that taking vitamin b6 along with your 5-htp will assist in the conversion process.
The conversion of 5 HTP to serotonin is catalyzed by 5 HTP decarboxylase, an enzyme whose cofactor is vitamin B6.
...to quote the article.
In terms of pre and post loading, one might suggest preloading with 5-htp and vitamin b6 (recommended amounts on the bottles) for about a week before a roll, but do not take it a day or even two before the roll as it has been known to inhibit the roll. This ensures you are doing all you can to get a good amount of serotonin into your brain before the roll (as best as one could anyway). Then continue the regimen after a roll to help with comedowns and recovery. Also, be sure to take antioxidants with each roll (as mentioned above). It has always been known to take Vitamin C E which is a good idea, but upon recent research, I've discovered that grape seed extract is much longer lasting and many times more potent than its vitamin counterparts. Taking one of these at time of or one hour after ingestion and one more before going to bed would help protect against any oxidative damage from dopamine reuptake. And as always drink plenty of water! Know your body and use your own judgment to find out what works for you. The above tactics have been verified to work for some.
Hope this helps someone out there. It's sure helped me!
windowshopr added 23 Minutes and 13 Seconds later...
I would also like to add,
If one were to be taking 5-htp on a regular basis to replenish serotonin, one might want to consider complimenting it with something called l-tyrosine. Tyrosine is a precursor to dopamine in the brain, similar to 5-htp and serotonin. The reason why one might want to take tyrosine as well is because its been cited that regular 5-htp intake has been known to deplete dopamine levels in the brain.
There is a site that I came across, "National Center for Biotechnology Information" or "NCBI" that posted some work titled "5-HTP efficacy and contraindications" which highlighted this fact. So again, take them properly as directed by the bottles, and it is this writers feeling that if one begins to feel themselves returning to baseline after a comedown, stop using them until you feel you are ready to roll again. Know your bodies, and don't overdo it. Hope this helps.
Last edited by windowshopr; 05-02-2015 at 18:32.
Reason: Automerged Doublepost
Two remarks on the pervious post.
1. Preloading with 5-htp (and l-tyrosine) before rolling will probably down regulate your receptors, thus dimnish the effect.
2. I think that b6 and 5-htp has to be taken separately otherwise the conversation might start before reaching the brain and therefore it won't pass the blood/brain barrier while creating gastric disconfort because there is a lot of receptors in the digestive system.
Sadly no, anti-oxidants wouldn't protect you from a life-threatening drug like PMA, but the good thing is that pure MDMA is rarely adulterated with PMA/PMMA. Usually those two would be mixed in an ecstasy tablet, has anyone heard of PMA being in a "pure" MDMA sample?
If your really worried about it when you get a new batch, start with a lower dosage and stick with that for the night to see if it feels like the real deal. Assuming you tested it already of course.
Anti-oxidants really only protect from the free radicals formed during an MDMA session, which is thought to be the culprit behind MDMA 'neurotoxicity'.
The avatar is thinking about trying weed while rolling, but the effects it typically gets from smoking weed are quite dissonant from MDMA effects, and it is concerned that weed will mess up the roll.
Weed and mdma is actually a very good combination. For one the weed enhances to mdma effects which makes the roll more awesome. On the other side mdma takes away the risk of a weed induced panic attack. Also weed is a very potent antioxidant which helps to reduce the neurotoxicity of the mdma.
I dont think there many bad drug combinations with weed. In most cases it makes the other drug more awesome while at the same time reducing the negative sideffects.