Don't take Amphetamines or MDMA if you want to preserve you're brain

[JWills20]

I didn't say binge drinking induced brain damage didn't apply to all of us. I just figured, being a moderator of a HR forum , that you would have the common sense to moderate your drinking enough to preserve your health.

Yeah but this is the whole point. It's exactly the same concept with MDMA: moderate usage and you're fine. No neurotoxicity.

 

[F1n1shed]

Yeah but this is the whole point. It's exactly the same concept with MDMA: moderate usage and you're fine. No neurotoxicity.

I disagree mate, we have gone back and forth a lot in the past if i remember correctly. I hardly visit this site anymore but even with moderate use i have seen many cases of people not being fine while using MDMA. Let's say they didn't experience neurotoxicity which i think they did to some degree, they still had many LONG term negative effects and issues. Anxiety, depression, cognitive issues, DR and DP, the list goes on. At one point i would stutter sometimes when speaking, STUTTERING that never use to happen and i have seen many other cases of people stuttering. You can't tell me that is fine.


On the methamphetamine ... well i'm not sure on which is more neurotoxic i do recall a reading saying MDxx was more overall. How ever i can always take low doses of meth and feel it, for instance 10mg at a time multiple times. In low doses it is hardly brain damaging, how ever MDxx does need a substantial initial dose to feel it. You cannot just take 20mg and call it a day, it will do nothing. And as we know the bigger the dose of a stimulant the chance of neurotoxicity goes up big time.

 

[mb-909]

You're very brave. I'm a bit confused about one thing, you said that MDMA helped you regain your feelings / emotions, but then you later said that all hell broke loose after you drunk a drink mixed with MDMA. Do you feel MDMA helped you overall?

You've taken fewer drugs in your life than I have, that's for sure. As someone previously posted, the brain is very plastic, so I don't think you have sustained any permanent damage from the small amount of drugs you took.

Your very smart and have a great life philosophy. I'm glad your feeling better and hope you make a full recovery

Being brave or being stupid? That's the question. A lot of brave heros died a meaningless death for what? It isn't the thing I want to be part of ^^. If you are stuck in mind circles, easy to break through in theory, but you are not able to for what ever reason, the last thing you do is calling yourself "smart". Selfdestruction doesn't really help you or the people around you and is therefor not really relevant.

Everybody in this thread should be careful to point to a singel argument. There is no real 100% evidence for either point of view and we shouldn't force our ideas on others, especially if they are not going to listen to us anyway. Everybody no matter of position has the same right to talk, but should consider the rules on the platform being used for free. Be open minded and give the other point of view a chance. If not you can still ignore it.

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"The findings reviewed in this paper allow a number of conclusions to be drawn with regard to MDMA-induced neurotoxicity. First, there is little doubt that MDMA targets monoamine transporters, and transporter-mediated release of 5-HT, DA, and NE underlies pharmacological effects of the drug. While MDMA has been considered a predominately serotonergic agent, certain adverse effects including cardiovascular stimulation and hyperthermia likely involve NE and DA mechanisms, respectively. There seems to be no scientific rationale for using allometric scaling to adjust doses of MDMA between rats and humans because the pharmacologically relevant doses are similar in both species (e.g., 1–2 mg/kg). Nonetheless, the complex metabolism of MDMA needs to be examined in various animal species to permit comparison with clinical literature and to validate appropriate preclinical models. With regard to MDMA-induced neurotoxicity, it seems that 5-HT deficits are not always synonymous with axonal death because doses of MDMA which cause marked depletions of brain tissue 5-HT in rats (e.g., 10–20 mg/kg) are not associated with silver-positive staining, reactive gliosis, or loss of SERT protein. Like many other psychotropic drugs, MDMA is capable of producing bona fide neurotoxicity at sufficient doses (e.g., >25 mg/kg), and damage is not confined to 5-HT neurons. Many aspects of 5-HT function appear to be normal in MDMA-pretreated rats despite significant loss of brain 5-HT, perhaps illustrating the profound adaptive capability of the CNS. On the other hand, MDMA-induced 5-HT depletions are accompanied by impairments in evoked 5-HT release and neuroendocrine secretion that suggest tolerance development. The clinical relevance of preclinical findings is often uncertain, but the fact that MDMA can produce persistent increases in anxiety-like behaviors without measurable 5-HT deficits suggests that even moderate doses may pose risks."

- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1705495/

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After the aripiprazole, MDMA and alcohol combo (aripiprazole was still in the system in really low doses), I had expirienced a withdrawal-anxiety-depressionlike induced behavior suggesting that I have done permanent brain damage by said drug/s. I was to impulsive, which was part of the combo and the depression, and didn't want to see the other point of view being made with good scientific reviews. 3-4 months later I was able to break through the mind circle and improved greatly. Right now I am able to look at many point of views, because my depression, while still being there, isn't to concerning for me anymore.

 

[laugh]

On the methamphetamine ... well i'm not sure on which is more neurotoxic i do recall a reading saying MDxx was more overall. How ever i can always take low doses of meth and feel it, for instance 10mg at a time multiple times. In low doses it is hardly brain damaging, how ever MDxx does need a substantial initial dose to feel it. You cannot just take 20mg and call it a day, it will do nothing. And as we know the bigger the dose of a stimulant the chance of neurotoxicity goes up big time.

lol on so many levels.
in primary school we learnt that a shoe box full of gold weighs more than a shoe box full of feathers.
when people like you vote, it should be counted as a half vote.

NSFW:

 

[JWills20]

I disagree mate, we have gone back and forth a lot in the past if i remember correctly. I hardly visit this site anymore but even with moderate use i have seen many cases of people not being fine while using MDMA. Let's say they didn't experience neurotoxicity which i think they did to some degree, they still had many LONG term negative effects and issues. Anxiety, depression, cognitive issues, DR and DP, the list goes on. At one point i would stutter sometimes when speaking, STUTTERING that never use to happen and i have seen many other cases of people stuttering. You can't tell me that is fine.

Of course people experiencing that isn't fine. But 1) I personally don't think moderate usage causes these kind of side-effects. At least not for the vast majority. 2) These side-effects are unlikely to be a result of neurotoxicity. MDMA has it's dangers and should be taken in moderation far more than other kinds of drugs but the main point is that these dangers and side-effects are not because of actual cell destruction but instead other consequences. Like Black said, consistent and sustained depletion of serotonin could likely account for a lot of the side-effects.

 

[Powerkain]

Hi, I have put this information together to inform anyone who had in the past, or plans to in the future, use substituted amphetamines (MDMA, Amphetamine, Methamphetamine)

MDMA (Methylenedioxymethamphetamine)
MDMA is neurotoxic to both the Serotonin axons of rats, non-human primates, and humans. In non-human primates and rats, this neurotoxicity appears to be only partially reversible. In humans, there is evidence suggesting the same, with some damage being persistent and some being reversible.

http://www.fable.it/ecstasy/MDMA (Ecstasy) neurotoxicity assessing and communicating the risks.pdf

Amphetamine and Methamphetamine
Amphetamine permanently damages the dopamine nerve endings in the Striatum of non-human primates (monkeys) at low doses:

http://jpet.aspetjournals.org/content/315/1/91.full

There is substantial yet inconclusive evidence that permanent damage occurs in humans:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769923/

Strong link between past amphetamine and methamphetamine use and parkinson's disease:

Amphetamine: http://www.medscape.com/viewarticle/737998

Methamphetamine: http://www.medscape.com/viewarticle/747240

For an overall review of the neurotoxicity associated with substituted amphetamines (MDMA, Amphetamine, Methamphetamine), I recommend reading the following article:

http://www.researchgate.net/profile...mechanisms/links/0deec5225fc33c8d95000000.pdf

The only advice that I can give for people who enjoy using stimulants is to use cocaine instead. It has not demonstrated neurotoxicity in animal models or humans, and has one of the most euphoric stimulant highs out there.

Best Regards,
Archie

I already know about this information but once try will be fine and do not definite.

 

[swisscurrie]

I find it irresponsible and misleading that you say "moderate usage and you're fine". A typical dose of MDMA for a regular user is around 100mg, such a dose would certainly have the potential to induce neurotoxicity in humans. I'm not saying that moderation is a bad thing, but the best would be avoiding it all together.

 

[swisscurrie]

mb-909- Interesting study you shared. I am trying to be open to criticism, but so far nothing has been very convincing. If anyone can provide a reputable study that refutes MDMA neurotoxicity from applying to humans, then I would be glad to look into it. I can relate to the depression you experienced from drug withdrawal. I'm glad that you are feeling better and managed to break through the mind circle.

 

[JWills20]

Doses as low as 0.3mg/kg have demonstrated persistent serotinergic neurotoxicity in rats

Now that one right there you're going to need a reference for. You're telling me that sub-threshold doses of MDMA that wouldn't even produce a 'rolling' experience with barely any serotonin release cause destruction of serotonin cells. Calling straight up bullshit.

 

[swisscurrie]

Powerkain- If you've never tried one of those drugs, I would avoid them all together. But if you think you know the information well enough to make an informed decision, then do what you thinks best for you.

 

[swisscurrie]

You're right, I misread the study I was reading. It says that "0.3mg/kg is sufficient to stimulate a significant rise in extracellular 5-HT in rat nucleus accumbends". I didn't read the following paragraph properly, which actually didn't associate the 0.3mg dose with neurotoxicity. My bad, but it still disproves your point of "barely any sertonin release" wrong.

The threshold dose in Rhesus Monkeys for neurotoxicity is 1.25mg/kg. If that applied to humans, then for an 80kg man, 100mg/kg would be the threshold dose. However, if an individual less than 80kg took a standard 100mg dose, then they would likely start suffering serotingergic neurotoxicity.

Two important quotes from the studies linked below:
" This has suggested to some that humans may be even more sensitive than nonhuman primates"
"estimated that as little as 1.28 mg/kg MDMA may produce long-term 5HT depletions in humans"



https://www.maps.org/research-archive/mdma/protocol/review4.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1705495/

 

[JWills20]

NEUROTOXICITY: The most sensationalistic and controversial issue regarding MDMA is claims of neurotoxicity in humans. At high doses in animals (mice, rats, monkeys, and baboons) a profound loss of serotonin axons (and dopamine axons in some species/dosing regimens) is produced.[48] The cell body itself is not destroyed. How or why MDMA was able to produce this distinctive pattern of damage has been the subject of a considerable amount of speculation, with a number of reasonable theories proposed, none of which quite fit all the experimental evidence. Recent research has compellingly tied together much of the disparate evidence by demonstrating that the key factor in MDMA neurotoxicity was hyperthermia.[49] Animals given MDMA do not normally suffer neurotoxicity if hyperthermia is avoided, which can be accomplished by any number of means, from sedation, restraint, or even simply placing them in a cool room. The exact mechanism of toxicity is still not known, but the most likely route is the metabolic breakdown of MDMA or a metabolite of MDMA within the axon producing reactive oxygen species (such as superoxide), that, if not neutralized by endogenous defenses (superoxide dismutase, etc.), will readily react with the local antioxidant supply, then, as antioxidant levels drop, damage the axon itself. It seems likely that the role of hyperthermia in MDMA neurotoxicity involves the reduced activity of one or more of these protective enzymes, but more research is needed. (In my opinion, the current best explanation of the source of reactive oxygen species is the N-demethylation/deamination of MDMA/MDA by monoamine oxidase.) As a practical matter, the role of hyperthermia in both neurotoxicity and death/injury makes the 'rave' settings in which MDMA is often used more potentially dangerous than home usage.

One of the interesting consequences of oxidation as the ultimate mechanism of damage is that antioxidants are experimentally very effective in reducing or preventing MDMA neurotoxicity, even at near-lethal doses of MDMA. Pre- or co-administration of large doses of vitamin C, vitamin E and alpha-lipoic acid are all effective.[50] [51] [52] The supplements tryptophan and 5-HTP (5-hydroxytryptophan, the immediate precursor to serotonin) are also somewhat protective, [53] presumably by reducing the access of the source of the (as yet unidentified) ultimately toxic species to the serotonin transporter. Likewise, pre-administration of SSRIs is also quite effective at reducing MDMA neurotoxicity. [54]

While the theoretical end of things is very interesting, a more pressing question is whether or not MDMA is neurotoxic in humans at recreational doses. In one experiment, human volunteers were given sensitive brain scans that measured the density of serotonin transporters (a marker of serotonin axon presence/health), then given 1.5 mg/kg of MDMA hydrochloride under lab conditions ('room temp', no dancing, etc.), then re-scanned a month later. There was no loss of serotonin transporter (SERT) density, indicating that the subjects did not suffer neurotoxicity at that dose and in that environment. [55]

Retrospective studies of users 'in the wild' are more difficult to evaluate. One group of extremely heavy MDMA users that had quite low SERT density (a study championed as proof of MDMA neurotoxicity in humans by the US government) were still within the range of densities normally seen in healthy humans [56], leaving causality a very open question. Other brain scan studies have failed to find any reduction in SERT density among some groups of heavy users and only transient reductions in others. [57] Transient SERT density reductions appear to be a function of time since last dose, suggestive of a neuroadaptive response rather than axon loss.[58] The largest study to date found small reductions in SERT density in current users, but abstinant users had regional and total SERT densities identical to non-drug users.[75] Regrowth of axons after neurotoxic 'pruning' could explain the recovery of normal total SERT density, but not the recovery of normal regional SERT density; serotonin axon regrowth in non-human primates after a neurotoxic dose of MDMA results in hyperenervation of regions near the raphe nuclei but fails to restore enervation to more distal regions, creating a profound redistribution of serotonin axons in 'recovered' animals.[76][77]

Cerebral blood flow measurements of users have also been done, both retrospectively [59] and prospectively [60] (on human volunteers). In both cases, the MDMA exposed group did not show persistently reduced or abnormal regional or total cerebral blood flow.

Some mention must also be made of retrospective user cognitive function studies, which tend to receive more press than the more technical study methods. The most common finding is reduced verbal memory in MDMA users vs. controls. However, these studies are consistently riddled with confounds, most typically the presumption of no preexisting differences between the groups, nonrandom sampling, and failure to address the question of reversible neuroadaptation such as serotonin receptor downregulation after MDMA exposure, which can take weeks to fully reverse.[61] To date, there hasn't been a single study that I would regard as rigorous enough to give meaningful data on the long-term effects of MDMA use in humans...hopefully better experimental designs will appear in the future.

Also important is the heavy concomitant marijuana use seen among the recruited 'ecstasy' users. When controlled for marijuana use, differences in cognitive function scores between ecstasy users and non-users are greatly reduced [62] or eliminated entirely. [63]

In the end, two statements can be made about MDMA's neurotoxic potential with complete confidence. The first is that this drug clearly has the potential to cause extensive destruction of serotonin axons at some (high) dosage under the right circumstances. The second is that there is also very compelling evidence that MDMA has been used recreationally by many humans, even hundreds of times, without suffering structurally detectable (much less clinically significant) neurotoxicity. The government view that MDMA users are inherently damaging their brains is contradicted by the totality of the research, but there is at least theoretically the potential for harm at very high doses and/or under the wrong circumstances. User beware. (For a detailed discussion of the current research, visit the Neurotoxicity page.)

Source

MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1–2 mg/kg), suggesting that there is no reason to adjust doses between these species. Typical doses of MDMA causing long-term 5-HT depletions in rats (e.g., 10–20 mg/kg) do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis.

Your own study?

estimated that as little as 1.28 mg/kg MDMA may produce long-term 5HT depletions in humans

Well, once again that's kind of what we've been saying. MDMA can cause long-lasting serotonin depletion. This is absolutely nothing to do with neurotoxicity.

 

[Black]

You're right, I misread the study I was reading. It says that "0.3mg/kg is sufficient to stimulate a significant rise in extracellular 5-HT in rat nucleus accumbends". I didn't read the following paragraph properly, which actually didn't associate the 0.3mg dose with neurotoxicity. My bad, but it still disproves your point of "barely any sertonin release" wrong.

who says barely any serotonin release? mdma produces its subjective effects through serotonin release, which is exactly what you can see at 0.3mg/kg.
jwills said that it doesn't lead to the death of serotonergic neurons.

Two important quotes from the studies linked below:
" This has suggested to some that humans may be even more sensitive than nonhuman primates"
"estimated that as little as 1.28 mg/kg MDMA may produce long-term 5HT depletions in humans"

mdma itself is not responsible for neurotoxicity [source]. the neurotoxicity we observe in animals could be either due to overheating (which could explain why we don't see any specific serotonergic damage in rats, which have pharmacokinetics for mdma that most closely match humans and also explain the great temperature-sensitivity in rats [source: the baumann papers]) or due to metabolites. metabolites are a very likely to be the culprit in nonhuman primates, who have a markedly different metabolism than humans do.
in humans you quickly reach saturation for the responsible CYP450s resulting in larger increases of mdma concentrations with higher doses but almost no increases in metabolites [source].
in nonhuman primates on the other side you don't see a saturation effect of a similar magnitude and therefore comparatively lower mdma concentrations and much higher concentrations of diverse metabolites [source, source].
as we are looking at toxicity caused by ROS, peak concentrations of the metabolites are extremely important. as i've already said, you don't see oxidative damage under a certain threshold that marks the natural ROS detoxification capability of your cells. for nonhuman primates we see way higher peak concentrations of the metabolites than in humans, in fact we see concentrations that you cannot possibly attain in humans because of the CYP450 autoinhibition by mdma.
if you then go to scale the primate doses for the completely irrelevant parameter of mdma AUC like ricaurte loves to do, you end up with even more disproportionally higher levels of the metabolites and therefore you get completely irrelevant results.

btw, that first comment you cite only refers to the decrease of serotonergic markers, which we've established doesn't imply neurotoxicity.


5-ht depletion is a well-known effect caused by mdma irreversibly inhibiting tryptophan hydroxylase. as you surely know tryptophan hydroxylase is the rate-limiting enzyme responsible for converting tryptophan to 5-ht and it is constantly broken down and regenerated by your cells. so what's your point?