which substances are Neurotoxic?

[ksi]

It's seriously annoying when young people get prescribed amphetamines (adderall), because it's goddamn neurotoxic

 

[VelocideX]

ksi -- I agree that it has neurotoxic potential, but it remains to be seen that it is neurotoxic at prescribed levels. Pretty much everything is toxic in excess...

Its funny how with some drugs people are willing to acknowledge a "threshold" before damage sets in (paracetamol/acetaminophen, for example) and agree that useage below that level is relatively safe. Other drugs are presumed not to have any level of safety; only relatively recently did Ricuarte admit that MDMA might have a threshold neurotoxic dose.

Again, it comes down to the degree of neurotoxicity to some degree. If amphetamine use accelerates dopamine cell decline by an extra 5%, would that be considered neurotoxic? Over what period/dosing regimes does a drug have to be administered to consider it neurotoxic?

I'm also curious as to whether anyone is looking for non-neurotoxic monoamine releasers with clinical applications. Some exist (m-CPP for example, though its not useful for treating anything). Is it possible even in principle to produce a dopamine releaser that isn't neurotoxic? Someone mentioned (can't remember who) that MDMA inhbiits intracellular transporters -- I cant remember what they are to be honest -- and that may be a contributor to neurotoxicity.

Or does dopamine release go hand in hand with neuronal damage?

 

[K'dOUTinAZ]

I'm sure that there are many amphetamine compounds that can be neurotoxic. I'm pretty damn sure methylamphetmine is but there are so many contradictories on that subject. Same with MDMA. There are literally hundreds of amp compounds. PCP and ketamine might have some mild neurotoxicity, I believe ketamine may have in large amounts as I am my own guiene pig and have felt some IQ points fall 8) PCP may be more a bit more damaging. Non-synthetics opioids I am positive have no neurotoxicity. I know that propoxyphene can be. Possibly fentanyl analogues? Personally I think many of these psychotropic meds that are prescribed to our children may be the most neurotoxic. Does anybody have any evidence on whether SSRI, tricylics, or MAO inhibitors have potential neurotoxicity? I don't trust those MAO inhibitors. Marijuana and cocaine are both proven non-neurotoxic but I still have tiny thoughts that massive prolonged IV or freebased cocaine use may be, but thats just me. LSD and many hallucinogenics like mushrooms and salvia shouldn't have any neurotoxicity.

All these drugs have contradictions on neurotoxicity but one thing is sure, alcohol is very neurotoxic and possibly the most, when only including recreational substances. Inhalants are neurotoxic. Delerients. DXM? I don't care, it could be in with prolonged use. I'm done, I've got to go back to my busy life licking myself like a dog watching tv and doin lines of k. No wife around. I wanna be Al Bundy

 

[Tranced]

Ok, not to sound like an ass, but some of you are clearly not familar

The only reason that they (neuro)toxicity of amphetamine

Seeing as you're being quite the pedant I thought that I'd point out these two spelling mistakes FAIR NYMPH.

Not that I give a shit, but you quite clearly do.

 

[Jamshyd]

^^^ lol!

I could swear that I came across an article that manetioned that DXM has been found to be actually neuroprotective! Unfortunately, I really don't remember where that was, or its title. If anyone else came across this, please post the link.

 

[Blowmonkey]

Whether my logic is circular or not, the evidence shows that primates simply are not affected by NAN/Olney's Lesions from ketamine or DXM.

The primates used in that study (from Jansen) were supposedly too young, and "supposedly "Olney's lesions can't manifest in children.. So that logic is flawed.

 

[BilZ0r]

You raise some good points the Velocide... What shocks me, is that no one has looked for neurotoxicity in people treated with amphetamines. I mean, it would be hard, you'd have to account for a lot of shit, but still, if amphetamines are neurotoxic, you'd think that'd be a damn good place to look...

Your fourth paragraph raises some interesting questions; MDMA does 'inhibit' the intra-cellular 'vesicular monoamine transporter' (VAT/VMAT). Though it doesn't really inhibit it, as much as compete at it.

It all boils down to definitions. After a single dose of any drug, you're brain is changed; receptors get internalized, electrical singals are modified etc... i.e. not cell death, but function changes... the brain is so plastic, that these must have a long term effect; though just so small it doesn't matter; THOUGH, with drugs that effect glutamate strongly, NMDA antagonists and 5-HT2A agonists, I suspect you will see an effect of those functional changes.

I've never known anyone who abused NMDA antagonists long term (though I hear long term DXMers get preety retarded), but people who take shrooms everyday for months go fucking crazy.


Meanwhile DXM is neuroprotective as hell, its true. It underwent human trials as a post stroke neuroprotectant. Here's the first link I could find... appropriate seeing as we were talking about MPTP

 

[VelocideX]

Does anybody have any evidence on whether SSRI, tricylics, or MAO inhibitors have potential neurotoxicity? I don't trust those MAO inhibitors.

The antidepressants certainly induce structural change e.g. increased neuronal cell growth. Why are you so suspicious of the MAO inhibitors? Any particular evidence? I personally believe that they represent a more effective treatment for depression. Moclobemide (Aurorix/Manerix) in particular, given its safety.

SSRIs given at extremely high doses (10x recommended dose or so) seem to make neurons behave very oddly... I think they create strange star-shaped neuron patterns. I honestly dont rememnber the end result, just that there was some concern over it.

 

[BilZ0r]

I'm always unsure about MAOIs, because they aren't antidepressants as such, they're euphoriants... they'll make you feel good whether you're depressed or not...

I'm sure in the future, we'll actaully be able to describe the etiology of a particular patients depression, and treat it accordingly.

 

[VelocideX]

I'm also unsure about how tolerance mechanisms work with MAOIs. I'm sure there's SOME lasting neurochemical change, but where it occurs I'm not sure.

I took moclobemide (a reversible inhibitor of MAO-A) for approximately 6 months for a long-standing depressive illness... Initially doctors kept trying to put me on SSRIs but eventually I just had to say to them that I didn't tolerate the side effects of the SSRIs well. Moreover my depression was classic atypical depression. Atypical depression sufferers respond much better to MAOIs (indeed this is the position of the national american psychiatry body; the exact name eludes me).

It seems to me that doctors are not taking enough care to distinguish the subtypes of depression and prescribe accordingly. SSRI-induced agitation (and subsequent suicide) may be a result of failing to diagnose adequately. Moreover, the serotonin-based treatment of depression has been so successful that doctors fail to recognise the noradrenic component, and treat with drugs like reboxetine (which I think holds a LOT of promise). I also believe, though evidence is sparse, that there is a subtype of depression with a dopamine component; evidence is sparse because no-one wants to play with the reward system in the brain (unless a kid has ADD, in which case prescriptions fly off the pad)

bilz0r -- is such a thing bad if it has no other impact? Hell that seems to be the aim of HedWeb

 

[BilZ0r]

Well I think Dave whatisname of hedweb is crazy, so... yeah..

BUT, anways, there's just something in my gut that tells me treating depression with a euphoriant is wrong... Kinda like how you shouldn't really treat depression with a laxative... You know? It's sorta like symptomatic treatment, not really causative treatment? I mean, you wouldn't treat a depressed person with amphetamine...

 

[Synapse999]

I mean, you wouldn't treat a depressed person with amphetamine...

Well, Dexedrine was developed in the 1920's for the treatment of depression and obesity.


d-amphetamines are sometimes prescribed for chronic depression that fails to respond to all other treatments and for very ill medical patients with depression

Amphetamines are also used for treatment of depression in patients with AIDS or other terminal cancer - when they are to sick for antidepressents.

 

[satricion]

Well I think Dave whatisname of hedweb is crazy, so... yeah..

BUT, anways, there's just something in my gut that tells me treating depression with a euphoriant is wrong... Kinda like how you shouldn't really treat depression with a laxative... You know? It's sorta like symptomatic treatment, not really causative treatment? I mean, you wouldn't treat a depressed person with amphetamine...

This is confusing...

SSRI's work by inhibiting the reuptake of serotonin. Now as I understand it, serotonin reuptake inhibition will make you feel happier if you're not depressed as well...I mean, ecstasy works for people who aren't depressed...

SSRI's don't go in and investigate the 'normal' level of serotonin in the brain and then restore it to that...they just inhibit the reuptake of serotonin so that there's more of it. Don't they?

 

[BilZ0r]

Now as I understand it, serotonin reuptake inhibition will make you feel happier if you're not depressed as well

Nope, they wont.

Ecstacy mainly works by causing the release of serotonin... not by blocking its uptake.

 

[satricion]

Can you explain why this is, or find some sources that I can read?

As I understand it the effects of SSRI's are pretty much the same for everyone...I've heard in classes about plenty of people who were misdiagnosed with depression, given SSRI's and then said that they basically felt happy now.

Why won't SSRI's make non-depressed people feel happier?

 

[Synapse999]

Can you explain why this is, or find some sources that I can read?

As I understand it the effects of SSRI's are pretty much the same for everyone...I've heard in classes about plenty of people who were misdiagnosed with depression, given SSRI's and then said that they basically felt happy now.

Why won't SSRI's make non-depressed people feel happier?

Becaues the opposite of depressed really isn't "happy". it would be - content? heh.

happier - would be based on what each person believes makes them happy.


If you are content with your life, and everything is going well. If anything, altering the chemicals in your brain in any way - may lead you to different decisions...different feelings.

and ultimatly.....no longer happy.

 

[BilZ0r]

Why won't SSRI's make non-depressed people feel happier?

Why WOULD they? SSRIs don't make depressed people -happy- either.

 

[satricion]

Okay right I agree with that but you know what I mean...

SSRI's result in a somewhat elevated mood for non-clinically depressed people in the same way as they would for people who have been diagnosed with clinical depression. Yes or no?

I haven't read anything to indicate that SSRI's "normalise" neurotransmitter levels in the brain...just that they inhibit the reuptake of serotonin.

I can't see why MAOI's would cause positive emotional changes in non-depressed people, and SSRI's wouldn't cause similar emotional changes in people just because they haven't been diagnosed with depression.

Why won't SSRI's change the mood of non-depressed people?

 

[BilZ0r]

Well I don't think you'll find that SSRIs just like... shift depressed peoples moods up 1 level, so that the bad times are okay, the okay times a good, and the good times are great.... Usually, it just means that the unbelievabley bad times are managable...

However SSRIs act, its probably secondary to the serotonin uptake inhibition... some peopl argue that its neurogenesis, though I don't think it is.

Some experiemnts report that MAOIs have a therapeutic lag, but others don't.... I personally suspect they don't (though I've never taken one clinically). Velocide, anything to add?

 

[K'dOUTinAZ]

Anti-psychotics....neurotoxic? With long term use? The atypicals...

I know that they may create long term problems with muscle degeneration or something to that degree, or was it spacicity and convulsions?