20 replies to this topic

[johnmk]

Here is a study performed by Yale showing that something not too far from human therapeutic doses may be cause for concern:

http://www.yale.edu/...-26-02.all.html

I am currently prescribed amphetamine, as it works wonders for me, whereas methylphenidate seems to do almost nothing for me even at twice (or more) the mg dose of amphetamine. In most people apparently 80mg of methylphenidate should be just as effective as 40mg of amphetamine. Can anyone theorize what in my particular biological make-up renders methylphenidate so ineffective in me vs. amphetamine? I could hardly even begin to theorize. Perhaps I have so little dopamine being produced that blockading transporters is simply not effective? I'm truly worried though. The above study seems to confirm the suspicion held by some that even low-dose therapeutic, chronic amphetamine use could age the brain more quickly, i.e. be relatively neurotoxic. Would that tend to be the consensus opinion here? What foods/supplements might mitigate such damage, and do you feel they would tend to so rather completely, or would their helpful effect be limited and small?

I've heard methylphenidate may be significantly less neurotoxic than amphetamine. Can anyone theorize as to why that might be?

Thank you,

-John

[johnmk]

Thank you for your comments. I've found not all informed and intelligent people are only in one forum so I like to cut a wide path. Any theories as to the mechanism of amphetamine toxicity vs. methylphenidate?

[velocidex]

Methylphenidate is a dopamine reuptake inhibitor, whereas amphetamine releases catechoamines and monoamines --- primarily dopamine and noradrenaline. Both methamphetamine and amphetamine release more noradrenaline than dopamine. The noradrenic component may be the key to your situation.

Much of the amphetamine damage appears to be due to oxidative stress. Fat soluble antioxidants may help reduce this. Vit E and ALA are good ones to consider. I'm sure the people here can recommend a lot more exotic things.

Methylphendiate is not neurotoxic, and this has been shown time and time again. Methylphenidate actually blocks amphetamine's neurotoxicity.

[johnmk]

Would you theorize that taking low-dose amphetamine concurrently with low-dose methylphenidate would be the recommended course of action, then, velocidex? I've heard of that approach before, and would love to see data confirming what I've heard, and what you've just stated. If it's easy for you to find, thank you, if not, I'll look around for it myself later tonight.

[johnmk]

Methylphendiate is not neurotoxic, and this has been shown time and time again. Methylphenidate actually blocks amphetamine's neurotoxicity.

Has it been demonstrated that over many years of use, methylphenidate is not harmful? If you have studies demonstrating it's safety over the long term I'd like to see them. Thanks.

I've seen many studies on pubmed showing that acute, very high dose methylphenidate (and cocaine, too) results in I believe zero lasting damage, whereas acute very high dose amphetamine produces evident, long-lasting damage that may be permanent. Aside from receptor down-regulation which I believe both substances may produce to an extent, the conclusion I have come to (sorry, I cannot provide links, but I've been researching this topic for months now, every day literally) is that if amphetamine is shown toxic at therapetic, prescribed low doses, an identical study using methylphenidate would probably show dramatically less (an order of magnitude) toxicity, if any at all. Aside from receptor down-regulation, which I don't know if that's reversable or not. If for instance you take methylphenidate for 50 years and then stop at age 70, would your brain's dopamine receptors up-regulate to the point where they would have been if you had never taken methylphenidate in your life? I just don't know that. I'm not worried one whit about methylphenidate toxicity though. Even if it's shown to have a small effect I think by the time I'm 70 (almost 50 years) we'll have far more understanding of how to optimize brain function, and methylphenidate will be so antique, ancient, and so much less effective than medications available in the future that any negative effects it may cause over that long of use will easily, easily be countered.

I'm currently invesigating whether or not taking l-deprenyl will benefit me and lessen my dependence on dextroamphetamine. Just research right now, I haven't ordered it. I may /should wait for my doctor's prescription first. In any event, I would probably not take more than 1mg or 2mg/day.

[ozone]

I've already concluded that I will no longer take Adderall/Ritalin or anything else. These studies along with several others I've been reading all suggest that even at low doses, neurotoxicity in reagards to Amphetamines is a serious thing.

@johnmk
If you are going to continue taking Amphetamines, then you must take NAC.

A novel thiol antioxidant that crosses the blood brain barrier protects dopaminergic neurons in experimental models of Parkinson's disease.

Bahat-Stroomza M, Gilgun-Sherki Y, Offen D, Panet H, Saada A, Krool-Galron N, Barzilai A, Atlas D, Melamed E.

Laboratory of Neurosciences, Felsenstein Medical Research Center and Department of Neurology, Rabin Medical Center, Beilinson Campus Tel Aviv University, Sackler School of Medicine, Petah-Tikva 49100, Israel.

It is believed that oxidative stress (OS) plays an important role in the loss of dopaminergic nigrostriatal neurons in Parkinson's disease (PD) and that treatment with antioxidants might be neuroprotective. However, most currently available antioxidants cannot readily penetrate the blood brain barrier after systemic administration. We now report that AD4, the novel low molecular weight thiol antioxidant and the N-acytel cysteine (NAC) related compound, is capable of penetrating the brain and protects neurons in general and especially dopaminergic cells against various OS-generating neurotoxins in tissue cultures. Moreover, we found that treatment with AD4 markedly decreased the damage of dopaminergic neurons in three experimental models of PD. AD4 suppressed amphetamine-induced rotational behaviour in rats with unilateral 6-OHDA-induced nigral lesion. It attenuated the reduction in striatal dopamine levels in mice treated with 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP). It also reduced the dopaminergic neuronal loss following chronic intrajugular administration of rotenone in rats. Our findings suggest that AD4 is a novel potential new neuroprotective drug that might be effective at slowing down nigral neuronal degeneration and illness progression in patients with PD.

PMID: 15733082 [PubMed - in process]

By the way, I think everyone should download this. It's a 52page PDF book published by the Society for Neuroscience titled "Brain Facts" http://web.sfn.org/c.../brainfacts.pdf

[velocidex]

Would you theorize that taking low-dose amphetamine concurrently with low-dose methylphenidate would be the recommended course of action, then, velocidex? I've heard of that approach before, and would love to see data confirming what I've heard, and what you've just stated. If it's easy for you to find, thank you, if not, I'll look around for it myself later tonight.

Methylphenidate blocks the action of amphetamines -- that's how it blocks the neurotoxicity -- so it's a pretty poor solution It denies amphetamine access to the dopamine transporter, though there may be some noradrenic effect.

[johnmk]

I've been experimenting with methylphenidate in the last few days, more diligently than in the past, and have found that I do get some beneficial effect from methylphenidate but only at low doses, and I can't "boost" the effect any more with a larger dose without elevating my anxiety & whatnot, and totally wiping out/rendering unnoticeably, any added cognitive aid. So if I'm to switch to methylphenidate . . . I'll be giving up some efficacy. At the same time, I'm more concerned with the long-term implications. Thank you everyone for your wisdom.

PS: By the way, I'd like to apologize that this thread is out of the scope of this particular forum. I understand now that a nootropic must not be toxic, and in fact must be neuro-protective if at all possible.

[lancelot]

Methylphendiate is not neurotoxic, and this has been shown time and time again. Methylphenidate actually blocks amphetamine's neurotoxicity.

that's not true. that's like saying coke is safe and non-neurotoxic. look up studies and you'll see that ritalin causes abnormal brain changes(brain damage) in children and growth retardation. ritalin and AMPs should never be used daily for any reason.

[johnmk]

Has this been shown in fully grown subjects, however?

[wraith]

Methylphenidate is a dopamine reuptake inhibitor, whereas amphetamine releases catechoamines and monoamines --- primarily dopamine and noradrenaline. Both methamphetamine and amphetamine release more noradrenaline than dopamine. The noradrenic component may be the key to your situation.

What do you think of the safety of noradrenaline reuptake inhibitors?

[johnmk]

My research on this topic (I admit to being a relative layperson) is showing that re-uptake inhibitors in general are safer than releasing or producing more of something, e.g. amphetamine. At least this is the consensus.

[wraith]

Well, thank goodness for that. And thanks for your reply.

[velocidex]

Methylphenidate is a dopamine reuptake inhibitor, whereas amphetamine releases catechoamines and monoamines --- primarily dopamine and noradrenaline. Both methamphetamine and amphetamine release more noradrenaline than dopamine. The noradrenic component may be the key to your situation.

What do you think of the safety of noradrenaline reuptake inhibitors?

I haven't seen anything that would suggest they're unsafe. Reboxetine (Edronax, etc) has been approved as a highly selective noradenaline reuptake inhibitor. Seems to be particularly good for anergic / amotivational forms of depression. It has shown some efficacy in ADD trials, though nowhere near as much as methylphenidate or amphetamine. If you believe the SSRIs are safe, then you'd believe that reboxetine is safe. If you question the long-term use of the SSRIs, you might want to think carefully about the NARIs.

There's plenty of research around...

[wraith]

I'm on Effexor, which is both an SSRI and NARI. I don't like taking it, but I kind of have to.

Your comments are reassuring, however. Thanks.

[velocidex]

Effexor works well, though most people report really bad discontinuation symptoms =\

[lancelot]

The long-term use of both amphetamines and SSRI's are definitely not safe esp for kids.

Ritalin may be "safer" than AMPs, but don't think it's a safe long-term viable solution to your health problems.

[cesium]

Effexor works well, though most people report really bad discontinuation symptoms

I have heard this from several people as well. They said that while Effexor was the most effective antidepressant they have ever used, discontinuation was extremely difficult and it was almost as if they were unable to return to the "baseline" state that they were in previous to their using this drug, almost as though it had effected permanent changes in their brain that created something of a physical dependency on it. Scarey stuff if true.