Combining adderall and ritalin?

[paqbum]

From what I hear, ritalin stops the reuptake, while adderall causes more to be released. I've also heard adderall is neurotoxic in the long run while ritalin is not (you just build up tolerance).

http://www.quora.com/What-are-the-long-term-effects-of-Adderall-Dexedrine-or-Ritalin-use

Can anyone provide any more input on these 2 drugs? I'm using them currently as study drugs, but some weeks I end up using them often and am worried about lasting effect.

 

[Nagelfar]

They will add to one-another only in so far as they add to the number of transporters affected at once, dosing higher with either one is better for getting the desired effect of whichever you prefer. Because the Adderall will eventually phosphorylate all your transporters and the Ritalin will stop having any efficacy. Because they are mutually exclusive to any single individual transporter at a time. Meaning, when Ritalin is bound to the re-uptake pump as a ligand, Adderall cannot go up through the Monoamine Transporters into the Vesicular Monoamine Transporters and phosphorylate both and cause release. Once MAT is phosphorylated it is compromised and is in it's death cycle as a cell (going to be "internalized" and regenerated a-new) whereas Ritalin protects this from happening, but has a shorter half-life and eventually, whenever an individual Ritalin molecule "dis-associates" an Adderall molecular has the chance to 'phosphorylate' it and therefore alter the transporters conformation (it malforms it, this is why dopamine, serotonin, etc., is released, because the normal working mechanism of the transporter cell is compromised, "broken") and Ritalin can no longer bind to the re-uptake pump on its outer surface. So they will combined to effect "more" transporters, but eventually the Adderall effect will take over the Ritalin effect (which protects the transporter cells for a time, as it's mode of action inhibits Adderalls mode of action)

Does that explain it for you? Cocaine & Methamphetamine have the same mutually exclusive method of action. Cocaine is neuroprotective to methamphetamine neurotoxicity, but N-meth-amp's longer half-life being less metabolic labile doesn't really prevent it in the event of the co-administration of the two drugs; the methamp's high/stimulation overtakes the cocaine's. (Now a covalent binding analog of cocaine would, in fact, completely prevent it for the same life span of the individual transporter, because it is associated until it is naturally internalized, in such a case, probably lasting longer than even methamphetamine.)

 

[paqbum]

Thanks, this does explain it well. I took both (5mg ritalin and about 15mg adderal -- half tablets) and I had a ton of anxiety after the first 2 hours.

I had no idea ritalin actually protects neurons while adderall is toxic to them, so this is good when choosing which to take when cramming. Thanks

 

[Nagelfar]

Thanks, this does explain it well. I took both (5mg ritalin and about 15mg adderal -- half tablets) and I had a ton of anxiety after the first 2 hours.

I had no idea ritalin actually protects neurons while adderall is toxic to them, so this is good when choosing which to take when cramming. Thanks

Yes. Studies have shown long-term amphetamine abusers to have higher instances of Alzheimer's disease later in life, and cocaine (close to methylphenidate / Ritalin, almost identical in mode of action; and structural benzene ring position, clycloalkane ring & carbomethoxy branch locations.) abusers have lower instances of Alzheimer's than even the regular (control) population (non-drug users.) … (of course risk of instant cardiac death at any age is highly increased, also mental disorders, depression, long term down-regulation of dopamine. etc.)

 

[endotropic]

Yes. Studies have shown long-term amphetamine abusers to have higher instances of Alzheimer's disease later in life, and cocaine (close to methylphenidate / Ritalin, almost identical in mode of action; and structural benzene ring position, clycloalkane ring & carbomethoxy branch locations.) abusers have lower instances of Alzheimer's than even the regular (control) population (non-drug users.) … (of course risk of instant cardiac death at any age is highly increased, also mental disorders, depression, long term down-regulation of dopamine. etc.)

Alzheimer's or Parkinson's? The latter interaction I've heard of and makes sense from a mechanistic standpoint (stimulants damage dopamine neurons; dopamine neuron damage leads to Parkinson's). I've never heard of stimulants contributing to Alzheimer's though.

 

[Nagelfar]

Alzheimer's or Parkinson's? The latter interaction I've heard of and makes sense from a mechanistic standpoint (stimulants damage dopamine neurons; dopamine neuron damage leads to Parkinson's). I've never heard of stimulants contributing to Alzheimer's though.

Alzheimer's IIRC.

 

[Voyager3]

I can confirm something - ritalin doesn't work on me at all on its own. I have brain damage which has somehow wrecked most of my dopamine releasing system, and only amphetamine can kick it into life. When it has been thus kicked, Ritalin does have an effect, by reducing reuptake. Hardly worth bothering with unfortunately.

 

[Nagelfar]

I can confirm something - ritalin doesn't work on me at all on its own. I have brain damage which has somehow wrecked most of my dopamine releasing system, and only amphetamine can kick it into life. When it has been thus kicked, Ritalin does have an effect, by reducing reuptake. Hardly worth bothering with unfortunately.

I know some who say smoking freebase cocaine "calms" their methamphetamine high. Smooths it out. I assume it's the serotonin reuptake affinity. (I believe cocaine has greater affinity as a ligand to SERT for the reuptake pump than methamphetamine has for phosphorylating SERT, though higher than regular amphetamine's affinity.)

 

[Seppi]

Alzheimer's IIRC.

AFAIK, the only neurodegenerative disease of which high-dose meth use in humans is associated with an increased incidence is Parkinson's. See Methamphetamine#Neurotoxicity on Wikipedia for reference.

To my knowledge, amph/meth have no known effect on Alzheimer's incidence. Based upon other research that doesn't involve drugs, I'd suspect that amphetamine might actually facilitate the prevention of Alzheimer's if it's used at therapeutic doses for intellectually challenging pursuits (again, this is entirely my speculation). Even if this is true, it wouldn't preclude the possibility that chronic high-dose amph/meth use promotes Alzheimer's incidence though.

 

[Voyager3]

I noticed that Adolf Hitler was suffering from Parkinsons quite noticeably towards the end of his life, having been taking large amounts of meth for several years. Even so, seeing that Parkinsons is caused by a chronic lack of dopamine, and meth and other amphetamines boost its release, I can't help thinking that this might be the reason the two are connected? I myself suffer from achronic dopamine shortage, and suffer many of its symptoms, including depression - for which the only reliable 'cure' (or or ather, temporary relief from on a symtomatic basis) is amphetamine. I have begged to try levodopa and other dopamine agonists with no success.

 

[endotropic]

I'm a bit skeptical that adderall is any worse for the brain than methylphenidate. Has anyone seen clinical evidence for long lasting cognitive/neurological deficits linked to either of those medications?

 

[Voyager3]

No, and to sound a bit arrogant, I should know! But that is in my experience, and there definitely seems to be something a bit odd about my brain chemistry. Even so, despite a good 25 years of very heavy, regular amphetamine use - both legal and illegal - no harm has been done whatsoever AFAIK, and my health in general seem far, far better when taking the stuff - no asthma, almost no hayfever, weight ideal, far fewer colds and flu, sleep far better, and 'wake' worth living. Slight BP rise over the years, but that runs in the family and just age. Concentration, focus, logic and reasoning far better, freedom from panic attacks, alcohol consumptin safely controlled, and far fewer injuries at work. The only possible 'downside' is on the dental front - upper set now almost gone, and no enamel left at all... but IMHO well worth the sacrifice!

 

[Seppi]

The only paper I ever found on evidence of amphetamine-induced neurotoxicity (technically, it's just neuronal dysfunction, sans cell death) in humans is summarized and linked here. I spent many hours searching for a paper on that topic before I finally found that one. Based upon those findings, and assuming there's no bias in that sample, dextroamphetamine appears to produce markedly less dopaminergic neurotoxicity than methamphetamine when it's chronically abused... for over a decade, although there may still be other decrements which have not yet been documented.
Edit: This paper was recently published and cited the one I mentioned above - PMID 25394786 "Dopaminergic system dysfunction in recreational dexamphetamine users." The significance of those findings IMO sounds comparable to the first paper; a reduction in D2-like receptor density, and not much else, from long-term recreational use isn't particularly notable, since D2-receptor density (not D3) is reduced in amphetamine addiction anyway. I imagine the reduction in presynaptic dopamine release could partly arise through fewer D2-TAAR1 heteromer + D2short receptors if the presynaptic D2 receptors were similarly affected.

In any event, given everything I've read in papers on neuroimaging in therapeutic amphetamine/methylphenidate users with ADHD, the call for caution in ADHD users in the last sentence is a bit uninformed/misguided. The only thing that 3 literature reviews of the aforementioned neuroimaging studies found/concluded was improvements in gray matter volumes and associated function in certain structures (e.g., the caudate nucleus) following amph/mph use for several years. No functional decrements, like the one found in that recreational use study, were reported in any of the reviews (links to those three reviews can be found as references in the medical uses section of amphetamine on wikipedia).

 

[Voyager3]

Harmless in other words? Beneficial for me... I must have taken at least four times my own bodyweight (100kg... tut tut!) in pure amphetamine sulphate, with no ill FX whatsoever! Except maybe going on a bit....

 

[aced126]

Yes. Studies have shown long-term amphetamine abusers to have higher instances of Alzheimer's disease later in life, and cocaine (close to methylphenidate / Ritalin, almost identical in mode of action; and structural benzene ring position, clycloalkane ring & carbomethoxy branch locations.) abusers have lower instances of Alzheimer's than even the regular (control) population (non-drug users.) … (of course risk of instant cardiac death at any age is highly increased, also mental disorders, depression, long term down-regulation of dopamine. etc.)

How is ritalin close in structure to cocaine? Ritalin has an amphetamine skeleton?

 

[Nagelfar]

How is ritalin close in structure to cocaine? Ritalin has an amphetamine skeleton?

The above is a 3-dimensional overlay of methylnaphthidate & cocaine derivative WIN 35428. See the closeness of the nitrogen, the carbmethoxy oxygens, the benzene and the cycloalkane?

Methylnaphthidate:

WIN 35428:

EDIT: Note: the lower 2D images are reversed in orientation from one another compared to the overlay.

 

[squashee420]

the Adderall will eventually phosphorylate all your transporters

Is this permanent?

If so, is there methods of mending or treating the negative consequences of such?

If not, is this a temporary situation in which the body eventually fixes/heals on its own over time, assuming one takes a break from amphetamine use?

Also, if not. Is this at all related to the MAOI benefites I've read about substances such as DXM that remove calcium deposites and other damage caused by amphetamine use? I've also read that it can "lower" your tolerence, or maybe sets you up for a window where tolerence is lowered.

In relationtion to the potential benefites of DXM therapy, would this also, improve the efficiency or affect the tollerence of ritalin, in any way?

 

[Nagelfar]

Is this permanent?

Once phosphorylated the individual transporter is compromised, and goes through a process called "internalization", meaning the cell dies, it "decomposes" back into the membrane, and the body generates a new one. You're killing it in one sense, but it's still functioning, though, differently. (A "zombified" transporter, you could consider it), and the body notices there is something wrong and 'metabolizes' it (regenerates a new one in its place). It's no different than your skin cells flaking off and a new layer of epidermis under it taking its place on top.

However, doing this a lot might change how your body tends to react to it in certain permanent ways. This is not entirely understood.

 

[Black]

meaning the cell dies

the cell doesn't die. it's just that a protein is removed from the membrane into the cytosol and degraded. and not even that is certain to happen. neurons typically have a pool of intracellular vesicles to store monoamine transporters, which aren't in use at the moment. phosphorylated transporters might be degraded or they might just sit in this pool for a while...

 

[Nagelfar]

the cell doesn't die. it's just that a protein is removed from the membrane into the cytosol and degraded. and not even that is certain to happen. neurons typically have a pool of intracellular vesicles to store monoamine transporters, which aren't in use at the moment. phosphorylated transporters might be degraded or they might just sit in this pool for a while...

Well, "degradation" is what I mean by death, inside your body cells regenerate, so it's like a sprig growing off of a stump in the forest of life than a full-stop end, but that was my meaning.