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Methylphenidate VS Amphetamine

CoastTwoCoast said:
You're right that in the end you will end up raising your doses with either Adderall or Methylphenidate, especially addicts. Just can't help it.

Amphetamines have way more euphoria. That's why I was too out of control and quit, you just want to ride that euphoria all day. It turns into psychosis and possibly death. I hate amphetamines. I feel it's way more toxic than methylphenidate, that's just me.

At least when I go for days without Concerta, I can still get out of bed and function. When I was on Adderall and went without it, I couldn't get out of bed at all. I didn't want to do anything without it. It's like it left me lifeless. I can go without Concerta with no problem. When I'm back on it, it's fine. That's why I prefer Concerta. If you don't have Gabapentin or kratom to take the edge off of Ritalin or Concerta, you'll feel like a crackhead. lol

I just got Intuniv, it's supposed to help with the stimulant crash. I was prescribed 1 mg. I'll see how it works with my Concerta when I get it Monday.
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Does amphetamine affect your heart rate much?

Do you feel a crash at then end of it's half life?
Or manage to keep going until bedtime?
 
JohnBoy2000 said:
Does amphetamine affect your heart rate much?

Do you feel a crash at then end of it's half life?
Or manage to keep going until bedtime?
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Yes, it does effect your heart rate, but mostly if you abuse it. I started out with 20 mg Concerta. If you stick to a dose like that, you'll be good. I've moved up to 40 mg now.

If you abuse it, your heart will be pumping fast and more than likely you'll be super agitated. There's really not much euphoria to it, so basically it feels like shit anyway to abuse it. Like I said, you'll feel like an agitated, sweaty crackhead. Haha

Yes, I do feel a crash around 1 or 2 pm if I take it early am. I just got prescribed Intuniv. 1 mg. That's a nonstimulant for ADHD and it's taken along with stimulants to stop the crash. So I'm gonna try Intuniv with it when I get my Concerta on Monday. I take a 20 mg pill in the am and one in the afternoon.

There can be some agitation or edginess with Concerta so that's why I mentioned Gabapentin or kratom helps take the edge off. Maybe all I'll need is Intuniv with Concerta from now on. I gotta try it together Monday and see.

Edit: I'm sorry I just noticed you asked about amphetamines. Amphetamines effect your heart rate for sure...to the point where you can have a heart attack. Stimulants in general do that. I quit amphetamines though. I liked it way too much because of the euphoria and it turned on me, started backfiring and changing my personality for the worst. I can't stand amphetamines. I've been off of amphetamines for over a year. I prefer methylphenidate.
 
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JohnBoy2000 said:
I gotta ask - given the cost difference, doesn't that basically mean that big-pharma are violating the common man with a genuine health condition?
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Physicians decide whether to prescribe someone with ADHD methylphendidate or amphetamine, not "Big Pharma." In any case, amphetamine and methylphenidate, including extended-release formulations, are all available as generics.
 
AlphaMethylPhenyl said:
In fact wikipedia has a pretty good rendition of how amphetamine works.
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It's actually not 100% up-to-date, but for all intents and purposes, it does still accurately portray the basic mechanics: amphetamine's interactions at TAAR1 and VMAT2 mediate its dopamine-releasing and reuptake mechanisms.

The part that isn't up-to-date with the current literature is the signaling cascades portrayed; while the ones depicted in https://commons.wikimedia.org/wiki/File:TAAR1_Dopamine.svg are entirely accurate, it doesn't depict the following cascades:
Amphetamine-->TAAR1-->RhoA-->ROCK-->DAT phosphorylation-->DAT internalization
Amphetamine-->TAAR1-->RhoA-->ROCK-->EAAT2 phosphorylation-->EAAT2 internalization
Amphetamine-->TAAR1-->PKA--|RhoA
NB: "--|" represents functional inhibition of RhoA in this case
And, if I add the glutamatergic pharmacodynamics of amphetamine in DA neurons (i.e., EAAT2 internalization), I'd need to add glutamatergic synaptic vesicles which express VGLUT2 in the dopaminergic axon terminal, as all DA neurons contain glutamatergic vesicles which express that reuptake pump.

I've been meaning to update the diagram ever since this paper (NB: the involvement of ROCK in the RhoA-mediated DAT internalization cascade is covered here: https://en.wikipedia.org/wiki/Talk:...-Amph_RhoA+ROCK_signaling_to_DAT_-_primary-21 - also see the excerpt in reference #8 immediately after that) was brought to my attention in the Amphetamine and TAAR1 question thread, but editing SVG images in Inkscape is a pain in the ass; hence my procrastination. :p

Since it probably won't be clear to most people as to whether PKA-mediated or RhoA-mediated DAT internalization is more relevant to amphetamine-induced dopamine reuptake inhibition (via DAT internalization), I'd need to clarify in the image caption that RhoA-mediated internalization is fairly transient and only dominant for a period of < 30 minutes post-exposure (I'd estimate that it peaks somewhere between 5-20 minutes post-exposure, based upon the time course of cAMP accumulation/PKA activation and RhoA activation post-exposure as well as the fact that ROCK is a downstream target of RhoA in this cascade), after which PKA-mediated RhoA inhibition and PKA-mediated DAT internalization is the dominant mechanism.

For reference, see figure 2, figure 3, and figure 4.

@OP: methylphenidate and amphetamine have completely different pharmacodynamics in dopamine neurons. The only similarity between them is that they share one mode of action at the dopamine transporter: reuptake inhibition. How they accomplish that - the underlying mechanism of action - is entirely different. Obviously, amphetamine has an additional mode of action at DAT since it also induces transport reversal (via CAMKII-alpha and PKC-mediated DAT phosphorylation), which causes dopamine efflux. The release of dopamine from synaptic vesicles by amphetamine - via its uptake at VMAT2 and the subsequent collapse of the vesicular pH gradiant - augments its effect on dopamine efflux through the dopamine transporter. Methylphenidate on the other hand doesn't directly affect/alter vesicular stores of dopamine.

TAAR1 is expressed in many tissues and cells outside the central nervous system (e.g., in white blood cells, the stomach, intestine, pancreas, kidney, lung, liver, prostate, skeletal muscle, spleen, and tonsils) as well as in non-monoaminergic neurons (e.g., some GABAergic neurons) and glial cells (e.g., astrocytes) in the brain. Since TAAR1 has rather widespread expression in both the body and brain and since methylphenidate does not act on that biomolecular target, TAAR1 agonism by amphetamine explains why it produces markedly different physiological and cognitive effects than methylphenidate. E.g., methylphenidate does not produce TAAR1-mediated effects like this, whereas amphetamine does.

NB: I'm not going to comment on TAAR1 activity in the neuroimmune system.

The immunological effects of TAAR1 activation in white blood cells (see https://en.wikipedia.org/wiki/TAAR1#Immune_system, specifically the 2nd paragraph) explain why some people experience an exacerbation of their allergies following amphetamine use. In a nutshell, some white blood cells express both TAAR1 and TAAR2, and it is strongly suspected that TAAR1-TAAR2 hetero-oligomers (probably heterodimers of those receptors) form in those cells; upon activation of TAAR1 by TAAR1/TAAR2 co-expressing T-cells, interleukin 4 is secreted. This doesn't occur in TAAR1⁺/TAAR2⁻ T-cells, which is why it's likely mediated by TAAR1-TAAR2 heterodimers. Also, TAAR1 agonists cause immunoglobulin E (IgE) secretion from B cells that co-express TAAR1/TAAR2 (but not from TAAR1⁺/TAAR2⁻ B cells). Since IL-4 induces B-cell proliferation and since IgE (technically: IgE-allergen crosslinking at the FcεRI receptor) is the primary biomolecular mediator of all true allergies (type-I hypersensitivity reactions), the induction of IL-4 and IgE expression in white blood cells by amphetamine binding at TAAR1 is the mechanism by which it exacerbates symptoms of allergic diseases (e.g., allergic rhinitis, asthma, hay fever, etc.) in some people. In the event you're familiar with the Th1/Th2 model of immunity, the effect of TAAR1 agonists on IL-4 and IgE expression exclusively promotes Th2-mediated - i.e., "allergic" - immune responses. Since this is a toxicogenomic effect, it's strongly dose-dependent. Even though amphetamine exacerbates allergic reactions via this mechanism, it also indirectly activates alpha-1 and beta-2 adrenergic receptors through the secretion of norepinephrine and epinephrine into peripheral blood plasma (NB: methylphenidate also does this), which has the opposite effect on allergy symptoms. This is the primary mechanism by which it alleviates the symptoms of allergic reactions in some people, as well as why it was prescribed for treating asthma and nasal congestion in the 1930s and 1940s.

In the event you're interested in references, the IUPHAR page on TAAR1 covers what I mentioned about its expression pattern in the "Tissue distribution" section. The "Functional assays" section and the corresponding citation covers what I've mentioned about TAAR1/TAAR2 and IL-4/IgE secretion by white blood cells. For comparison, table 2 of this paper shows serum Th1 and Th2 cytokine levels in healthy controls vs in amphetamine-dependent individuals (at baseline and at 1 month abstinence). Medication guides for several brands of amphetamine list allergic rhinitis as a statistically significant side effect with an incidence between 1-10% (e.g., https://dyanavelxrpro.com/side-effects lists 4% incidence vs 0% for placebo; https://www.drugs.com/sfx/amphetamine-side-effects.html lists 1-10% incidence).
 
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Anyone comment on what the equivalent dose of methamphetamine to amphetamine (adderall) would be?
 
I had pure meth back when I first started seeing a psychiatrist. It was Desoxyn. It felt way too good and I fucked myself right out of that script. You'd probably get thrown in jail for even inquiring about Desoxyn now. These psychs are scared as hell because of the way the government is coming down.
 
GENGAR said:
What’s Desoxyn?
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Pure methamphetamine in a pill. It was prescribed to me for ADHD like a decade ago. Best thing ever. I was only given 15 pills at a time and did something dumb to try to get more. I won't go into the details here. It was just too good.
 
CoastTwoCoast said:
Pure methamphetamine in a pill. It was prescribed to me for ADHD like a decade ago. Best thing ever. I was only given 15 pills at a time and did something dumb to try to get more. I won't go into the details here. It was just too good.
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Sounds like a fun time
 
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