Stimulants Why does methylphenidate feel so inferior to amphetamines?

[riverofheaven]

Hello guys! This is my first post ever on this forum, iv'e been lurking it for quite some time.
So what i have wondering for a long time is why are the effects from methylphenidate so different compared to any time of amphetamine (2-FMA, amphetamine sulfate, adderall, meth).

I'm diagnosed with ADHD in my country and have been prescribed concerta. I started with 18mg and i just couldn't feel this dose at all, so i adjusted the dose with my doctor to 36mg. Now here i could barely feel the effects, so it wasn't good as well. At last we went to 54mg and this one did have obvious effects, but they were not in any way quite good...
Basically at this time i still didn't know any other stimulant then methylphenidate so i couldn't compare effects yet, but basically they were wierd, main problem was this constant background anxiety and dry heaving like feeling (will compare effects in the next part with amphetamines i tried).

Now cause i was a 1st year medical student at that time and had a crisis that i will completely fail university because the only adhd med present being concerta, i looked into the darkweb realm and grey market of research chems. So i decided to buy 2-FMA. Now this God sent chemical saved my whole semester and im still thankful for it till this day. I used it the next semester as well and it still made me pass it. But after this i started having health anxiety about the rumor of 2-FMA being very cardiotoxic so i stopped taking it and instead turned to the dark web and bough amphetamine sulfate. Now amphetamine sulfate was...different from 2-FMA, it was still miles better then Concerta but it had more like body stimulation compared to the calm feeling of 2-FMA. I may make a future thread on some interesting stuff i noticed between these two.

To get to the main differences i noticed between methylphenidate and amphetamine:

Methylphenidate: Kicks in after 30 minutes, half of the time it kicks in with an alert feeling but SOMETIMES it actually kicks in with making me yawn a lot and have a heavy feeling on my eyelids which stops later. The huge problem with methylphenidate is how the best part of it is basically the first 1 hour at best, actually i may like that "euphoria" more then the one from amphetamines. It's more cold, edgy, empathethic, talkative, i love talking with someone during that first hour, can feel amazing. But then it happens, after the first 1 hour it has this almost abrupt change where i get this constant background paranoia and anxiety, for example unexpected noises terrify me, when my mom opens some door in the house i get this cortisol attack in my body. Next is how asocial i become and how i lose my emotions, i just can't talk with people about anything other then something super technical, it feels like i become autistic during the whole duration. Now for helping my ADHD it's honestly trash, the anxiety is too much to study as well as this wierd dry heaving feeling i constantly have.

Amphetamines: Kick in around 20 minutes, the initial rush feels very different from methylphenidate yet still a familiar stimualant feeling. It is more like a warm feeling in my torso, legs and arms rather then a cold edgy feeling of methylphenidate, but its not social like methylphenidate, it makes me hyperfocused on something im doing. The rush fades after 1 hour but in comparison to methylphenidate, the effects are absolutely lovely, they are the same like the rush just much more mellow, there is just slight background anxiety at best but its laughable small compared to methylphenidate, and the motivation keeps going for hours, so it manages my adhd quite well.

 

[ninjapirateroberts]

The general difference between methylphenidate (MPH) and amphetamines (AMPH) is that MPH is only a norepinephrine-dopamine reuptake inhibitor (NDRI), whereas AMPH is both NDRI and catecholamine releasing-agent, so AMPH also induces the release of dopamine (DA) and norepinephrine (NE) neurotransmitters from presynaptic vesicles. MPH only inhibits the reuptake of DA and NE by inhibiting the activity of dopamine transporter (DAT) and norepinephrine transporter (NET) but does not induce release. AMPH also makes DAT and NET "work in reverse" (neurotransmitter efflux), thus causing higher concentrations of DA in the synaptic cleft. Although DA plays a major role with ADHD and NE not so much, NET should also be inhibited because NET also reuptakes DA along with NE.

So this causes a higher extracellular concentration of DA, which is what makes "methylphenidate feel so inferior to amphetamines".

That's the general high-level understanding, although I've left out many pharmacological mechanisms of action between MPH and AMPH. But everyone's different; some people like MPH and vice versa.

 

[ninjapirateroberts]

MPH is the first line of treatment for ADHD. Doctors will generally start you with MPH, and if you don't react to MPH, they'd switch to AMPH. So you can tell your doctor that you're not reacting to MPH, and they'd switch your medication. If you live in the US or Canada, you'd be started with MPH and then to AMPH (usually dextroamphetamine-based drugs like Adderall, Vyvanse, Dexedrine, etc.) if you live in the UK or Europe I have heard from my friends that Adderall is usually not much prescribed (especially in the UK) so the second line would be Elvanse (Europe's version of Vyvanse).

But if you're self-medicating, don't buy amphetamine sulfate. It's almost always stepped on too much. Instead, get yourself a milligram scale, crystal methamphetamine, and empty capsules. Start with 10mg of crystal meth (weigh it and put it in the capsule) and increase the dose gradually. 25mg is the maximal meth dose for ADHD. I'd usually feel better with about ~23mg (that's my maintenance dose). At least that way you know you're taking an actual amphetamine, not some sugar power or heavily cut shit sold as "amphetamine sulfate".

 

[sonicwhite]

To each there own. Adderall helps. But I like methylphenidate too. I'm hoping cuz my doc no longer prescribes Adderall with all the crap happening that he will prescribe serdexmethylphenidate. It's a pro drug. You can't abuse it. Vyvance made my anxiety go thru the roof. Focalin helped too.

 

[BourbonMac]

It just differs from person to person. I think methylphenidate feels way better than amphetamines (minus MDMA). Although it feels closer to MDMA euphoria wise than Adderall for me personally. Adderall just makes me feel deadened and not like myself at all.

Your experiences with Adderall and Concerta are basically reversed for me. Methylphenidate is very smooth for me, no anxiety, no tics like caffeine or Adderall. Just euphoria, reduction of anxiety, better focus.

 

[sonicwhite]

Yes but like me. I wished we all could just take it as prescribed. We're the ones who get ourselves in trouble.

 

[plumbus-nine]

Yeah, guess it's just different between individuals. I heard of people swearing on concerta (though they probably never sampled amphetamine before) and I liked it too when I was prescribed it but yeah, compared to amphetamines and specially meth, Ritalin has a rough edge. It makes me panic when I overdose while amphetamines feel like partying, huge euphoria at supra therapeutic dosages. I remember the very first 5mg of dexamphetamine I got (previously only MPH) and thought, wow this stuff is nice. But MPH is more functional, with amphetamines I need to dose every day or I'd become depressed for one or two days, the kind of which locks you into the bed. MPH doesn't do that.
As for why, I dunno. Amphetamine is more closely related to the endogenous phenethylamine but that hasn't to say anything as I read that PEA itself wasn't too good. Amphetamine and methylphenidate lead to different neuronal firing patterns, being a releaser vs transporter inverse agonist (Ritalin isn't a transporter blocker, those tend to hit autoreceptors and not exhibit any beneficial immediate effects, see SSRIs and their latency period)

 

[sonicwhite]

We who actually suffer from ADD, and since my parents did not take my childhood seriously. I can't get what I need. I beg God bring relief. It sucks when you're doing one thing but you are focused on 10 things. Maybe I'll just pray until I'm healed. Cuz if you haven't seen what's going on in the world I beg you to wake up.

 

[plumbus-nine]

We who actually suffer from ADD, and since my parents did not take my childhood seriously. I can't get what I need. I beg God bring relief. It sucks when you're doing one thing but you are focused on 10 things. Maybe I'll just pray until I'm healed. Cuz if you haven't seen what's going on in the world I beg you to wake up.

I'm having adult attention deficit disorder, the inattentive kind but also some hyperactivity (permanently switching between a couple of tasks, even when watching a movie, and finishing none of the tasks) and I'm a bit mad at people abusing prescription stimulants because since I moved I can't get any more prescriptions for stims, the docs here don't understand English and many are retarded and believe controlled substances like amphetamine were evil and a person with attention deficit couldn't sit in front of a screen for a considerable time, sigh. Some years ago anyone could buy amphetamine from the pharmacy and people did mad shit high as hell (using amph to lose weight etc).

 

[BourbonMac]

ADD really does suck, especially if you're stoned. I've had the greatest epiphanies of my entire life, bits of poetry or music that i'm like, holy shit, I need to write that down. 5 seconds later "what was I doing?" it's not THAT bad sober, but when I'm stoned I get the best ideas and then they disappear in a flash, at least with oil which is what I use mostly these days. It's just too strong, I need to get on that dry herb vape train. I've literally had multiple life changing epiphanies that could've seriously helped me and I instantly forgot them lol. "Wait... it was like... wait... what? no... you think of the train and the strings... fuck I lost it" is just an example of how it tends to go down for me. Just throwing random objects in there, but sometimes if it's something like poetry I just forget it instantly. I need a pen and paper everytime I get stoned and yet I forget that too. My short term memory was always bad, but damn, I become dory when I'm too baked.

 

[plumbus-nine]

I'm not into weed because it gives me anxiety but for me ADD isn't so much about forgetting stuff but about directing attention. I just can't focus longer than a couple of minutes unless I find something seriously and deeply interesting or fascinating, specially the latter but sometimes not even that helps much. On stims one has a hyper focus and without stims ADD is hypo focus, scattered attention. But forgetting sucks as well, I had this on dissociatives, they help with my ADHD but at the same time, if dosage isn't exactly right, make me forgetful as well. Yet pregabalin is worse, imagine watching a blockbuster and not being able to follow the story. This never happened to me on dissos but on 600+mg of pregabalin.

 

[Pissed_and_messed]

Although DA plays a major role with ADHD and NE not so much, NET should also be inhibited because NET also reuptakes DA along with NE.

can you argument about this?
Because it was not long ago when someone somewhere here claimed, with some scientific data if I am not false memorizing, that it might be primarily NEP which is the issue
But I don't want to say that your approach is just wrong, most probably ADHD/ADD is very complex issue that is defined on higher level than single neurotransmitter system, and so maybe it is futile to point on that and that system function without looking at bigger picture, but as that has been now challenged, I need to get on group with the questioners, as is the common habit of science-promoters
I would not be in the least surprised even if someone pointed out that there were multiple pathological conditions that had symptoms so similar that they were all filed under one diagnosis while being multiple disorders.

 

[plumbus-nine]

can you argument about this?
Because it was not long ago when someone somewhere here claimed, with some scientific data if I am not false memorizing, that it might be primarily NEP which is the issue

I tend to agree with that dopamine is the primary culprit in ADHD, and read as well that in some brain regions the NE transporter takes up dopamine as well. I am experienced with the norepinephrine reuptake inhibitor antidepressant reboxetine and it did nothing to help me with ADD symptoms while most dopaminergic drugs (releasers, reuptake inhibitors, not necessarily agonists) including recreational, indirect ones like dissociatives or opiates do help me. But of course you might be right in that different people have differing brain chemistry and some so seem to benefit from atomoxetine but I'd say it's the minority. I also think that dopaminergics do induce a state of flow sometimes which greatly aids with attention and norepinephrine doesn't do that.

 

[ninjapirateroberts]

can you argument about this?
Because it was not long ago when someone somewhere here claimed, with some scientific data if I am not false memorizing, that it might be primarily NEP which is the issue
But I don't want to say that your approach is just wrong, most probably ADHD/ADD is very complex issue that is defined on higher level than single neurotransmitter system, and so maybe it is futile to point on that and that system function without looking at bigger picture, but as that has been now challenged, I need to get on group with the questioners, as is the common habit of science-promoters
I would not be in the least surprised even if someone pointed out that there were multiple pathological conditions that had symptoms so similar that they were all filed under one diagnosis while being multiple disorders.

IMO, although ADHD is not completely understood, it's said that the "reward" system of people with ADHD has executive dysfunction when compared to normal individuals. I think the current understanding is that since DA plays a major role in "reward" and "motivation", and since ADHD individuals have defects with the "reward" system (like, I have both ADHD and autism spectrum disorder, and I tend to be hyperactive, hyperfocus, or least motivated on certain things), increasing the activity of the neurotransmitters involved in the "reward" and "motivation" system might subvert the ADD symptoms (that is, by increasing DA, I get an increased "reward" and "motivation" towards things I generally don't find as stimulating). Some people with ADHD, like myself, "seek" DA by being overly hyperactive, as I switch between multiple tasks that I find "stimulating" at that particular moment. And I get a (false) sense of "reward" when I do the thing that I find stimulating in that particular movement. I can give you an example: when I have a deadline for an assignment that I don't find stimulating, I substitute it with things I find stimulating (meaning I do things I like rather than the actual coursework), and I get a false sense of "reward" from doing that other thing (but I end up failing the course since I couldn't do required work). This becomes a major problem for many people who are hyperactive and can't stick to something because they don't find it "stimulating enough" (many others, including myself, get physical restlessness if we force to do something we don't find stimulating). I think norepinephrine (NE) is mostly associated with a "fight-or-flight" response, so it increases peripheral effects like heart rate and BP (the increased "anxiety"). I think currently, there aren't drugs that have a selectivity towards just dopamine receptors (take amphetamine for example) but global catecholamine release. But more affinity of amphetamines towards DA and NE.

There are two stages in neurotransmitter reuptake (reuptake is the recycling of excess neurotransmitters in the synaptic cleft, but not all of them are recycled; some will be metabolized by special enzymes). So the first stage in reuptake is bringing the extracellular neurotransmitters DA and NE from the synaptic cleft back to the cytosol. Once inside the cytosol, again various sets of neurotransmitter transporters that are present in the vesicles will take those neurotransmitters and put them back in vesicles for later use (this is stage two). But in stage two, as far as I understand there is more selectivity between NE, DA, etc., when putting them back into the vesicles. But there is not much selectivity in stage one (that's why NAT reuptakes both DA and NE).

But I think an increased concentration of NE is inevitable since DA is a precursor to NE (this conversion being catalyzed by various enzymes). I assume this is why people have increased anxiety on the "comeback" after the "dopamine rush" (due to DA → NE conversion within the synaptic vesicles).

Plasma membrane monoamine transporters: structure, regulation and function - Nature Reviews Neuroscience

The classical biogenic amine neurotransmitters — dopamine, noradrenaline, and 5-hydroxytryptamine — control a variety of functions including locomotion, autonomic function, hormone secretion, and the complex behaviours that are associated with affect, emotion and reward. A key step that...

www.nature.com

 

[ninjapirateroberts]

And, regarding how amphetamine-type stimulants "work in reverse" resulting in neurotransmitter efflux, and thus why methylphenidate feels "inferior" to amphetamines-type stimulants:

 

[Fertile]

I believe methylphenidate is used because it has fewer side-effects than amphetamines. Euphoria would be considered a side-effect.

Phenmetrazine was briefly used in Sweden but it was patented in 1952, introduced into Sweden in 1954, controlled in Sweden by 1956 and banned in 1963.

The RCs based on the phenmetrazine scaffold are potentially dangerous. Yes, a 3-TFM WILL add SERT activity, but it's likely to be a 5HT2b ligand - which caused heart-valve damage.

 

[sonicwhite]

Well given the fact I'm on two AP's Latuda and Zyprexa. Which both upregulate dopamine so I'm not getting what I need but unfortunately coming of the antipsychotics isn't an option yet. I wanna wait and take it slow. I guess when I finally am free to go into a long term ward. When I was on the Adderall yeah it had valleys which sucked but it was helping. The Vyvanse just wasn't 4 me. Given the fact we are at war we're going to have to make our own generics. Cuz all this crap comes outta China. Since we're helping Ukraine China is sanctioning us for that. The war started when China let out a virus on their own ppl. They don't give two shits about their ppl. They want worshiped. If they do that to them what will become of us??





It's going to be an interesting year's ahead. I'm not in Russia so I don't know what is said there. I'm not in China so I don't know what their thinking. Balloons that are to find our airfields.

It doesn't take a genius to see this. Our second amendment right will come in handy but I'm to lay my life down. As Christ's commands. You live by the gun you'll die by the gun.


All I can do is pray, meditate and fast. For ppl don't see the clear signs. Squeezing our meds. Even diabetes meds. This is why Our Nation Can only rely on itself. God would be pissed if He saw another Hitler. Trust me. In the Book of Joel. It talks about the Holocaust. They just put it in a way that we can't immediately interpret. Yes God is thankful to America. But we have many stains. Israel is the Apple of His Eye. I promise you He will never allow another hit on His ppl. I do believe that future generations will suffer for what those psychotic animals did to them.

 

[fastandbulbous]

My oldest niece got a diagnosis of adult ADHD. After a beautiful bit of prose (from a good mate who writes for a living), that stopped her feeling in some way inferior, because of the diagnosis, I advised her to try Ritalin first (she's only 5'4" and 50kg) as it fucks with appetite much less (it was about her getting help, not getting high).
Since starting medication, 3 months ago, she has her mother's focus and drive and her self employed business is really doing well. Even her mother thanked me for convincing her to give the meds a chance (and if ever a younger sibling would be justified in getting revenge on an older brother, she would be justified in anything short of sadistic murder, she's top of the list!)

 

[Neuroborean]

I FINALLY...
Got my prescription for ADHD... in Spain, a difficult country for that, specially when having 34 years and being recently diagnosed... I wasted a lot of money on this, but I finally got it.
I got a bit depressed when I found the meds are Concerta.
I do like, more or less.., 4f-mph but I thought that they were going to prescript ritalin or focalin or perhaps atamax (atomoxetine/strattera) but no.. they gave me the baby dose of MPH extended release... Concerta 18mg

So well, it kinda works, but it's barely noticeable in terms of euphoria and in terms of drive, I guess the dose is too low but I don't see how 36 or 54mg are going to be better.. doesn't seem so. I tried 36 one day, but not at the same time, 18 morning and 18 evening. It wasn't interesting, just more zombieish.
Good batches of 4f-mph feel pretty good, but it's difficult to find good batches of RCs lately.. and for me 2-fma feels like absolute shit, like absolute poison, specially the last batches I got.

I honestly don't know how to find a proper ADHD medication, I guess I need to settle for Concerta... it does help in some aspects, but it barely increases the motivation

 

[ĐmantuNJofra]

maybe this is off topic but as adult 35yr ol ADHD with neuropathic pain who takes pregabalin and tried both phenibut and in the past GHB
I can say that Concerta or methylphenidate in doses like 72mg which is prescribed to me with 600mg pregabalin
It somehow stabilize my dosing of pregabalin, meaning it doesn adds to euphoria, just lower compulsivity that sometimes can go with dosing pregabalin.

To clarify more in laymans terms: amphetamine with pregabalin almost just erase amphetamines, but MPH somehow cuts through with energetic and even helps with bloating or edema which can be in summer hot times like these days more often.
So with Concerta if and this is hard; to hydrate and not forget to hydrate cause:

With these two types of meds Mania can overwhelm sometimes and person like me or you can forget to drink water or more important to drink something with electrolytes.

I just want to say that we all need to be a bit of our own doctors as we know ourselves best so testing on yourself is only if you know what you are doing, or if you've been through a lot with meds like these.
Also I sometimes use Clonidine as it helps peripheral and not like benzodiazepines so it does take a bit, but clonidine with pregabalin will get me good sleep and
only if used in low doses to not have that like dry mouth and actually waking me up and need to eat anything just to go back to sleep.
I red that it also helps with ADHD and I think that it can be:

A magic combo for all of us that cannot use amohetamines or doen't have Elvanse yet like Germany has or to import it.

Clonidine that acts centrally on alpha-2 adrenergic as an agonist but: There is a release of norepinephrine from the descending inhibitory bulbospinal neurons that binds to alpha-2-receptors in the dorsal horn to decrease afferent pain transmission and produce analgesia. Therefore, drugs like clonidine that target alpha-2 receptors can influence the transmission of pain.
Clonidine for ADHD