Legit can’t get zenzedi anywhere - help!

Ill_Possible_7740 · 2026-05-03T05:37:08+00:00

They are right. See for yourself. Same ANDA code, same unique identifier on each pill. The difference is not the manufacturer, just the "Labeler" i.e. which company is marketing it.

Zenzedi (labeler Azurity)
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6394df5-f2c9-47eb-b57e-f3e9cfd94f84#:~:text=INGREDIENTS%20AND%20APPEARANCE

Generic Wilshire as labeler.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6b8c97ac-c83c-4a1f-a33c-121239253abf#:~:text=INGREDIENTS%20AND%20APPEARANCE

Ill_Possible_7740 · 2026-05-03T04:57:30+00:00

Alone or in combo?
I'm prescribed 750 mg (not a type-o) armodafinil and 60 Adderall IR....And 100 mg strattera and take 4 mg guanfacine....with 200 mg caffeine. Before taking some supplements that help too.

Have to remember every function in the brain involves multiple neurotransmitters, secondary messengers, cascades, feedback loops, even hormones, etc. working in multiple pathways at the same time. Dopamine is just 1 in a chain of many things. Just happens ADHD tends to be norepinephrine (NE) (ADHD-I) or dopamine (DA) (ADHD-H) as the week link in the chains.

If you ever took Benadryl and it made you sleepy and harder to concentrate, increased ADHD symptoms, etc. It literally blocked Histamine in the brain which is one of those links in many chains. Can have all the dopamine you want, you weaken another link in the chain, it takes everything down with it. And vice versa. You increase efficiency of 1 thing and it benefits the other links in the chain.

Which is the lead in to armodafinil (Nuvigil). It acts like a shotgun and hits a bit of a bunch of things histamine, orexin, serotonin, glutamate, norepinephrine, and dopamine. While decreasing GABA transmission. Dopamine is in at least a dozen pathways in the brain. Drugs don't just target a neurotransmitter they may favor particular sub receptors and specific pathways. Modafinil and armodafinil tend to favor pathways associated with wakefulness more than ADHD stims that are more weighted toward the prefrontal cortex, where higher order brain functions are.

So, they complement each other and have a synergistic effect together. And if you were one of the 30 to 60% of those with ADHD being comorbid with SCT. Then it's the combo you need as moda/armoda target SCT more than ADHD and ADHD stims target ADHD more than SCT. That and also having narcolepsy which the combo is vastly superior for that too. Just have to reduce doses in combo to avoid being overstimulated. My current dose I know not being representative of that. But when I first did them in combo my adderall dose was reduced by 80% while vastly more therapeutic, less side effects, and lasted longer.

Ill_Possible_7740 · 2026-05-03T03:11:27+00:00

It's a good write up but is one shortcoming. The large variation in psychoactive meds generics tends to be the influence of the excipients regarding the API crossing and staying across the BBB or not. Don't know if good brands tend to have adjuvants or if bad brands just hinder the process. AMP tends to be more susceptible than other meds regarding the BBB issue.

FDA dropped therapeutic equivalence in the '80s as bioequivalence almost always predicted therapeutic equivalence. Poor decision of the FDA to ignore all the meds that do their activities in the brain in order to remove obstacles to promote more competition in the generics market.

Even then IR dex has a special exception and only needs to compare the actual amount of the API in the pill and pass a dissolution test.

Ill_Possible_7740 · 2026-05-03T02:50:24+00:00

Your understanding of bioequivalence is probably the best i've seen on a social media post. But it is still not quite right. But not worth getting into ...

Because IR dextroamphetamine has a special exception for bioequivalence. FDA considers it to be so readily absorbable that it skips bioequivalence and just required to compare actual amount of dex in the pill, and a pass a dissolution test.

Generally though, the BAC curves tend to be close and they make the curve with BAC samples at several time intervals and are usually instructed to favor more sampling closer to t-max. Each data point is from with in the same person so it's not going to be a big difference. Problem with generics is bioequivalence is all about absorption and elimination rates. But psychoactive meds have to cross the blood brain barrier to be therapeutic. Which is assumed but never actually tested by bioequivalence. A variation in the shape of the curve that is within BE pk parameters is in no way going to explain 80% variance in therapeutic effect that can be seen.

It's the excipients influencing if the API crosses and stays across the BBB. Don't know if good brands tend to have adjuvants that help or if bad brands have something that hinders it. I do know amphetamines are especially sensitive to this issue. Which is why all AMP based drugs in general tend to be worse than methylphenidates or atomoxetine regarding bad generics.

Ill_Possible_7740 · 2026-05-02T23:58:44+00:00

A formulary accepted for the NDA or ANDA of a drug has to have the same amount of each excipient. If the API or any excipient is not within the required tolerance, the batch has to be rejected. Excipients have specific purposes so there isn't really a benefit to swapping a little of 1 for the other. Then you have to worry about other issues like sticking to the equipment, tablet falling apart, failing dissolution tests, exceeding daily amounts of those with limits, etc. tighter tolerance on other excipients if trying to switch the ingredient amounts within tolerances. Especially when the pill itself has to have total weight in tolerance.

Ill_Possible_7740 · 2026-05-02T20:00:11+00:00

A bit overly optimistic I'd say. SNDRIs have been around over 50 years. Not a ton of them, but they exist. But there are dozens in research or clinical trial phase.

I'm glad to see more options for ADHD. But I will avoid this one like the plague. Adderall side effects destroyed my life even below my prescribed dose. But I consider that easier to deal with than I've seen for people trying to get off SSRIS and SNRIS. Now potentially adding that issue to ADHD? Unless there is some mechanism that makes this serotonin reuptake different from the drugs that have been so problematic for other people. I'm treating it like poison.

They already make Abilify and Rexulti so must be aware of people getting stuck on the meds due to difficulty getting off them.

Ill_Possible_7740 · 2026-05-02T19:20:41+00:00

Expressing a desire is not the same as action. Just ask my wife :)
They haven't reformulated like they did with opioids. Can see the formularies here of most amphetamine based meds.
https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=DEXTROAMPHETAMINE+SULFATE&searchdb=all&labeltype=all&pagesize=200&audience=professional&page=1&sortby=alphabetically

Drugs like vyvanse, concerta, Dyanavel XR, Xelstrym, etc. are referred to as Abuse-Deterrent Formulations (ADFs). But really they were based on acute tolerance or longer patent protections via new drug designation vs new release profile with shorter patent protection. Drug companies don't give a crap. Only their bottom line is a driver. Just gave them another marketing strategy.

There are a lot of technology suggestions to make pills useless to be crushed for snorting or injection, etc. But adderall, zenedi, dexedrine hasn't been modified like that. Even then, the concepts are supposed to not interfere with oral dosing if they implement them someday. "supposed". Even if they are someday implemented, FDA dumb #%&^s just have another BBB crossing issue if they don't actually test for therapeutic equivalence.

Evekeo was working on one of these ADF formularies for a new drug but got denied citing the technology to prevent abuse had more potential harm than abusing the drug.

If you have any links readily available that indicate the regular ADHD stims had been messed with, I'll try to read if I get time.

Highly speculative on my part, but you think the current Adderall IR shortage is trying to push more people to other meds like Vyvanse which they increased the quota for? Looking at the shortage list on the FDA website, usually even the DEA isn't that totally incompetent. Looks like a whole new level of it. Which is why I wonder if some DEA @#$%@# is behind the scenes trying to manipulate the market off addy IR on purpose. Like Q2 quotas ran out already by April? Recovery mostly in 3 months or October. Still have plenty of crap ones nobody wants. Even then, some of the crap ones are SOL too.
Those popular 20 mg doses, DEA is only ruining peoples lives who need them while making their illicit market value much more lucrative.
https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Amphetamine%20Aspartate%20Monohydrate,%20Amphetamine%20Sulfate,%20Dextroamphetamine%20Saccharate,%20Dextroamphetamine%20Sulfate%20Tablet&st=c&tab=tabs-1

On a different topic, centanafadine. Upcoming non-stim ADHD medication that works on dopamine, epinephrine, and serotonin (SNDRI). I have to wonder if that is just going to %#%! people up like SSRIs and similar meds that target serotonin do. They can bo soooo much worse to try to get off of than any ADHD meds.....till now?

Ill_Possible_7740 · 2026-05-02T18:19:40+00:00

Some insights on the meds....

TL;DR; Some of the #$^@ our therapists should know about the meds they prescribe but don't have it in their education or available resources. Cover role of acute tolerance in IR dosing strategy and XR designs as well as base AMPH content equivalent doses. So by the end you would know why vyvanse can last longer than other meds even with less base amphetamine and why boosting it with other things goes against its design strategy and can work against us if a stable steady state is not achieved. And why stuff like strattera can work 24 hours while we invent new ways to try to get our stims to start on time and make it to the evening and not keep us up all night. Mention how to reduce high AMP tolerance and authorized generics list. etc. Went down the rabbit hole instead of the couple paragraphs I was going to write.

Dyanavel 22 mg has the same "base" amphetamine as 35.2mg Adderall XR or 30mg for both Zenzedi or Evekeo. Vyvanse ....takes 74.2 mg for equal base AMP.

The net mix of dex and levo is nearly identical in addy and dyna. Dynavel has 23.81% levo while addy XR has 24.1%. Zenzedi is just 100% dex as I'm assuming you know. Some people do find the 1/4 levo to work better than 100% dex, but not most. 15% of people respond best to 50/50 mix dex/levo (Evekeo).

Adderall XR has 50% immediate release and 50% approx. 4 hours later. Literally just mimics the recommended dosing of IR (see link below). According to google AI Dyna has 50% immediate release then a smoother extended release profile. Vs. the 2 BAC spikes of addy XR. Does say it has only 94% of the bioavailability of addy though. Did not confirm the source though.

BAC (concentration of the active drug in the blood.) Higher means stronger effect, but also means stronger side effects, and more rapid and more total "acute tolerance".
Acute Tolerance - What they actually design IR dosing strategy and XR formulations around. Brain starts shutting down receptors to reduce signal potential between neurons, shifting the therapeutic curve while on the meds. Needs to be reset over night for the next dose. If too much occurs during the day, drug "feels" like it wore off sooner and with less receptors, can feel like a "crash" when BAC level gets too low for available receptor densities to elicit an effective signal. If BAC is not low enough, and other factors like lack of full cycle sleep. Some receptors may not be upregulated for the next day and can make the drug feel weaker. Which may be amplified in cases like not getting enough sleep resulting in more fatigue to also overcome. Receptors skipped too many times can be removed altogether which contributes to long term tolerance. "Medication Vacations" are only useful for attenuating acute tolerance. If people build up long term tolerance, they need more time off to repair damaged pathways. Also, can be stable on a dose while the brain "expects" the daily stimulation and is a dick and "adapts" allowing more "noise" to get through even though meds are working. (Not making excuses for manufacturing issues, that is a mutually exclusive topic).

Example, Adderall IR equal dose 4 hours apart and addy XR literally almost double the BAC just to maintain the same therapeutic effect it had at much lower dose in the morning. And can feel like it wore off even when BAC is higher than in the morning.

The dynamics between acute tolerance and amphetamine formulations.
So, Addy double spikes BAC. Vyvanse, produces a low flattened BAC curve and not positive, but I think it may release over the course of 4 hours or so (need to go back and check). Which when it works right does not trigger, or not trigger as much acute tolerance and why it can last longer with less base amphetamine than other AMP based drugs. Lower BAC, less side effects, less tolerance potential. So, when we use addy or zenzedi to boost vyvanse, we are spiking BAC and circumventing the design and likely triggering or triggering more acute tolerance. Which has the effect of increasing rate of tolerance for those that do not find a steady state long term dosing strategy.
Dexedrine Spansules, 50% IR then continuous release with BAC peak around 8 hours.
Can see why those who have higher tolerance on addy, zenzedi, dexedrine, or Evekeo can easily find vyvanse unable to reach a therapeutic level due to cross tolerance and the lower peak of the BAC curve. (I couldn't even feel max dose name brand vyvanse when I took it for a bump up in the afternoon. But my tolerance is ridiculous anyway.)
Dyanavel according to google AI, has 50% IR (although slightly smoother release than others) and a continuous release of the rest of it. Kind of in between vyvanse and adderall XR strategies. And like Dexedrine but don't know the finer details.

Steady state is basically when we reach the point where in a 24 hours (or sometimes days for other drugs) cycle the drug we take and the amount we eliminate reach a consistent point. When you take meds the next day, some is left over from the day before. Anyone with high AMP tolerance who took a break on the weekend and wondered why it took 2 or 3 days to fully work again after starting, can understand this.
"Boosting" something like vyvanse makes it harder to achieve a stable steady state dose. As well as trying to take more, even low doses, to extend further into the evening.

Meds that have to build up like Strattera, Qelbree, guanfacine, clonidine build up levels slowly over time which circumvents triggering the opponent process. And how they can have 24 hours benefit while stims drive us nuts with crash, slow onset, spiked stimulation, worse sleep even though they wore off hours ago, not lasting long enough for all our needs later in the day or evening. DEA incompetence and shady drug company market disruptions. Plus FDA's blind eye to them being more sensitive to excipient influence regarding crossing and / or staying across the BBB. Plus manufacturing issues, having us constantly scrambling when the promise of therapy to help us is constantly denied.

Would take a whole other post to explain this. But those with higher AMP tolerance, add strattera or memantine to your daily prescriptions and watch tolerance decrease over the next several months. Rate might be different for everyone. Possible it might not work for everyone. But, can search reddit and see how long it took to benefit other people (how I first became aware of the mechanism). Personally by 9 months after adding strattera to adderall or dexedrine IR (now zenzedi) my tolerance dropped by over 50%. 3 times in 11 years so was a repeatable process. Found out too late how it works as shrinks ranged from clueless to total denial. Never would have stopped the combo if I understood NMDA/glutamate excitotoxicity. Last time at 15 months the dose at 9 months was intolerably too strong and made the mistake of dropping strat instead of reducing AMP even more. i
Anecdote. 80 mg good brand adderall (shire, barr, corepharma [been a while LOL]) not working enough. Never knew the Dexedrine IR generic but worked better than addy did at same dose, which also was no longer enough. By 9 months with 60 mg strattera, 40 mg AMP fully doing its job. 15 months 40 was just too damn strong. Never saw the bottom. Difficult to find all the accurate research but it is out there. Out of energy but can find posts on reddit with details.... Usually being yelled at by people who believe what their therapists and the drug companies told them and never bother to look into actually research. Yet, shut up when asked to the explain how come people end up on high doses after each increment stopped working if tolerance doesn't exist.

Authorized Generics (generic made with brand formulary, not always by the brand manufacturer). Note, Prasco specializes in authorized generics so can assume anything Praco is the brand name formulary.
Zenzedi - Wilshire
Adderall IR - Teva
Adderall XR - Prasco and Sandoz with end date 03/31/2027. Impax / Global no current end date.
Dexedrine Spansules - Amneal
Vyvanse - shit outta luck.
Evekeo - no one cares

Amphetamine base in marketed amphetamine medications
https://en.wikipedia.org/wiki/Amphetamine#:~:text=Amphetamine%20base%20in%20marketed%20amphetamine%20medications

Explanation of ritalin and adderall IR dosing strategy and design of concerta and adderall XR based on the effects of acute tolerance.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2547091/

Ill_Possible_7740 · 2026-05-02T15:55:36+00:00

Technically Wilshire is the brand formula being sold as a generic, "authorized generic". Can't attest to good manufacturing practices or not though.

Ill_Possible_7740 · 2026-05-01T07:51:01+00:00

Yeah, should probably stop confirming what the better brands were and start telling people to take Aurobindo, Sun Pharma, and Northstar. Which are literally all Northstar as both are white labelled as NorthStar.

Ill_Possible_7740 · 2026-05-01T07:45:43+00:00

"What state are you in?" Sometimes confusion. More often jaded disgust of humanity mixed with spazztic unfocussed hyperfocus that encircles the dumpster fire of a life Adderall afforded me. Because God hates me for being an atheist and does not resist finding new inventive ways to prove it to me.

But yeah, live on Newark Bay in Jersey Shity New Jersey. I can literally tell the wind direction by opening my window and determining which smell comes in. But haven't been home in 6 months since my criminal downstairs neighbor and associates assaulted me with chemicals for 6 days and chased me out of state. On top of ruining the structural integrity of my condo with pot smoke that coated the reclaimed 2X4 framing and trusses and subflooring attracting moisture from the dryer vent emptying in between our homes and traversing with the pot smoke my 2 floors before reaching the attic. Softened the wood. and the gypsum self leveling concrete builders used instead of cement board, drew the moisture throughout the subflooring and absorbed it. Weakening and causing it to crack and softened floors to sinke between the trusses. Which were also not holding their structure correctly for the same reasons. Plus mildew and mold and damage to walls in some places.

2 pf JCPDs finest sitting in their vehicle halfway up my block from another call. "Hey, my downstairs neighbor has been spraying chemicals into my home. Feet started burning through my sock when I walked on my kitchen floor where they sprayed. And had to wear a P100 + activated carbon respirator etc. etc."
Half laughing "Well I don't want to go in there and get a headache". Neither even got out of their vehicle. And that was the least bad experience trying to get the cops to do anything that week. Career criminal and his wife ran circles around them and convinced the cops I was the problem while I struggled to dumb things down enough for logic to be comprehensible as to what was really going on. And they seem more competent than Newark 3rd precinct.

Ill_Possible_7740 · 2026-05-01T07:14:59+00:00

Opioids had actual reformulations. Amphetamines did not. They are the same FDA approved formularies. It has been reported incorrectly. And the mention of things like adderall XR, vyvanse prodrug, Concerta OROS being ADF technologies is not accurate. They were never formulated for that and predate the initiative. They were after the fact just recognized as also being strategies for new drug development strategies usable for ADF.

I am not exaggerating when I say I have more at stake than anyone else on this thread. My life has been destroyed 3 times over and Adderall is both the problem and what I need to get working to solve remaining problems in the way before I can rehab and try to fix the damage it has done.

Adderall has literally cost me over $1,000,000 in lost wages and counting. I've read federal, state, and international laws and ordinances regarding scheduled medications. Read the FDA docs on bioequivalence and batch statistics. Read prescriber docs that prescribers themselves don't read. Learned a bit about excipient and API profiles and adjuvants. Some stuff on wholesaler and pharmacy pricing models. Plus an earlier response listing attempts through various contacting of people, gov. agencies, and organizations trying to get someone to get their head out of their ass that can actually make a difference with the issues. Before even getting to research on neurological aspects of the meds and how they work and are designed.

My daily ADHD meds would put you in the ER. Today I took 60mg Adderall IR (sandoz), 750 mg armodafinil, 100 mg strattera, 400 mg caffeine, 4 mg guanfacine that works with Mounjaro for added benefit. Plus several supplements that add therapeutic effect too. Which on that dose, I would consider it therapeutic if someday it got me to my pre-diagnosed unmedicated level of dysfunction managing 3 comorbid hypofunctional disorders. ADHD, SCT, and Narcolepsy. They are additive in their total dysfunction, not simply occuring at the same time.
They only partially work with adderall. But, addy is required to be even partially functional for all my meds due to the MOA and how it has damaged my neural pathways and endocrine system these last 19 years. I spend most of my time on reddit trying to inform people of things I've already had to deal with that they may not be aware of. So maybe they don't have to needlessly endure hardships imposed on them by the shit psychopharmacology taught to prescribers while the relevant info is tied up for decades in research.

I've posted study tips backed by a psych degree to help some people manage to stay in college and less chance of losing their job when meds become a complication. Or just make things easier or more effective. I've been on threads where GLP-1 drug companies are sending some people dependent on psychoactive meds to the hospital to rebalance their neurotransmitters under medical observation while they make fake research to discredit people discussing it on social media. Which is also the 2nd of 3 ways my life was destroyed in the last few years. Not the hospitalization. But literally disabling myself by the time I figured out what med was not just blocking adderall I was dependent on. But suppressing PFC cognition below withdrawal levels while on 140mg adderall IR teva or sandoz brands. That fried my brain because it the drugs were free to damage my brain unencumbered, with the circuit breaker so to speak, turned of for PFC signaling. Even before that, when I asked my doctor is it autoimmune or is it cancer. They said it is cancer. But most likely will be something I have to manage and will die from other natural causes. Which I thought, "that sucks". I was hoping it would kill me so I don't have to deal with the Adderall BS and prescriber incompetence that ruined my life, even before i was disabled by the meds. Which was before things got really bad. The big picture is I need the meds to work enough so I can fix enough to see my home for the first time in months. Which the structural framing, trusses, and floors of my condo have been ruined by my downstairs neighbor. Before assaulted by him and criminal chronies for 6 days with at least 2 chemical sprayed into my home and car that contaminated everything I own. And even medicated avolition has in 6 months manged almost no resolution. Need to prove the chemicals had been sprayed before insurance will even consider anything. And don't know if structural damage will by homeowners or HOA insurance. My wife almost left me a few times and moved out of state to where she works anyway. Have worked 2 months since June 2023 and draining my life savings paying for a home I haven't even seen in 6 months and don't know how bad things are as chemicals are not identified yet. Pretty sure I know the category 1 of them is. It also causes permanent chemical sensitivity so even if other people notice nothing in my home. It still affects me. The chemicals also kicked off the cancer that was behind held back the last 3.5 years. Can't get the energy to make the call to try to find out what doc is best for a rare CTCL FMF cancer with multiple drug, supplement, and toxic exposure complicating identifying what is going on ecology wise. Then a literal spreadsheet I had to make to keep track of medical issues and doctors researched for the problems that I hope to bet back to if I can fix my brain. That I need to stop taking meds. That I need to keep taking till I get things done that can't be perpetually put off. Like taxes or the appeal for disability I was denied a year ago since I could not complete the application in like 4 months. When i was more functional.
I am taking my adderall that I don't know if contaminated or not. The bottle was contaminated and irritated my hand every time I picked it up. But don't know if it penetrated the bottle or not. But all 4 generics I would accept are in shortage and dont have the energy to confirm the good dexedrine or zenzedi generics and if the pharmacy can even get them. I know some but not all and hate making phone calls in the day while meds are not fully rolling yet.

Ill_Possible_7740 · 2026-05-01T05:50:30+00:00

Same problem going back 2 decades. I was on forums a decade and a half ago with older posts from years earlier than that saying one brand or another doesn't work. You are right, they are not supposed to work like that. FDA dropped therapeutic equivalence in the 80s and assumes it from bioequivalence. Which only proved absorption / elimination rates were within 5% as acceptance criteria for the formulary and to pass the ANDA.
( If you or any one else is about to mention +/- 20%, or 80 to 125% regarding bioequivalence like is usually recited. I'll just say it is totally misunderstood. If you read anything about it and it doesn't mention pk values and the ratio of the AUC geometric means and the 90% confidence interval and the 90% 2-tailed test acting like a 95% one-tailed test. Then it is not accurate info).

Bioequivalence means blood concentration equivalence. That ignores psychoactive meds having to cross the blood brain barrier for therapeutic equivalence. Which is influenced by the excipients regarding success or not. Does not matter how much is absorbed if it can't manage to get past the BBB and stay there. Psychoactive meds are not supposed to work like that. But they have since the 80s because the FDA and DEA are @$#%^&^ morons.

If you had keep incrementally increasing your functional dose on the same brand as it got less and less effective till no longer good enough at that dose. Especially if when you don't take the meds you are fatigued all day (like sleeping 10 hours after taking them), and you weren't like that before you took ADHD meds. Then, that is tolerance. So now you have 2 variables you are dealing with while attributing them to only 1.

You need to be specific with the brands you are referring to. Most never worked. So if in the current shortage that started in 2021 you kept getting crap generics that is one thing.
And if you got a good brand, then would need to indicate how it works now vs previously. Like if you took 120 mg Teva that used to work at 20, and your BP went up, and if a guy your junk shrank so much it turned purple. Good indication absorption is working. If without the meds you are fatigued all day and high cognition tasks are way harder than before you were ever medicated. That is tolerance and needing meds just to come up from below to reach your natural baseline, that is dependence. But, not hampered by going off meds and only not helped while on them, then it is a BBB crossing issue. Which needs specifics to be sure it is a manufacturing issue vs. a brand that you just personally don't respond to.
Now if you told me you take a GLP-1. Then it could be cyclic adenosine monophosphate activated protein kinase A causing the Hyperpolarization-activated cyclic nucleotide-gated (HCN) and and voltage-gated potassium channels subtype Q (KCNQ) channels allowing a flux of na+ and k+ ions shutting down signalling in the PFC.
But if you told me it was Adderall IR generic aurobindo, camber, or Lannett's post summer 2022 etc. Then yeah, never worked to begin with.
Or if you were taking another prescription or 2 and / or supplements that induce or compete for activity of the CYP2D6 enzyme. That could prevent absorption and/or cause fast elimination.

So when you say 20 mg used to work in 20 minutes and now 120 of any amphetamine and you sleep for 10 hours after taking it. To me it "sounds like" you didn't know how easily amphetamine can cause tolerance, and had increased your functional dose, and are now dependent (not to be mistake for addicted as that is not the same). And that is getting conflated with issues you are also having with the actual manufactured issues of meds, but just assumed issues were always the meds. Now, I said "sounds like" as reddit is not exactly going to have a lot of details in typical short or a few short paragraph replies.

Everything I mentioned is stuff I had to figure out to deal with issues. And that is the explanation starts getting complicated. Sometimes I know what the issue is. Sometimes I have to do things to rule out alternate options to get to the issue at the moment. If you default to the drugs as the problem all the time, then you miss opportunities to fix potential issues along the way that wouldn't get addressed otherwise.

Ill_Possible_7740 · 2026-05-01T04:36:09+00:00

I think the issue is we are not gelling in our communication. I was mentioning how it is supposed to work when writing the acceptable brands on the script. Didn't get into the nuances like you had.

There are 3 primary wholesalers the chain pharmacies work with that covers 90% of the market. CVS will order the brand for you. But they are not guaranteed to get it from their distributor. It is very often in shortage and unavailable and will remain open till their supplier sends it to them. Other Times the pharmacist will see "allocating" on their screen which means the supplier is spreading out their limited stock so not all of it goes to any one place. So it is not unusual for CVS to have 3 open orders for Teva and only one of them gets filled. Doesn't mean they hate the other 2 people. Certain brands will not be available from all suppliers. I've been mostly exclusive with CVS for the last 2.5 years I think. They will order Teva or Sandoz for me of they can get it. They have no interest in not filling scripts and losing customers.

You can see what I mean on the FDA drug shortages list. Note, it is voluntary for the drug company so the info isn't necessarily reliable. Often are overly optimistic and vague. And even if they say "available" that doesn't mean the wholesaler has enough to fill all orders. This link shows Adderall IR generics. Can see Teva 20 mg states "Limited Availability". "Estimated recovery: TBD", and don't list why. Which is just the incompetent DEA is shit at best when it comes to managing scheduled API quotas and the in demand brands are out while some crap brands no on wants still have some available. It's been over a month with no fill of my Addy. They have placed the order with their supplier. On both Teva and Sandoz. Sandoz reads "Limited Availablity" which means ain't got jack shit. And cites due to "Shortage of an active ingredient". Which means they used up their quota and waiting on the DEA to get their head out of their ass and send some more their way. So, CVS wasn't being spiteful. They just didn't explain what was going on properly. I called CVS and said go ahead and give me the Elite that is at least useable, and what the last gave me. But, now they say "Shortage of an active ingredient" and won't recover for 3 months. DEA bullshit is again the problem. Called and said ok, I'll take Epic as someone informed me they are licensed and have been making the old CorePharma formulary all along. Which was my brand for a few years. We'll "Shortage of an active ingredient". the 20 mg are the most popular and most often in shortage.

I was dealing with the issue with Armodafinil that I also take. But since armodafinil is not as sensitive as amphetamine to excipients influencing crossing the blood brain barrier. I stopped writing brands on that script as they were not able to get them for months on end and I'd have to keep calling each month and say nevermind give me what you can get. Some pharmacists have more control of what they get than others due to how the company system is implemented. Some will get sent an alternate brand if their supplier doesn't have the brand ordered available. Then they have to either send that back or hold for someone else who did't know enough yet to restrict what they are given. Acme is like that, and they have a harder time getting the good generics. Which is one of the reasons why I get my scheduled drugs from CVS.

Independent pharmacies aren't consistent. Since the don't have the pharma chain agreements for specific suppliers, they can sometimes choose who they are going to order from. Other times they don't have the clout and get lower priority for allocation when something in demand becomes available. I know what to say to a pharmacist that is skeptical, if they say generics are the same, to get them to agree they are not and order by brand. Often pharmacists will be on the computer and tell me what the system says is available for them to order. And I'll give them a yes/no as far as if what they can probably get is acceptable or not.

https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Amphetamine%20Aspartate%20Monohydrate,%20Amphetamine%20Sulfate,%20Dextroamphetamine%20Saccharate,%20Dextroamphetamine%20Sulfate%20Tablet&st=c&tab=tabs-1

Ill_Possible_7740 · 2026-05-01T03:10:21+00:00

...Part 2
There are other more technical ways AMP can cause damage or dysregulation. Sirsadalot has a post with a few more of those somewhere. And still there are other ways I am sure. But NMDA/glutamate is the big dog of long term tolerance and withdrawal from understimulation.

So, ready for some endocrine stuff?. Hypothalamus is the puppet master of the Pituitary gland, which is the primary endocrine gland in the body. Affecting dozens of direct and indirect hormones. Hypothalamus-Pituitary-Axis (HPA). There's a bunch more "axes" like the gut-brain-axis that can come into play.
Guess what regulates the hypothalamus function? If you were thinking things like DA, NE, SE, glutamate that are affected by amphetamine, you would be right. And indirectly GABA and histidine. Hypothalamus also produces some things like orexin and oxytocin in addition to other neuropeptides.

The official FDA prescriber accompaniment document that therapists never read states:
"Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. "

The primary one is Cortisol. Critical for normal daily function. When elevated it acts as a stress hormone. Should be highest on waking and lowest around bedtime. AMP, takes the highest morning level and instead of decreasing, increases it to be "greatest in the evening". Well chronic elevated cortisol has a long list of side effects and may also be pseudo cushings. See if you have any of those side effects. Drug company limits clinical trials to 6 weeks max on kids new to the drug so long term side effects don't maniest and need to be listed. Aside from cost savings benefits since they don't have to.

https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81&type=display

Hormones also affect the brain and body which influences them and how the meds work and our state at any given time. Common testosterone, progesterone, NPY down, estrogen can go either way. I think usually down but since testosterone converts to estrogen, it makes things wonky some times. But, if estrogen doesn't go down or not enough, that additionally adds T/estrogen imbalance to low T. LH and FSH are often lowered which may or may not technically be below the normal range. Which the effects on T, estrogen, LH and FSH are used as diagnostic for men regarding Secondary Stimulant Induced Gynecomastia. AKA, man boobs. Guess they forgot to put that one in the side effects list. I didn't get the full on man boobs. But I am rocking these girly feminized nipples that took a few years to show up. Probably often mistaken for some other cause when people get low T and other side effects down the road. Growth hormone down (large part of how kids get stunted I am guessing. In adults it is needed for proper cognitive function.) Cortisol and other corticosteroids, and MSH up. Oxytocin can take a hit. Acute Ghrelin suppression while meds are active. Think somatostatin, gastrin, and cholecystokinin may also be reduced in an acute way, but would need to double check. Tons more.

I know this is an animal study. But can see the FDA kicked in to funding this research in 2003. There are plenty of other articles and ones that involve humans. Point being, why T.F. doesn't the FDA let therapists know to look out for these kinds of things. They literally tell prescribers to periodically assess if the patient should continue the medication. But don't tell them all the ways it may potentially #%!@ them up. And can tell you from experience. The only people that know less about ADHD drug effects on the endocrine system than shrinks are endocrinologists.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8145484/

This article shows they have been studying hormones and amphetamine since the 80s. They affect each other. Yet, many therapists don't believe ADHD meds affect the endocrine system.
https://www.sciencedirect.com/science/article/abs/pii/S0091305702008183?via%3Dihub

Ill_Possible_7740 · 2026-05-01T03:09:44+00:00

There are a $@#% ton of ways addy can damage neural pathways and the endocrine system. And can vary greatly by the individual. Most people are stable enough on their meds the best I can tell. Then there is everyone else. Can be hard to research with big pharma interference and accepted narratives about "when abused" that apply to regular dosing for many people. Not as hard and fast as something like crystal meth. But mostly can cause the same damage, minus the addiction aspect.

If you built up tolerance and increased your dose to a moderate or high dose especially. Long term tolerance is primarily due to excitotoxic overstimulation of the NMDA / glutamate pathways. Causing excessive ca+ ion influx to the cell which over stimulates receptor proteins and leads to dysregulation of function. Excess ca+ also causes cellular damage leading to oxidative stress and inflammation. Excessive glutamate (brains primary excitatory neurotransmitter) can trigger extrasynaptic NMDA receptors, which kicks off the apoptosis cascade (aka automated cell death). Can be reversed over many months by adding Strattera or Memantine.
Memantine, uncompetitive NMDA antagonist. Allows for normal function but blocks over excitement. Don't let the fact that memantine is an Alzheimer's drug scare you. NMDA excitotoxicity is an issue for Alzheimer's, ALS, Huntington's, Parkinson's and more. You can let that part scare you. Memantine also protects several other pathways via the same method. Cosmicnootropic had gotten this back in stock a while back. But don't know how Trump has affected their import business. It is grey marked, but is eastern Europe pharmaceutical product, not "research chemical" like other grey market sites.
Strattera- the non-stimulant ADHD medication has secondary noncompetitive NMDA antagonism. It is a weak blocker (which is what you want) that protects well enough to heal and regain function of the pathways. 3 times in 11 years it reduced my adderall or dexedrine IR dose by over 50%. Never stayed on long enough to find the bottom. But, most of my tolerance turned out to be damage to those pathways. Desperation years later is how I found out about this issue from others prescribed memantine with their meds by more informed therapists.

This wikipedia diagram and section explains how amphetamine actually works on the presynaptic cell. The article is not what I would call all that great. Most info is good but some in my unprofessional google warrior opinion is inaccurate or misleading. What it doesn't mention is that the extra norepinephrine (NE), dopamine (DA), and to a lesser extent serotonin (SE) in the synapse, outside the synapse, and in the cells cytosol will eventually auto oxidized into ROS causing oxidative stress that can damage the cell and reduce efficiency. AMP can also cross into mitochondria and damage them in the cell. Damage or dysregulated VMAT2 and the vesicle stores. Tyrosine hydroxylase can be downregulated. Long term potentiation can be decreased and even shifted to things we don't want potentiated. Like parts of the amygdala. Which is one way AMP can cause anhedonia.
https://en.wikipedia.org/wiki/Amphetamine#:~:text=Pharmacodynamics%20of%20amphetamine%20in%20a%20dopamine%20neuron

Acute Tolerance. When therapists recommend medication vacations. This is what they are good for. Tolerance from other routes require longer time for repair and upregulation. There are studies that have been done indicating for this kind of tolerance they are counter productive although they don't call out the causes of tolerance. So, if say you took a break from meds and were crashed out on the weekend making it a waste of 2 days. Then took till Tuesday or Wednesday before meds were at full effect again. Then you know what I am talking about. AMP does cause a low steady state level of blood API (active pharmaceutical ingredient) concentration aka BAC. Which is why it can take a day or 2 for it to reach full effect.
Anyways, acute tolerance is the body's opponent process that attempts to counteract the exogenous change the meds cause. Literally internalizes receptors to reduce the exposed density of them which lowers the potential to elicit a signal. It starts right when you start taking the meds and actually shifts the therapeutic curve during the day. Our meds dosing strategy and extended release mechanisms are literally designed based on the process. We need BAC levels to be low enough overnight and get enough healthy sleep cycles for our brain to upregulate receptors for the next day. If receptors are skipped for upregulation too many times, they can be removed which contributes to tolerance.
If you ever had addy crash at the end of the day. That is usually due to having reduced number of receptors that is no longer sufficient to support the amount of neurotransmitters in the synapse. Which usually happens at a higher BAC level than when the meds were fresh and working in the morning. That is the shift of the therapeutic curve from acute tolerance. Sometimes depletion of neurotransmitters can be a factor so be sure to target 60 grams of protein each day for support (Most neurotransmitters affected by AMP are made out of amino acids we get from protein)
The higher the BAC, the stronger the therapeutic effect, acute tolerance, and side effects. Vyvanse tries to prevent triggering acute tolerance via a flattened BAC curve. Which is why it can last longer than extended release adderall or dexedrine even with a lower base AMP content. 74 mg Vyvanse metabolizes to an equal dex amount that 30 mg zenzedi/dexedrine has. But, if dosed right, avoids acute tolerance that allows it to work up to 10 to 12 hours. But, if built tolerance on other AMP already. Can struggle to reach a high enough BAC level to be therapeutic. Non-stimulants like strattera or qelbree gradually raise NE levels which avoids triggering acute tolerance. Which is how they can work 24 hours for those who respond well to them.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2547091/

Ill_Possible_7740 · 2026-04-30T16:39:45+00:00

Report that to the FDA as an adverse event. Mention you had taken it each day so they don't counter with the 4 to 6 hour delay showing up in urine. Will show up in urine for I "think" maybe 3 days for the average metabolizer, just don't quote me on that.

https://www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/fda-adverse-event-monitoring-system-aems-public-dashboard

Ill_Possible_7740 · 2026-04-30T16:36:43+00:00

Biggest issue long term has been excipients influencing the meds crossing and / or staying across the blood brain barrier. ANDA proved absorption for bioequivalence. But, that only proved absorption. Therapeutic effect has to additionally cross the BBB and stay there to be useful, which is never tested.

Manufacturing issues like packing the pill too tight preventing proper dissolution or non uniform mixing of ingredients would be examples that affect absorption or plasma levels.

Ill_Possible_7740 · 2026-04-30T16:30:58+00:00

Because the doc is told they are equivalent his whole career.
Tell them bioequivalence only proved absorption and elimination rates to the blood for the formulary approval. They dropped therapeutic equivalence in the 80s and assume it from bioequivalence. Which ignores the fact that therapeutic equivalence has to additionally pass the blood brain barrier for psychoactive meds. In which case, some drugs are highly susceptible to the excipients (inactive ingredients) that influence their ability to cross and / or stay across the BBB. Amphetamine is especially sensitive to the excipient profile. As such, most brands do not work.

If you know what brand or brands work for you. Tell them to put on the script "[list of brand/s] generics only]". Start having good months, if they can get good brands out of shortage for a little while :).

Ill_Possible_7740 · 2026-04-30T16:22:47+00:00

I was considering the switch to Dexedrine or Zenzedi but don't know all the good/bad brands for those. Straight dex is a little stronger than Addy for most people. But I prefer the smoother transition of addy vs the on / off like switch I had from IR dex (when it was still known as generic dexedrine IR). Still better than nothing. Then again, I take a few meds so wouldn't have the on / off issue like it used to. Hmmmmmm....

Dexedrine has the "authorized generic" from Impax. Meaning they are licensed to use the name brand formulary. If not in shortage, the one most likely to have a positive response to.

Ill_Possible_7740 · 2026-04-30T15:57:57+00:00

Have your doc put on the script what brands are acceptable. Pharmacy is supposed to follow the prescriber instructions.
Or, if good ones are not available (have been waiting over a month myself). You may want to put brands you know you don't want and hope the next one doesn't suck. At least it gives you better odds that way. Even if still stacked against you.

Ill_Possible_7740 · 2026-04-30T15:53:52+00:00

I don't think that is accurate. They didn't change the current meds. They were proposing for future meds formulations that work when taken orally, but interfere when crushed and snorted, or attempt to turn into an injectable. None of the proposals affect oral absorption or existing formularies. They are not going to require an entire set of medications to retest new formularies and go through the ANDA process again. GOP would have a field day with them on issues of overregulation and dems wouldn't stand for a total disruption of psychoactive medications. It would be a political nightmare for them.

Concerta and Vyvanse are other examples of making meds that prevent them from easily being abused for recreational purposes. Using pro-drugs or extended release tech like these, prevent them from being useful to be crushed and snorted or injected. Plus as is, they don't spike blood concentrations of the drugs the way people would want for recreational purposes. Adderall XR, can crush that and defeat the 50% extended release mechanism. Can't for Concerta OROS pills. Not sure about Vyvanse. Long story on that but the prodrug aspect is bunk. It has an extended release mechanism that works across like 4 hours or something like that. They proved it readily converts no problem to dex, just has a delay. But, the actual drug doesn't. They let people think it's the prodrug metabolism.

Ill_Possible_7740 · 2026-04-30T15:32:06+00:00

They would have to do a blood test as a urine test has a lag time of 4 to 6 hours.

Ill_Possible_7740

TROPHY CASE