How many mg did yall take?
Positive effects?
Negative effects?
Im concerned that it does nothing
Hi,
usually the dosage is from 1 to 4 mg / day.
Starting with 1 mg and slowly dosing up.
Important: a dosing of guanfacine should be closely monitored by a doctor who keeps an eye on your blood pressure.
Guanfacine should also not be stopped suddenly if you are taking a higher dose, as this can lead to a hypertensive crisis.
Please discuss all of this with your doctor.
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Hey I went to 3 mg but now I’m at 1 mg again and getting off it 
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There are quite a significant number of people who take it either alone or more often at night to reduce stimulant insomnia and add therapeutic benefit the next day. So, there is quite a lot of examples of benefit. Plus to be approved by the U.S. FDA for ADHD it had to prove effective in clinical trials so there is also the medical backing in that regard. I’m guessing you’ve tried it by now. But may or may not still be titrating, or steady on a dose, or quit? It is worth a shot as if it does help, that avoids pitfalls and side effects of the other options.
I am probably not the best example as when I started it, it was after I had damaged my brain with high dose Adderall to the point of being disabled and unable to work anymore. I had been off meds for 2.5 months then tried guan for 3 weeks. For me it sucked. All side effects, no benefit. Mind you at that time 40 to 60 mg Adderall IR (good brand like Teva) + 400 mg modafinil + 300 armodafinil + 100 mg strattera + 200 mg caffeine was my minimum to feel comfortable driving. But still was long ways from truly working. With my extreme tolerance, damaged pathways and endocrine system (people aren’t informed just how bad that can get for those sensitive to the side effects of amphetamine), not much chance it would have been therapeutic. So, all side effects, no therapy. Also note I have SCT and narcolepsy which both make me extra sensitive to anything with even a slight sedative effect. Even before the whole destroyed my brain and endocrine thing.
Also Note: Guanfacine XR (Intuniv) approved for ADHD, is only 60% as bioavailable as the IR (forgot the branding) blood pressure version. With the long half life, either could be taken. I was prescribed IR. IR will have a stronger peak effect, as well as stronger as it provides more to the system. IR may have a stronger sleep benefit taken before bed, but more likely to wake you up early due to the 5 hour or so peak effect. But, all depends on how you respond. Need more sleep induction and don’t get woken up early, IR. Wan’t a smoother steady dosing or do get woken up taking it at night. XR. Or, shift time of day when taken. I take mine most often in the morning. But sometimes take it middle of night to help fall back to sleep and the peak will be after I get up and take my other meds anyway.
Side effects (everyone responds their own way. Was off other meds except I think very low dose modafinil that can help repair some Adderall damage and low dose strattera to counter persisting Adderall side effects.):
–More sleepy, less energy
–Stomach was a little off, but not to the point of nausea
–minor heart palpitations (common as it literally is a repurposed blood pressure medication. It increases one of the timing to reset mechanisms for some part of the heart. Which the body may increase heart rate to make up for it. Which may have contributions from Cialis taken for Adderall side effects. Which is also a repurposed heart medication, for boners and BPH symptoms 
–Could decrease sleep. As I think it would peak in about 5 hours, which woke me up early and not able to fall back to sleep. Ironically, the SCT makes me extra sensitive to stimulation at night. Changing the dose timing of it was how I managed that.
–My use for it is literally the only time at that point someone had used it with the same purpose I did. As such, I had experimented. Had gone up to 6mg. Did have slightly more benefit at each increment. And had to deal with the temporary sedation each time. But, didn’t feel it gave enough benefit at each increment to to justify potentially causing more tolerance. And higher chance of issues if I took something that is contraindicated with it by accident. This was all done with guidance from a neuropsychiatrist.
–Other drugs or supplements that affect the CYP3A4 enzyme can potentially affect guanfacine which is metabolized by it. Body I am guessing can handle another drug or 2 that reacts with it in some way. Just in case, I’m mentioning it.
As I took 5 including guan that are metabolized by 3A4 and a 6th medication that is a potent inducer (increased activity) of it. As is 1 of the other 5 (potent inducer). And some supplements that affect it. When I started the 2nd potent inducer, that is when my simvastatin cholesterol meds stopped working and had to find a different statin after my cholesterol doubled from it.
If you want to know how guan works for ADHD:
Simple version: closes HCN and KCNQ channels in the prefrontal cortex which increases signalling efficiency. Easier signalling, more signalling, stimulates the functions of the PFC. Like executive function, concentration, memory, etc. This is one of norepinephrines (NE) jobs. Guanfacine is stronger at it. The receptors activated act as autoreceptors (feedback loop) and shut down NE release. Checks and balances naturally. Guanfacine doesn’t get shut down by the autoreceptor, hence its ability to more strongly influence the PFC signalling efficiency.
If you’re a masochist and want to read more poorly written stuff… detailed version (ish) by a non professional Google based knowledge: guanfacine works by literally doing one of the functions of norepinephrine, just stronger than it. An alpha2a-adrenergic agonist. In the front of the brain, it prevents adenylyl cyclase from making cyclic adenosine monophosphate (cAMP) there. Normally cAMP activates protein kinase A (PKA) which has a phosphorylation fetish that results in the HCN and KCNQ channels being opened. When opened in the PFC, there result in na+ flowing into the cell and k+ ions out, makes signalling very hard. Blocks the constant signalling needed for higher order function like executive function, memory, and concentration. Acts like a brake, or throttle depending on how you think about the balancing function.
So guan causes the closing of the HCN and KCNQ channels in the PFC, which increases signalling efficiency, which is stimulating. alpha2a also works as an autoreceptor (feedback loop) and shuts down additional norepinephrine release from those cells. Does affect other brain areas that benefit things like anxiety and can modulate emotional responses. Calms activity in some places. Forget which place/s the sedative effect happens. Can find that easily on google. That is actually the high level basic explanation as the brain is much more complicated than people realize.
**This part below won’t relate to you but adds context to my experience. Can skip it.
Note, I was taking it for an experiment as I am one of the negative cognitive responders to GLP-1 based meds. (Big Pharma is trying to hide the fact that some people have the negative response while doing clinical trials for the positive responders as a second line med for drug drug resistant depression and anxiety).
Mounjaro alone shuts down signalling in my PFC (front of brain associated with higher order function) making all ADHD meds less than useless). Fried my brain with high dose Adderall unsuccessfully trying to overcome it before I figured out what big pharma was hiding. Had been off for 5 months before starting it again.
So, guanfacine sucked, mounjaro destroyed what Adderall accumulated side effects from 2007 to 2022 hadn’t quite finished off yet.
Guanfacine 1 mg + going back on mounjaro at the 2.5 mg pre therapeutic starter dose: within 12 hours no more guan side effects. Together they were actually the most therapeutic drug there could possibly be fore me. Less than a week, was able to leave home for first time with no Adderall (lower dose of other meds though). First break in anhedonia in over a decade and a half. But, it all got quirky as I increased my guan to 2 mg to see how it may differ from 1. Plus some other factors. Think optimally mounjaro may have been best even lower than the minimum starting dose. Which would need a compounding pharmacy to measure that. Also, a bunch of other factors I’m not going to get into. 2 years later, still on them. But have had a bunch of other factors affecting things that others are not likely to come across. Also, I actually do take Mounjaro for diabetes and it has had many other health benefits. Hence my stubbornness to find a way to make it work.
Currently take 4mg guanfacine IR and 5 mg Mounjaro, its first therapeutic dose after the 2.5 starter dose. Long story on that which includes experimentation that likely added some of the guan tolerance.
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Fuck bro. You know a shit ton, i have so many questions.
- Where did you acquire all that knowledge???
Im currently on 30 mg Elvanse and stopped taking the 3mg guanfacine. To sleep I take daridorexant. I didnt understand you regarding mounjaro? I dont know much about it but its not only a glp-1 agonist but also a GIP agonist. I didnt understand if mounjaro is bad for you or how it reduces the activity in the prefrontal cortex. Well I just understood that it reduces the activity there. And yeah obviously pharma doesnt talk about it, to make money. Retatrutide might be better but who am I compared to your intelligence hahah.
Im very very sensible to meds, i get strong side effects from freaking 18 mg concerta or 20 mg Medikinet. My hunger completely goes away with 30 mg Elvanse/Vyvanse.
Im really concerned about you saying that adderal fucked up your brain. How? I dont get it? Cuz of overdosing or cuz of adderall in general? Go deeper into that. Will talking elvanse also give me brain damage or what???
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[The simple answer is you probably won’t have to worry about issues like mine. Just need to pay attention and learn about what to look out for so you know if things are starting to cause long term side effects or not. GLP-1 based meds can be good or bad. More often good or neutral than bad. My meds are not doing all that well at the moment so a bit harder than my usual dysfunction to focus. ]
I did cover some very basic stuff in psych classes in college. But, vast majority I learned online reading research and putting pieces together. It was out of desperation that started me down the research path. Then finding actual answered to problems therapists didn’t even know about, which was the reason they failed me, made it addicting. Then the GLP-1 thing on top of it and finding a solution, albeit too late.
I took my Adderall / Dexedrine at or below my prescribe dose from 2007 to 2022. I only went over a handful of times for job interviews as the prescribed dose (60 mg) just wasn’t fully working at those times. Even then, neither was adding another 20 mg (80 mg total), but was better. Started at 30 mg which was more than enough to downregulate and damage neural pathways and my endocrine system. Most of the time I was taking between 40 and 60 mg. It was a steady increase in cognitive and endocrine side effects at any dose I was on. I did not expect to be able to make it to retirement.
It was going up to 140 mg trying to overcome Mounjaro that exponentially accelerated the damage and left me disabled. Mounjaro blocked signalling in the PFC. But did not block Adderall which damaged my brain with going from 40 mg that I had been taking at that point. Going 3.5 times that to 140 in the end before I couldn’t go on any more.
Most people as far as I know find a stable dose of ADHD meds. Lack of sleep was the biggest factor for me driving tolerance. But, you have that covered. For amphetamine, Vyvanse is the least likely to have long term issues. If you start having tolerance issues with Vyvanse or other amphetamine based medication, you can try adding Strattera or Memantine to prevent tolerance from NMDA/glutamate overstimulation resulting in damage to those pathways. Can take months to see the benefit of reduced amphetamine tolerance. If that didn’t help then those pathways may not be damaged by meds (assuming the case where you did have tolerance issues and had to increase meds because of it.)
If you have endocrine like those of high cortisol or pseudo cushing’s, that could be Vyvanse. (look up a few sources that list symptoms as never seen one that has all of them together)
Can also search on how amphetamine can affect the endocrine system and see if you have any of those.
Long term cognitive side effects can be things like not feeling sharp anymore even on meds. Anhedonia, low motivation, reduced focus. Avolition has hit me the hardest. I also had some GI issues where is slowed down stuff moving through.
If you just have side effects that are only seen when on it like blood pressure goes up. Then not a worry long term for issues like mine. But would want to attenuate the BP issue as that can have its own long term issues.
GLP-1 drugs can be positive, negative, or neutral for cognition. It can be totally different for people even with the same disorders and symptoms. For some people it might not cross the blood brain barrier and enter the brain. Which may explain the neutral responders. For others, it has both positive and negative effects on cognition at the same time. And the net result of the dominant effects for a person is what we see in the end.
GLP-1s can have huge benefits. I have been back on mounjaro for 2 years now, even after I ended up disabled cognitively trying to overcome the negative response I had by taking very high doses of Adderall.
Think of it this way. On one hand, they increase neurotransmitter release and make signalling more efficient. Which is stimulating.
But in the Pre Frontal Cortex (PFC) where higher order cognitive function is based. It can block the signal between cells. Which, the way it does it, is also what guanfacine attenuates to improve stimulation. Can think of the negative responders as having a reverse guanfacine effect.
For some it’s the best thing they ever tried. I’m unfortunately the polar opposite side of that. Mounjaro took GLP-1 and added GIP agonism. Which the way they did it actually increases cAMP better than GLP-1 alone. Which is why it is stronger than Ozempic that is GLP-1 only. Retatrutide ads glucagon receptor agonism to Mounjaro’s GLP-1 and GIP. Which like GLP-1 and GIP use cAMP to signal the cascades of functions. But the result is having some same and different aspects as Mounjaro and Ozempic. Van’t say for sure, but I would guess it may have the same cognitive pitfall of earlier GLP-1 based drugs too. But may get lucky and somehow elicit different net reactions to it.
People vary a lot in how sensitive they are to side effects of different medications. Adderall for me damages my brain at moderate doses. Haven’t tried low dose before as I started on medium dose due to incorrect equivalence guide that only works for starter doses.
“Im very very sensible to meds,” Think you mean “sensitive”. It depends on what side effects you are having on how to characterize them. There are side effects which can be neurological, endocrine, digestive, etc. Then there is tolerance.
The important thing is how you respond. And to recognize issues if/when they come up. My brain gets going too often and I probably wrote way to much in these replies, which can be confusing.
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I dont quite get, how and what did you damage in ur brain? I suppose the high adderall dose was the cause of it. Am I at risk with 30 mg Vyvanse and would going up in dose give me a higher risk? I want to understand if me taking vyvanse is still somewhat safe?? I suppose ur just a rare case due to overdosing, right?
I’ll try to give a simpler answer.
I can’t be sure how you would be affected long term. Chances are you would be fine even going up a dose.
People can vary a lot in their response. Most people are stable on a their dose. If you have increased it and it worked for a while. Then had to increase it. And done that more than once then you may need to work on managing your schedule and habits to stay stable on a dose. Getting enough quality sleep is critical. Sometimes the meds still work but your brain adapts and starts letting more distractions through again. In which case it is better to try non-medication therapies to manage first. But if you do keep building tolerance, you’ll want to get that managed and not keep the cycle going.
Your resulting dose of amphetamine from 30 mg Vyvanse (Elvanse) is about equal to 12 mg zenzedi or 14 mg Adderall. Plus, since it is Vyvanse, it spreads out the release and keeps the blood concentration much lower so less potential to be an issue long term than what I was taking.
Adderall had ruined my life between 30 and 60mg a day. It would have done so at lower dose too but was started at 30mg Adderall XR due to therapist not understanding cross tolerance correctly. Long before I had the dosage escalation issues caused by Mounjaro.
If tolerance becomes an issue, or if you start having endocrine issues. Like Low testosterone or estrogen dominance. Or trouble with high cortisol symptoms. Then you may need to move to another medication.
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Okay and I have other questions.
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How do you know that the meds destroyed your brain pathways etc.? Did you get more stupid or how?
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I had a phase without adhd meds a few months ago and I got into tulpamancy and then the voices became realer and realer and I also got bad voices that scared me a lot. I could/can differenciate the voices from a real human voice and the voices arent thaaaat real, though at night they do get pretty real. Now since im taking adhd meds again, they have been gone. This shows that im not schizophrenic since adhd meds alone wouldnt make them go away if i were schizo. I also got prescribed olanzapine but im not taking it since studies show that the shit eats up your prefrontal cortex, so yeah no thanks!
My question is: Are you able to find any correlation between the adhd making the voices go away??? -
My therapist and psychologist arent believing me and my therapist just said that its from hyperalertness. They dont believe anything I say and they even ghost me!!! Im having a hard time trying to change the clinic. Hopefuly I can, any advice?? I cant tell my parenst about the voices, they will freak out if so…
Best regards
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- Cognition declined and hadn’t felt sharp in years. Also caused things like anhedonia, lack of motivation, avolition, lack of energy, etc. Was a steady decline taking between 30 to 60 mg from 2007 to 2022. Then over the course of 10 months trying to get around what turned out to be Mounjaro blocking PFC signalling, I had increased to 140 mg that exponentially accelerated the damage. (again, not everyone has a negative cognitive response to GLP-1 based drugs). Leaving me disabled and unable to work. Then off for 4 months and an ultimatum to go back to work or lose my contract position. Then gave up trying to find a therapist for answers and self medicated based on research I found. And managed to make myself functional again on a vastly superior combo of meds. But with the high existing tolerance and damage done to pathways. It just picked up from where things left off and started escalating my dose for 2 more months which did more damage and again disabled, but worse off. Wouldn’t say I was stupid. Most stuff I posted I figured out during the ordeal or after. Memory is not as good and if things get to complex my brain shuts down. Takes more repetition to learn things that I can manage. Also, quite noticeable is it is hard for me to organize my thoughts and plan what I am going to write. I have a thought, I write it. It elicits another one. Often going back to stick a though in somewhere when it comes to me. Unplanned, unorganized. Just stream of consciousness. Doesn’t work well for complex tasks that require planning and steps to work through.
Avolition makes goal oriented tasks difficult to start and see through. Can’t maintain a regular sleep schedule. As a software engineer writing code and figuring out new things, it is all brain all day. I struggle to focus, lack alertness and working memory capacity, etc. Easily find myself off task without intending it. Lots of things end up unfinished. Like the 150 or so chrome tabs I have open across a bunch of chrome instances.
Meds, especially amphetamines, can also mess with the endocrine system. Which I was able to see on blood tests. Which just makes things harder and ads more symptoms to deal with. Hypothalamus sits on top of the pituitary gland and makes some hormones and directs the pituitary gland and dozens of immediate and downstream hormones. Which also influences the brain. Neurotransmitters affected by psychoactive meds modulate hypothalamus activity so it is easy to see the connection when thinking about it that way. Have to watch kids on meds for stunted growth. Well, they just ignore the other dozens of hormones affected by the hypothalamus. FDA prescriber doc does say amphetamine can raise corticosteroid levels and be highest in the evening. Well, supposed to be lowest in the evening and highest in the morning. Take meds in the morning and instead of cortisol (primary corticosteroid) going down, it can go up instead. If you looked at symptoms for chronic high cortisol levels and pseudo Cushing’s disease. You can see many more potential long term side effects. People stable on low dose would be less likely to have issues. 30 mg Adderall XR was way more than enough to damage both my brain and endocrine system.
- I had to look up tulpamancy. I’ve never had issues with voices or hallucinations fortunately. I can believe what you are saying though. Twice in my life on being woken up I observed myself talking to my father. The “me” consciousness and inner voice was like “wow, this is weird, wonder what I am going to say next”. Literally was not controlling or participating in the discussion, but instead was a 3rd person listening to myself have a conversation with my father. Literally had no idea what I was about to say.
The mind is a powerful thing. There are warnings about medications causing psychotic episodes. More likely to happen for children but can happen to adults. I do know that I suffered depression until I was 23 which my own brain caused the deep depression and changes to brain chemistry just by having negative thought patterns. Had experienced occasional dissociative episodes where I felt like I was a passenger in my own body. I was in control, but felt disconnected from the real world. Which when I looked into it years ago is not as uncommon with ADHD or depression as I was expecting it to be. I also fixed my life long depression the week I started college and stopped making excuses and negative thought patterns and actually excelled.
Tulpamancy though. Brain may still have not normalized fully since last taking meds which may affect how the practice goes. Have to consider that for it to work, you have to actually induce physical and regulatory changes in your brain. I am honestly guessing about factors related to Tulpamancy. Just pointing out some things to think about which may get across the complexity of everything involved.
Maybe think of it like tripping on acid. The “trip” will depend on your state of mind going into it. Not in the right state of mind, can result in a bad trip. Tulpamancy, having some pathways not up to par, no way of knowing how that might go and potentiate changes in the brain. Plus ADHD is a hypofunction disorder to begin with which has under performing pathways from the start. I am only guessing as I don’t actually know how it can relate for sure or not. But, it could be possible that underlying conditions could make it more challenging to work as desired. Remember, each function in the brain relies on many pathways all working together. And many various neurotransmitters, secondary messengers, nutrients available, kinases, gated channels on the membranes of cells and mitochondria. Hydroxylases, catalysts, electrolytes, RNA and DNA and mRNA expression, and a whole lot more beyond my comprehension. These pathways and factors are both stimulatory and inhibitory and both are happening at the same time. Might have been the wrong timing to try Tulpamancy. Or may not have had the guidance available you needed.
There are other ways people induce an altered state of mind and is a part of ritualistic activities. There are also certain cultures and religions that have a large focus on the power of the mind and body. Some practice being self aware and controlling their dreams. In Japan, they are know for martial arts. But there is a difference between a martial art like Karate and the way of the martial art like Karate-Do. When they end in “Do” it indicates it is an all encompassing lifestyle built on philosophical and spiritual practices. India often has gurus who have mastery of some discipline or whatever and guide people etc. Sometimes these things are referred to as a “discipline” for a reason. So, the power of the mind and body is well documented and out in the open. But western cultures, it is not so much practiced or even accepted. I don’t know your background so don’t know if you have a background with cultural spiritualism or disciplines etc. Or if Tulpamancy was your first experience with mind and body oriented things.
One thing that is kind of funny though. Took till 2024 to find a therapist with the right background ( both neurology and psychiatry and works with people stuck on high dose meds and no help from other therapists.) He needed additional education and understanding the science of the brain to be the only person I found who could work with me. But, he also provides spiritual guidance as part of his practice. He I assume has an Indian background. I never asked for sure but definitely from the same region otherwise. Now, I have been a born again atheist since first grade and have zero spirituality, nor believe in any way in anything supernatural. So, I don’t utilize that aspect of his practice. But, do still believe in the power of the mind. I had influenced my dreams a little here and there. I could always become aware and purposely wake myself up if having a nightmare. Till one day I woke up and was like, wow, that was so cool. Then realized I love horror movies and sci-fi and began to think of nightmares as free horror stories so didn’t bother to wake myself up. Then my nightmares switched to being in school and unable to remember where my locker is. And forgetting what classes I have and not able to find them. Basically undoing the part of my life that turned everything around for me and made me successful and excelling in life. Haven’t been having the nightmares much anymore. Just realizing now it is probably because I’ve been living it for so long.
With the ADHD meds, they may have strengthened certain pathways or connections that were able to attenuate or suppress the voices. Schizophrenia is just one of a number of disorders or states of mind that can cause a person to hear voices. I wouldn’t get too hung up on Schizophrenia.
Since Tulpamancy was a cognitive exercise you had to practice, and not triggered by a psychotic episode or delusion. And you remained aware of what was real and what wasn’t. And it resolved when going back on ADHD meds…
Question is, are you sure you still need to change the clinic? They can still treat ADHD even if they don't believe you about Tulpamancy and the issues you had with it. Since it seems to be resolved with the ADHD meds. I would expect the changes you caused in your brain will normalize over time. As long as you stick to the regular voice in your head and try to suppress the temptation to engage Tulpamancy. If it is something you still want to pursue. I'd recommend doing it with a guide who knows what they are doing. If any are available. I'd be weary though. Such as if these frequent medication shortages you found yourself out of meds. If you were practicing Tulpamancy while on meds. Then ran out. That would put you at a significant decrease of function that "may" cause a much deeper issue that could lead to a psychotic episode. (again, guessing)
I know all too well what it is like for doctors and therapists not to believe me. Only to find out the research already exists. Other times, other therapists are already doing the thing they don’t believe. The worst is when a therapist is contradicted by the FDA prescriber document that is for them and comes with the meds they prescribe. I would literally double this reply if I tried to tell you all of the times I was dismissed by doctors when all the information was readily available. The latest, literally figured out a treatment for lymphomas and leukemias that the medical community is not aware of. Which has been treating mine for 3 years now. Just found out 2 weeks or so ago. Same mechanism they use PDE inhibitors for and studies they are doing with forskolin…turns out GLP-1 based drugs actually do it far far better than any of those and it is their underlying method of action responsible for all the things it does that people are aware of.
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Caffeine and Stimulants?
I can’t stress this enough… It goes wrong so often because of the side effects.
Are you sure it was the Adderall that caused the problem, and not the combination with caffeine?
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Let me explain a little better. Adderall alone destroyed my life from 2007 to 2022 with cognitive and endocrine side effects. 30 mg XR was more than enough to do this but most of the time I was taking 40 to 60 mg. 3 times I had added Strattera which reduced my tolerance by more than half and never stayed on long enough to find the bottom dose achievable. Because medicine is ignorant about much of the decades old research. Strattera has a secondary effects as a noncompetitive NMDA antagonist. Amphetamine can cause excitotoxic overstimulation of NMDA which causes function dysregulation and oxidative stress that can leave cells damaged or even kill some off. It also causes excess glutamate release which triggers the extra synaptic NMDA receptors. Which start the apoptotic (automated cell death) cascade in those pathways that have them. Research has indicated this is the primary way amphetamine causes long term accumulated tolerance. Therapists with more insight prescribe memantine to prevent and even reduce tolerance. Which is a better way to go as it allows normal function but only blocks for overexcitement. Strattera can be confusing if pathways are already damaged as the dynamic changes as they heal and regain function. Since none of this is in standard curriculum or prescriber resources, therapists were unable to help me manage the damage they caused. With therapists talking points supplied by the drug companies during their NDAs which became their own self biased narrative as curriculum and resources.
Obviously this is not the most common scenario as most people are stable on a reasonable dose with manageable side effects. But for me, I accumulate tolerance on any drug. Strattera to start, then Ritalin / concerta. Before Adderall and back and forth with Dexedrine a couple times. Skipping details on shy I cause tolerance easily and will just say ADHD + SCT (CDS as of 2022, not in DSM but will be a huge media topic when it gets there, probably in a couple decades give or take) + narcolepsy.
July 2022 I started Mounjaro which blocks all psychoactive meds for me (except guanfacine, more on that in a moment). There are positive, negative, and neutral cognitive responders to GLP-1 based drugs. Being a negative responder, it shuts down signalling in my PFC. A typical person would describe it as brain fog. People dependent on psychoactive meds would call it devastating. While for positive responders in some cases it is the best drug they have taken for their mental health.
I was not sure which medication change was causing the problem and Mounjaro was the last one I suspected. Took a bit to rule out the others. Then, took a bit to prove Big Pharma was full of shit blaming delayed gastric emptying for everything. It’s a factor, but not what causes the primary issue for the negative responders.
Thinking Mounjaro was blocking my Adderall that I was highly dependent on, I kept increasing my dose trying to overcome it. Was desperate to keep my contact position as it had already greatly held back my career and the main reason I was not up to date on current teck stacks as a software engineer. Took 11 months just to get that contract and was hoping to ride it out till I retire. Figured Adderall would disable me before that, but Mounjaro exponentially sped things up and I was disabled cognitively in 2023 and unable to continue. Not knowing that it was damaging my brain at the higher and higher doses uninhibited till it was too late. Big pharma is actively trying to hide this process due to an FDA black box warning that would ensue if the FDA got their head out of their ass.
Before all this, I limited myself to 1 can of soda a day during the week and that was with my lunch. In general no caffeine after 5pm or it would keep me up way too long. (Due to SCT but longer explanation). But I did start titrating caffeine in 2023. Long explanation about how SCT affects me and related stuff I will skip. Caffeine is nothing compared to the potential side effects of amphetamines. In combo caffeine may cause cardio issues but that is different from Adderall killing off brain cells, causing oxidative stress and inflammation. Messing with long term potentiation. Downregulating and damaging dopamine and norepinephrine pathways, downregulating tyrosine hydroxylase, damaging VMAT2 and vesicles and NET and DAT. Especially damaging to NMDA/glutamate pathways. Downregulation of MAO. Can also cross mitochondrial membrane and cause oxidative stress and damage to mitochondria. Amphetamine unlike other stimulant and non-stimulant ADHD meds is a releasing agent. It can diffuse through the cell wall aside from being taken in via NET and DAT. Most other meds act as reuptake inhibitors. Which is why amphetamine is so much more potent. It does reuptake inhibition due to competitive inhibition and causing the reversal of NET and DAT. As well as temporary closing of the some transports through internalization. There are a bunch of other things it can do that I don’t recall off hand. But I coveted the bigger ones. Again, most people are stable with manageable side effects. But the rest of us can be screwed.
Caffeine, lightweight compared to modafinil and armodafinil. They are synergistic with amphetamine in combo. Caffeine I built up a tolerance and it doesn’t have side effects you may be concerned about. Titration is the key. People can have vastly different responses to meds and combos of meds. Some people would not be able to titrate a second stimulant. Others are much less affected.
Modafinil or armodafinil with amphetamine can be vastly superior a treatment with vastly reduced side effects from amphetamine alone. But, at vastly reduced doses from either alone. The combo is also theorized by a clinical trial comparing an ADHD stim (forget if it was Ritalin or Adderall) and modafinil for SCT symptoms and for ADHD symptoms. And concluded that those comorbid may benefit most from a combination approach. My blood pressure was 15 points lower on all those meds than Adderall alone at higher dose. And heart rate was lower. But, with my high doses, it does not work without memantine. Strattera was strong enough to reverse tolerance of 60mg Adderall or dexedrine. Technically, those doses were not fully working and had tried 80 a hand full of times for job interviews. And even that was not fully working. So, even at 80 mg about 80% therapeutic strattera at 60 mg in 9 months each time had me down to a fully working 40mg. (But side effects were still accumulating). 3rd time I had stayed on strattera till 15 months and the 40 mg was intolerably too strong. Indicating much more than 40 mg of tolerance was NMDA/glutamate pathway damage. But, going higher doses for Mounjaro in which I didn’t go on strattera again till I was already on 140 mg and close to having to stop work as I was not making all my hours across a whole week and still declining.
Forgot to mention, people who have taken amphetamine with modafinil or armodafinil have 2 reactions. 1, vastly more therapeutic at vastly lower doses. or 2, way overstimulated and never tried it again. In which case most likely did not know how to titrate properly from very low doses.
Currently, I am on 100mg strattera along with 28 mg memantine XR. Both are weak NMDA antagonists
(you do not want strong ones!!). But together they don’t over suppress those pathways. At least for me. Not any research on that to go on. Just tried together (while titrating memantine) and found it was ok.
So, caffeine didn’t come into play till I was already disabled and desperately trying to hold on. Modafinil / armodafinil I did not try till a few months after I stopped working and stopped Adderall.
Memantine I got online but not till I was already disabled. And ran out just before I started working again after an ultimatum 4 months later. Which I was functional with Moda/armoda synergistic effect with Adderall. But had zero chance with Adderall alone. But, starting with a high tolerance and existing damage, it just made things much worse as I built up tolerance more and more damage over the next 2.5 months. And 2 weeks after that in late January 2024. Finally found a the only therapist I came across who can work with someone with issue like me. As therapist have zero useful education regarding high tolerance of medications. Medication vacations only work for acute tolerance that occurs on a daily basis and resets with enough sleep overnight. Have some that hasn’t upregulated and medi vacations can help. But they are useless for someone with long term tolerance building up. Which has been shown in clinical trials therapists have never heard about.
My current therapist is a neuropsychiatrist. And the only person I came across who helps people on high dose meds like Adderall transition to something else. As nothing else alone can reach therapeutic effect due to amphetamine cross tolerance. My therapist is an associate professor at NYU (program ranked 2nd in U.S.). And former practitioner, researcher, and director of the narcolepsy program at NYU Langone (Neurology hospital ranked number 1 in U.S.). Also has additional education/training on narcolepsy which has precedent for combined stimulants being a better approach. Also, former colleague of the person who gave SCT the name SCT. As they did SCT research at NYU Langone so he is the only therapist how has even heard of it. Which is a large reason why ADHD medication only approach failed me. Lots more research needs to be done on SCT as I believe you are aware. Some info on it is in the information resources on this site. A bit thin and dated. But, just having it deserves a lot of accolades in my opinion.
Guanfacine before I forget. Pretty sure I mentioned that relation in other posts on the site. But high level. GLP-1 drugs under the covers primary MOA is accumulating intracellular cAMP. Which acts as a secondary messenger and does the things we think of when we think of GLP-1 drugs. But, in the brain it had negative and positive effects at the same time and the idiosyncratic net result can be totally opposite for people with the same disorders and on the same meds. The negative is cAMP-PKA opening HCN and KCNQ channels in the PFC that shuts down signalling. Guanfacine alpha2A-adrenergic agonism (One of NE’s jobs but guan is much stronger at it) prevents adenylyl cyclase from making cAMP. Which prevents PKA from opening HCN and KCNQ channels which is stimulating and increases PFC signalling. That stimulation plus stimulation in other areas makes the Mounjaro - guanfacine como stimulating and helps other meds to work better. Note, guan may or may not add any benefit for a neutral or positive responder. There is no research on this as I literally had to put together research I found on my own to figure this out. My therapist just determined that there was no obvious risk letting me test my theory. Which was exponentially more effective than I had even hoped, at first. Got quirky due to some confounding existing things.
Endocrine. FDA prescriber doc says Amphetamine increases corticosteroid levels that are highest in the evening. Which is when they are supposed to be lowest. Chronic high cortisol is pseudo Cushing’s disease. Which has a long list of side effects that therapist are not taught about. Or taught to check hormone levels. Many don’t believe it can even effect the endocrine system. Which is stupid as they know they have to monitor to make sure kids taking ADHD meds don’t stop growing. Don’t know what system they think involves growth (sarcasm implied). Hypothalamus sits on top of the Pituitary gland. Pituitary directly and indirectly modulates activity of dozens of hormones. Hypothalamus…is what tells the pituitary what to do. Hypothalamus is managed by DA, NE, SE, and other neurotransmitters that ADHD meds affect. Hormones also feedback and act on brain function as well. Which is why there is Stimulant Induced Secondary Gynecomastia. Skipping what I do know about more endocrine effects.
Only took a couple months for tolerance and endocrine effects to start after I moved to Adderall. But, it was a long slow downhill decline. No therapist helped even a little bit. Or why they had me try they didn’t understand and made things worse. And these were therapists who claim to be experienced and treat adult ADHD. And none of them could tell me what the “other” symptoms I was dealing with were. Turned out to be SCT ( which I had to self diagnose tentatively). And Narcolepsy which they did not understand as much as my current therapist and why it was dismissed each time till 2024. I don’t have the symptoms for narcolepsy listed on health websites and what not which were more like how someone was affected. My current therapist instead brought up the actual diagnostic symptoms they look for during sleep tests. In which the diagnostic symptoms fit like a glove. And talking about my experience as a young adult, he responded “classic narcolepsy”.
I self medicated late summer 2023 desperately trying to get back to work after being turned away by over 3 dozen therapists and offices since a couple months before I first tried Mounjaro. As I was far far beyond fed up with my life long since destroyed by side effects, career held back massively. But, I was able to justify everything I was doing and how everything related. Since he also has the full neurologist background on top of the full psychiatry background, he was far more able to understand the relationships and reasoning from research that led me to my approach. Also, a big fan of memantine himself as it protects many pathways in the same way as it does NMDA.
Also, in my experience, endocrinologists know less about how amphetamine can affect the endocrine system than psychiatrists know about any side effects not listed in the basic guides. Even though like other fields, there is a lot hung up in research and unknown to most medical practitioners.
Note, my generalizations about medical or mental health practitioners is based on those in the U.S. From interacting with people outside the U.S. over the years on social media. I suspect the fact that many are also using the DSM as their primary guide. That they also have not been provided the deeper psychopharmacology aspects of the drugs being prescribed that is hung up in research. But do hope maybe they do have more resources or more willing to look into research etc. Otherwise the outliers like myself will keep slipping through the cracks. I mostly blame those who decide the curriculum and provide other resources to therapists. But, too many I have looked to for their expertise were clearly clueless about the things they had me try. Even before I started to deep dive research out of desperation. Some stuff they said just logically could never make sense. But, I deferred to the experts like I was supposed to and hoped I would be surprised that I was wrong about how I interpreted what they said.
I am very in favor of mental health and therapy. And in favor of psychopharmacology. And a huge critic of the of the ignorance on some very basic things the meds can do to people and just their basic way of working. I know incomplete research can’t be 100% reliable. But a single resource that mentioned the things missing from the resources provide that could have prevented almost 20 years of my life being ruined after I had turned it around on my own in my mind 20s and did 4 college degrees managing 3 unknown hyper functional disorder and struggling, having to work harder than others at work. Before my first diagnosis and the promise of being helped by therapy. That was broken and destroyed everything I worked for.
Would have been better to start this reply when my meds were working and not 13 hours after I had taken them. Intended to make this short and simple. Could have a long time ago.
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Short (ish) version of reply that I failed in the other. Caffeine came about 16 years after Adderall started to ruin my life. And caffeine, I don’t have side effects from it, Even if I take 200mg when I wake up and another 200 when I get out of bed 2 hours later. At this point it just adds a little bit more wakefulness. Adderall was doing all the damage. Strattera actually reversed it 3 times but didn’t stay on it like I should have. I was already disabled and desperately trying to hold on when I started using caffeine and building a tolerance to it. Was disabled and out of work before I tried modafinil, armodafinil, memantine.
On my full dose of meds, last time at a doctors office a couple years ago, at peak effect. Blood pressure was exactly 120/80. Which was actually up from the last couple visits. I don’t get shaky or anything from caffeine. Nor do I crash when it wears off. Was starting to reduce what I was taking. But, I have crappy luck and will have to get back to that another time.
On a side note, do they use piracetam or phenylpiracetam, or other racetams for that matter over there? They don’t in the U.S. since big pharma can’t exploit it with patent protected name brand drug profits. There are a few niche racetams that are actual prescriptions. But the low impact stimulation of the ones I mentioned might have a lot of benefit alone or in combo with other meds.
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Man, you’re killing me 
Your knowledge would be worth its weight in gold if it were backed up by sources so that anyone could verify it…
Would you be interested in writing something about this for ADxS? With or without author’s name—whichever you prefer.
Just list one fact after another and link each sentence to the sources on PubMed that confirm it?
That could save so many people…
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[Started this reply a while back and hadn’t gotten back to it. So, still a mess and wasn’t the best timing to have been working on it with meds mostly worn off. Might find something noteworthy in it. I’ll have to try to track down sources sometime in the future for most of the stuff I’ve mentioned on this site. ]
I wouldn’t be able to get to that. It’s not like I don’t want to. It’s that I have a ton of things I desperately need to get done that I have been failing to. And have a hard time with goal oriented pursuits (Avolition). And a lot of the links would be hard to track down again.
Even taking my full dose of medication, I am barely functional.
Plus I was run out of my home and state by a former tenant who lived in the conto below mine. Bathroom fans were never hooked up by builder so air gets blown through and around my place and out the attic. They have bottom floor. My condo is 2 floors then the attic above. They were smoking pot all the time and it was getting blown into my place and they did not care when informed. I have a very negative reaction to pot smoke and it screwed me up for over a year. Also, the clothes dryer duct got disconnected, probably during a yearly cleaning. And all the moisture was vented between our homes. Which soaked through my underlayment and into the cheap gypsum based self leveling concrete the builders used. Plus trusses and framing are all reclaimed 2X4s. So, gypsum broke up and sank with the underlayment between trusses. Wall on side of stairs was between trusses and sank, pulling upper floor out of whack. On top of softening trusses that shifted and sank. So, my entire home has structural issues.
Things had escalated and former tenant blew 2 unknown industrial chemicals into my home. After camping out in my bedroom and trying to deal with it, eventually I had no choice but to leave. Had also sprayed into my car and everything I had in there more than once. Trying to find a place that will test for chemicals as insurance won’t do anything about replacing my stuff with out it. Will need to see if my insurance, HOA insurance, or owner downstairs insurance will cover the structural issues. Which may not be covered since insurance likes to exclude moisture damage. TBD.
Which doesn’t even get into the health issues exacerbated and new I am trying to deal with. To give you an idea. I have to take extra statins to get my cholesterol down, to get my toxic level vitamin A down. So it will stop inducing CYP3A4 which metabolizes 4 of my medications. Including guanfacine that without it working right, my Mounjaro blocks all psychoactive meds and suppresses signalling even below withdrawal levels. Mounjaro is also a potent inducer of 3A4 as is my very very high dose Armodafinil. Which had blocked my simvastatin that is metabolized in it causing my LDL cholesterol to double, and my elevated Vitamin A that it is one of the transports of to go into toxic levels. I can’t reduce my Mounjaro because it is actually treating my cancer. Which took off with activity after the 6 day chemical assault and temporarily reducing my Mounjaro dose for 6 weeks.
Ran out of 1 of my meds and out of state so doc won’t refill till I see in person since its been a couple years. 1 Less drug to compete for 3A4 means my armodafinil and guanfacine gets metabolized too fast and meds are even worse than before.
This link is I think the second best I had, shows GLP-1 drugs accumulate cAMP which other research shows can result in a large range of cognitive effects from extremely therapeutic, to totally devastating for those dependent on psychoactive meds.
Not everything I read was on PubMed. PubMed is just an index of research, not all of it is on there and it does not dictate which is good and which is crap. Some articles I read in 2023 I have not been able to find since. Spent many many hours trying to find a few of them again. An example, the one with modafinil vs an ADHD stimulant as applied to SCT and ADHD symptoms. That concluded (educated guess based on results) those who are comorbid may benefit best from combined medications. As each did help symptoms of either disorder. But moda was best for SCT and the ADHD stim (forgot which) was best for ADHD. Did have that bookmarked but the default text does not identify what it is. I had read it at least a half a dozen times and even posted it a few times somewhere on social media. Have not been able to find it again since. Based my medication approach on it (did a lot more research before actually trying it). Out of desperation i was reading things and would hit the bookmark button but wasn’t organizing them. Did not plan to be sharing what I found.
This link has historical FDA prescriber accompaniment docs for Adderall IR. Can also find them for other drugs on this site. Some of the things I mentioned can be verified in there. If you search for “dependence” and “tolerance” it defines them and states they can happen. And does not state anything about abuse of medication being necessary. Many of the talking points therapists (in the USA) have say they only happen “when abused”. Have to read that section carefully. Before it it does talk about abuse and what not and says it can lead to dependence. But, the section is “DRUG ABUSE AND DEPENDENCE” in which “Abuse” and “Dependence” are equal sub sections. also mentioned withdrawal under Dependence section. Which I was told only happens “when abused”. Which is total BS for anyone with built up tolerance and especially dependence. I am highly dependent. I have never been addicted. Withdrawal sucks and can last months.
Also, search for “corticosteroids”.
“Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening.”.
Cortisol is the most prominent corticosteroid. If taking meds every day, it is elevated every day. Only need to look into “elevated cortisol” to see the long term side effects not mentioned. Like Pseudo Cushing’s disorder. Therapists and doctors were sometimes dismissive when I mentioned endocrine side effects I was having from Adderall. By 2 pm an ACTH / Cortisol test had my levels already over double the max range the lab had set for 4pm. And long ways to go before “greatest in the evening.”. Normal cortisol cycle is highest on waking, lowest around bed time. Amphetamine takes cortisol from its highest. And can cause it to go up instead of down. My testosterone, Estrogen, LH, FSH I saw go up and down following the dose I was taking at the time of the tests.
Also note, Glucocorticoids are a subset of corticosteroids. Which manage metabolism, suppress the immune system, etc. My natural body temperature was 99.6F all my life (98.6 is usually what is stated as most common). A few years into Adderall it was averaging 97.1. That’s 2.5F decrease in body temp. Extended break from Adderall, it did come up a little bit but quickly went back down when taking it again. Also manages glucose and insulin. Can’t know if it played a part in becoming diabetic or not as it runs in my family. But, is a possibility (mentioned in research but don’t know if I have links anywhere).
Low testosterone and estrogen imbalance that moves with my dose. TRT meds, testosterone went up, even above normal range. Felt almost no difference at all and still had symptoms. Indicating it is far more complex and involves other hormones too.
Only short term studies 6 weeks max have been done. (6 weeks specifically mentioned in certain versions.). Seen Barkley say he knows of no research indicating ADHD meds can be harmful long term. Yeah, if you only look at drug company sponsored trials that don’t last long enough to develop long term side effects.
“Long-term effects of amphetamines in children have not been well established.”
Search the document for the term “Adult”. It is not in there. Mentioned that it is indicated for children. And only assumed for adults based on studies in children. Who also metabolize it quicker.
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011522
From the link above you can also see that modafinil no longer lists max dose as 400mg. (I do not know if DSM still does or therapist resources. ) Now states that adverse events were not seen at over 2 grams. Considering modafinil the drug is a racemic drug of equal parts modafinil and armodafinil. And my 750 mg prescribed dose is armodafinil is still less than the greater than 1 gram armodafinil portion indicated in modafinil document as not having adverse events. Then it is a little easier to understand why my therapist prescribes that dose. Where others would be hung up on outdated max 300mg for armodafinil. Before even mentioning my other meds.
Some links I found quickly in my bookmarks. This stuff is about lymphoma and leukemia that may be relevant to specific people.
GLP-1 drugs can treat certain kinds of lymphoma and leukemias. And Doctors don’t even know it!!! It’s that cAMP thing I keep talking about. cAMP is known to be a treatment for some cancers in which they sometimes use PDE inhibitors to increase it. And HDAC (?) inhibitors activate some cAMP pathways as a secondary effect. Came across research on cAMP and these things using forskolin. Forskolin is used by research to study the effects of elevating cAMP. But, it is weak at it compared to GLP-1 drugs. Can also treat a number of other cancers that respond to cAMP secondary messaging. But, some cancers and situations it can exacerbate them. Which people are unaware of. Digging into that research thing can get complex fast and well beyond my capacity and knowledge. But, the high level understanding is enough to understand why all of a sudden when I increased my Mounjaro from 2.5 to 5 mg most symptoms subsided and activity slowed to a crawl for the next 3 years. Plus a bunch of other health issues.
If you know anyone with lymphoma or leukemia this would be a good start regarding cAMP. And the GLP-1 drugs that cause it to accumulate. I have more but don’t know exactly what is in each link. Also can help other disorders like psoriasis and other skin disorders. Think I recall something about prostate cancer.
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Not sure if I was clear before, but I had started researching out of desperation to fix my issues and desperate to keep the contract position I had, which took me 11 months to get. Adderall had already ruined my life from 2007 to 2022 with no help from therapists or endocrinologist. But Mounjaro blocking cognition had me spending half my time online reading and the other half trying to get my work done. And kept researching after I could no longer work. So, didn’t organize the info well and lost track of somethings I could not find again. So, a lot of effort that I don’t have right now. But, I do assert that the things I’ve stated are available online, or were. And I do try to filter out biased, poorly done, etc. research. Which increased my extreme dislike of drug companies and their manipulations.
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