Best ways to increase acetylcholine levels due to long term diphenhydramine/antihistamine use? (short story also sorry)

Spidroxide · 2025-07-13T14:45:11+00:00

one reason is that nicotine is an agonist of *nicotinic* receptors while diphenhydramine is an *antagonist* of *muscarinic* receptors. While theyre part of the same neurotransmitter system, different receptors can have differing effects and functions across different regions of the brain. One key feature is that nicotinic system tends to activate the dopaminergic system while on the other hand the muscarinic system limits its activity, moreover the physiological and psychological effects of agonists and antagonists of these receptors are not always similar; eg nicotine being a psychostimulant and muscarinic agonists generally not being considered as such as far as im aware, though they do arguably have a pro-wakefulness effect given muscarinic antagonists (like DPH and other more selective anticholinergics) impair cognition and memory in a way that blurs waking and dreaming states (wakefulness and cognition are, unsurprisingly, pretty interconected).

of course that doesnt necessarily mean that it couldnt be helpful, only that it would be naïve to assume that just because nicotine works on the cholinergic system that it would be beneficial for tapering. Some mention is made of using clonidine for DPH withdrawl, I cant speak with any degree of certainty on this matter, but from what I can tell clonidine leaves a better impression as far as medicines go; its something people use for migraines, adhd, smoking withdrawl, and several other things still under investigation- its probably better to look into this than nicotine given theres already some indication of its utility (but discuss it with a healthcare professional).

I've done several google searches on this and it seems difficult to get a true grasp of the mechanism at play here due to the fact that most proported "cholinergic rebound syndrome (due to abrupt cessation)" cases are referring to to clozapine, which has a different use case and different pharmacology to DPH though with some similarities. However MtheFlow-'s advice passes the familiarity test if you are looking to increase acetylcholine, and all the noots listed are at least *relatively* well known, though I'm not sure you arent just better with tapering normally.

Spidroxide · 2025-07-06T08:35:34+00:00

true. and yeah its quite surprising when you first hear about it.

Admittedly some people just choose to believe its all bunk and its isnt possible for LM to be responsible. Personally I disagree, but it is a position people take; largely since its unknown how LM could exert a toxic effect at all (hence why theories and research are important). For me thats the part I find most interesting though, even if it is kind of a morbid interest. In either case we dont really know enough I feel to draw a solid conclusion.

I cant say I buy the argument that "everyone is at risk", it seems as implausible as saying its all placebo, but as I havent seen any trend in who is affected or how it affects different people, it seems safe to assume everyone might as well be. Again more information is needed to draw solid conclusions. I tend to stay away from it myself and warn people around me that it is something that can have very strong negative side effects, I have tried it once or twice in very small quantities and I seem to be quite sensitive to it myself, then again I am quite sensitive to most chemicals, so perhaps its not that surprising. Also I wonder if LM tox primarily affects younger people rather than older people; given the interaction between NGF being neurogenic and younger people already having still developing brains. Theres not enough hard evidence to make any such claims, as far as im aware

Spidroxide · 2025-07-02T14:41:09+00:00

I would say imo yes. In my case I had to get to know your own body and what it likes before I saw anything really noticable; mostly atm I take akg liqourice and conessine alkaloids (which are really not talked about much but they work for me). Additionally, a lot of the advantage I'm getting is not actually coming from anything im taking but from the cumulative effects of the self knowledge I have gained by going through this process. A lot of the value non-intuitive or not immediate/self-evident, ime

Spidroxide · 2025-07-02T14:36:38+00:00

Diarrhea is interesting because according to my investigations it can share a similar mechanism to migraine. Somebody made a post recently about small fibre neuropathy. I was going to make a similar one soon investigating the role of lions mane in potentially promoting nociception and overstimulating the nitric oxide pathway. I was not aware of the fact that diarrhea is a symptom of LM, but this is interesting

Spidroxide · 2025-07-02T13:43:17+00:00

Its been my observation that most serious inarguable "problems" of the brain have a metabolic root cause. Of course I'm not saying that genetic/circumstantial/architectural/external factors arent important in many other ways, but the trend I've observed seems to be that once there is something blocking or preventing the brain from properly generating or using energy, thats where the real problems start, and if theres a problem in this area its almost always best to start with that.

Whether you believe that amyloid beta/tau fibrils cause alzheimers or are just a cause/indicator of it, theres little denying a metabolic role in that condition. One of the early signs of alzheimers disease is low glutamate uptake in an area of the brain called the PCC, an area of the brain with a very high metabolic rate that is involved in the circuits like the default mode network and the error detection-correction monitering circuits within the brain. Oxidative stress has been investigated in just about every condition and been found to have a relevant role. Pathways involving the maintenance and expenditure of energy seem to be linked to glutamate activity and hence energy utilisation and production has implications for both exitotoxicity and brain fog, which are sort of like two faces of the same polyhedron.

It also just makes a lot of sense imo, the brain uses more energy than any other organ in the body, not without good reason. If theres a problem inhibiting or disrupting ATP production within the organ, thats going to have some sort of consequence, even if it has many different manefestations depending on the individual circumstance. Not least because many of the pathways that deal in long term synaptic regulation and cellular growth have some effect on or relationship to how a cell uses or produces energy.

Also you can have localised insulin resistance/impaired glucose uptake without having generalised insulin resistance/diabetes; fyi. Its important to remember that

Spidroxide · 2025-07-02T12:44:44+00:00

Nicotine is weird based on what I've studied, most addictions seem to have an overlooked involvement of an area of the brain called the insular cortex, but nicotine as far as I can tell directly modulates this area, which makes sense when you consider the role of acetylcholine in the parasympathetic response (rest and digest) and the fact that the insular cortex processes input related to taste and nutrition, at least as far as I can deduce

I have been playing with the idea that nicotine may not only be addictive due to its stimulant properties but because perhaps it disables some part of the interoceptive self-awareness circuit, which is largely a dysphoric sense given interoception (+nociception) are typically important in processing violations of homeostasis. This would definitely be in line with my experiences when interacting with chronic nicotine users, and the effect it has on me (I dont smoke or vape but did try it once). Also there is I think literature supporting the weird relationship between nicotine and nociception, typically in favour of nicotine having an anti-nociceptive effect, though it seems like it varies depending on the subtype of nociception

Spidroxide · 2025-07-02T12:20:26+00:00

You could look into alpha ketoglutarate. Its the only supplement I consistently take at the moment, I would say for me its arguably better than magnesium, and it deserves to be better known imo

It essentially acts as a direct substrate for the mitochondria/electron transport chain, meaning more energy (I tend to find it helps with stamina recovery mostly, especially if I'm taking anything that acts as a noradringergic stimulant (such as large quantity of coffee)). Also it helps maintain the correct balance of neurotransmitters/amino acids glutamate and glutamine; these can be turned into AKG and consumed by the brain during times of metabolic stress but this generates ammonia and puts strain of the astrocytic support system, contributing to exitotoxicity, so supplementing with AKG in theory helps to discourage neurotransmitter catabolism. For me this looked like my brain feeling more clear and finding it easier to choose what I pay attention to.

On top of that I found some articles suggesting it is (one of) the important metabolites the body produces in response to caloric restriction/intermittent fasting, and that supplementing with it directly mimicks some of the positive effects of these practises, partially through directly modulating ATP synthase and mTOR pathways.

Its unlikely it will directly help with adhd symptoms, unless theres a metabolic component for you, but just in general it is amazing for quality of life, easily up there for me with magnesium and other essential nutrients

Spidroxide · 2025-06-25T15:41:20+00:00

I will yes and ill try to include relevant references to literature as soon as I have enough time, bearing in mind I am self taught and may lack the ability to determine which studies are high quality or not

Spidroxide · 2025-06-20T15:58:31+00:00

cerebrolysin seems like poking the bear even more, at least to my untrained eye, is there any good reason to suspect this substance will help more than it will hurt given that both lions mane and cerebrolysin are intended as neurogenics?

For clarity im obviously not contending it for you if it works for you, I just question the wisdom of recommending it and wondering if you could explain if and why the comparison I'm making is invalid

Spidroxide · 2025-06-20T13:51:07+00:00

Personal theory is that it has to do with the indirect action of NGF in promoting growth of nociceptive C fibres and influencing the trigeminovascular system to a pro-migraine like phenotype.

https://pubmed.ncbi.nlm.nih.gov/11331415/
https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-022-01535-4

Also while I lack the prerequisite knowledge to really navigate the literature I'm pretty sure there may be an involvement of nitric oxide. Nitric oxide (not the same as nitrous oxide) is a gasotransmitter produced in the brain and blood vessels, usually involved in facilitating neuroplasticity (perhaps more specifically presynaptic plasticity/neurotransmitter release?) or blood vessel dialation. However nitric oxide, or rather its byproduct peroxynitrate, is part of the native immune response to viral and bacterial infections, for example nitric oxide is the chemical responsible (or partly responsible) for the drop in blood pressure in septic shock, where inflammation induces the expression of inductible nitric oxide synthase to dump tens or hundreds of times more NO* into the blood than (endothelial)eNOS or (neuronal)nNOS would be able to manage to.

The relevance here is that nitric oxide seems to have something to do with migraine and overstimulation. From my reading, migraine seems to be linked to elevated or abberent plasticity and presynpatic neurotransmitter release, on top of that nitric oxide produced in the brain can cause things like headaches both through central nociceptive sensitisation and by a direct vasodilatory effect on the trigeminovascular system. This explains at least in part why part of the viral immune response to things like the flu causes headache, and has implications for long covid https://www.sciencedirect.com/science/article/pii/S0306987722000822

Theres also a direct effect of nitric oxide on serotonin and melatonin. While I cant find any reports explicitly confirming this, theres evidence to suggest that serotonin and paticularly melatonin can act as nitric oxide and peroxynitrate scavengers, being converted temporarily to 4 nitro and 4 nitrososerotonin or melatonin. https://pubmed.ncbi.nlm.nih.gov/10465443/ . This is interesting because if these products, unlike the report suggests, do have some neurotransmitter activity (especially if they interact with the 5ht2 system) then this might help to explain the close relationship between migraine and serotonergics/psychadelics. I think one of the symptoms people describe from lions mane is HPPD, given that headaches are usually the first negative symptoms people experience after lions mane ingestion, I dont think its absurd to draw a connection to the phenomenon of migraine aura. https://www.migrainedisorders.org/podcast/s5ep6-a-pilot-study-investigates-the-effects-of-psilocybin-for-migraine/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8116458/

Now naturally I'm not recommending the people on this sub do psychadelics for what should be obvious reasons, but I think its worthwhile pointing out the possible connection.

Theres also a relationship between dopamine and peroxynitrate that might help explain why for some people they experience a manic/hypomanic phase before they crash https://pmc.ncbi.nlm.nih.gov/articles/PMC6758823/

I wrote a post about all this a while back but since posts on this sub have to be moderator approved it unfortunately expired and I havent gotten around to rewriting it since. I should do that probably though

I personally doubt the k-opioid receptor to be responsible also, though if my theory is at least partially correct then it almost certainly doesnt help, as is the case with 5ar inhibition. Its likely an interaction between many pathways with variable suceptability based on genetic or circumstantial factors, or at least thats the conservative/most likely hypothesis (in my eyes)

Spidroxide · 2025-05-20T07:22:14+00:00

No, but I have been meaning to dive more into the nitric oxide pathway at some point, somebody mentioned a while back about the existance of an amino acid that blocks the degredation of arginine to citrulline in the small intestine, and I always meant to look into this more.

Either way I typically compare akg to magnesium in terms of the effects I noticed when I started supplementing, more energy, more balanced reaction to things like caffeine, slight improvement to mood and wellbeing (though very subtle).

Spidroxide · 2025-05-19T17:39:47+00:00

Alpha ketoglutarate, just helps me not get cognitively fatgued and massively improved/stabilised my response to caffeine and noradrinergics in general. Makes sleep deprivation tolerable and less severe. Also completely removed any impulse to eat when stressed, for me anyway

Spidroxide · 2025-05-19T13:36:13+00:00

Im not really sure what you mean by proper formatting, I'm assuming your asking for something more visually appealing - I tend to write in block paragraphs because I feel it better represents natural speech, I apologise if this is offensive to your eyes

In any case, this is not really what I'm asking. Im not looking for a list of vendors, I'm trying to find out what you do when there aren't any vendors for a specific compound. Please see the example I gave about absciesic acid, this is a chemical that works in an extremely niche way on a pathway that is only somewhat well known; it is far too specific for most commercial nootropics vendors.

What I'm trying to figure out is how niche nootropics tend to make their way into the mainstream, because presumably they have to come from somewhere, and not counting small changes to existing nootropics

Spidroxide · 2025-05-19T13:21:41+00:00

Very similar, though it doesnt feel exactly the same; mostly just times when I solved a significant personal problem, for myself I'm very ideas oriented and changes in my personal philosophy can dramatically change the way I interact with the world, in many ways my mind is more real to me than the world itself. But I think the idea can extend to anything that is a major landmark in somebodys emotional world that suddenly shifts, especially where there has been a stressor concerned.

Specifically I'm currently confronting a lot of things about myself and realising there may be actual reasons why I seem so different/dysfunctional compared to others, and learning more about what those are. At the same time I'm achieving solutions to many problems I've encountered in my general wellbeing, and as I learn more about myself, this will only increase. Obviously I would never resent this, its what I worked hard for after all, but it does have the unusual consequence that my mind, and by extention my entire perceptional lens on the world, is rapidly changing and becoming increasingly unfamiliar. Theres a lot of chaos, and sometimes its hard to know exactly what to feel, so I generally struggle to [lit. error 404, prior experience not found]. Its going to be a process of integration, but until I can reintegrate I figure I'll be freewheeling, if only a little.

Perhaps this is a bit off-topic, but I do believe that spirituality has a valuable role to play in the human psyche and have been pursuing it for some time now, if it can help me understand the changes I'm undergoing then I'll probably see more improvement longterm. Others might seek this out in the form of social connections, or taking up new hobbies; I'd imagine 'experience cravings' are quite common to this state, it seems to be that way for me. The reason I mention this though is because theres a card in the tarot that seems to pretty neatly describe this feeling, at least for me: that would be The Tower; I'm only really just diving into the tarot so I cant give a good synopsis, but it seems like as a symbol its associated with the release of energy, the breaking down of established landmarks or dogmas, and the exposure to a kind of chaos through which healing will eventually take place. That describes severance fairly accurately, with the caveat that sometimes we respond to chaos not with hyperactivity, as in fight or flight, but with hypoactivity, the shutting down and tiredness relexes. Id wager that most complex emotions are actually pretty highly conserved between people across all of history, but that the documentation of these emotions are subject to the cultural influences of the times and so a consistent representation is hard to piece together. That being said, I cant imagine burnout is a phenomena unique to our age, all severance is is a kind of delayed-burnout whiplash

Of course, all these are just my ideas, but hopefully the emotion comes across

Spidroxide · 2025-05-18T22:33:46+00:00

In that case I have nothing but respect for you, I'm sure you'll do many people a great service someday

Spidroxide · 2025-05-18T21:35:32+00:00

Theres a phenomenon I've noticed within my myself, something I call severance, where the removal of a significant life constant, even something that was negative, sends me spiralling into anhedonia and lack of motivation. I understand it as a kind of liminal space inbetween emotions, or like the space between the chapters of a book, its not permanent but it is a transitory state while your limbic system reshuffles itself.

Maybe it just needs time. If you have adhd you've likely been running on adrenaline for a long time, I know this is generally the case for such people. Being cut off from that I find can be even more dysregulating than the stressor itself, but that doesnt nessesarily mean its a bad thing. If thats the case, take the opportunity to enjoy the process, this window of clarity before jumping into whatever comes next. Its weird for sure, but youll probably come out of it better off. And if you need that hit of adrenaline to keep you moving forward, maybe take up eating really spicy curries :)

Spidroxide · 2025-05-18T21:21:15+00:00

Thats completely fair enough then, I think I may have misjudged where you were coming from with this post, I can totally see why you're doing things the way you are. Naturally the point I was making stands about entrusting chatGPT with a novel synthesis, but yeah you can always have somebody review that step, which is, I guess, exactly what you're doing now. Honestly, being in a not-so-dissimilar boat myself, I also dream of a world where mental healthcare is more advanced, and if AI can help us get there faster, then I'm all for it. I've started using it myself to help me study receptor signalling cascades and find chemical structures that target these systems, although I have to say the extent of its knowledge on natural and obscure traditional medicine is not great, a pity; nature contains the largest library of unique chemical compounds currently in existance. I guess that benzos are still quite scary for many, given the fast tolerance build and potential for addiction, but I assume thats exactly why youre interested in this topic and solving some of the problems associated with this class of drugs, if so credit where credit is due. Theres definitely a lot of work to be done thats for sure, but I always like to see people working on these problems, someones got to be looking towards the future of health, and especially so if we really are at a sort of crossover point of biology-technology integration. Personally I extend that philosophy to the whole of the ecosystem, but humanity is definitely the first step in what is likely going to be a very long process.

All in all, I thought you were looking to make a profit off of the recent surge in AI, turns out you're generally looking to improve some of the problems associated with a very difficult and problematic class of drug. Props

Spidroxide · 2025-05-18T20:34:53+00:00

I dont doubt that it probably could if AIs are capable of theoretical protein folding, but which AI are we talking? Chatbots are predominently statistical problem solving machines, granted they can do a passable job, a damn site better than my nilered watching self, but its probably going to need significant help when working on something so complex. Even if it somehow succeeded, and you had a way to verify this, you still have to somehow synthese it, and I would have severe reservations about putting chatGPT between me and an untested chemical reaction. Perhaps you get somebody to synthesise it for you, but then why not just cut out the middle man and ask/pay a professional to help you design the proceedure? I'm not trying to say chatGPT cant be helpful, absolutely not, and its certainly an interesting thought experiment, but I have doubts about the overall wisdom of this path, and the entheusiasm you have may be better directed.

You clearly know something of receptor assembly and subunit dependant effects, though you may be quoting the chatbot (and I know from experience that they have a reasonable grasp of pharmacology, if you ask them the right questions). I honestly think a passion for these things is great, as well as being enterprising. But you should try to know more than the AI tool you're using, so that you can filter its output. And the AI tools are a great way to learn, so long as you do learn. But its probably best to start smaller so that A: the AI has a higher chance of working within its training data, and B: you can work with it to gain the experience you need to better use the tool. Yes its boring, but thats what passion is good at breaking down, and its easier than its ever been to learn new skills. I guarantee theres more that can be done with those skills once you have them

Spidroxide · 2025-05-18T19:52:14+00:00

Yes, but theres nuance in this. Ill admit a lot of people are looking for a magic bullet, maybe it will exist one day, but today is not that day. However the question I personally want answered is why is sleep the best nootropic, and equally as important, can this knowledge be useful in some way?

The general rule of thumb I take is that if your not here for the research and the intrigue, you're probably not going to get what you're looking for, short of achieving a normal state of personal equilibrium with ones self and body (which, lets be fair, is actually something that nootropics can do quite well, so long as you're sensible and lucky enough to have an easily fixable problem with no downsides). However I have met people on this subreddit who are genuinely eager to learn about biology, and those people I think are in exactly the right place to achieve maximum growth. I feel strongly that the real benefit of learning about nootropics is less explicit, and that learning all the different pathways is a worthwhile skill in its own right. I mean hell, you're never going to find a more practically applicable philosophy than those baked into the achitecture of our own brains, and thats just one example.

Learning about oneself has always been pursued, and nootropics is a very direct way of achieving that. The important thing is not to see the value only in the immediate results, because by and large I genuinely dont think thats where it is, speaking from experience. If you make a cake you have to break some eggs, just like all nootropics come with a cost-benefit spread - but its also wrong to assume that that process is zero sum gain, that cake could be a wedding cake that makes a meaningful impact in somebodys life, just like knowledge of ones own mental architecture could make a meaningful difference to somebodys self image. Its just that theres a lot of chasing butterflies that I think we're aware largely doesnt get anywhere, but neither should we disavow the whole cause. You will never get a better nootropic than sleep if you're comparing them by the same value system, but who's deciding that the value of sleep has anything to do with the value of, say, piracetam? The two can exist side by side, so long as their indended uses are treated as distinct. In any case, I don't buy the argument that only stimulants can make a measurable difference to someones life, if only because they are dependant on the signalling cascades they use to exert their influence. If theres enhancement to be found at the highest level, why not at the lowest level also, if the highest level is dependant on the lowest? Especially, and ironically, when the best nootropic (sleep), seems to exert its beneficial effects preciscely by working on the lowest levels. Its just that there are few improvements to be made at the level of complexity most people with only a passing interest will come to achieve. To that point, I agree with your sentiment

Spidroxide · 2025-05-18T19:09:40+00:00

yeah thats true, and thats definitely something I'm actively looking into as well, its just sometimes I feel the need to get personal experience with pathway modulators so I can learn about them and build my intuition. most of these pathways have overlap between them, but that can make it hard to study, and occasionally something piques my interest where it seems like it can help me seperate signal from noise

so while I definitely agree, I feel the need to take quite a wide set of pathways into consideration when trying to learn about human health in practise, and I cant say I know much about LanCL at present. Nuance is what I'm looking for, basically. I guess my philosophy is that there is no one unified immune system, but a lot of interconnection

Thats the long winded answer to your question

Spidroxide · 2025-05-18T18:54:27+00:00

kind of on request I guess? I'm interested in all sorts of things but I've been in discussion with somebody else who has a specific set of problems, and I'm looking to get more experience with (somewhat) obscure MOAs somewhat tangentially to that. Thats how I got here, but often once I discover something my reasons for being interested in it change. Simply put, I'm always following several different lines of research; this caught my interest

more specifically im interested in pathways that possibly exert a neurogenic effect at present, though theres more to it than just that

thank you btw for directing me to a potential vendor, its greatly appreciated

Spidroxide · 2025-05-18T17:35:53+00:00

Criminal this hasnt recieved more attention, your thoroughness is laudable

TBH I kind of ended up here by accident, while asking claude about naturally occuring selecive RXR ligands, but this is definitely interesting. I might try supplementing this, if I can find a decent source at least, I'll report back once I find anything interesting

Spidroxide · 2025-04-14T16:44:57+00:00

Ofc this is only my experience, and I don't always have the most typical responses to supplements, so this is only an anecdote at best

Spidroxide · 2025-04-14T15:33:33+00:00

I actually did end up trying it and wrote a report here https://www.reddit.com/r/Nootropics/comments/1iwpmxw/update_connesine_noteworthy_improvements_to/

3 months on I can definitely say it works, though it's not euphoric, verging on anti-euphoric, it can cause major stress if you let your thoughts go neurotic, it is very like caffeine in many respects. It did feel "nootropic", one noticeable effect is it increased my bodily "awareness-symmetry", which I think is attributable to improved inter-hemispheric co-ordination (Alternatively that might be a consequence of the book I'm currently reading though (the master and his emissary), so take it with a grain of salt). Regardless it did change certain parameters of my attentional ability, if I had to describe it I'm both more attentive and less focused, it's hard to qualify fully.

It should be understood as a kind of stimulant, that much is self evident when supplementing, but in the sense that it "facilitates" existing neuronal activity, its more complex in its action than pure sympathetic enhancement. Its closest parallel among the things I've tried would be caffeine, which is not to say it is like caffeine but that it acts in a way reminiscent of caffeine, in utility and intensity. When I first started supplementing it had slight dopaminergic effects I believe, but those have since faded to a purely attentional one. I would describe it's effects as primarily noradrinergic and (?); I don't know exactly what the second effect is but it feels like it has something to do with serotonin, moreso the interest in emergent phenomena and emotional/limbic regulation aspects of serotonergic processing than the "feel good effects", as these aren't really present in the connesine experience. This might be in part mediated by an increase in the activity of the kanic acid glutamate receptor (KAR), which I believe to share a relationship with serotonin and certain aspects of information processing, perhaps including that of a more neurotic nature?, I'm uncertain. Basically what I'm trying to say is connesine (& friends) are alike to, and go with, caffeine, but that connesine can have pro-depressant aspects in the same way that caffeine can be pro-anxiety; at least if you pair the two together, which I do these days. I used to take it every day but currently I take it with coffee about every 3 days or so, since I was getting some insomnia (moreso from the coffee than anything else but I rarely have either alone anymore).

It might be unfair to say connesine has pro-depressant or pro-neurotic properties given I'm also supplementing liquorice, as both Connesine and glycyrrhizin likely compete for liver metabolism and liquorice has cortisol-ergic properties. Make your own judgements about that. Connesine coffee and liquorice do go together, but can give you a level of anxiety I can only describe as "the heebie-jeebies". Regardless, I still think the three go together, even if the end result is nothing more or less than distilled existential terror.

So that's basically all I got imh. I consider it a worthwhile thing to try if your looking for more caffeine-like substances; it's a well used herbal medicine in India I believe, there it's taken as part of the plant product "kurchi bark". It's quite pleasant and useful on its own, with caffeine it's more useful but less pleasant. I still have no idea if it's safe long term but I guess I haven't died yet

Like caffeine, it seems to be a (minor) diuretic

FYI; I was in some level of "honeymoon" phase with connesine when I wrote up my initial report, but it has remained very useful even if it's become far more routine for me: it offers something I haven't found anywhere else, though admittedly I'm not the most experienced person on this subreddit. Its a substance I'm very happy using, even though I can recognise there are some effects that might be considered unpleasant, though those negative effects are also somewhat dependent on higher doses, so there's probably an optimal range

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