Stimulants Caffeine, Safe but counter-productive stimulant?

[Neuroprotection]

Caffeine is inverse agonist, so it does opposite of what adenosine does in the target neuron https://pubmed.ncbi.nlm.nih.gov/25268872/ Also preventing adenosine of binding in the first place
Theacrine binds to different site in neuron than adenosine does, but it decreases the amount of signaling adenosine causes once it binds to its site

Also; I found this claim:
"At high doses, however, it has been demonstrated that caffeine may not act as an adenosine receptor antagonist, and other underlying mechanisms seem responsible of its negative effects (for a recent review Fredholm et al., 2017)."

"The mechanism(s) underlying high dose effects of caffeine are less well known. There is an association between caffeine-induced anxiety and one genetic variant of the A2AR gene (Alsene et al., 2003), but not with several other variants (Rogers et al., 2010). The down-ward slope of the biphasic dose-response curve to caffeine remains in A2AR knockout (KO) mice even though the stimulatory effect was eliminated, and it was suggested that A1 receptors may mediate the negative effects (El Yacoubi"

Does anyone have any knowledge if caffeine has any affinity to any other system? I recall, and I am pretty sure about this, that I once found complete affinity chart and there was affinity for some serotonin receptors and stuff, but I can not recall any Ki-values or stuff (not like I would be able to relate them to each other and be definitive about relevance of such anyway).

The main stimulant effects of caffeine at any dose are due to adenosine receptor antagonism. at high concentrations, caffeine may inhibit phosphodiesterase enzymes and trigger intracellular calcium release from endoplasmic reticulum sites if I remember correctly. however, these effects are likely irrelevant to the psychoactive effects of caffeine in humans and animals, even at large doses. assuming this is correct, the question becomes which adenosine receptor is responsible for negative effects of caffeine when blocked. The holistic answer is that both A1 and A2A adenosine receptors are involved. however, A1 receptor blockade is likely the main cause of caffeine induced anxiety/stress, unpleasant arousal and perhaps temporary cognitive impairment. blocking this receptor is somewhat similar to, though nowhere near as dangerous as blocking GABAA receptors with antagonists used in scientific research to mimic seizures and panic disorder. A1 adenosine receptor activation can promote sleep, suppress anxiety and general arousal and protect against seizures. caffeine does the opposite of these effects.
A2A receptor blockade is actually associated with all the positive effects of caffeine like mood lift, antidepressant and reward enhancing affects. Unlike A1 receptors, A2A receptors mainly function to restrain dopamine D2 receptor signalling in the indirect pathway of the striatum through various mechanisms. activation of these receptors can induce depressive behaviours, decreased locomotion and apathy. due to their unique role, selective antagonists are being investigated for Parkinson’s disease and major depression as they can increase dopamine receptor signalling via a novel mechanism. though not clear, it is possible that A2A blockade by caffeine might contribute to symptoms of insomnia and heightened alertness which could indirectly contribute to anxiety. However, I don’t believe there is a direct link to this mechanism of caffeine and anxiety.

I’m going to do more reading on this and I’ll get back to you all if anything I said needs to be updated.

 

[Neuroprotection]

for all the negative impact it has had on me and many others, I feel like there’s a good reason why it remains one of the most popular drugs in the world. basically, despite being a stimulant and dependence forming drug, it reportedly doesn’t act directly on the reward pathways and so lacks the Real psychologically addictive component of most other drugs of abuse. I also feel that years of caffeine induced anxiety Will help me truly appreciate life once I quit. it has also taught me the important of working at the times which best suits our biological rhythms and energy levels. last but not least, reflecting on my past experience being caffeine free, I hope that quitting for good Will help me truly appreciate my own natural energy and the energy that comes through food/nutrients.

 

[Mycophile]

Good luck on your journey to quit caffeine. everyone is different and you know yourself better than anyone, but my General advice would be to stay away from caffeine permanently, especially when you have an anxiety disorder. it might also be a good idea to avoid any xanthine stimulants including theobromine, theophylline and paraxanthine. I know they are said to cause less anxiety, perhaps because they don’t cross the blood brain barrier as well as caffeine, but I’m pretty sure they’ve been linked to other side-effects, like headaches and insomnia and they can still cause anxiety. it might also be the case that using paraxanthine as a caffeine replacement May lead you to inadvertently consume larger doses in order to achieve similar CNS stimulation to caffeine.
Stopping caffeine should certainly help you get off the Clonopin. you need your adenosine for extra inhibitory support as your brain readjusts to any GABA deficit caused by long-term benzodiazepine use and withdrawal.
In terms of looking for a replacement stimulant, I would recommend you try B vitamin supplementation, especially B12 and B6 under the supervision/guidance of a doctor. also, daily doses of inositol and tyrosine might go a long way.
I wish you all the best.

Thanks. Well, I am going to do my best to avoid caffeine and most other stimulants, but I have purchased some just in case I need them. It's unlikely that there will never be a time in my life when I need some more energy quickly, so I have paraxanthine and Ginseng, and also, out of curiosity, I ordered some Semax, Selank, Theacrine and Dynamine Methylliberine. From what I have heard, all of these have fewer negative side effects than caffeine, but they still have stimulant properties and are less well known, so I'd use them sparingly and carefully. If I ever use paraxanthine I will not up the dose beyond what it says on the bottle or mix any of these stimulants. However, I will look into B12, B6, Inositol and Tyrosine. In the past I never noticed anything from B vitamins. Not sure they are meant to be noticeable. But honestly I am with you on getting energy as naturally as possible through things like exercise, nutrition, good sleep hygiene, and I also do the Wim Hof method involving breathing exercises, cold showers and ice baths, all of which can wake you up and calm you down simultaneously. There's also brain technology like my Photosonix Nova Pro which is goggles with flashing lights and synchronized binaural beats. It can be used for all sorts of purposes like waking up and as an antidepressant and anti-anxiety aid and it's really effective.

I also tend to wonder what I could end up using instead of Klonopin specifically if my social anxiety should flare up again. Do you have any ideas? My doctor has suggested putting me on Abilify but I definitely don't want to be on an antipsychotic. Too heavy a drug it seems and would prevent me from ever tripping or using certain other drugs I like. Not that this is more important than mental health, but I don't want to take it regardless. Kratom works sometimes for my social anxiety but it's just too addictive, often doesn't give me the results I want, and keeps me up if I take it to late.

 

[someguyontheinternet]

Semax and selank are interesting. Please let us know how they work out for you, I don't see them mentioned much here and there is almost no research in english

 

[Mycophile]

Semax and selank are interesting. Please let us know how they work out for you, I don't see them mentioned much here and there is almost no research in english

I will. I am kind of anxious about trying them though, moreso than Theacrine and Dynamine as at least those are related to caffeine, but they are prescribed in Russia and said to be relatively safe by Russian doctors, so I mean, that's not nothing. I would just NEVER go over the recommended doses of either, especially Semax, which I read can cause QT prolongation. You absolutely DO NOT need to tell me twice regarding that. Anything that fucks with your heart is a no-no, but that's only if you go over the recommended dose (or maybe mix with other stimulants which I won't do). It sounds like low doses are safe, and they say "the dose makes the poison," but really, who knows.

Sometimes I think I'm a bit dumb for experimenting with certain lesser known substances, but then people on this forum experiment 100 times more than I do. I mean, I figure that if I did coke a bunch of times in my 20s and was fine that sticking to normal doses of these things isn't going to hurt me too badly at 43...not sure that's really a fair statement, but I mean, Semax, Selank, Theacrine and Dynamine don't strike me as being as dangerous as a whole number of drug combos I've tried. So yeah, I'll just be careful and if I remember I'll let you know how they are.

 

[someguyontheinternet]

I would try them on their own before mixing too. Can't be too careful yaknow

 

[Neuroprotection]

Thanks. Well, I am going to do my best to avoid caffeine and most other stimulants, but I have purchased some just in case I need them. It's unlikely that there will never be a time in my life when I need some more energy quickly, so I have paraxanthine and Ginseng, and also, out of curiosity, I ordered some Semax, Selank, Theacrine and Dynamine Methylliberine. From what I have heard, all of these have fewer negative side effects than caffeine, but they still have stimulant properties and are less well known, so I'd use them sparingly and carefully. If I ever use paraxanthine I will not up the dose beyond what it says on the bottle or mix any of these stimulants. However, I will look into B12, B6, Inositol and Tyrosine. In the past I never noticed anything from B vitamins. Not sure they are meant to be noticeable. But honestly I am with you on getting energy as naturally as possible through things like exercise, nutrition, good sleep hygiene, and I also do the Wim Hof method involving breathing exercises, cold showers and ice baths, all of which can wake you up and calm you down simultaneously. There's also brain technology like my Photosonix Nova Pro which is goggles with flashing lights and synchronized binaural beats. It can be used for all sorts of purposes like waking up and as an antidepressant and anti-anxiety aid and it's really effective.

I also tend to wonder what I could end up using instead of Klonopin specifically if my social anxiety should flare up again. Do you have any ideas? My doctor has suggested putting me on Abilify but I definitely don't want to be on an antipsychotic. Too heavy a drug it seems and would prevent me from ever tripping or using certain other drugs I like. Not that this is more important than mental health, but I don't want to take it regardless. Kratom works sometimes for my social anxiety but it's just too addictive, often doesn't give me the results I want, and keeps me up if I take it to late.

Good to hear, I wish you all the best. let me start with your last question about a drug for your social anxiety, as that is the most important. personally, I would avoid antipsychotics and prescribing them for an anxiety disorder is a little unusual, especially social anxiety, which I’m pretty sure they could severely aggravate. I think occasional valerian route or kava extract may help with anxiety flare ups, but be aware that these drugs can also be somewhat addictive. if your social anxiety doesn’t improve and you require medication, I’ve heard that tranylcypromine is an excellent last resort for treating social anxiety but it can simultaneously fight fatigue as well through it’s dopaminergic affects. however, it really should be a last resort as it is a non-selective MAO inhibitor requiring severe dietary and Drug restrictions.

Just to clarify, in regards to my desire to give up caffeine, that’s because of its anxiety provoking and mind scattering effects. without caffeine in my system, I’m hoping I can explore occasional use of other stimulants like methylphenidate or even regular use of selegiline which is apparently excellent for long-term motivation. I know i’ve asked others this question, but it really interests me. if you can remember any time where you didn’t consume caffeine, how did that affect your experience with other substances? personally, when I went for a year without caffeine, I developed a greater interest in other substances and I found nicotine to be both much more pleasurable as a euphoriant, but also much more effective as a functional drug to help me get work done. others have understandably questioned how it is that I consider giving up caffeine only to replace it with nicotine, which is a much more addictive stimulant. my answer to that is I don’t actually have a problem being dependent on something so long as it is cheaply available and easily accessible. I think my main problem with caffeine is not the fact that it is simply a stimulant, but rather, it’s mechanism of action (adenosine antagonism) is likely exacerbating my anxiety and producing a non-functional aversive stimulation. this is one of the reasons why caffeine doesn’t work for ADHD in almost everyone, with some suggesting it can actually exacerbate ADHD symptoms. apparently, caffeine can also render Adderall or Ritalin toxic and ineffective. it’s not a simple case of potentiation, but blockade of adenosine receptors bye caffeine can alter the brains response to psychostimulants.

I’m actually really interested in trying ginseng, but I would only want to do it once I’m completely off caffeine. i’ve always wanted to know how good of a stimulant strong ginseng is on its own, but I have not yet been able to get hold of some.
In regards to your experience with B vitamins, you shouldn’t really get much Direct stimulation from them unless you were previously deficient. However, The idea of extra B vitamin supplementation is to help maintain stress resilience(Ability to resist breaking down physically or mentally under pressure).

 

[Neuroprotection]

Is it true that Kratom, A relative of the coffee plant which lacks caffeine, is quite a good stimulant. It would be one of those things I want to use very occasionally/sparingly once I have completely quit caffeine. I would never use it as a replacement for coffee, as this disturbing article/advertisement is promoting.

How Kratom Can Be An Effective Replacement For Caffeine | Dakind Botanicals

Have you ever heard that joke of adults needing their morning coffee in order to function for the rest of the day? Well, it’s no surprise that many thinks of coffee as a necessity considering 150 million Americans drink coffee, with an average of three cups per day.

dakindbotanicals.com

I do understand why some people may prefer it as a permanent daily replacement for caffeine. I imagine the stimulation of kratom alkaloids feels far cleaner and better than that of caffeine, but the problem is if you run out I guess you’re in a lot more trouble than you would be with caffeine withdrawal. additionally, I’ve heard a few anecdotal reports that long-term kratom use can cause Brain fog and someone suggested it could cause physical brain changes like a reduction in grey matter. then again, caffeine has been shown to do the same thing Though grey matter volume rapidly returns to normal after A very short period of abstinence.
Could anyone who has used kratom as a stimulant or caffeine replacement share their experiences?

 

[Anabasis]

Great thread. Caffeine is without a doubt no-close-second my favorite drug ever but I use it responsibly and have virtually zero tolerance because I go every single Monday with no and a couple of times a a year go 5-7 days without any. Doing that, I have never felt more than a mild fog in terms of withdrawals and so I plan the longer periods without caffeine for when I can read in bed.

Caffeine is always there for me when I need it. I take 200mg tablets once in the morning and do not re-dose. Very occasionally I will take 300mg or will re-dose once in the day. This is usually when I'm on vacation and day drinking.

My parents have had multiple cups of coffee every single morning for the last 60 yrs and can't be challenged to go one day without it. They get virtually no stimulation from multiple cups and suffer hideous headaches if they delay drinking it.

My wife loves the ritual of coffee and could not be challenged to go one day without until recently. She went the first day and upon my urging went multiple days without. She drank herbal tea instead. Now she feels like she broke up the dependence and tolerance and is going to join me weekly in going without.

I urge anyone who has even the mildest dependence or tolerance to break that shit up. You can do it!

 

[Burnt Offerings]

A moderate amount of caffeine can be useful in combination with a decent amount of sleep imo. It won’t really paper over a real lack of sleep like other stimulants can though and redosing is not very useful ime, just brings out bad effects with nothing gained

 

[jasperkent]

My 2 cents' worth--

I've been drinking black unsweetened coffee (dark roast)  almost every day for 50 years. The only periods I abstained were when I was drinking massive amounts of alcohol-- and when withdrawing from same.
I usually drink 12 to 14 cups daily, but I generally don't drink it after 6pm.
I sleep well-- 7 to 8 hours per night.
I don't experience anxiety unless something happening in my life is causing it.

YMMV

(edit) One annoying side effect is having to pee a lot.

 

[Anabasis]

My 2 cents' worth--

I've been drinking black unsweetened coffee (dark roast)  almost every day for 50 years. The only periods I abstained were when I was drinking massive amounts of alcohol-- and when withdrawing from same.
I usually drink 12 to 14 cups daily, but I generally don't drink it after 6pm.
I sleep well-- 7 to 8 hours per night.
I don't experience anxiety unless something happening in my life is causing it.

YMMV

(edit) One annoying side effect is having to pee a lot.

Can you go without?

 

[jasperkent]

Can you go without?

I can if I must, but I'd much rather not.
Without it I get brain fog and headaches.

 

[CFC]

Is it true that Kratom, A relative of the coffee plant which lacks caffeine, is quite a good stimulant

It can be. It can also be hella addictive for a substantial group of folks and a real PITA to quit.

 

[jasperkent]

It can be. It can also be hella addictive for a substantial group of folks and a real PITA to quit.

I've withdrawn from kratom, alcohol, benzos, caffeine, cocaine, meth, nicotine, and opioids.
For me, WD from kratom is relatively mild.
Worse than caffeine but not as bad as nicotine.

 

[jasperkent]

Could anyone who has used kratom as a stimulant or caffeine replacement share their experiences?

See above post about withdrawals.
I've never used kratom as a substitute for caffeine but I can imagine that it might work.
Personally, I was wash down my kratom caps  with coffee because I love the combo.

 

[Anabasis]

I can if I must, but I'd much rather not.
Without it I get brain fog and headaches.

I guess I'm weird but I hate, hate, hate a substance controlling me. I feel so liberated when I use a substance and get away with it. I'd take a week off, lay in bed and fight that shit off.

BTW, I love Chattanooga!

 

[jasperkent]

I guess I'm weird but I hate, hate, hate a substance controlling me. I feel so liberated when I use a substance and get away with it. I'd take a week off, lay in bed and fight that shit off.

I don't really look at my habits like that. I look at psychoactive substances as tools or even partners. Admittedly, some of my chemical relationships have been abusive and toxic-- I try to avoid those these days. But my affair with coffee has always been pleasant. It's not that I can't live without it, it's that I don't want to live without it.

BTW, I love Chattanooga!

Me too!
But I didn't always feel that way. When I left here for college back in 1977, I was certain that I'd never return. Chattanooga used to be a real shithole of a town. In the last 30 or so years, Chattanooga has really reinvented itself. It's now one of the most desirable places to live in the US. I'll be here for the rest of my life.

 

[Neuroprotection]

Great thread. Caffeine is without a doubt no-close-second my favorite drug ever but I use it responsibly and have virtually zero tolerance because I go every single Monday with no and a couple of times a a year go 5-7 days without any. Doing that, I have never felt more than a mild fog in terms of withdrawals and so I plan the longer periods without caffeine for when I can read in bed.

Caffeine is always there for me when I need it. I take 200mg tablets once in the morning and do not re-dose. Very occasionally I will take 300mg or will re-dose once in the day. This is usually when I'm on vacation and day drinking.

My parents have had multiple cups of coffee every single morning for the last 60 yrs and can't be challenged to go one day without it. They get virtually no stimulation from multiple cups and suffer hideous headaches if they delay drinking it.

My wife loves the ritual of coffee and could not be challenged to go one day without until recently. She went the first day and upon my urging went multiple days without. She drank herbal tea instead. Now she feels like she broke up the dependence and tolerance and is going to join me weekly in going without.

I urge anyone who has even the mildest dependence or tolerance to break that shit up. You can do it!

You seem to be like I once was, i’ve loved caffeine all my life until recently when it began giving me severe anxiety. my theory is that perhaps the stress of Office type work and having to use my brain every day, Which I find extremely difficult, has caused caffeine to act as a severe Chemical stressor. nevertheless, even when I loved caffeine and didn’t yet notice side-effects, it must have been negatively impacting my academic performance. This is because, whenever I quit it for the month of Ramadan, my focus and productivity were paradoxically improved and I achieved some of the highest grades ever at university. I suspect the caffeine served me best when I wasn’t doing any sort of work or studying for a long period of time such as in the holidays or the COVID-19 pandemic lockdown. during these times, I had practically no stress so caffeine would behave more like an energiser and perhaps produce the optimum level of arousal/ brain activity.

 

[Neuroprotection]

I've withdrawn from kratom, alcohol, benzos, caffeine, cocaine, meth, nicotine, and opioids.
For me, WD from kratom is relatively mild.
Worse than caffeine but not as bad as nicotine.

Nicotine is the drug I want to use at high doses frequently on a daily basis as a replacement for caffeine. i’m really surprised you found kratom less addictive than nicotine. i’m not doubting your statement/ experience, just wondering if it is your unique body chemistry or is this actually more common than I thought. some people think I may have a unique body chemistry due to my unusually intense positive reactions to chronic nicotine use.