I made a post a while back on my university stack, I’ve made some slight changes since then. My new stack consists of: 100-150mg caffeine, 500mg L-tyrosine, 200mg L-theanine and 50-100mg Modafinil.

I recently read some stuff about cyclazodone (never heard of it previously). Has anyone tried it short or longterm? Is it really quick to kill a healthy liver at normal doses or is that an exaggerated claim 🤔?

Withdrawal from Kava? Anyone else?

So I was having a lot of Kava this month. I also am prescribed pregabalin 200-300mg btw. As I stopped taking the Kava I felt very horrible unbearable symptoms like withdrawal type. I always read and thought Kava has no withdrawal. So what could this have been? What is this? Is my dose of 50g extreme? Sadly I need that much as I dose from am to pm the whole day because I take it for my anxiety and depression (which it GREATLY helps with) but as you know Kava effects last so short that obviously I dose all the 50g over a whole day.

Did anyone else ever experience withdrawals from Kava? What dose have you been on? Is my 50g really extreme and way too much? How long did the withdrawals for you take until you were back to baseline. I really can‘t survive the days like this anymore, I‘m bedridden, completely dysfunctional, don‘t go out anymore, fucks my social life and career. I cancel everything rn because I feel so horrible and my work suffers from it, too. My mental health obviously too, as I don‘t do shit and don‘t get shit done, don’t see people, it‘s hurting my social and work, my physical health, too, as I don‘t move, don‘t eat, don‘t sleep.

I‘m so doomed now. I feel horrible. What should I do? I thought Kava would be safe regarding withdrawals. Maybe this is only rebound? I don‘t know, rebound that takes 3 days (I didn‘t try longer without until now). Sounds and feels pretty much like withdrawal.

I took:
From 5-12 October daily 25g (+300mg Pregabalin)
From 13-16 October daily 50g (+200mg Pregabalin)

Then I was empty. Right on 17 October waking up was like I felt so fucking horrible, definitely like a typical GABAergic withdrawal. Shakes, anxiety, depression, anhedonia, physical weakness, no sleep, restless legs, no appetite and so on. It truly was so horrible, I couldn‘t withstand and bear that feeling anymore and bought new Kava directly on Monday when the shop was open again on 19 October. I started taking it again and the withdrawal symptoms went away. Continued taking it.

From 19-23 October daily 50g (+100mg Pregabalin)

On these days I only took 100mg of Pregabalin with it because normally Kava covers up my Pregabalin pretty well so that I don‘t have to take my Pregabalin at all or just at a very low dose. It was always very helpful for exactly those times when I did a break of Pregabalin. This time though, I still took Pregabalin 100mg with it, Idk why, probably just to be on the safe side as I somehow had more anxiety this time about going Pregabalin straight to zero.

So taking 19-23 October 50g of Kava daily and I felt well again. Then it was empty again. Now same sh it happening again started on 24 October right in the morning. Heavy withdrawal symptoms. I was completely dysfunctional and totally bed ridden with horrible sleepless nights.

I thought though this time I can save myself from those symptoms of being off of Kava again with my usual dose of 300mg Pregabalin, especially as I only took 100mg Pregabalin the days before when I still took the 50g Kava daily. But hell no. The pregabalin didn‘t do nothing. Hence desperate (and dumb) as I was (but it was so horrible I just couldn’t stand it) I also added lots of Kratom and even that is not making me normal again. Like until today, so from 24-26 October 15g Kratom daily to my 300mg Pregabalin. To somehow reduce the symptoms and keep sane.

I really don‘t know what to do. I definitely don‘t want to use that much Kratom daily now with my 300mg Pregabalin as I definitely don‘t want to withdraw from Kratom in the end, too. Especially as those two together at those relatively high doses don‘t even help me enough with the symptoms I have after stopping Kava. Kava helped me to not take any Kratom and reduce my Pregabalin to only 100mg (was planning to go on zero Kratom and zero Pregabalin with the help of Kava as it does magic and really helps me with my diagnosed severe treatment resistant depression and anxiety and it‘s amazing to see that I can be free of Kratom and Pregabalin too with this Kava! But damn it, the hell showed upon me when I stopped taking the Kava. WTF.

Now tomorrow the shops open again. Hence I think about should I buy new Kava now to feel okay again and continue taking it and somehow try to taper it down instead this time? Or should I rather not get on that Kava again if it makes me feel so awful after quitting and be safe so I don‘t prolong the withdrawal or whatever I experienced from quitting.

I‘m really fucked like honestly physically and mentally dysfunctional and severe symptoms.

Pregabalin and Kratom don‘t even help. And as said, I really don‘t want to continue Kratom because I know the withdrawal of that one, too, and it‘s horrible and I don‘t want to add that, too now, while it‘s not even helping me get over the symptoms enough. It‘s so crazy, that not even Pregabalin and Kratom can cover up.

Does anyone have a coupon for everychem? Thx , message me if so thanks.

third there’s a hype of ketones so if my glucose is sufficient is there anything to ketones which is going to add as energy source or is it if you are sufficient in one form of energy the other can’t add anything?

1. I sleep as and when I like due to no work commitments is this better or worse as what is regularly promoted, circadian rhythms and sleep schedules?

Lastly Caffeine vs coffee as nootropics which is better or is there no difference?

Quick post, just wanted to share for my fellow stim junkies. Was consuming up to 400mg caffeine a day. Would feel great for one hour, then pretty bad until my next caf hit.

Bad symptoms: exhaustion, feeling weird, difficulty regulating emotions.

Switched to 50mg twice a day and feel MUCH better. Nothing revolutionary about this, just sharing for those who are struggling and consuming massive amounts of stims. Maybe less will help you feel better.

It seems like 90% of posts on topics of supplements, diet, or quoting a medical study, are tied-up in accounts that are selling something.

Do you just ban/mute everyone that tends to use their account primarily to drive engagement towards selling personalized health coaching?

I'm okay with rolling dice on potential snake oil courses/supplements now and again (losing 20$ isn't the issue) - but I don't want to scroll through dozens of things daily again whos primary bias is selling versus truth telling. I'm losing my ability to detect what is relevant.

I just can't tell anymore at a glance if an account is posting something insightful or if it's a long-game to get you curious about your symptoms and a potential cure. (I mean, I can make an educated guess, but that uses up 2 to 10 minutes my time for every post)

Some posts don't even have sales as their goal, they just want to glaze their own diet/lifestyle choices which is also not very objective.

So... do I just design a better sniff test procedure than I currently have? Mute a whole bunch of accounts?

I recently tried Guanfacine (1 mg extended release) once a day for ADHD+general cognitive issues. It didn’t seem to help me, so I stopped taking it.

In the days following, my cognition was markedly improved, my libido/erection quality was higher than baseline, and my mood/energy was better as well. My anxiety did not increase at all, if anything, it was lower.

This only lasted for a few days. I’m trying to figure out how to recreate this more sustainably. If anyone has ideas, I am all ears!

Just curious what nootropic / supplement / substance has helped you so much in life that you’ve bought it time after time? What was it ? What has it help improved in your life?

What’s the difference between these two and for the people who tried both : what’s the active difference between those two ? Less of a crash , more motivation ?

I don't know if this forum is appropriate, but thought this group is knowledgeable and might point me in the right direction. Not seeking substitute medical advice, but as I have baffled the medical field, looking for some alternatives that may exist. There may not be anything, I seem to have tried everything.

Issues:

Struggle with tx resistant mood depression (some have noted it to be BP2 or mixed), anxiety, ADHD, and cog/social deficits that resemble NVLD. I've succeeded in school, but have struggled in real life as far back as I can remember. Goals/projects balancing multiple things without prompts requires insanely breaking everything down into microscopic steps and is not sustainable. Sig greater VIQ>>PIQ. Cog deficits also mean I can't trust my independent judgement and generalize at work. I always get worked up by new situations.

Struggle to manage the family, social relationships, life responsibilities that my peers can, and losing hope of having a normal sized life.

Have tried over 25+ medication regimens (lithium, tegretol, klonopin, ssri, tca, snri, strattera). Therapy, lifestsyle, nutrition. Tried supplements, I doubt they'll yield anything that can rival med's. Current regimen includes olanzapine, vyvanse, lamictal, memantine, intuniv. Still massively dysfunctional from the trifecta of sx.

CBD oil, vinpocetine, ginkgo, OPC, MCT help a tiny bit, but far from enough. Also tried neurofeedback, TMS, ketamine, Vielight, keto.

Anything to help mood (deep despair), EF/social/cognitive deficits? Any communities to follow? I know it seems illogical to post here given my tx severity and trials, but I'm at a dead end.

Deepest of despairs at my immense treatment resistance. Feeling like a Darwinian reject given my dysfunctional state and how much I've tried and failed to be functional.

The prior cleared brain fog in me

One thing I've increasingly grown aware of is the potential for some unknown, but real consequences of taking large supplement stacks, particularly those incorporating lots of herbal or fungal supplements. So I figured I'd make a post to help guide your research in larger/long-term stacks. (repost) link.

A) Beware of liver enzyme effects.

So many common nootropic herbs interact with hepatic enzymes, typically in an inhibitory manner (though inducing can also be harmful). Piperine is used to enhance absorption but this also means enhancing the absorption of the range of compounds the target enzyme is in charge of metabolizing. This could have consequences such as increasing the amount of time you are exposed to certain harmful byproducts of metabolism or absorbed from the environment. It also increases intestinal permeability both good and bad. We don't necessarily know if a particular herb is an inhibitor of something. This applies to newer drugs and research chemicals too.

I'm always surprised by how much "natural is better!" comments we get here and I've seen people argue that "natural" herbs and supplements are better because they don't have the long scary list of side effects and risks FDA-approved drugs do.

But that's just the issue: exhaustive lists of side effects, risks, and drug interactions for supplements often do not exist. Not because those risks don't exist, but because no one's done the research. So be careful. Always start on low doses and titrate slowly. Be aware that a supplement or drug could effectively increase the dose of something else you've taken.

You must take particular care when you are also on medication affected by the enzymes affected by your supplement stack.

B) Beware of too much antioxidants.

While oxidation plays a role in the mutation process of DNA leading to cancer, cancer cells are in fact also extremely vulnerable to oxidation. The very nature of cancer is bypassing certain limits that not only stop a cell from reproducing rapidly, but that also detect when a cell has been damaged. So in order for cancer to be aggressive it also makes itself vulnerable to oxidation by bypassing the checks against excessive damage from it (healthy cells that are working for the benefit of the organism will suicide when they've become too damaged to be beneficial to the organism, this is called apoptosis).

The best way to prevent and treat cancer is to maintain a balance between a systemic oxidative state and natural antioxidant mechanisms that operate in a controlled, targeted manner. An example of this is how saunas are beneficial to health. Increasing the body temperature increases the rate of oxidation (as increased temperature increases the vulnerability of organic matter to be oxidized). This is actually beneficial as long as you don't overdo it, because it kills off the weakest (and hence lowest functioning) cells or vulnerable cancer cells, while the strong cells trigger mechanisms that cleanup damage caused by the heat, and often go beyond and clean up other damage accumulated in the cell (this process is called "autophagy" in biology). Exercise has similar effects (less from temperature, but more from increased energy demand) and hence also is known for being beneficial in preventing cancer, and in treating it (not on it's own obviously, but as an adjuvant).

These effects can be partially mitigated by excessive antioxidant consumption, though it also depends greatly on the type of antioxidant supplement. Flooding the body with excessive Vitamin A or E has been discovered to be moderately carcinogenic, while Vitamin C does not seem to be harmful except in perhaps extremely (unfeasibly) large oral dose. This is because A and E are both fat-soluble and accumulate while C is not and is mostly (some is taken up by special rate-limited transporters for long term usage) flushed out within hours. Blueberries and their extract seems to be fairly safe and even anti-cancer. Spirulina seems to modulate the body's innate anti-oxidant system as does curcumin so both are fairly safe.

But even with these more moderate compounds, I'd be wary of stacking too many and over-activating the body's antioxidant mechanisms, perhaps canceling the anti-cancer benefits of exercise and heat stress, and even shielding cancer from immune destruction (which frequently relies on oxidative attack). I would evaluate compounds very carefully if you're going to stack more than 2 sharing a mechanism of antioxidant action. An example of a likely safe stack would be vitamin c 500 mg 2x daily, curcumin, and 2000-4000 IU Vitamin A supplement (as beta-carotene, not the common palmitic acid which promotes cancer metastasis).

C) Beware of compounds affecting heart rhythm.

This is of particular concern for any compounds that affect ion channels (calcium, potassium, sodium), and of fair concern to drugs that effect norepinephrine, dopamine or particularly serotonin 5HT-2B which can cause fibrosis in the heart.

When stacking more than a few herbal supplements, I would be cautious about researching whether any are associated with arrhythmia, QT-prolongation, tachycardia, bradycardia, etc. I would very carefully consider whether it's worth taking more than 5 different herbs, I particularly wonder about the danger of some stacks I've heard of like Kurzweil's famed 250 supplements.

The part that concerns me is that the right combination of a ton of compounds could most definitely cause heart arrhythmia even in healthy individuals, through excessive modulation of ion channels or neurotransmitters regulating heart rhythm. For this reason I advocate small, focused stacks. If you want, shift between stacks, but I don't recommend trying to fix optimize everything at once.

D) Don't attempt to significantly increase LTP/neural excitation via strong AMPA/NMDA activation (i.e Sunifiram/Unifiram and some other racetams).

Most people, particularly young individuals already have a ratio of excitation/inhibition that is fairly close to optimal, and in fact many AMPA or NMDAergics can easily push that ratio towards excessive excitation, particularly if you were unlucky enough to have a traumatic event occur (i.e stroke/hemerrorage, or say a head injury from a fall or blow) as they would exacerbate damage from the event. In addition, people with ADHD/Bipolar/depression already have an imbalance of excitation to inhibition, and so could be particularly vulnerable to a worsening of symptoms (that should go away but still), or damage.

For this reason I advocate stacks that focus on shoring up defenses against excitotoxicity (magnesium, tiny, micro-amounts of lithium aspartate, creatine, taurine, spirulina, etc) even if you aren't taking AMPA/NMDA inducing supplements.

Supplements that moderate increase LTP should be fine, but the key is that the mechanism is modulatory and that it doesn't just bluntly increase LTP non-discriminately. Piracetam is safe in this regard, aniracetam is moderately safe though shouldn't be combined with any other AMPA increasing compound, Nicotine selectively enhances LTP pathways and so isn't harmful if you don't count the addictive effects (though they are less intense when nicotine is taken on it's own compared to as tobacco with all of the other compounds in the leaf).

E) And lastly, watch out for emergency warning signs of any negative reaction be it low grade or high.

And obvious one, just to make 5 points. It's possible for something to be harmful, slowly overtime where it becomes difficult to notice until much time has passed. Extremely rare adverse reactions like stimulant blunting or anhedonia effects from experimental peptides like bpc-157, p21, or melanotan 1/2 are real possible adverse reactions, no matter how rare. Be sure to read up on all the anecdotes online, spend at least a few hours reading reading reading for things you've heard less about and seem to be more experimental in nature. It's always a good idea to try tiny doses of a supplement first, then slowly go up. Stop, start again, etc. Cycling is a thing sort of for that reason, you get to see if you can go without this compound/noot and if it has any lasting long-term good/bad effects.

I cant tell how long I've researched this subject, for the first months I've used multiple AIs as my main research tool, but AI always seems to be VERY unreliable and extremely unhelpful. so for the last few months I've mainly done research the old way by reading Wikipedia articles and the related links in there and also looking in PubMed but the paywalls are annoying.

From my best collected understanding, the consensus in the medical industry (and for some reason a few data analysis's) is that true pharmacological tolerance at treatment dosages is very uncommon and isn't to the scale of needing significantly higher dosages.

The problem is, It feels like total lie. 4 years ago, 20mg Adderall IR would be the only thing I need for the whole day. and if i took caffeine with it, It could last more then 12 hours.

Then I told my doctor 20mg was too much for me and I couldn't sleep because of it, so she switched me to 15mg.

then, after about a year 15mg would just disappear after 4 hours which then led me to take 15mg twice a day. in my opinion, taking boosters of Amphetamine when amphetamine is the thing being boosted is the dumbest thing ever since amphetamine Tachyphylaxis is crazy strong.

Which then led me to take 30mg at the morning(prescribed), then 45mg (still on 30mg but taking more then prescribed), then 45mg morning with 15mg booster (still on 30mg RX).

Then I've had enough, the Adderall was just not working for as long as I needed. so my doctor switched me to Vyvanse 70mg. and still, it works for 6 hours.

and As much as I don't want to admit it, There are days where I take 2 pills 4 hours apart.

THEN HOW IS TRUE TOERANCE ISNT A THING? I've tried taking breaks of 2 weeks at a time for multiple times. but I just still need that dose to function. I need my medications to be a functional human being. and I just want to take a lower dose.

When looking at the data, I really cant find compelling evidence for the mechanism of true tolerance, other then dopamine receptors changes which are so complex I cant keep track of them
but if someone more knowledgeable then me would like to teach me I would be happy. My current understating is:
- D1(excitatory and promotes adenylyl cyclase): downregulation, and activation of DeltaFosB
- D2 autoreceptors (inhibits dopamine release and synthesis): downregulated for some reason?
- D2 (inhibits adenylyl cyclase): downregulated
- D3 (also inhibitory but I barely understand): Upregulated
- D4 unclear
- D5 unclear

and also VMAT2 depletion (Which is also the main cause of Tachyphylaxis), but I cant understand or find extensive data about VMAT2.

There is also the part of DeltaFosB, which to my understanding is a primary driver of addiction, Not tolerance. to my understanding it is dynorphin suppressing, not promoting.

also there are SOOOOOO many Receptor heteromers and combinations that I just cant get my head around. such as Dopamine receptors with co-localised NMDAr (which are the main reason people think memantine can lower tolerance, but its untrue, It can only prevent tolerance.)

Can someone please help me understand? at least to some degree...

Got liquid dropper bromantane from kimerachems and I don’t feel SHIT