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Is there long term side effects to these supplements? Have been interested in trying out the brain type (focus/neuroplasticity) in the past but worried about fucking up my brain/getting depressed or something. Or not being able to focus without them if I stop taking them in the future

Concerns might be unfounded but any thoughts on how to approach these for someone that's curious but also kinda scared

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So the herbs / shrooms have been used in traditional Chinese medicine / Ayurvedic so have 100s to 1000s of yrs of safety data. Some rare mild side effects sure, DYOR.

Off the top of my head, higher doses of alpha gpc might have the opposite effect of brain fog in some people, bacopa might lower dopamine synthesis (can counter with NALT btw) and reduce focus.

As far as the "getting depressed" concern, refer back to the beginning of the post where it explains that a lack of neuroplasticity CAUSES depression. This is an entire rabbit hole I encourage you to go down.

The "serotonin theory of depression" is debunked at this point. In fact, it appears that the only reason SSRIs sometimes resolve depression is because they increase neurogenesis / neuroplasticity.

Here are some studies to check out:

https://www.sciencedirect.com/science/article/pii/S266656032200038X

https://www.nature.com/articles/4000712

https://diginole.lib.fsu.edu/islandora/object/fsu:267045/datastream/PDF/view

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I’d also like to understand that. What are the side effects if you use these compounds for months and suddenly stop?

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don't. never. always plan the on/off cycle first. can be something like 5/2 days, 3/1 weeks, 1/1 week.... depends on the stuff, the effect wanted, the quality of 2nd opinions you get. one thing is having a doctor/experienced/phd biohacker on your shoulder, another is scrounging up a schedule/dosage from a rando reddit post.... ;)

get a plan. stick to it.

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Alpha GPC & Sabroxy (can make a case for saffron and polygala) are mostly just acute performance boosters to use 2-3x a week

Everything else has more of a cumulative effect and requires weeks/months to achieve peak results.

Mostly achieved through an increase in BDNF in different regions of the brain, so quitting = decrease in BDNF. You're not going to have "BDNF withdrawals" per se, but will notice a slow decline over the coming days/ weeks until you're back to normal cognitive function.

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thoughts on carnivore diet? i am 38 years old, went full carnivore (eat mostly just ribeye and ground beef) back in June 2023. i immediately lost 20 lbs of water and fat, and all my lifts went up, i'm now lifting more at 38 than i was at 23. a few weeks after going carnivore i was able to quit coffee (had been drinking 2-3 cups a day for past 2 decades), quit weed, and get out of a toxic relationship. its amazing the effects that a proper diet can have on your willpower and the cascade of changes it leads to in all areas of your life.

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The carnivore diet isn't magical, but it forces a lot of people into a low appetite and low inflammatory state due to its ketogenic and high protein nature.

It's a lot better than the standard american diet, but you'd probably perform better if you included some fruits and vegetables that agree with your body

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Is it the carnivore diet or the will power surge that caught you on to the carnivore diet which resulted in all the cascading benefits?

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If you go from standard american diet to carnivore / keto, you'll get a huge surge in energy / mental clarity from the amelioration of systemic inflammation. Also a huge drop in appetite from the high protein & ketogenic state - making weight loss a lot easier.

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Great information, thanks Biohacker.

Wha is the 1 supplement from each category, Focus and Neuroplasticity, would you recommend for someone just starting out on this protocol?

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Focus would have to be Sabroxy. It's a pretty potent dopamine reuptake inhibitor.

Neuroplasticity? Lion's Mane (somehow disappeared from my list o_o ) or Bacopa

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Thank you so much.

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One caveat- Amphetamines caused neuron death in rat studies, no human studies showing this .

Saffron as a Dopamine/NE reuptake inhibitor is how stimulants act, Adderall is a Dopamine/NE reuptake inhibitor. Point being if Adderall/Ritalin can cause neuron death, so could Saffron (dose dependent) as biological mechanism is the same.

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There are ethical barriers to conducting studies where you give humans amphetamines and then slice their brains open to assess neuronal death.

Absence of evidence is not evidence of absence. We know stims impair cognitive performance longterm, so extrapolate that how you will.

The pharmacodynamics of Adderall/Ritalin/Saffron are all different.

Safron is regulatory aka you will get a boost if you are low, but you won't get an additional boost if you are normal or high. This is because it primarily acts via 5ht2c antagonism. The DAT / SERT reuptake inhibition is VERY weak, MAOI is also weak/theoretical.

These compounds are all more / less active in different regions of the brain.

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Don’t know what you are trying to say here. Saffron was compared directly to Ritalin in children and had the same efficiency. “ Short-term therapy with saffron capsule showed the same efficacy compared with methylphenidate.” Were all the children coincidentally low in neurotransmitters? Supplements/herbs have there place, but people are misleading themselves if they think there are no potential adverse effects. I had multiple patients with psychosis from cannabis alone. Ashwaganda and hepatotoxity is well known, etc.

I’ll end by saying medicine treats based on diagnosis not symptoms. Taking antibiotics for a viral illness is useless even though the symptoms are similar in presentation. It’s why we take cultures. People for example can take herbs for the symptom of poor concentration if they want, but don’t pretend it’s medicine.

https://pubmed.ncbi.nlm.nih.gov/30741567/

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For those already acclimatized to daily stimulant use (e.g. 20mg Adderall IR, 500mg caffeine) do any of your recommendations change? Would you advise a slow taper or immediate stop? Are there special steps you’d take to address the damage?

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Caffeine works completely differently than stimulants, it displaces the adenosine in your brain. If you are on a prescribed medication, need to ask your prescriber for advice, not the internet.

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Aenosine receptor antagonism increases catecholamine (dopamine / norepinephrine) concentrations in different regions of the brain

Anyways, 500mg of caffeine is too much. Even the FDA will agree on that. https://www.fda.gov/consumers/consumer-updates/spilling-beans-how-much-caffeine-too-much#:~:text=4.,associated%20with%20dangerous%2C%20negative%20effects.

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I'm curious as well, if someone is used to amphetamine I wonder what dosage is considered neurotoxic

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Would like more info on this as well. I suspect there are a lot of daily stimulant users here

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Several of references refer to studies only done in rats

Some of these have effects that can be dangerous if mixed with other medications, ie those with MAO inhibitor-type activity

Dosage, side effect profiles, medication interactions not included

Overall outcome measure of neuroplasticity unclear. How is that tested and measured?

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The MAOi effects of polygala and rhodiola are no where near the strength of prescription MAOi like selegiline or phenelzine and do not carry the same risk of drug-drug interaction or drug-dietary interaction

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Concern is rx-strength drugs have tightly regulated drug dosages whereas supplements can vary widely in dosages from container to container.

Combining some of these items with other medications such as Adderall or cold meds with phenylephrine can lead to rapid rises in blood pressure.

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That's why ND was recommended. Every batch is 3rd party tested, everything is standardized (meaning you can expect the same % of phytochemicals every time), and they have a clean track record

You have a very low risk tolerance, and that's totally fine, but this post is for people who don't

Rodent studies, 1000s of years of use in TCM, and 1000s of anecdotes online = good enough for me to give it an experiment

BTW - the MAO inhibition in polygala is very mild. If you have a hypertensive crisis from combining with a med, you're more than likely overdosing on that med

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This. Like those geniuses who took DNP for weight loss and literally killed themselves.

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It may be something on your Substack and will check, but given this information, would combination therapy with Transcranial Magnetic Stimulation be too much or a complimentary therapy if someone was to research that? Especially now that don't need visit to a clinic to do TMS with at home units now on market.

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not sure i would trust home-administered TMS...or even lab TMS for that matter. it has shown some results for helping with depression, but its only used as a last resort.

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I don't even know where it is placed etc but now that sending folks home to treat headaches with it from behind the head I naturally started wondering if a way to biohack that given it's success with migraine treatment. But that's an interruption of the neural signal not necessarily behavioral

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Honestly, no clue. I haven't researched TMS enough to have an opinion.

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Why not mention BPC-157?

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Too many to mention. BPC-157 is definitely promising in healing the brain, especially when it comes to addiction / stimulant damage.

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Funny you mentioned selank and semax. Have run into these from searches along with other peptides. Do you do consults? Might be interested in grabbing 30 mins to do a deeper dive.

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Yeah, you can check out my consultation rates at five.me/bowtiedbiohacker

But I'd wait. Semax/Selank article dropping this weekend on the stack and you can drop questions in the comments.

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This post is fantastic! Question about the supps. Do you take any of them daily for general brain health? Or are they all for immediate effect?

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Thoughts on zyn/nicotine pouches?

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There's a good chance the artificial sweetener ( acesulfame K) they use is no good for you

Otherwise, oral nicotine at like 3-4mg a day has some nootropic and neuroprotective benefits.

Inhaling nicotine provides too much of a spike in dopamine which leads to compulsive redosing / addiction

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Appreciate the response!!

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Great post.

Bull, do you still recommend the Now Chlorella?

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hey biohacker, any experience with psilocybin for neurogenesis, and associated results, improved mood, memory, learning?

not the get high version, the low/micro dosage-long running plan... asking for a friend... ;)

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Theoretically, it should increase neurogenesis / plasticity if microdosed daily for an extended period. However, that would also take away the focus/creativity boost you get from occasional microdosing.

Macrodoses will fry your brain if done often, but every once in a while can be useful for increasing self awareness IMO

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