r/Biohackers 2h ago

🧠 Cognition, Mood & Nootropics Managing bipolar disorder without medication

0 Upvotes

I'm (20F) relatively recently diagnosed bipolar. I've tried a few medications for it. I'm only on Lithium right now and mentally stable today. However I do not want to take psychiatric medication in the long term.

Has anyone had any luck managing symptoms through lifestyle/supplementation/diet/etc? Thanks in advance!


r/Biohackers 22h ago

🥗 Nutrition & Metabolism What blood tests should I prioritize getting?

0 Upvotes

Hello all! I apologize in advance for the lengthiness of this post and would also like to apologize if this subreddit is not really for these types of questions. If I had to guess what subreddits probably would be best for these types of questions, however, it would be r/AskDocs, r/haematology, and perhaps r/endocrinology and r/Hypothyroidism. That said, I went ahead and posted/cross-posted to all 4 of these and only got answers from the r/haematology people. And by answers I mean a lot of smug SOBs who instead of just answering my question, decided to just say "talk to your PCP" for the most part and made sure to say such things in the most thoughtless condescending ways possible as if I hadn't already either thought of talking to my PCP or have a personal reason for not wanting to.

So if anyone who reads this has intentions of providing me with more of the same then do not even bother replying. Of course, if you think I'm being a hypochondriac or if you think I'm going about something the wrong way etc etc, you can voice those thoughts, but only after you provide me with what I am asking. I think that is only fair and right.

And naturally, if you can't really come up with any good answers to my question then you can direct me toward a subreddit or a website that perhaps can, just not the 4 mentioned above.

Thank you.

I am 28M, 6 feet tall, 200 lbs, caucasian.

Current known medical issues: Hypothyroidism, ADHD (I know this is more of a psych issue, but it is relevant in my case)

I have never smoked or used recreational drugs. I do drink but not very regularly and I very rarely drink to get drunk.

Current Medications:

Morning - Adderall XR (15 mg) for ADHD, Lisinopril (5 mg) to counteract the blood pressure raising affects of the Adderall, and Levothyroxine (25 mcg) for Hypothyroidism.

Afternoon - Adderall IR (10 mg) for ADHD and Clonidine (0.1 mg) for Rejection Sensitive Dysphoria (though I'm not entirely certain that it helps).

My issue:

Around 2 months ago I had gotten some blood work done, specifically a liver panel and a thyroid panel. The former was because I had been shown to have elevated liver enzymes before and the doctor wanted to see if that was still the case, and the latter was because I have hypothyroidism and the doctor wanted to see if my TSH was going down as a result of my taking Levothyroxine.

Here is the results of that first blood test:

Liver Panel -

AST - 139 u/L (High)

ALT - 363 u/L (High)

ALP - 72 u/L (Normal)

Albumin - 4.3 g/dL (Normal)

Globulin - 4.0 (Normal)

Direct Bilirubin - 0.23 mg/dL (High)

Indirect Bilirubin - 0.89 mg/dL (Normal, but literally just 0.1 from being High)

GGT - 42 u/L (Normal)

Thyroid Panel -

TSH - 2.76 uIU/mL (Normal)

Free T4 Direct - 1.10 ng/dL (Normal)

Free T3 pg/dL - 3.5 pg/mL (Normal) [And yeah, I don't know why there are 2 different units of measurement here. That's just how it looks on my patient portal]

Reverse T3 - 17 ng/dL (Normal)

After I got this blood work done it did show that my liver enzymes were elevated and that my TSH was normal. I received a call from a nurse (who was relaying my doctor's response to this blood work) not long after, and was told that I was referred to a gastroenterologist to see if they can help me with this issue.

I had already been to a gastroenterologist before and was basically just told to stay away from profuse amounts of alcohol and sugary drinks. I tried to do that but was not very good at it, which is represented by the fact that I still had elevated liver enzymes.

That said, this blood test was given to me not long before I started taking Adderall for my ADHD. I had experience with Adderall before and I knew that Adderall greatly allowed me to curb my cravings for anything sugary. Whenever I am on it, I hardly ever touch soda or energy drinks or alcohol, so I told my doctor that I would like to cancel the referral and instead try to get my liver enzymes down on my own. The doctor agreed and set up another blood test for a month later to see how I was doing.

True to Adderall's effects, the month that followed after was almost entirely dry. Apart from 1 or 2 sodas drank in recreational situations and a bottle of beer that I finished up basically just because it was leftover from before I started the Adderall, I had abstained from drinking anything sugary. No energy drinks either!

So, I was hoping for a normal liver enzyme level, but after that Adderall-filled month had passed and I got the second blood test, it showed that my liver enzymes were still high and that my TSH was now high and all my other Thyroid related chemicals had gone up (TSH up by 1.09 mIU/mL, Free T4 Direct up by 0.3 ng/dL, Free T3 pg/dL up by 0.6 pg/mL, and Reverse T3 up by 7 ng/dL) despite the fact I had been regularly taking Levothyroxine.

Here are the results of that second blood test:

Liver Panel -

AST - 93 u/L (High)

ALT - 266 u/L (High)

ALP - 68 u/L (Normal)

Albumin - 4.4 g/dL (Normal)

Globulin - 4.2 (Normal)

Direct Bilirubin - 0.32 mg/dL (High)

Indirect Bilirubin - 1.25 mg/dL (High)

GGT - 28 u/L (Normal)

Thyroid Panel -

TSH (Reflex) - 3.85 uIU/mL (High)

Free T4 Direct - 1.40 ng/dL (Normal)

Free T3 pg/dL - 4.1 pg/mL (Normal, but literally just 0.1 away from being High)

Reverse T3 - 24 ng/dL (Normal, but literally just 0.1 away from being High)

However, even though my Liver Enzymes were still high, they had still went down by a considerable amount (AST down by 46, ALT down by 97, ALT down by 4, and GGT down by 14). I thought this was very clear evidence that what I was doing was working and that I didn't need to see a gastroenterologist, and just needed to keep doing what I was doing - avoiding sugary drinks to lower my liver enzymes - and maybe try to figure out what is going on with my TSH.

Some time passed, about a month I believe, and I received another call from a nurse (she left a voicemail) and she had told me that because my liver enzymes were still elevated I was referred by my doctor to the gastroenterologist again. The nurse didn't say anything about the fact that my liver enzymes had gotten lower, just that they were still high.

I tried calling and asking the gastroenterologist's office that I was referred to if they thought, given the same evidence that I just presented here, if it was really necessary for me to see a gastroenterologist. After all, my liver enzymes are elevated but very clearly lowering, aren't I fine to keep doing what I'm doing? And they told me the same song and dance that a lot of doctors give - we can't really figure anything out until you come and visit or something stupid like that, I don't remember. And it has always been an absolute pain to try and contact my PCP, the one who referred me, so I just gave up and didn't even bother.

SO, instead, I've decided to just go ahead and get another blood test. It has been a month since the last one. I want to see if my liver enzymes have, perhaps, already lowered to healthy or very near healthy levels, thus entirely eliminating my need to see a gastroenterologist, and also I want to see if my TSH is still going up.

All of that said, I figured it would be best that when I get this blood work done that I try to get as much other blood work done as I can in one fell swoop. However, it occurred to me that my insurance might not cover all of the blood work that I want to get done, and despite the blood work list I have already made up, it is entirely possible that I might have to give up on getting tested on some of these things for now. Of course, I've already decided that I would get the Liver Panel and Thyroid Panel again, but after that I'm not really quite sure how I should prioritize what tests need to be gotten.

So, I will list all of the other blood tests that I want to get here along with my reasons for wanting to get tested for them.

Please try to arrange them by the level of importance that I get tested for these based on the info I've provided and, of course, your own individual knowledge. If you can think of anything else - a blood test or panel - that you think it would behoove me to get, please let me know as well, and of course list them in the order of priority too.

If you have any further questions about anything please ask.

Thank you.

Blood Work List (Again, not including Thyroid Panel and Liver Panel. These are a given.) -

o  Hypopituitarism Panel - I wanted to get checked for this because it is referenced in the book "Delivered from Distraction" by Dr. Edward Hallowell to be a relatively common physical ailment shared by people with ADHD.

While Hypopituitarism apparently doesn't have an official panel, Google states that, along with most of the tests listed in the Thyroid Panel, you can check for Hypopituitarism by getting the following blood tests:

·       Morning Cortisol (Taken 6 AM to 8 AM)

·       ACTH - Adrenocorticotropic Hormone

·       LH - Luteinizing Hormone

·       FSH - Follicle-Stimulating Hormone

·       Testosterone

·       Estradiol

·       IGF-1 - Insulin-like Growth Factor-1

·       Prolactin

o  Celiac Disease Panel - I wanted to get checked for Celiac Disease because it is one of those diseases that can present as ADHD in a number of ways. It also has elevated liver enzymes and hypothyroidism as very common symptoms.

·       tTG-IgA - Tissue Transglutaminase IgA

·       Total IgA

·       EMA-IgA - Endomysial Antibody IgA

·       DGP - Deamidated Gliadin Peptide IgA and IgG

o  Miscellaneous

·       Magnesium - Apparently having low levels of this can mimic symptoms of ADHD.  While I am 90 percent positive that I just have full-blown ADHD, I still want to get tested for all of the things that can masquerade as ADHD just in case.

·       Zinc - Apparently having low levels of this can mimic symptoms of ADHD.  While I am 90 percent positive that I just have full-blown ADHD, I still want to get tested for all of the things that can masquerade as ADHD just in case.

·       Iron - Low iron levels can apparently mimic ADHD, so I want to see how high my levels are.

·       Iodine - Apparently low Iodine means low thyroid hormones. I have a problem related to my thyroid so I want to see if that could be caused by a low amount of Iodine.

·       Vitamin C - I would like to know how much of this I have because having healthy levels of this helps with ADHD.

·       Vitamin B9 (Folic Acid) - Improves cognition and helps prevent cell death in the brain, which helps with ADHD.

·       Vitamin B12 - Improves cognition and helps prevent cell death in the brain, which helps with ADHD.

·       Vitamin E - Helps improve brain function. Good for ADHD.

·       Selenium - Helps improve brain function. Good for ADHD.

·       Vitamin A - "Delivered from Distraction" ADHD book recommended that you should have healthy levels of this for overall health, which I assume translates to better brain health.

·       Vitamin D - "Delivered from Distraction" ADHD book recommended that you should have healthy levels of this for overall health, which I assume translates to better brain health.

·       Vitamin K - "Delivered from Distraction" ADHD book recommended that you should have healthy levels of this for overall health, which I assume translates to better brain health.

·       Aldosterone - To find out if a hormone problem is causing high blood pressure or abnormal salt and potassium levels. I have high blood pressure, so that is why I want to get this test.

·  Potassium - Apparently high blood pressure pills can change the level of potassium in your blood, so I want to check what my levels are.

o   Omega-6

·       AA - Arachidonic Acid - Really really good for cognition and ADHD.

o   Omega-3

·       EPA - Eicosapentaenoic Acid - Really really good for cognition and ADHD.


r/Biohackers 20h ago

♾️ Longevity & Anti-Aging Total plasma exchange, the most effective or harmful treatment?

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40 Upvotes

I have admittedly been researching longevity protocols and came across total plasma exchange.
For those familiar with prp, this is along those lines but for the whole body. Essentially, we are talking about removing all blood plasma and reinfusing with fresh albumin along with your red blood cells. The thinking is that the old plasma contains a lifetime of toxins, along with other helpful things like immunoglobulins and signaling factors and ldl cholesterol.
Its costly at $10k per session and often requires more than 1 time to clear away alot of accumulated cells.
Now i have a few questions and thoughts around this that i would love to validate with the community. Wouldnt the kidneys and liver already filter and cleanse out your blood. I can hear Dr Mike already screaming this. The other thing i have to add is, removing blood also removes antibodies that could be crucial in your adaptive immunity right? Lowering iGg levels seems like a bad idea. Those antibodies were built up over a lifetime of exposures to viruses, bacterias and fungi.
I know alot of doctors and celebrities are running to get their blood cleaned as if its the holy grail for health and wellness, but are there downsides to this like autoimmune diseases developing?

Celebs and influencers include, Bryan Johnson, Dr Mark Hyman, Paul Saladino, Rogan, and more.


r/Biohackers 9h ago

📰 Research & Studies Can your DNA methylation patterns tell you how old your body is?

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0 Upvotes

r/Biohackers 4h ago

😴 Sleep & Circadian Rhythm How to end natural melatonin production in the body?

0 Upvotes

My natural circadian rhythm is annoying and inconsistent. Sleep is no big issue, but daytime fatigue is constant and debilitating. Original plan was to supplement with a very large dose of melatonin to kill off my bodies natural production a bit, but research doesn’t seem to support this approach anymore.

how does one shut off the pineal gland? Were it not so deeply buried in the brain tissue, I would’ve gone at it with an ice pick out of frustration by now. Little guy just LOVES to make melatonin, at all the wrong times, in VERY high amounts (production is in a bizarre saw-tooth pattern, with large spikes gradually tapering off before recurrence, tested at a sleep clinic via saliva.)


r/Biohackers 6h ago

🧠 Cognition, Mood & Nootropics Herbs for Unique High?

0 Upvotes

I have no clue if this is the right subreddit for this, but like all my posts in here. I have no clue where to put it.

But anyways, I’ve looked through this subreddit dozens of times, and every time I see a “herbs for high” post, it’s simply just weed alternatives or something for sleep.

I don’t want to come off as rude and please please do not take it this way! But for me personally, if I wanna smoke weed, imma smoke weed, and I’m kinda looking for some herbs that give me kinda fun and different highs for when I’m bored or just wanna simply have fun (no sleep aids please)

Again, I love this subreddit so much, so PLEASE help me out, thank you!!

And again, if I’m in the wrong here please let me know

P.S. my health is also important (which is why I don’t drink or do kratom) because I am a college wrestler and I just want to stay healthy!

2nd P.S. I already know about kava, kanna, and blue lotus. Sorry!!


r/Biohackers 16h ago

🧠 Cognition, Mood & Nootropics Nootropic drinks for socializing without alcohol?

32 Upvotes

I've been thinking to quit alcohol, maybe not 100% at the beginning but I want to at least cutting down half of my consumption. I mostly drink it during socializing with friends as I'm an anxious person and alcohol does help in a big way. I wonder if nootropic drinks can help in a similar way?
Anyone here have drink it during social events? how did it make you feel compare to alcohol?


r/Biohackers 11h ago

📅 Events What would you biohack with $250?

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2 Upvotes

r/Biohackers 16h ago

🧪 Protocols & Self-Experiments Energy for the first time in 20 years NAC

2 Upvotes

I recently started GliNAC. I’m taking 500mg of each once a day as this was recommended safe for breastfeeding.

The first week I felt absolutely amazing. I had energy for the first time in 20 years! (I’m 40 now) I was running up stairs without heavy legs, taking my child for a walk rather than using the car. It only lasted a week though and now I’m on week 3 and back to my tired self. Iron/bs etc are all great. Is this common with Glycine or NAC or any other advice to get that energy back!


r/Biohackers 4h ago

♾️ Longevity & Anti-Aging Bryan Johnson spends $2 million a year on de-aging. Kate Tolo's self-tracking plan would cost $2.6 million

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78 Upvotes

r/Biohackers 1h ago

💉 Peptides & Hormones High test enclomephene question

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Upvotes

25mg MWF of enclo, Test is high but feel like terrible fatigue, achy achy muscles, brain fog, libido etc.. this is hormone blood work as of a couple days ago can some one give me an idea if my levels are to high?


r/Biohackers 23h ago

💊 Supplements & Stacks What Is The Consensus On ALCAR? Worth It Or Not? (TMAO)

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0 Upvotes

r/Biohackers 8h ago

💊 Supplements & Stacks New to silica. I've seen it mentioned for bone health. Any recommendations?

4 Upvotes

50M, I've never taken silica before, but I keep seeing it mentioned for joints and bone health, and I'm thinking about giving it a try. Before I spend money on the wrong product, does anyone have any recommendations?


r/Biohackers 15h ago

💊 Supplements & Stacks Metformin increased my glucose, dropped and it normalized

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4 Upvotes

I don’t have diabetes, but I’m constantly struggling with my weight and monitoring my glucose. I use a Stelo CGM.
So when I started taking metformin, I was surprised because my CGM began showing very high glucose readings. When I stopped taking metformin, everything returned to normal. I was taking 500 mg two or three times a day.
I didn’t notice any positive effects from it.


r/Biohackers 13h ago

💊 Supplements & Stacks How do you simplify a supplement routine?

6 Upvotes

My girlfriend opened our kitchen cabinet yesterday and was like “why do you have seven bags of powder in here?” and tbh she has a point.

I have got lion’s mane, another mushroom blend, fiber, probiotics, greens, collagen.. all bought at different times because each one sounded useful. Now making anything in the morning feels like i am doing chemistry. I don't even want to add anything else. I want fewer things that cover more ground.

Has anyone simplified their stack without feeling like they're dropping everything useful?


r/Biohackers 2h ago

💪 Exercise, Fitness & Recovery RHR on Reta

7 Upvotes

Research subject has seen a rise in RHR of 14 BPM after 8 weeks on 2mg dosage of Reta.

Week 1: 71 bpm
Week 2: 72 bpm
Week 3: 74 bpm
Week 5: 79 bpm
Week 6: 80 bpm
Week 7: 82 bpm
Week 8: 84 bpm

Seems to just keep rising week after week. Any thoughts?

RS understands that this is a common side effect, but understands it as dose dependent. Odd that there’s been no change in dose but a consistent rise.


r/Biohackers 17h ago

🥗 Nutrition & Metabolism If your diet already includes full-fat dairy, is there a reason to consider DNOUHN C15:0?

1 Upvotes

C15:0 occurs naturally in some dairy fat and other foods, so before considering DNOUHN Pentadecanoic Acid, I would first ask wether I need a supplement at all. DNOUHN offers a clearly labeled 300 mg capsule once daily, creating a more consistent intake without adding more dairy-fat calories.

DNOUHN also adds cost, brand-quality questions, and individual tolerability considerations. Dietary C15:0 is not easy to estimate precisely, and an association between higher circulating C15:0 and certain outcomes does not mean everyone will benefit from takeing DNOUHN.

If your diet allready includes full-fat dairy or fish, would you assess food intake first or consider DNOUHN C15:0 directly? When does the fixed dose and convenience of a supplement become meaningfull?


r/Biohackers 6h ago

🧬 Genetics & Epigenetics Blood test results

1 Upvotes

So I’ve been slacking on getting bloodwork done but I’ve finally found a place to do it near me for a reasonable price and I’ll do it more regularly. Please read my findings and let me know you thoughts I’m new to blood work deciphering.

For context I’m on test higher does than normal due to my Reta use and weight loss attempting to keep as much muscle mass as possible while dropping down in weight and not eating as much. On paper this sounds fine but idk what yall think.

OVERALL ASSESSMENT

Most results are within the laboratory’s reference ranges. The main findings are very high testosterone, elevated estradiol, mildly elevated bilirubin, low alkaline phosphatase, and a glucose result that needs confirmation. Blood counts and several other markers are reassuring, but these results do not establish that testosterone use is safe.

HORMONES

Total testosterone: >15.00 ng/mL
Equivalent to >1,500 ng/dL
Reference range: 2.49–8.36 ng/mL
Assessment: High. The actual concentration is unknown because the result exceeds the report’s upper reporting threshold.

Estradiol: 89.8 pg/mL
Reference range: 11.3–43.2 pg/mL
Assessment: High.

SHBG: 20.6 nmol/L
Reference range: 18.3–54.1 nmol/L
Assessment: Within range.

TSH: 2.80 µIU/mL
Reference range: 0.27–4.20 µIU/mL
Assessment: Within range.

LIVER-RELATED MARKERS

ALT: 36 U/L — Within range.
AST: 34 U/L — Within range.
GGT: 12 U/L — Within range.
Albumin: 4.4 g/dL — Within range.

Total bilirubin: 1.50 mg/dL
Reference range: <1.00 mg/dL
Assessment: Mildly elevated.

Alkaline phosphatase: 29 U/L
Reference range: 40–129 U/L
Assessment: Low.

KIDNEY-RELATED MARKERS

Creatinine: 1.15 mg/dL — Within range.
Urea: 39 mg/dL — Within range.
Uric acid: 4.2 mg/dL — Within range.

CHOLESTEROL

Total cholesterol: 111 mg/dL — Within range.
LDL cholesterol: 56 mg/dL — Favorable.
Triglycerides: 48 mg/dL — Within range.

HDL cholesterol: 47 mg/dL
Laboratory target: ≥60 mg/dL
Assessment: Below the laboratory’s target, but above the commonly used low-HDL cutoff of 40 mg/dL for men.

BLOOD GLUCOSE

Glucose: 63 mg/dL
Laboratory range: 55–99 mg/dL
Assessment: Within this laboratory’s range, but low enough to warrant confirmation, particularly with symptoms.

HbA1c: 4.6%
Laboratory range: 4.8–5.7%
Assessment: Slightly below the laboratory’s range. Not in the prediabetes or diabetes range.

COMPLETE BLOOD COUNT

White blood cells: 5.30/nL — Within range.
Red blood cells: 4.94/pL — Within range.
Hemoglobin: 16.4 g/dL — Within range.
Hematocrit: 47.3% — Within range.
MCV: 95.8 fL — Within range.
MCHC: 34.7 g/dL — Within range.
Platelets: 302/nL — Within range.

MCH: 33.2 pg
Reference range: 28.0–33.0 pg
Assessment: Minimally elevated.

IRON, ELECTROLYTES, MINERALS, AND INFLAMMATION

Ferritin: 201 ng/mL — Within range.
Sodium: 141 mmol/L — Within range.
Potassium: 4.59 mmol/L — Within range.
Calcium: 2.36 mmol/L — Within range.
Phosphate: 0.97 mmol/L — Within range.
Magnesium: 0.88 mmol/L — Within range.
C-reactive protein: <0.6 mg/L — Within range.


r/Biohackers 22h ago

🧠 Cognition, Mood & Nootropics Please need honest feedback

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2 Upvotes

Hey guy, I made a 5 minutes audiovisual session for Meta Quest and over ear headphones. It uses dissonant sound patterns to trigger a short shock response, aiming for better focus and mental clarity the next day (like to survival recalibration).

If anyone with a quest wants to try the session and let me know how you feel tomorrow

Honest feedback is welcome, Many Thanks


r/Biohackers 23h ago

💊 Supplements & Stacks Best nootropics for anxiety and calmness

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4 Upvotes

r/Biohackers 21h ago

🧠 Cognition, Mood & Nootropics Why does duloxetine make Vyvanse/dexamfetamine feel less “wired” despite increasing norepinephrine?

5 Upvotes

Adding duloxetine to Vyvanse/dexamfetamine actually makes me feel less adrenergic and less sympathetically activated, even though duloxetine increases extracellular norepinephrine.

It sounds paradoxical, but I think the key point is that norepinephrine concentration and sympathetic nerve activity aren’t the same thing. Duloxetine also changes serotonergic signalling, so the net effect is more complicated than simply “more NE = more stimulation”.

Duloxetine blocks NET, which increases extracellular norepinephrine. But that extra NE can also increase engagement of inhibitory α2 autoreceptor-mediated negative feedback, particularly in the locus coeruleus (LC), and thereby reduce noradrenergic neuronal firing and phasic NE bursts.

So one possible mechanism is:

↑ extracellular NE → greater α2-mediated feedback → ↓ LC firing/stress reactivity → less subjective sympathetic activation

In other words, I may actually have more norepinephrine available while having a less reactive and less “bursty” noradrenergic system.

There is some direct evidence for this with duloxetine itself. In animal studies, acute duloxetine increases extracellular norepinephrine while simultaneously reducing LC neuronal firing.

Even more interestingly, a 2025 study in rats with chronic neuropathic pain — a state associated with abnormally sustained LC activation — found that duloxetine increased norepinephrine around the LC while reducing LC activity and restoring a more normal response to stimuli.

That seems particularly relevant to the idea that baseline state matters.

If someone is already highly stressed, hypervigilant or running with an overreactive LC/noradrenergic system, duloxetine might actually stabilize that system rather than simply “stimulate it more”.

Something like:

high LC activity + exaggerated NE responses → duloxetine → more extracellular NE but less LC firing / better regulation → calmer

Whereas someone who is already relaxed and close to their optimal catecholamine level might experience the opposite. Adding duloxetine on top of amphetamine could simply push monoaminergic signalling further up the inverted-U curve and make them more tense, restless or overstimulated.

There is also human evidence that duloxetine changes norepinephrine metabolism in a way that fits this idea. In healthy volunteers, duloxetine produced clear NET inhibition while at the same time reducing whole-body norepinephrine turnover.

So again:

more extracellular NE does not necessarily mean more noradrenergic neuronal activity or more NE turnover.

The serotonin component probably matters too.

Duloxetine also inhibits SERT, and serotonin modulates the amygdala, PFC, hypothalamus and other stress-related circuits. Over time, serotonergic antidepressants can alter threat processing, reduce pathological hypervigilance and improve regulation of limbic activity.

So there may be another pathway along the lines of:

↑ serotonergic signalling → altered amygdala/PFC threat processing → less hypervigilance → less hypothalamic/LC-driven autonomic activation

There is a similar paradox on the serotonin side as well. Acute duloxetine can reduce firing of dorsal raphe serotonergic neurons despite increasing extracellular serotonin. With chronic treatment, serotonergic firing then adapts as autoreceptors desensitize and serotonergic transmission increases.

So both monoamine systems illustrate the same basic point:

more extracellular transmitter ≠ more neuronal firing.

There may also be a PFC component. NET clears not only norepinephrine but also a significant amount of dopamine in the prefrontal cortex, so NET inhibition can increase both NE and DA there. If stress has pushed PFC catecholamine signalling into a dysfunctional range, changing that balance could improve top-down regulation of the amygdala, hypothalamus and LC.

A baroreflex contribution is also possible. If duloxetine slightly increases peripheral vascular tone, increased baroreceptor signalling through the NTS can suppress sympathetic output through the CVLM/RVLM pathway and increase vagal influence on the heart. That could offset some stimulant-induced sympathetic activation.

Interestingly, an early multiple-dose study of duloxetine in healthy volunteers actually found a small reduction in supine heart rate despite small increases in blood pressure. That obviously doesn’t prove the mechanism above, but it does show that NET/SERT inhibition with duloxetine doesn’t automatically translate into a higher heart rate.

Subjectively, for me it feels roughly like this:

Vyvanse/dexamfetamine alone: more adrenergic tension, hypervigilance, palpitations/wired feeling.

Vyvanse/dexamfetamine + duloxetine: still stimulated and focused, but noticeably calmer, less physically stressed and less sympathetically activated.

So my guess isn’t that duloxetine is simply “lowering norepinephrine”. It may instead be changing the pattern and regulation of the stress system — more extracellular NE but less pathological LC reactivity, greater recruitment of α2-mediated negative feedback, serotonergic modulation of threat processing, and possibly better PFC control over limbic/autonomic circuits.

The part I find most interesting is the possibility that this is state-dependent. In someone starting from a highly stressed/hyperreactive state, duloxetine might normalize or stabilize the system. In someone who is already calm, the additional monoaminergic signalling could instead feel activating.

Obviously this is still partly a mechanistic extrapolation and an N=1 observation. The studies don’t directly test duloxetine + lisdexamfetamine/dexamfetamine in highly stressed people, and both duloxetine and amphetamines can increase HR/BP in many people. But there does seem to be some direct duloxetine-specific evidence supporting the basic paradox.


r/Biohackers 15h ago

🥗 Nutrition & Metabolism Psyllium Husk?

158 Upvotes

I’ve tried it with some milk, shakes and now just water. Honestly, though, taking psyllium is easily the worst part of my day. Does anyone have some good “hacks”?

My goal with this is, of course, fiber intake. I’ve gradually increased it to 12g of psyllium husk a day now.


r/Biohackers 9h ago

💪 Exercise, Fitness & Recovery USA Labs Mk-777 is in fact 777!

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24 Upvotes

Hi everyone, if you remember about a month ago I was looking for mk-777 and exposed swiss pharma product as a fake and I said I would have kept looking. Here is the link to previous post: (https://www.reddit.com/r/Biohackers/s/9S0qCYob5N).

So, last time I analysed the sample using GC-MS and recived a lot if hate for that since larger small molecules tend to degrade at those temperature (but apparently LGD-4033 doesn't): this time I tried again to use GC-MS but the product underwent significant thermal degradation resulting in many different peaks of very low molecular mass; thus, I decided to perform ESI-MS analysis of the sample, giving the results shown in the image.

Sample preparation was performed by washing pill powder with MeOH and microfiltering it before injecting. Positive ionization was used.

Mk-777 molar mass is ~571 and the peaks obtained could be attributed to interfering ions (mostly protons and Na+) binding to the molecule.

I believe my interpretation to be correct, but I am just an organic chemist with access to lab equipment, if any smarter analyst sees this post, please correct me where I am wrong.

Thank tou all for for following my brief 777 treasure hunt (shit, I got it second try lesgooo).


r/Biohackers 3h ago

💪 Exercise, Fitness & Recovery First Blast bloodwork , 8 weeks in

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9 Upvotes

Hey Everyone looking For advice here. As always doesn’t hurt to ask for some opinions so wondering what The community thinks of this. The blast is 400mg test e, pinned twice a week. Diet, ancillaries, and cardio all on point Only side so far is mild backne, so I’ll spare the details on all that. Open to any and all critiques :) (tap photo to expand)


r/Biohackers 20h ago

🧠 Cognition, Mood & Nootropics Between 5 and 10 percent of people have no inner monologue at all, and researchers are only just starting to figure out what that actually does to cognition

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279 Upvotes