nootropics & friends

cross-posted from: https://metawire.eu/post/105642

A study found that people who had suffered the herpes virus had an 80% increased risk of Alzheimer’s disease.

Our findings revealed AlCl3 exposure induced significant neurobehavioral deficits, oxidative stress, neuroinflammation, and loss of the Purkinje cell layer of the cerebellum. Treatment with apigenin attenuated neuroinflammation and enhanced learning and memory with significant improvement in recognition index.

Scripps Research scientists created a stable form of carnosic acid, observing greater memory function and other disease improvements in mice.

Researchers at the University of Reading tested participants who ate a walnut-enriched breakfast and found significant cognitive benefits compared to a nut-free meal. The study highlights the potential of walnuts as a natural brain enhancer, but more research is needed to fully understand their impact.

Seven days after their splurge had ended, the junk-food group had lower brain activity in two regions associated with memory and response to visual food cues.

Now, a new study that will be presented at the American Academy of Neurology’s 77th Annual Meeting in early April 2025 provides further evidence of a link between more exercise with less risk of developing certain neuropsychiatric diseases.

New research suggests that certain antidepressants can accelerate cognitive decline in people with dementia. At the same time, some drugs appear to be less harmful than others, which can help doctors make better treatment decisions, according to the study.

A new study suggests that omega-3 and vitamin D supplements, when combined with regular exercise, may help slow biological aging by several months over a 3-year period.

Researchers analysed data from the DO-HEALTH trial, which tracked over 700 older adults and found that those who followed this regimen experienced measurable benefits at the molecular level.

The researchers said that even though the effects might seem small, they could still make a big difference for public health — helping to lower the risk of age-related health issues and improving the well-being of older adults.

• The primary finding of this analysis is that resistance training significantly improved brain-derived neurotrophic factor (BDNF) among older adults aged 60 years or more. • The effects of resistance training on BDNF levels were significant regardless of intervention duration or gender. However, the effects were more pronounced in older adults with poor health. • Resistance training caused improvements in depressive symptoms in older adults.

Saw this new supplement carried by Cosmic. Big fan of bromantane so was curious when I saw this being compared to it. The reviews of all though seem to imply that it’s being used for workouts when I’m more interested in the anxiolytic affect, fatigue reduction, and focus.

Nootropics Depot

Tiger Milk | Could It Be The New Lion's Mane? | This Rare Malaysian Mushroom Is Finally On The Prowl

Tiger Milk Mushroom is highly sought after for its respiratory and cognitive benefits. Learn about this fabled mushroom and our new mushroom research in this month’s podcast episode!

Buy Tiger Milk Mushroom from Nootropics Depot https://nootropicsdepot.com/tiger-mil...

On this episode of ‘In Search of Insight’ (episode #21), we explore Lignosus rhinocerus, better known as the tiger milk mushroom. Tiger Milk is a newcomer to the functional mushroom scene, and up until recently has been extremely rare. Traditional knowledge about tiger milk mushroom comes from Malaysia, where the indigenous population has been using this mushroom for hundreds of years. Its rarity is due to the fact that tiger milk mushrooms do not tend to grow close to each other in the wild. According to traditional knowledge, the tiger milk mushrooms seem to grow many kilometers apart from each other. This makes gathering sufficient amounts of tiger milk mushroom in the wild extremely difficult! The logical answer is to cultivate the tiger milk mushroom.

A little over a decade ago, Dr. Tan Chon Seng made major advances in the cultivation of tiger milk mushroom. Once a viable cultivation method was scaled up for production, research on tiger milk mushroom started to boom. For the first time in history, researchers had access to sufficient quantities of tiger milk mushroom. In a short period of time, there are fully fledged human clinical trials coming out about the unique respiratory effects of tiger milk mushroom!

Despite cultivation and research in the last decade, there are still plenty of knowledge gaps. Within the United States, there wasn’t a botanical reference material (BRM) that could be used to verify whether a tiger milk mushroom product is Lignosus rhinoceros. We needed to get our own BRM made for tiger milk mushroom. This project was undertaken by our lab director, James Jursich (Jay)! With this in mind, and the hard work Jay put into this project, we thought it would be interesting to have Jay as a guest on our podcast.

We are the first major U.S. functional mushroom vendor to come out with a very high quality tiger milk mushroom product, and are sure to make waves in the functional mushroom space! Tune into this episode to find out why we are over the moon about this unique mushroom!

Courtesy of /u/wefashionnow

After recently purchasing some Gotu Kola, I came across studies linking ingestion to decreased testosterone and decreased sperm motility.

The studies can be viewed here: http://www.ncbi.nlm.nih.gov/pubmed/20589353, http://www.ncbi.nlm.nih.gov/pubmed/21870191

Unfortunately, the full texts are behind a pay wall. I'm trying to determine if these studies actually demonstrate a very real problem with Gotu Kola, or if it's simply alarmist. One thing to consider is the high 100+mg/kg dosage used in the first study. Comparatively, humans take below 50mg/kg.

Thoughts on Gotu Kola? Is it safe?

*** Some Comments ***

• Again, anecdotal, but Gotu Kola seems to stimulate skin regeneration for me (scars and blemishes seem to go away more quickly when taking it). I take it for my acne.

  • That's interesting. Do you have any references for gotu kola helping with scars?

    • http://umm.edu/health/medical/altmed/herb/gotu-kola Edit: in that reference they seem to recommend topical application to treat scars and wounds, while I ingest it. I don't know what the bio-availability is for the triterpenoids when ingested, but again, it works for me.

• It works extremely well for me, I use tulsi + gotu kola. Tolerance develops pretty quickly but it is very reliable anxiolytic if I don't have it all the time.

• Ashwagandha might help mitigate the anti-androgenic effects. Traditionally, they are often taken together. You may need more research.

  • Holy basil (usually also taken together) can also be used to increase testosterone

It is also dirt cheap.

Nicotinamide Adenine Dinucleotide Augmentationin Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study

This study was just published Feb 6. It is sponsored by Metrobiotech, a company co-founded by Dr. Sinclair, and used their patented form of NMN called MIB 626.

MIB-626 is a special crystalline form of NMN created to be more stable than the standard NMN that was used back in 2016, but has little or no advantage over NMN now available on the market.

30 overweight adults (over 45 years old) were given either 1,000 mg NMN or placebo twice daily for 28 days. Significant improvements were:

Lower LDL Cholesterol

Lower Total Cholesterol

Lower Diastolic Blood Pressure

Lower Weight

Over 200% increase in NAD+ levels

There was a trend towards lower Systolic Blood Pressure and increased strength, but did not reach statistical significance.

Certainly not as striking as Dr. Sinclair's research in mice, but not bad considering the short time frame and limited number of participants which make it harder to reach statistically significant findings.

It is yet another positive result for NMN in human studies. Some quotes from the study below:

a regimen of 1000 mg of MIB-626 twice daily was safe and efficacious

MIB-626 treatment was associated with a substantial increase in blood NAD level from baseline to days 14 and 28

Circulating NMN levels did not change significantly in either group, except transiently 2 hours after the dose on day 28

Body weight decreased in the participants randomized to the MIB-626 group and increased in those assigned to the placebo group; between-group difference in change in body weight was statistically significant

Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and non-high–density lipoprotein (HDL) cholesterol levels decreased from baseline in the MIB-626 group

Diastolic blood pressure decreased from baseline in the MIB-626 group

Conclusions: MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure.

Renuebyscience for NMN info

credit: u/melljo2013

Very satisfying and effective combinations of what I'm going to call over-the-counter stimulants and energy supporting stacks can achieve a lot of the results of 'proper-stimulants', but contrary to a lot of online literature, can never match or replace them. The ones I listed (Theacrine, Zynamite, EnXtra, Primavie, GS15-4 and plain old caffeine) stand out personally. There are endless potential combinations but I will put an examplar stack here as a guide, note that this would be an elite stack and using just several of these will produce a good result. The below should provide very high levels of motivation, energy and focus for 6 hours

Zynamite 300mg, Theacrine 300mg, Caffeine 50mg, GS15-4 100mg, Alpha-GPC 300mg, CDP-Choline 150mg, ALCAR 1g, Magnesium (ATA-Mg is worth the money IMO but L-theronate is very good, I'm also very impressed with bio-optimisers blend of 7. Doses will vary but tend to the high to very high,. Rhodiola Rosea (preferably in 5-2 but 3-1 is fine) in 250-500mg. B-vitamin stack (again doses vary, worth adding in modified b-vitamins IMO, sulbutiamine, emoxypine, benfotiamine). NALT 500mg, DL-Phenylaline 250mg, L-Phenylaline 250mg, EnXtra 300mg, Primavie 200mg, L-Tryptophan 300mg, Trans-Reservatrol 250mg, NMN 500mg, L-theanine 400mg. I could go on, but this is a good example; some of these you might want to take twice or even three times, but you will have to do the research yourself I am afraid. I have referenced branded or patented ingredients here; I don't take a particular view on branded vs non-branded. Look at it case by case, in many cases (e.g Theacrine and CDP-Choline) you can get an identical product with the same effects at a lesser price. In other cases, e.g Zynamite and Primavie, the patented form offers genuine and worthwhile benefits.

I will address this in other posts, but since I have offered a stack I will quickly address it. Most of the time preformulated stacks are useless and a complete waste of money. For example, I came across this energy product from Motion Nutrition promising 12hr energy when the very well formulated and high dosed stack I just offered would, by my estimation, offer 6hrs of peak energy and a further 2-3 petering out. https://motionnutrition.com/products/power-up. Rip off! Qualia products are an exception, they are very well formulated but it is cheaper to copy their stacks–buy the ingredients in bulk and DIY–but I will talk about this another time.

The best approach is a long-term approach to your body's own energy and mitochondrial capacity, which I will briefly turn to in my First Priorities Section.

H) Phenibut and it's other forms. Phenibut stands alone in its effects and its medical-grade anti-anxiety potency. For writers or creatives it is a must. I will write a separate article because using phenibut properly is so powerful, hence it's inclusion on the list, but very difficult to achieve.

I) Practices - Most powerful practices with intelligence enhancing benefits are Dual-N-Back for fluid intelligence, and CWM and meditation for a variety of reasons.

2. Powerful Nootropics To Avoid.

A) Sunifram, Unifram and (Controversially) Nooept. I will be brief here, the 'frams' are exceedingly powerful to be sure, they are cheap and provide a good output-to-price ratio. I am sure some people respond very well to them, and I have from time to time caught that very valuable 'flow-state' these substances can provide. A lot of the time though I just don't see it; I feel uninformed about them, and tolerance is a huge problem as well as, again, the risk-output ratio. Its study by DARPA is a good indication to me. But IMO, with the frams, I just don't see it. Similarly for nooept, it is great value for money in terms of potential output. It clearly does have potent neurogenic effects across multiple pathways and it has the potential for good application in analytical, logical or otherwise cognitively rigid tasks. Most of the time though I just don't see it; it can have strange effects on personality, can dampen creativity and produces similarly strange effects on short-term memory. Complex working memory is, for me, a cornerstone of higher order intelligence, anything that jeopardises CWM should be approached with great caution.

B) PRL-8-53, IDRA-21, NSI-189, J147, Memantine, Kratom, Tianeptine, DMHA. I don't think there's anything there, I haven't seen many credible reports that there is. I grouped all these together because they all belong to a similar family of at times hyped nootropics with big promises that I have personally found to work very sporadically, or not at all. Or I fear they could be seriously damaging. (IDRA-21 just does not work; I seriously cannot make out any difference or see changes in any cognitive metric at all. It's as if it is pharmacologically inert). NSI-189 dosed low at maybe 20mg might have some promise, and I've seen hints of potentially great benefits, but the emotional and attentional side effects you encounter–especially when dosed at the standard 40mg/day–concern me given the behavioural reinforcement that neurogenics can establish. I am not completely writing these off, actually, I will write off IDRA-21. It is useless, but these are only for the psychonauts to explore, or those obsessed/fascinated with exploring nootropics.

C) Unstable or otherwise difficult to manufacture peptides. Although the peptides I am talking about here show potential, and in my experiences have been in the rarified league of Dihexa, the difficulty and complexity in producing the genuine article of these nootropics means you are very unlikely to be getting a reliable or accurate product. I have been able to get these in what I believe to be genuine form very few times and at great expense. With the demise of science.bio, the dubious status of cymnootropics, and in the EU Suaway, the creation of a truly professional and reputable nootropic industry still seems some way off. Hence, I advise against: Adamax, P21, HA-FGL and GSB-106 alongside any other very complex peptides.

3. Priorities. Although I have listed some very powerful individual nootropics, I will briefly discuss something I will write a seperate post about. The two foundational priorities you should IMO focus on first: Brain Structure and Health and Energy Production.

Brain Structure. This is a loose catch-all term for all the different aspects of brain physiology we can influence. Membrane fluidity, blood flow, neurogenesis etc. This is the core of all aspects of intelligence and long-term cognitive health, I won't look at it in depth, but a quick list of essentials per day might look like this:

DHA 600mg, Phosphatidylserine 300mg, Uridine 250mg, Bacopa Moneri 450mg, Gotu Kola 900mg, SAM-e 400mg, Vinpocetine 30mg, B-Vitamin stack

Energy. Well-functioning energy creation, in particular mitochondrial function, is increasingly seen as integral to all aspects of cognitive function. Very briefly you might consider:

PQQ 20mg, COQ10 100mg, R-ALA 100mg, ALCAR 1000mg, Creatine 5g, Methylene Blue, L-Carnosine, Reservatrol, Psterobilene, NMN, NADH, NAC or NACET.

credit: u/melljo2013

My focus here will be some of the most powerful nootropics that genuinely contribute to the different modalities of intelligence in the biggest way.

1. Most Powerful Nootropics For Broad Spectrum Intelligence Gains: Though there is no consensus, I will assume a schema of intelligence that takes fluid, crystal and procedural intelligence to represent the core modalities. Creating your own understanding of intelligence and what aspects of intelligence are most relevant to you is an essential first step. Even if it is a rough list of intelligence goals, it is very helpful and makes the nootropic journey far more streamlined

A) Dihexa. Bar none, and by a huge margin, the most effective and risky nootropic I have tried. Again, I stress the magnitude of this nootropic's effectiveness is huge, nothing comes close. The same is true of the risk of the compound. It is able to generate curiosity. The motivation and drive to learn more and think about ideas in a novel way–that is priceless. Its effects on fluid intelligence, creativity, learning, memory, social skills, motivation and perspicacity are incredible. It does leave lasting effects, but they decline somewhat over the medium term. The affective disposition of Dihexa is most intense during the initial two months. The experience of it is similar to microdosing alongside a huge stack of nootropics, but it is unique. It is expensive and increasingly difficult to find. I recommend application via transdermal DMSO, 15-30mg every 3-5 days for at most 5 weeks. Again, I stress that in my opinion this is the most risky nootropic in terms of potential complications down the line.

B) Nefiracetam. Most effective racetam by far. Broad spectrum effects via multiple bio-pathways. Enhances learning, creativity, motivation and alleviates low mood, specifically apathy and anxiety, very effectively. In particular, if you are trying to learn something new it is very effective and the mood stabilising effects are an under-appreciated component. It is very subtle and has to be taken repeatedly over a long time frame. It is unable to provide the 'feel' of phenylpiracetam which is so alluring, but in terms of broad-spectrum and long-term improvements to intelligence, it is the best racetam by far. It is, however, prohibitively expensive. I am not sure exactly why it is so expensive, but if you can afford it, I reccomend prioritising this one nootropic over a stack of ten cheaper ones. Take 150-300mg three times a day at least 5 days a week, with all the usual choline stacking and MCT oil.

C) Centrophenoxine, Sulbutiamine and Phenylpiracetam. Far better known than the first two, but still under-utlised. This is the most high impact 'short-term' stack, i.e what is going to give the greatest cognitive benefit over the next 4 hours. They don't need much explanation given their popularity. (Again typical Choline and MCT Stacking)

D) PAO, Pramiracetam, Aniracetam, Oxiracetam. Again, very well known but it really does work. Dose the aniracetam high and the pramiracetam and oxiracetam low, combine with low doses of centrophenoxine and sulbutiamine for even greater effects. (Again typical Choline and MCT Stacking). Coluracetam is highly effective for some as a substitute or even very low doses alongside pramiracetam. As for Fascoracetam, I have at times found it useful in dealing with anxiety. If you can find them, RGPU-95 and Methylphenylpiracetam take the racetam effect to a completely different level–but you won't find them. In general, Pramiracetam, Phenylpiracetam and Nefiracetam should be your priorities. Almost all racetams can be put to good use at something and their effects can be endlessly and fruitfully augmented, but stick to what I have said if you're time/cash poor. I do not particularly like Oxiracetam; its MTOR pathway can create strange effects. Racetams, for now, have to form a central part of any nootropic stack that claims to be amongst the best or credible in manifesting it's aims, but pay attention to what you can use consistently and what you can deploy rarely but deliberately. For every racetam other than aniracetam and nefiracetam, you should dose low, below the typical recommendations, but you can find sensible guidelines online. Racetams, probably more than anything else, deserve experimentation and personalisation. They are very adaptible and responsive in stacks. I maintain that other than RGPU-95 and Methylphenylpiracetam, which you most likely cannot acquire, nefiracetam offers the most comprehensive benefits along unique pathways. There is no reason to take plain old piracetam when we have more effective alternatives, don't do it.

E) Selank and Semax in the NASA form. Again very well known, but as I said, I am listing the (or some of) the most powerful nootropics for broad spectrum intelligence gains. Research is needed, but the combination works wonders across mood and emotive-related intelligence. Semax in the NASA form has a very appreciable stimulatory/motivation effect via multiple pathways and contributes to long-term brain health as well as the main cognitive goals I have listed. Selank manages anxiety/stress/adaptivity along multiple unique pathways and works synergistically with semax. Selank also offers strong cognitive benefits indirectly and directly through it's contribution to mood in addition to homeostatic and adaptive regulation of the nervous system. IMO there is a significant difference between NASA form and others, and I think for the dual short and long-term effects, NASA is actually very good value for money. Recommend 100mcg-300mcg (stay as low as is still productive for you) of both 1-3 times a day, depending on your response.

F) 9-mbc. Can be spoken of as similar to Dihexa. Motivational effects are unparalled (except for perhaps Dihexa itself). Contributes to long-term brain health and provides short term effect after first 2-3 days of use. Noted for tolerance reduction. In a similar vein to Dihexa, it nearly crosses the boundary from cognitive augmentation to actual personality changes. It is very useful for setting new habits. Very useful guides can be found on reddit. I have combined it with Dihexa; this is very risky, risk increases exponentially on combination, but it was incredibly effective. Probably deserves number one ranking in the motivational and ADHD type symptom management category, as well as a high place in analytical improvement. Recommend 7.5-15mg sublingual for at most 28 days.

G) N-Methyl-Cyclazadone (NMC). By far the most functional stimulant I have ever taken. Broad-spectrum effects, very high sense of motivation, energy and mood but never in a way that is comparable to adderall, ritalin, modafinil etc. The serotonergic component seems to be very important in creating the contented and productive state that is hugely ergogenic and just as potent as other stims in providing stamina without creating the speedy, jittery, robotic and cognitively limiting effects that adderall etc can create. It has a broader spectrum of effects than other stimulants, and instead of just generating 'drive' or 'energy' it offers perspectival and cognitive benefits as well, far beyond other stims. It is absolutely wonderful, 9hrs of studying and music becomes a joy. It does create very euphoric and enjoyable– and I can imagine habit-forming–effects somewhere between 25-35mg. This is obviously to be avoided, and these effects are absent at 20mg and below. I don't recommend pushing above 15mg, up to 20mg if you really need to, but 15mg potentiated by our favourite light nootropic stimulants (Theacrine, Zynamite, EnXtra, Primavie, GS15-4 and plain old caffeine) is preferable. This is also becoming very difficult to find, but it is the ultimate nootropic stimulant in my opinion.

F) FlModafinil is very nice in my opinion, offering a smoother and slightly broader range of effects than other afanils. I cannot recommend the likes of adrafinil, hydrafinil etc. I am sure there are good stacks that optimise these, and they are available and cheap, but it is absolutely worth having a true nootropic stimulant in your rotation–which I do not think the pro-drug afinils are. PPAP, Selegine, Deprenyl, RGPU-95 (which deserves a special mention as an incredible if hard to acess nootropic) are all in the same league as NMC, but are far more specialised and complicated to use.