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The Little Known Truth About Smart Drugs And Nootropics (Audio & Article)

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The following is a guest post by Dr. Andrew Hill, Lead Neuroscientist at truBrain. Click here for a fascinating audio podcast that accompanies this article. featuring Ben Greenfield and Dr. Hill.

Dr. Hill received his PhD in Cognitive Neuroscience from UCLA in 2012, studying how attention operates in the brain. He has been employed as a Lecturer at UCLA over the past few years, teaching multidisciplinary courses on both Healthy Brain Aging and courses in Neuroscience and Psychology. Dr. Hill has published chapters on measuring and modulating human attention, and continues to research self regulation.

Prior to UCLA, Dr. Hill obtained extensive experience working with both psychiatric and developmental populations as well as gaining experience in high technology areas. He received his B.S. in Psychology/Neuroscience from UMass Amherst, and is a key adviser in the formulation of the truBrain’s cognitive blend (get 20% off on your purchase with the code BEN20).

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The Limitless Pill

In the 2011 movie Limitless, Bradley Cooper’s character gets his hands on a smart drug (NZT-48) that enables him to be cognitively super human.  

The only known side effect is that his eyes change color while he is on the drug, but that changes over the course of the movie as side effects, including withdrawal symptoms, begin to get worse and worse.  It’s a sci-fi thriller with a not-so-feel-good message about addiction and performance enhancing substances.  And goons chasing you.

Makes smart drugs sound dangerous, right?

Like any good sci-fi , this movie questions our assumption on the limits of science.  And some of what it is suggesting is not science fiction today. Smart drugs and nootropics are a current reality, being used more and more not to treat or remediate any active condition or complaint but towards boosting already typical or superior performance, in colleges, board rooms, military theatres, and by forward thinking gerontologists.

With the wide variety of compounds available today that have some research support for cognitive effects, it is important for you to understand the risks and benefits associated with usage, or at least how to choose smarter, when choosing things that affect your brain.

For example, one of the most popular misconceptions about smart drugs is that they are the same as nootropics.  This may be due to similar benefits that people use them for, but ultimately they do not share the same range of effects, mechanisms of action, safety and side effects.

So – what are smart drugs?  What are nootropics?  How do we know if something is safe or effective?  What are these drugs actually doing to my brain?  Why am I asking so many questions without answering them?  Keep reading to get this and more information you need to understand these questions, and start formulating your own answers – and your own strategies for selecting nootropics. 

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Smart Drugs vs. Nootropics

A smart drug is generally a prescribed medication or off-label drug used primarily to treat some kind of mental or cognitive disorder.

The most common are drugs such as Adderall (dextroamphetamine) or Ritalin (methylphenidate) in the stimulant class used to treat symptoms related to ADHD – although legal and illegal off-label use is rampant.  And while they may promote focus and energy in some people, others have dramatic side effect, to body and brain.  Smart drugs in the stimulant class also tend to be reinforcing, producing spikes in dopamine and norepinephrine.

This leads to tolerance and habit formation, including adverse effects on appetite, mood stability, cardiac function, stress levels and possibly many other unwanted effects – especially on younger brains such as teens and young adults.  Irritability and mood swings, anxiety, sleep issues, and other forms of emotional or cognitive regulation problems can crop up over time with stimulant use, as well.

A popular atypical stimulant “smart drug” includes the narcolepsy agents Modafinil / Adrafinil, although their effects on cognition beyond wakefulness are unproven, and side effects – while rare – can be life threatening.  If attention problems are already present the side effect risk appears to be significant increased, as well. (Kumar, (2008), Approved and Investigational Uses, Drugs. 68(13):1803-39.).

In contrast to a smart drug, a nootropic is generally a non-prescribed compound, including vitamins, herb, other supplements, natural or synthetic compound that may increase or protect cognition in some way.  The preponderance of research in the past 40 years shows some effects on focus, attention, effects on aging, and possibly cellular metabolism.

To paraphrase the definition of “nootropic” as initially coined in this article by the researcher Girugea in 1972, it is something that improves cognition without appreciable side effects, or provides from protection to the brain.

In a modern context we think of nootropics as something used not to treat any mental condition or pathology directly, but instead to provide support to peak function, protect against long term risk, and provide daily boost.  Across the field, true nootropic ingredients and full blends can now be found largely sourced from natural ingredients.  Nootropic blends are designed to leverage synergy effects suggested in the research and subjective experiences.   The goals with nootropics should always be to allow for greater and more consistent cognitive effort and flow, without the side effects of a stimulant or other harsh substance.

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How Do I Know If A Smart Drug Is Safe?

As a rule of thumb, it is the nature of science to be wrong at times.  

We’ve come a long way since we accepted that the theory behind the Earth being the center of the universe was wrong.  We understand that new research may overturn old knowledge.  So how can we truly know the risks and benefits of long term use of nootropics or smart drugs?

A red flag in understanding the harm of a substance is the body’s ability to handle an overabundance of this substance.  Small amounts of toxic substances may be beneficial in the short term, but the magic happens when we look at what is happening in the body when we get too much.  Something as simple as a cup of coffee may seem harmless, but caffeine in high amounts can cause dizziness, anxiety, and even cardiac arrest or death.  Caffeine mimics the action of the neuromodulator adenosine in the body.  This leads to higher adrenaline and cortisol levels.

Even in typical doses caffeine can deeply affect our sleep and cause heart arrhythmias for some people.   Alcohol has even worse short and long term toxicity symptoms at non-moderate doses, and some people struggle to keep their dosing moderate.  In better doses – perhaps a couple cups of coffee a day (without sugar) and a drink or so per day on average, these substance are actively health promoting, and reduce risk for many brain and cardiac diseases.  When you are picking substances and compounds, dosing should be cautious at first.

From this, a couple rules come out –

1) don’t take any compounds, substance, or blends of substances that don’t list all their ingredients out in plain amounts.  

Proprietary blends with lump-sum amount hiding buzzword-compliant list of magical ingredients known as “fairy dusting” in the supplement industry.

Don’t be fooled.

Read the ingredients.

Figure out why and what is in there, and if you want it.

2) don’t chase suspicious research chemicals without much history of use or safety profile.  

Experiment on yourself if you like, but you only have one brain – make rational and cautious choices.  There are nootropic, smart drug, and cognitive enhancers that have been around for decades – something released last week as a “Research Chemical” with a bunch of numbers and letters for a name and no human studies isn’t worth the risk to you.  Not for years.

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What About Adderall & Modafinil Safety?

Smart drugs such as Adderall can cause dangerous lows, psychosis with extreme use, rebound fatigue, and depression, even at lower use levels.  As an amphetamine, Adderall can act as a reuptake inhibitor, meaning that it can compete with other neurotransmitters for reuptake.

Specifically it is thought to block the uptake of dopamine and norepinephrine, which are associated with reward behaviors and our nervous system functions, respectively.  This causes a flood of these neurotransmitters onto multiple receptors, causing neurotransmitter depletion and overexcited receiving neurons.  This large “signal” is the reason for the focus, but also responsible for some of the side effects that go along with this class of prescription drugs.  Existing research is also a bit weak on any improvement that Adderall or other stimulants may have on short term memory or cognitive function, and some actually may impair function.

Modafinil, also known as Provigil, is an example of a smart drug that has been used like a nootropic.  Modafinil is prescribed to treat sleep disorders, but when combined with a normal functioning brain, can potentially cause increases in cognition and awareness.

Just like Adderall, the use of these drugs outside the medical field does not make them a nootropic.  Modafinil is also a reuptake inhibitor for dopamine, causing the same type of neurotrasmitter flood as Adderall.  However, Modafinil may also affect the histaminergic pathway, which deals with wakefulness and the delicate immune response of the body.  Histaminergic neurons in the brain are more active during wakefulness and slow their firing pattern as we rest or sleep.

Modafinil’s “beneficial” side effects may come from this heightened histaminergic neuronal activation, but too much activation can cause apoptosis, or cell death.  In addition, this has been shown to cause adverse skin reactions that required hospitalization since the histamine pathway also deals with our immune system.  Modafinil may increase your intelligence, but can be extremely dangerous to the health of your brain and body.

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Enter Nootropics

Nootropics, like truBrain’s cognitive blend, and a few other products on the market, have dose-toxicity levels much lower than salt, caffeine, and especially Adderall.  

There doesn’t seem to be any neurotransmitter depletion, tolerance or habit forming potential, adverse body side effects, or impaired brain function, from most true nootropics, by Girugea’s definition.  The mechanisms for nootropics lie within the structural connectivity of the brain, the optimization of blood flow and oxygenation, and the fortification of brain regions over long term consistency.  Nootropics act more as a super supplement to protecting the brain.  Girugea’s own first synthesized nootropic (in 1964) is still in use today and has been shown to have effects on mitochondrial metabolism, cell membrane fluidity, and functional connectivity in the brain.

Piracetam is this poster child for nootropics, and one of the main ingredients in truBrain nootropic blends. It is one of the only compounds used in that formulation that can not be found in nature, however it was originally derived from – and has structural similarities to – the neurotransmitter GABA.

Since Girugea bought piracetam to light in 1964, there has been lots of research to support the benefits of piracetam.  It has been shown to positively affect our cell membranes and to have neuroprotective and pro-metabolism effects on cells.  The fluidity in our membranes changes with stress and old age, as well as moment to moment as one method of regulating receptor activity. By keeping our membranes healthy we can promote the cells ability to communicate.

For example, truBrain combines other membrane oriented supplements – including choline. The cell membrane – especially in the brain – relays ongoing control signals and messages from other cells to the inner processes of the cell.  Neurons’ membranes in the axon (wiring) and soma (cell body) help generate and propagate electrical signals, sum distant signals, and even have computational and complex learning functions related to changes in membrane function.  Healthier and more active cell membranes bring us increased activity and cell communication, and hopefully better cognition.

Piracetam along with other truBrain ingredients such as magnesium, choline, and DHA, increases in brain plasticity and are designed to improve cognition and efficiency under processing load – or peak performance, versus remediation.  Nootropics may support increased cognitive potential as well as long term protection.  The truBrain team added L-Theanine and L-Tyrosine to support neurotransmitters of GABA and Dopamine, respectively.

You can use a similar or different strategy when building your own nootropic regimen, but use a strategy.  Know why you are putting an ingredient in, know how it might interact with the others, and be sure that dosing is safe.

When you are planning your nootropic or nutraceutical regimen, think in terms of nutrition support to cell metabolism and function, amino acids, natural or near-natural compounds, and avoid bad fats and harsh chemicals that give a momentary boost at the cost of later crashing or having other more serious side effects, such as excess sugars and caffeine.

And don’t forget what else you put in your mouth – additional DHA and other omega-3 fatty acids (in grass fed meats, deep sea fish) are excellent for brain health. Craft your diet like you craft your brain supplement regimen – or have both catered / curated for you in a high end product.  If you do create your own blend, think precise selection, not shotgun approach, and add slowly to your regimen.

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The Problem With Instant Gratification

As a culture, we often hear false marketing claims or create mindsets about what is possible with our health.  

We see ads that advertise a pill that gets rid of “stomach fat fast”.  Truthfully, fat is lost uniformly in the body and the fastest and healthiest way to lose weight it about 1-2 pounds uniformly a week.  So we eat poorly and don’t exercise for 2 years and then criticize our healthy workout plans and diet 1 month in when we don’t get the results we want.

The healthiest and most effective things in life are often the ones that we do routinely.  Consistency is key.  This is true if you are talking about athletic performance, academic or intellectual training, or nutrition and supplement support.  While not “necessary” like supplements or medicines, nootropic use follows this principle as well.  There is another rule, emerging.

If something is strongly “felt” dose to dose – if it gets you high, or wired, or sedated…it’s a smart drug, recreational drug, or something that may enhancing some aspect of performance (perhaps at the expense of another), but is definitely not a nootropic.  And finally, nootropics should be sustainable.

With some nootropics there is an initial loading phase followed by a maintenance phase, and while subtle, results can be felt fairly quickly on the timescale of a few days.  The contrasting quick highs / crashes of coffee, alcohol, smart drugs, and even quickly digesting carbs are definitely experienced more immediately, but have consequences that make them unsustainable for many people.

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Summary

So in summary – here are a few initial rules to help select your own nootropic or cognitive enhancing blend:

  • Know your ingredients, and their amounts.
  • Don’t spend your money on obfuscate fairy dusting or expensive blends that are full of caffeine or random research chemicals.
  • It’s not a nootropic if it has side effects.
  • Your nootropic solutions should focus on mild nutritive and metabolic support, for long term gains and protection.  Break the cycle peak and crash that you get with too many stimulants, and avoid the more serious side effects that you risk with smart drugs.
  • Nootropics don’t get you high, altered, or wired.

And don’t forget the other accessible and evidence-based brain and cognition improving methodologies we have at our disposal today: meditation, yoga, and other contemplative (attention training) practices, biofeedback and neurofeedback, diets high in good fats, and other modifiable behaviors you can implement to take control of your brain health and performance.

So take care of your brain – the tools are out there, to support health and shift performance.

Leave your questions, comments and feedback below. Also, if you want to try the nootropic that Dr. Hill helped design, grab truBrain and get 20% off on your purchase with the code BEN20.

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27 thoughts on “The Little Known Truth About Smart Drugs And Nootropics (Audio & Article)

  1. At 28:19 you mentioned mitochondria, and how they become damaged with age. A great way to repair and also build new mitochondria is a proposed B vitamin called Pyrroloquinoline Quinone (PQQ). Here is a podcast about it: http://www.healthquestpodcast.com/064-want-more-e…
    and an article that says that PQQ provides anti-aging effects due to repair and creation of mitochondria, but when teamed up with CoQ10 and shilajit the benefits are multiplied: http://www.lef.org/magazine/mag2013/aug2013_Three…

  2. He mentions know the ingredients and amounts but on the True Brain site I don't see the amounts of the ingredients. Anyone know the amounts of the ingredients in TruBrain?

  3. Below is the breakdown of the ingredients in truBrain's capsule formula

    Piracetam – 2.4 g
    Omega-3 Fatty Acids – 200 mg
    DHA (docosahexaenoic acid) – 200 mg
    Acetyl-L-Carnitine 250 mg
    L-Tyrosine – 250 mg
    CDP-Citicoline – 250 mg
    Theanine – 200mg
    Magnesium – 80 mg

  4. jeez Ben: It's "nootropics" as in new-trope-icks — not neuro-trahp-icks.

    But anyway, thanks for one of the few discussions that touch on the racetams –wish there was more info on these out there. would have been good to discuss in more detail the racetams and ciltep and alphabrain and other things out there too. maybe next time.

  5. He mentioned, almost in passing, not to take sugar w/ fat & you replied w/ no banana w/ BPC…

    You have anything more on this?

    Anything more than ‘sugar is the root of all evil’..?

    Specifically sugar taken w/ fat

    1. Sure, as you can read about in studies like this: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC37045… – advanced glycation end products can form when sugars adhere to fats and proteins, especially in situations where they are heated together – whether inside or outside the human body. Based on this, high levels of acute blood sugar (from fruit, starch, etc.) even when from safe carbohydrate sources should be avoided when cholesterols are also high in the bloodstream (from BP Coffee, steak, etc.).

  6. Don't forget this side effect of "smart drugs." Sudden death. My sister-in-law died from overdosing on Adderall. Even FDA lists sudden death as a side effect! Stimulant amphetamines are dangerous drugs. In my day, we used to say speed kills. It still does. I'll stick to decaf and dark chocolate, thank you very much.

        1. I can't speak to the quality of these ingredients whatsoever! I can tell you that many nootropic folks don't source high quality ingredients, so vet carefully and proceed with caution. You typically get what you pay for.

      1. I am interested in purchasing NSI-189, Methylene Blue, and possibly other nootropics that can be added to the stack to safely treat my refractory depression, PTSD, etc.

        I have just completed six ketamine infusions, and will be receiving a compound prescription in a few days to supplements those treatments.

        So far I am not as confident as I’d hoped to be after my treatments and would like to help the process along (as well as get out of bed each day) as much as possible.

        Any thoughts or suggestions would be greatly appreciated.

        Thank you so much,

        Barbielanell

        1. I'm actually going to be getting a guy on the podcast soon to talk about ibogaine and some other substances for PTSD… So stay tuned… And in the meantime, I would grab my book at BeyondTrainingBook.com and read the chapters about the brain and how to fix the brain and also the effects of antidepressants.

  7. Great information and agree about truBrain. I run a site that provides information, tips, resources and recommendations to those struggling with ADD/ADHD, as well as those just looking to improve overall cognitive function and brain health. We are always looking for more natural and safe solutions and more recently discovered nootropics. While, some are definitely riding the hype machine, others are really effective. I've been shocked by a few and truBrain was one of them, even though it's a little pricey. We also covered our experience with truBrain. I'll have to let our readers know about this article, too. Feel free to drop by and share any other info you think may help. Thanks!
    http://focushereandnow.com/nootropics-that-work

  8. Greetings to all.

    A very intuitive and good article Dr. Greenfield. Thank you.

    I’ve amunated myself with the most important and required Aminos; Vitamins and Minerals natural supplements (Nootropics), for my anxiety, panic (amplified anxiety), lack of focus, unable to concentrate, poor memory, (forgetting things in a second), fatigue, etc. Resuming… my neurotransmitters, hormones, blood flow, heart function, and main internal organs were, and some things are still very unbalanced, and in a bad state. Though after so many exams, doctors keep saying all its OK with me. But the signs, and alarms are so many that I refuse to believe them. And if I wasn’t/am determined and precistent, own intuition truster, I wouldn’t have found that all this unbalance led me to a prediabetic condition… Just one more condition… that basically it’s now controlled, after I started to increase my gaba levels. And one more time I was the one to ask the doctor for specific exams and analysis. Finding out something I already knew, cause my intuition told me, and my system and body warned me.

    My inner powers still work… poorly, my intelligence and cognitive functions though decreased are still here. I’m still ambitious, I’m still a fighter, I’m still alive, and getting better.

    After so many years of an hedonistic life that practically ended in 2006. And after stuffing so many other killing drugs prescribed by the ones that call them self’s Medics… i decided to go even more natural, and harder regarding health, and auto curing myself as my own doctor.

    Some of the suplements cause me some negative side efects… and as i was thinking, the dosages were too high. (My own system alarm was telling me I was feeling unwell cause of dosages). The “Make your own now tropics blend”. Great article also, led me here. So I’m now on the process of finding out the sweet point in where and with what I feel better.

    My next buy will be the lions mane mushroom, in powder from, so I can make my own dosage. I’ll just do the research for the better one… Along with the daily recommended value of all the Nootropics I have, so I’ll get a Nootropics customised smart pill blend.

    I already can remember names and many other things. I don’t really need to write memos for everything. I’m constantly testing my memory… and before I use to forget people’s names very fast… now I can remember allot of them, new ones, and even people I met a long time ago. I can also remember song’s lyrics, actors names. My brain it’s again turning itself into an organiser… now with some updates. Also feel more aptitude to exercise like before. There where already 2 days I woke up and done some push ups and more again. All the time I run, climb stairs running, walk much more. For years I was stopped. But i lost fat and noticed muscle tonification and volume before that. I only started this self treatment in less than a month. No medic is gonna kill me… I ratter kill myself. Which I don’t believe it will happen cause I’m feeling much better.

    Victan, Xanax, Alzen, Valium killed me enough for years… and I said enough.

    I’m very glad for this kind of medicine and naturopathy to be spreading so widely and fast. More people will start living better lives.

    Keep up the good work Doctor Ben Greenfield.

      1. Thanks you Ben.

        There are those that call them self’s doctors, they’ve studied, they have a diploma… but I don’t think they are doctors… cause they just got that profession cause it’s easy, or for other motives than really care for people, cure them, help them… instead i see them killing people, some die fast, others die slowly… cause the only thing they do is prescribe quimicals, without explaining first the side effects, the cons and pos of long term use. Many can’t even be used for more than 2 months… I’m living proof of that… my doctor was killing me, till I decided “it’s enough”, cause I felt damaged, and I really am, cause of years of usage of valium, xanax, victan, alzen, and others.

        Been told i was paranoid, that had a chronic disease… “You have IBS symptoms” (I never knew before what tha heck was that) “Go online and get more info about it”. “But I’ll prescribe you some Propranolol, and you will feel fine”… Went to read first the specs online… wow, this is just the same or worst as the other chemicals I was taking before (I still take them in SOS cases). (And yesterday I was able to control a anxiety/panic attack without victan). I’m completely decredited by they’re actions and attitudes… but still not generalising of course.

        Anyways, and by the way…

        I stopped bodybuilding since 2007, and light exercises since 2010, cause of my health deterioration. Even studied to get a Fitness Instructor course in 2007… but unfortunately somethings went wrong.

        I recently started exercise again, since my autocure process is going well, and my neurotransmitters are getting fixed. Got my abs back, my muscles are getting bigger and sculpt again. But there is a problem that might be big, or little… I have some stomach upsets, bad digestion, and I think my liver, and even maybe kidneys are not very well. I know i have an infection in my intestines, kind of like, almost, or now a ulcera, that gets worst, swelled, it’s nervous, and closes, making me feel really bad, stopping my digestions, and consequently provoking me anxiety and panic after (normal). I’ve recently had some exams, and the results were fine… that’s what the doctor said. But I don’t feel well (that was long before I started this new autocure process), the skin peeling on my right hand is advancing covering my hand, I also have 2 white marcs on 2 of my right hand nails, and those are indicators that something is wrong. Plus, the swelled feeling on the liver and galblader area, and my intuition. Most probably I have to be seen by a naturopath.

        I reduced the intakes, and also cutting out with some natural supplements that make me feel unwell.

        So I have 2 questions.

        1st – Do you think that is bad if I don’t take the capsules? Since I open them, and just take for example 2 times per day 60mg of tyrosine (trying to find the sweet spot). The capsules usually contain 500mg.

        2 nd – I’m thinking in acquiring something to make my imune system stronger, to help my digestion get better, and also other internal organs get better. Read that Lion’s Mane mushroom is good for all that. But there is also a 7 mushrooms complex, including the Lion’s Mane, that is good to strengthen the imunitary system. Should I just stick to one, or to the 7 mushrooms complex?

        I’m asking, cause maybe you already know about it. Otherwise, I have to read some more.

        Your opinion will be useful so I can make a good filtrage, and choose better between all the other info I’m gathering.

        Sorry I speak and write so much Ben. But I think it’s good I fetch info, and also speak about with people that knows about this, and maybe even gone through a similar fase of the process.

        1. Lot's of questions here! I should begin by clarifying the fact that I am *not* a physician and this is *not* to be interpreted as medical advice. Please talk to a licensed medical professional about all of this! But I'd be happy to help you via a personal one-on-one consult. Just go to http://greenfieldfitnesssystems.com/product/ben-g… and then choose a 20 or 60 minute consult, whichever you'd prefer. I can schedule ASAP after you get that.

          1. Hi Ben.

            Thank you for your polite reply.

            I understand all that.

            For personal reasons… I just have to keep being my own personal doctor/ fitness instructor, etc.

            Going to restart with baby steps, doing it little by little.

            7 years away from bodybuilding threw me back… now I have to go back on track, till feel confortable,and ready to advance forward full power again… I’ll make it… not even if that leads me to death… At least I tried.

            About the 2 questions I made before… I found it all out in the next day of the comment, even before I read your msg. I felt I was going to get a reply like that from you… not only cause you are a professional, but also cause I shot gunned you with too much information… and information is one thing I’ve always loved to assimilate, and now even more… I’m hungry of it.

            Sorry about that.

            All the best.

            Keep up the good work.

  9. Awesome article Ben,

    I myself have been playing with nootropics for the past few years and I feel that there’s only a few win-win substances that have worked exceptionally well:

    – L-Theanine (with Caffeine)

    – Coffee (From light roasted, whole beans)

    – Lions Mane

    – Yerba Mate Tea

    – Sencha Green Tea

    I’d love to know what nootropics you have used and received a win-win situation with.

    Cheers,

    Oli.

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