Brain-elevating nootropic supplements are finally becoming a key frontier of health, wellness, and performance.
While some online sources claim they’re little more than placebo pills, experts, researchers, scientists, and real users will tell you otherwise.
These cognitive enhancers have tremendous potential when used appropriately. Some ingredients have pronounced effects, stronger than caffeine. While others provide benefits in the background.
Each ingredient impacts brains differently.
I’ve used about 200 different ingredients, formulas, and products. In this post, I’ll share a synopsis of each, along with personal subjective ratings and use cases. To help you understand this seemingly infinite web of mind-expanding substances.
Important Background
Let’s begin with some context.
I’ve been researching and testing nootropics for about a decade now. I’ve tested everything from potent so-called “smart drugs” to botanicals and extracts.
On top of that, I’ve optimized the biohacking basics (sleep, stress management, breathing, light, movement, nutrition, circadian health, resilience, etc). I rarely drink (alcohol). I do exercise and meditate daily, and sleep at least 7 hours per night.
These have improved my cognition and health more than the best nootropics can. They amplify these brain-enhancing substances. Increasing the benefits and reducing the side effects, all at lower dosages.
As far as I know, I’m neurotypical. Although I’ve worked as a Brain Consultant & Nootropic Formulator at a startup, helping neurodivergent folks build their ideal stacks.
According to the Braverman brain typing quiz, I’m likely:
- GABA deficient
- Acetylcholine dominant
In this review, I’ve classified the substances into several categories. For each compound, I’ve listed my rating (out of ten), and a few sentences describing the best use case and my experiences.
Although I’ve used 200+ ingredients over the years, I’ve decided to highlight a select few to keep this from becoming a 25,000-word article.
Before buying any, make sure they’re legal in your locale.
My Personal Experience/Ratings of Nootropics: Choline Sources
Choline is an essential nutrient, structurally similar to the B vitamins, used throughout the body and brain.
It’s also the building block of a key neurotransmitter called Acetylcholine.
Used alone, these choline sources (called cholinergic) generally produce minor effects.
The simplest effective nootropic stacks often combine one of the below cholinergic with other substances that speed up brain activity.
Choline acts as the fuel for other nootropics which act like the accelerator.
Alpha GPC (8.1/10)
Alpha-GPC (sometimes called a-GPC) is a highly bioavailable choline source which research suggests can also increase power output. It also supports cell membrane health in the brain. I notice the biggest effect (increased mental and physical stamina and focus) when stacked with other ingredients. It’s also great for memory, recall, and clarity.
CDP Choline (8/10)
Cytidine diphosphate-choline (often called Citicoline or CDP-Choline) is the other most popular choline source, usually synthesized from eggs, beef, or seafood. CDP-Choline is a precursor to acetylcholine and supports the production of phosphatidylcholine. It’s better for mood, motivation, and neuroprotection [R, R].
Choline bitartrate (6.4/10)
Choline bitartrate is the cheapest choline source and is often used in multivitamins. It’s best used in very low dosages and has the least bioavailability. Consistently gives me brain fog when used at therapeutic dosages.
Uridine (8.3/10)
Uridine monophosphate (UMP) is a building block for RNA and helps the synthesis of essential components of cells (phospholipids like phosphatidylcholine). It’s neuroprotective, helps neuronal growth and communication, and notably improves energy & motivation. It has a slight linearizing effect, making it good for logical work. Uridine is my favorite cholinergic substance and it works great as a standalone. There’s also its molecular cousin, triacetyluridine (TAU). TAU is even more powerful at lower doses, helping it stack nicely with other nootropics.
Centrophenoxine (7.9/10)
Centrophenoxine (Meclofenoxate) is a synthetic derivative of DMAE used to boost energy, alertness, mood, memory, and overall brain health and protection. I feel a surge of energy and stimulation from this one, uncommon to the class of cholinergic. I’m a bit leery as there’s less research on it and it tastes absolutely horrendous.
Phosphatidylcholine (7/10)
Phosphatidylcholine is a phospholipid bound to choline. As you’d expect, it promotes acetylcholine production. It’s not as strong as the other choline boosters and is better for neuron cell membrane health and protection. I rarely use it.
My Personal Experience/Ratings of Nootropics: Vitamins, Minerals, Nutrients
These essential nutrients are often not classified as nootropics.
Yet they often have astounding health, wellness, and performance benefits. If you’re deficient in any of the below (most people are), increasing your intake can produce powerful nootropics effects.
Magnesium (9.4/10)
Magnesium is an essential mineral and one of the biggest universal deficiencies. It’s the mineral of chill, rest, and recovery. I read a 200+ page book called The Magnesium Miracle and began taking these powerful magnesium supplements. I immediately noticed huge improvements in my sleep, workout recovery and soreness, tension, headaches, digestion, and subsequent ability to perform the next day. Mag amplified the felt effects of my nootropics. I’ve taken it almost daily for years.
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Fish oil (6.7/10)
Omega-3 fatty acids contain EPA and DHA which are heavily involved in brain development, cognition, neuroprotection, and neuronal membrane structure and function. I take a clean omega-3-rich oil daily, but don’t notice much. There’s a ton of research behind it, so I use it for overall brain health. Make sure to get a clean source and oil is the optimally absorbed (and utilized) form. Like this one.
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Zinc/Copper (6.4/10)
Most minerals require precise balances to work well. Taking large doses of zinc without copper, for example, can cause serious issues over the long term. These two are considered a functional pair. I found that zinc, in the form of ZMA, dramatically improved the lucidity of my dreams and overall sleep quality. Increasing my intake of zinc and copper slightly increased my total testosterone levels. Little to know about acute cognitive effects though. Best to get these through a clean all-in-one trace minerals supplement.
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Vitamin A-D-K (8.3/10)
This is a fat-soluble vitamin trio that impacts all kinds of pathways throughout the body. Many modern humans also lack adequate levels of all three. Of the three, vitamin D is the most universal recommendation. It, however, requires other nutrients as cofactors to activate the exert its full benefits. These support optimal mood and general mental health. It’s best to get vitamin D (and a whole lot more) from natural sunlight exposure. For those who live far north, a comprehensive vitamin D complex supplement makes sense. This is another that I don’t really feel but is so essential to overall health that it makes the list.
Vitamin B Complex (6.8/10)
If you’re vegan or vegetarian, taking a complete vitamin B complex will make a huge difference. Especially if the ingredients are in the “activated” form. The family of B vitamins is involved in so many processes, that it’s a good prophylactic. I notice a little boost from what I presume is vitamin B12 and niacin. But I likely already get enough from my diet, so I rarely take it.
Creatine (8.4/10)
Creatine is a non-essential amino acid that improves nutrient delivery throughout the body. Creatine binds with phosphate in the brain [R]. By improving cellular energy and nutrient delivery, creatine may improve memory, mental endurance, and decision-making. Especially in vegetarians and anyone under heavy stress. I’ve been taking creatine most days for years as it’s among the most studied supplements. I don’t notice much cognitive effect from it, although it does seem to improve my long-term focus.
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My Personal Experience/Ratings of Nootropics: Botanics & Herbal Supplements
Unlike vitamins, minerals, and essential nutrients, this class of ingredients is entirely optional.
The body can work fine without them.
Nevertheless, they can really improve the quality of life and ensure optimal balance. Plus, they often help humans adapt to changing environments, and build resilience, and the modern lifestyle.
L-Theanine (9/10)
L-Theanine is another conditional amino acid typically found in high-quality tea leaves. It notably and powerfully takes the negative edges off stimulants (anything from caffeine to amphetamines). Less tunnel vision, racing heart, irritability, headaches, etc. Theanine, on the other hand, is non-addictive and quite safe. It’s often used as an anxiolytic and promotes the generation of highly beneficial alpha brainwaves. I use this most days in my coffee and it compliments many stacks.
Coffee (7.7/10)
Caffeine is in the family of methylxanthine substances and is one of the most popular drugs used worldwide. It actually wasn’t even the first nootropic I ever used. It’s best and most effective when used intermittently. Daily use results in habituation and lower baseline performance. For the caffeine “naive”, it certainly improves energy, processing speed, alertness, and motivation. I personally enjoy the morning coffee ritual 3-4 days per week. Nevertheless, there are better caffeine alternatives. I also highly recommend everyone do a 7-14 day caffeine tolerance reset 2-4 times per year.
Paraxanthine (9.5/10)
Paraxanthine is the dominant metabolite of caffeine, comprising about 80% of what your body breaks down. This alkaloid also exists in small quantities within certain plants. Paraxanthine is often touted as the ultimate caffeine upgrade, responsible for nearly all the benefits and none of the side effects. Including, no known habituation/addiction. It’s also more dopaminergic, motivating, and better for physical performance. Plus, slow caffeine metabolizers can also enjoy paraxanthine. Paraxanthine feels much cleaner and smoother than caffeine, and I like to combine half-caf coffee with 200-300mg of paraxanthine.
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Dynamine (8.6/10)
Dynamine is the patented form of an ingredient called Methylliberine. which is a natural extract derived from the Kucha tea leaf. It’s an energy-boosting stimulant and focus-enhancer. Dynamine also improves focus and mood. On days I use Dynamine, I’m significantly more productive. Plus, it doesn’t have the jitters, crashes, or side effects of caffeine. This ingredient also stacks quite nicely with other nootropics.
Theacrine (8.2/10)
Theacrine (1,3,7,9-tetramethyluric acid) is yet another naturally occurring compound, structurally similar to caffeine, found in some plants like Camellia assamica. You can also find the patented version, similarly named Teacrine. Theacrine has a weaker stimulatory effect than caffeine, without the jitters or tolerance build-up. It also doesn’t last nearly as long as some of the other stimulants. I notice that it improves my mood and physical endurance. It also doesn’t feel like it strains my cardiovascular system like caffeine. It exhibits a strange dose-response curve. Small doses can be slightly sedating, while dosages above 100mg are stimulating. It’s not very expensive and easy to find, so I use this one on occasion for an early afternoon pick-me-up.
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DHH-B (8.6/10)
Dihydrohonokiol-B is a natural derivative of the bark of the Magnolia officinalis tree. Dihydrohonokiol-B is a newer discovery, showing tremendous promise for its therapeutic properties. Its neuroprotective and anxiolytic (anti-anxiety) effects stand out. Earning it the name “nature’s chill pill”. This is a powerful molecule to rapidly calms nerves. I often carry this in my backpack in case I come across someone experiencing a panic attack. Unlike benzos, DHH-B is much safer.
Lion’s mane (7.2/10)
Lion’s mane is an adaptogenic mushroom known for its neurogenic properties. Theoretically, it’s great for learning and memory. Most of the products I’ve tested haven’t done much. I barely felt anything. The only exceptions have been a large dose of Real Mushrooms or the highly potent CollaGenius. I’ve come across some rare case reports of people experiencing loss of libido or apathy as a side effect. I often add Lion’s mane to my morning coffee.
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Cordyceps (8.5/10)
Cordyceps is another functional, adaptogenic mushroom revered by ancient medical systems. This was the first mushroom supplement I tested, and I immediately felt the effects. I got a slight tingly sensation, my energy increased, and my endurance went way up. I now use this in my DIY pre-workout formula, but it appears to have some nootropic effects too. This is one I give to supplement skeptics. So far, everyone’s felt it.
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Saffron (8.4/10)
Saffron is a spice often used in cooking. Well, was used. It requires manual harvesting and thus is incredibly expensive. I first tried it in Thesis’s amazing Confidence nootropic stack. They use the patented “affron” saffron extract along with many others. Within about 30 minutes, I reliably feel far less anxious and in a better mood. To me, I prefer this over DHH-B or theanine. But it was expensive, so I didn’t buy it for myself.
Ashwagandha (9.1/10)
Ashwagandha (Withania somnifera) is the star herbal remedy of the ancient Ayurvedic medical system. It’s a potent adaptogen, dramatically helping the body adapt to stress and build resilience. This was the first adaptogen I tried, and I quickly noticed that it made me feel relaxed, calm, and focused. Longer-term, I saw improvements in my memory and ability to retain new info. It’s also neuroprotective. Ashwagandha is one of the best overall herbals recommended for modern humans. Different extracts have different effects. Ashwagandha has earned a spot in my long-term stacks.
Coca Leaf (5.5/10)
Coca leaf (Erythroxylum coca), contains naturally stimulating alkaloids. Yes, it’s also the plant that’s processed and turned into cocaine. Locals chew on the leaves or brew it into tea. Either way, it produces a stimulating effect—stronger but shorter-lived than caffeine. When I traveled to a location where it’s legal, I noticed that the effects lasted only 90-150 minutes. When I was down there. I used this instead of caffeine when I needed to work later at night. I don’t really like the feeling of it though. Like ephedrine, this one feels more taxing on the cardiovascular system and overall body. I also feel a little off the next day.
Rhodiola (9/10)
If Ashwagandha is the most popular adaptogenic herb, Rhodiola is a contender for second place. Where Ashwagandha is the “feminine” nourishing and soothing adaptogen, Rhodiola is energizing and invigorating. There are two main varieties, Rhodiola rosea, and Rhodiola crenulata. Both help you better handle stress, improve mood, reduce fatigue, and alleviate feelings of burnout [R]. I use it for mental stimulation, and it’s excellent as a pre-workout. Plus, it improves adaptation to high-elevation and intense training. Rhodiola pairs amazingly with Ashwagandha, and I include both in my daily adaptogen stack.
Ginseng (8.7/10)
Ginseng is another family of adaptogenic herbals, used for millennia to boost brain function and overall vitality. Panax ginseng (Asian) root is the most common and well-studied form. It improves mental performance while reducing brain fatigue [R]. It’s a potent neuro-anti-inflammatory and reliably helps focus and stress. I don’t know exactly how to describe it, but Panax ginseng just makes me feel more vital. It feels similar but slightly less potent than Rhodiola. I usually combine several forms of ginseng with Rhodiola and ashwagandha in my ultimate adaptogens stack.
Huperzine A (3.5/10)
Huperzine-A is an extract of the plant Huperzia serrata. Traditional Chinese medicine has used it for a long time. In the brain, it works as an acetylcholinesterase inhibitor. By inhibiting the enzymes that break down acetylcholine, levels stay elevated. Although it’s a popular ingredient in products, I hate it. Huperzine gives me a headache. The half-life is absurdly long, so it accumulates in the body and should be cycled. Plus, most products get the dosage totally wrong.
Ephedrine (8/10)
Ephedrine is an alkaloid derived from a plant called Ephedra sinica and has been used for centuries in Traditional Chinese medicine. It’s a potent stimulant often used for energy and weight loss. Indeed, it works great for energy, focus, motivation, productivity, and mental stamina. Compared to other stimulants, ephedrine taxes the cardiovascular system considerably more, and the effects feel “dirtier”. It doesn’t put me in as beneficial of a headspace. Because of its mechanisms, I consider it “fight or flight in a pill”. Overall, I like the stuff but don’t use it often. I subtracted points because it’s harder to find, banned by the FDA, and not quite as safe as some of the other stimulants on this list.
Kava (7.4/10)
Kava (Piper methysticum) is a plant native to the South Pacific islands. Traditionally, Islanders use the roots to make a drink that has sedative and anxiolytic properties. It also notably improves mood, often causing disinhibition and euphoria in high dosages. Kava is characterized based on the active ingredients within the roots. Some types are more psychoactive, while others have more systemic relaxing effects. It acts as a natural MAOI, meaning that it potentiates the effects of other nootropics. Personally, I prefer kava as an alcohol alternative for social events rather than as a standalone nootropic. If you want to try it, make sure to buy a high-quality product. Supplements made from the leaves are toxic.
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Kratom (7.1/10)
Kratom (Mitragyna speciosa) is a tropical evergreen tree native to Southeast Asia. Its leaves contain alkaloid compounds that produce opioid-like effects. Traditional users have long known that kratom is stimulating at low dosages and sedating/pain-relieving at higher dosages. When I take it, I feel any anxiety completely evaporate. It’s quite potent. Users consume it via powder (as I do) or as a tea. Since kratom works on the opioid receptors, it’s quite addictive. I never use it more than twice per week, and I often take long breaks. I docked some major points simply due to kratom’s addictive properties.
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Kanna (6.5/10)
Kanna (Sceletium tortuosum) is a succulent plant native to South Africa. Like many others in this list, it has a long history of traditional use by indigenous cultures as a mood enhancer, stress reliever, and induces states of euphoric relaxation. Kanna is also considered an empathogen, meaning it induces feelings of empathy in the user. Typical consumption these days is in capsules, but also via powders, extracts, tea, snuff, or by chewing the plant material. Of the multiple alkaloids within it, mesembrine is the most famous. I’ve tried this one about six times, and although I do like it, the effects feel quite weak compared to kava or kratom. I like it best as an addition to mood-enhancing nootropic stacks.
PQQ (6/10)
PQQ (Pyrroloquinoline quinone) is a compound derived from certain foods and bacteria. It acts as a cofactor in several enzymatic reactions throughout the body. Although it’s most notable for its mitochondrial supporting properties, PQQ is thought to also improve neuroprotection, learning, memory (through neurogenesis and synaptogenesis), focus, and mental clarity. It seems like another brain supplement that’s good for long-term health but has no discernible effects. I take it a couple of times per week in my mitochondria stacks.
9-Me-BC (8.2/10)
9-Me-BC (9-Methyl-β-carboline) is a compound derived from plant sources like Peganum harmala (Syrian Rue) and Banisteriopsis caapi (Ayahuasca vine). It’s also a metabolite of tryptamine naturally present in trace amounts in the human body. This is really in its own class, and there isn’t yet much research on it. It’s supposed to improve memory, mood, attention, focus, and mental clarity. Theoretically, it should also help regenerate the dopaminergic system. I notice a significant uptick in energy. 9-Me-BC also improves my ability to focus for hours on end without distraction. The other side effect is that it makes your skin more sensitive to light. This is a nootropic-only fit for advanced neurohackers.
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My Personal Experience/Ratings of Nootropics: Manmade Supplements
Some of the most popular and effective brain supplements are actually molecules synthesized by humans.
Usually, the effects of manmade nootropics are more pronounced and powerful than the naturals, but they can also come with more frequent and severe side effects.
In fact, the original nootropic that spawned this entire field fell into this category of manmade substances.
Piracetam (9/10)
The original synthetic nootropic molecule is also the most extensively studied. It’s often the recommended starting substance for nootropic newbies. A lot of the research investigated elderly folks with cognitive impairment, but it also can improve cognition in younger, healthier populations. This was one of the first I used. I feel a very mild stimulation from it, more alert and energetic without jitters or agitation of stimulants. It also feels more gentle on the body and sustainable over the long term than most synthetics. The water-soluble piracetam molecule also has learning-enhancing, brain circulation-promoting, and neuroprotective properties. It’s a classic, and I always have some on hand.
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Pramiracetam (4.3/10)
Pramiracetam is another member of the racetam family, theorized to be far more potent than most of the others. It shares many of the same properties as the others, with slightly increased stimulation over the original. What I noticed most, however, was the price. This is one of the more expensive racetams, for little added benefit. I’ve used it about six times and didn’t notice anything spectacular. So I gave away the rest.
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Oxiracetam (9.2/10)
Yet another racetam, Oxiracetam is more potent than the original and has some unique effects. Stimulation-wise, it’s the strongest racetam suitable for daily usage. On it, I notice increased wakefulness, alertness, and mental energy without restlessness or anxiety. Oxiracetam is also the star nootropic for linear, logical thinking and reasoning. It takes me about 30-45 minutes to feel the effects kick in. I use it about once per week on my most structured days.
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Aniracetam (9.3/10)
Aniracetam is another favorite of mine in the family of racetams. It was developed in the 1970s as a synthetic derivative of the neurotransmitter GABA. Aniracetam also shares many similar benefits and properties with others in its class. Where it stands out, however, is solid creativity, anxiolytic, and verbal fluency benefits. Making it awesome for writers, speakers, and social situations. In addition to Aniracetam’s favorable impact on mood, it also has decent neuroprotective properties. As a fat-soluble racetam, it’s best used alongside dietary fat. I use this frequently, often once or twice per week.
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Phenylpiracetam (9.3/10)
Although Phenylpiracetam (Phenotropil) fits within the same racetam class, the dominant characteristics are more stimulatory in nature. It’s not as much like the other racetams. Phenylpiracetam also builds tolerance quite fast. To maintain peak effects, I never exceed twice per week. Also, take it alongside fat. I mostly use it as a pre-workout or when initially coming off caffeine. The total duration of effects lasts about four hours for me. A few studies, including this animal model, suggest it can improve memory [R]. I like it for the big surge in motivation and focus it provides. Especially for physical coordination. This is also one of the more expensive racetams, so it’s best saved for special circumstances.
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RGPU-95 (8.1/10)
RGPU-95 (AKA “p-Cl-Phenylpiracetam” or “para-chloro-phenylpiracetam”) is a modified version of the popular racetam Phenylpiracetam. It shares some of the properties of phenyl. RGPU-95 still has powerful stimulating effects but also feels much cleaner and smoother. It’s also great for physical performance, although not quite at the same level as Phenylpiracetam. I consistently notice that it improves my energy, motivation, and wakefulness. I deducted points due to it being very new and having little safety data compared to the other racetams. Especially little on humans.
Noopept (9.1/10)
Noopept is another synthetic nootropic, structurally very similar to the racetam family. After extensive research, this was another of the first nootropics I tried. After a few dosages of 10mg, I quickly noticed that the color saturation and vibrancy upgraded from 720p to 1080p. I felt like I was seeing in HD for the first time. It acts very quickly, but only lasts a few hours [R]. As a student, I found that noopept sped up memory formation and consolidation, making it easier to retain info [R]. I also seemed to think quickly. I kept it on hand in case I experienced a TBI [R]. For whatever reason, after several years it stopped working as well.
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L Tyrosine (2/10)
L-Tyrosine is a non-essential amino acid that’s key to the production of various brain chemicals. Especially dopamine, norepinephrine, and epinephrine. In theory, this makes tyrosine great for regulating mood, motivation, focus, and stress response. Even more when under stress or after using potent stimulants (helps with the “comedown”). For me, tyrosine and N-Acetyl-L-Tyrosine (NALT) both give me terrible headaches and make me feel robotic. Not always, but about 75% of the time. I tossed an entire bag of the stuff. Although, when it doesn’t, it’s nice.
Melatonin (7.3/10)
Melatonin is a hormone intricately involved in regulating circadian rhythm (sleep & wake cycle), that’s naturally produced by the pineal gland in the brain. As well as in large quantities in the intestines. Unlike all other hormones, melatonin is not subject to a negative feedback loop, making supplementation much safer. Melatonin, especially in the optimal extended-release liposomal or XR forms, acts as a powerful antioxidant to accelerate recovery. It improves my sleep quality and duration. I wake up feeling more refreshed and rejuvenated from sleep. Making my other nootropics work better. I take it ~90 minutes before my target bedtime, several times per week. Then I naturally shut down melatonin production first thing in the morning by getting unfiltered sunlight into my eyes.
Exogenous ketones (8.4/10)
Exogenous ketones consist of a family of molecules that the effects of fasting or sustaining a state of ketosis. These supplements come in the form of ketone salts, ketone esters, and ketone oils. Once consumed, they act as an efficient alternative high-performance fuel for the brain and body. Improving cellular energy (mental and physical), mental clarity, athletic performance, and even reducing appetite. Exogenous ketone supplements also display neuroprotective benefits (I used them often while playing Football & Rugby). When I use a high-quality ketone ester, I feel a steady uptick in my energy, with no crash later. I’m more productive and can easily sustain longer fasts. I also test slightly higher on cognitive function assessments. Good ketones are certainly a bit more expensive than some of the other options I’ve listed. They also amplify the effects of other nootropics. But they’re incredibly safe and non-habit-forming too.
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Sulbutiamine (8.6/10)
Sulbutiamine is a synthetic version of thiamine (vitamin B1) that more effectively crosses the blood-brain barrier. Where it increases choline and dopamine levels in the brain. Although it supports many facets of cognition like memory and mental clarity, I notice a major mood boost. I feel more excited for the day. Even a tad euphoric. Sulbutiamine also has some stimulating properties too. Sometimes I like to use it with other things in the evening as a part of an energizing, caffeine-free social stack.
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My Personal Experience/Ratings of Nootropics: Drugs
Next, we have the category of drugs.
These are mostly man-made. They’re generally much harder to get as they’re either illegal in much of the world or require a prescription.
Please follow your local laws. This article is for entertainment purposes only. Talk to your doctor before changing your current regimen.
Modafinil (9.3/10)
Modafinil is a prescription medication primarily used as a wakefulness-promoting (eugeroic) agent and a central nervous system stimulant. Which is technically different than classic stimulants. Modafinil works primarily by increasing brain levels of three neurochemicals: dopamine, norepinephrine, and histamine. Modafinil is one of the stronger substances for promoting alertness, focus, motivation, productivity, energy, and even confidence. It has a few side effects but far fewer than traditional stimulant medications. This one also has a much lower risk of dependence. Modafinil is especially great for combating the effects of sleep deprivation [R, R]. I use a micro-dose on occasion, first thing in the morning, and really like the effects. Especially when traveling. Check out my ultimate guide to the smart drug modafinil for more info.
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FLModafinil (8.4/10)
Flmodafinil (CRL-40,940) is a modified and stronger form of modafinil. It too is a eugeroic agent and CNS stimulant. Compared to modafinil, it lasts even longer and is theorized to have less impact on histamine. It has very similar effects at a much lower dosage. I actually liked this one quite a bit more than modafinil originally. The stimulation and general effects feel much cleaner, even, and more smooth. Almost like a natural stimulation. FLModafinil is a grey-area drug, generally sold as a research chemical and too new to have much safety data. When the gut microbiome metabolizes fluoridated drugs, it liberates the fluoride ion which reacts with magnesium. Forming a brittle substance called sellaite, which can deposit in and potentially rupture tendons & ligaments & joints [R]. Although I had no issues at all, I rarely take it now and docked major points because of the lack of safety data and the issue of it being a fluoridated medication.
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Emoxypine (8.9/10)
Mexidol (Emoxypine) is a Russian pharmaceutical compound classified as a dopaminergic antioxidant and neuroprotective agent. Structurally similar to vitamin B6. They created it as part of a research program to develop new and effective neuroprotective antioxidants, especially to increase the brain’s resilience against shock, hypoxia, ischemia, and cerebral circulation issues. It works by reducing oxidative stress, stabilizing cell membranes, and modulating neurotransmitters. The dominant nootropic effects seem to include reducing neuroinflammation and exerting anxiolytic effects. Although I couldn’t find much data supporting this, I personally noticed a decent energy boost when I used it for about two hours pre-workout. Emoxypine also made me feel more motivated, social, and open than usual. Possibly due to the increased dopamine. It has good safety data as the Soviet Union developed it in the late 1980s.
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Tesofensine (7.3/10)
Tesofensine is a grey-area pharmaceutical drug researched as an anti-depressant and then later as a weight-loss medication. It’s one of the few selective triple monoamine reuptake inhibitors (SNDRI). Meaning that it keeps levels of serotonin, norepinephrine, and dopamine elevated in the brain. Its cognitive benefits come as a byproduct of increased energy. Tesofensine powerfully reduces my appetite. It’s also a strong stimulant and certainly increases wakefulness. Those are the major effects I feel from Tesofensine. Personally, I like it. Interestingly, real users confirm that it’s one of the few stimulants with little to no known habituation or withdrawal symptoms. Between its expensive price tag, only indirect nootropic effects, and the difficulty of procurement, I docked some significant points.
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Amphetamines (6/10)
I’ve previously used both Adderall and Vyvanse, which are two structurally similar prescription amphetamines. Both with different uses and strengths. I don’t like the way either made me feel. A textbook stimulant that gives me unnatural mood fluctuations. As it wears off, I usually go through a big crash of motivation, energy, and mood. The euphoric effects make it not as good for productivity and focus as modafinil. The slightest distraction will completely derail me for hours. I do like the big energy surge though. I’m concerned about long-term safety, tolerance, and addiction, so I haven’t used any amphetamines in nearly a decade.
Phenibut (8.9/10)
Phenibut is a grey area central nervous system depressant. It’s a derivative of the neurotransmitter gamma-aminobutyric acid (GABA) with a phenyl group attached so that it easily crosses the blood-brain barrier where it has mood-boosting, anxiolytic (potent), and even sedating effects. I like phenibut for relaxation and during situations in which my nerves are high. It’s also great for social events instead of alcohol. I use a low dose at night about once per week because it dramatically improves my sleep quality and duration. I love this compound, but had to mark it down a full point for safety. It has very high abuse potential and a long half-life. I’d never use it more than twice per week to avoid a nasty addiction. Plus, it interacts with other GABA agonists like alcohol and pharmaceuticals. Be very careful with phenibut.
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Picamilon (8.9/10)
Picamilon (nicotinoyl-GABA) is a synthetic compound formed by combining niacin (vitamin B3) with GABA (gamma-aminobutyric acid). Again, allowing it to cross the blood-brain barrier. It’s a better and safer version of phenibut, with far less abuse potential. But in my experience, the felt effects aren’t quite the same. Picamilon still has the same mood-enhancing, anxiolytic, relaxing, and mood-boosting benefits. Plus, this one also increases blood flow and oxygen supply to the brain. I don’t use it very often, but prefer picamilon over phenibut as a nootropic. Phenibut feels more recreational. Picamilon is more functional, productive, and a whole lot safer.
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LSD Micro-Dose (7.7/10)
LSD (Lysergic acid diethylamide) is a psychedelic known for producing hallucinations. At low (micro) dosages, it works differently. Without any hallucinations, it has significant dopaminergic properties. LSD is supposed to increase neuroplasticity and improve thinking by modulating the Default Mode Network (DMN) and corpus callosum. I find small (1/10th of a normal trip) dosages enhance my creativity, introspection, and pattern recognition. I tend to enjoy smaller more minute details and observations more. LSD also gives me a subtle all-day energy and boost. I use it on occasion, but due to its long-lasting and potent effects, I am worried about stacking it with other nootropics.
Psilocybin Micro-Dose (5.5/10)
Psilocybin is the main psychoactive compound found in certain species of psychedelic mushrooms. It’s serotonergic, primarily activating the 5-HT2A receptor. Theoretically, this should improve mood, empathy, emotional wellness, and creativity. More than LSD. That hasn’t been my case. I’m indifferent to this as a generic practice, but I don’t love it as a nootropic. There’s significant variability between mushrooms, making dosage difficult. Although I sometimes felt happier while using it, I had a tough time focusing and working productively. However, I sometimes do feel a minor lingering “afterglow” mood-improving effect for a few days afterward.
Nicotine (9/10)
Nicotine is a naturally occurring alkaloid found in tobacco plants. It’s usually vilified as the chief danger within cigarettes, but that’s unfounded when using a proper pure product. In fact, one of my favorite neuroscience professors opined that the class would do much better switching to low-dose nicotine as a nootropic away from the other popular study drugs. Administered via spray, patch, lozenge, or gum. Nicotine acts as a central nervous system (CNS) stimulant, also increasing levels of various neurotransmitters like dopamine, norepinephrine, and serotonin. Nicotine improves learning, memory, attention, alertness, stress relief, verbal ability, productivity, and mood [R, R]. Of course, nicotine can be addictive when abused, or deadly in extreme dosages. Minus a full point for abuse potential. I use it no more than four times per week, at dosages of <2mg per day. Although when I vape nicotine (organic, wild-harvested tobacco, not an e-vape, and at low temperatures), I can easily use it daily for a few weeks straight and then stop for a few weeks with no withdrawals or side effects.
Methylene Blue (8.3/10)
Methylene blue is a synthetic dye and the first drug ever synthesized. It’s also on the list of internationally recognized essential medicines. Although its primary medical uses differ from its cognitive-enhancing nootropic properties. Its nootropic effects stem from its ability to improve the efficiency of the cellular energy generation process. By increasing mitochondrial function methylene blue improves memory formation and retrieval, attention, mood, and overall cognitive function. Interestingly, in higher dosages methylene blue works as a MAOI, just like with SSRIs. This may explain part of the mood enhancement. the main side effects are stains everywhere (be very careful dosing the liquid!) and blue urine for ~8-12 hours after usage. I sometimes notice a slight improvement in my energy and mood. Although I generally don’t feel much. Methylene blue is considered a prescription medication in some countries and may also interact with some medications. As I described in my ultimate guide to methylene blue science, benefits, and the best products, sourcing is tricky. Most products repurpose industrial-grade methylene blue from fish tank cleaners. Avoid this at all costs. Industrial-grade MB contains all kinds of toxins and carcinogens. Make sure to get high-quality pharmaceutical-grade.
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Bemitil (8.9/10)
Bemitil HBr (Bemitil, Bemiton, or Metaprot) is a pharmaceutical developed in the Soviet Union in the 1970s as an actoprotectant (synthetic adaptogen). It helps buffer stress and build resilience against metabolic damage. It’s known for its antioxidant, regenerative, nootropic, anti-hypoxic, anti-mutagenic, & immunomodulatory effects. As well as for its ability to protect the brain against oxidative stress and neurotoxicity. Bemitil is especially popular among athletes, Olympians, and the military. To both increase performance in stressful conditions, as well as to accelerate recovery post-event. It also synergizes nicely with other nootropics and has a great safety profile. I mostly take it for the energy-enhancing effects, and sometimes add it to my morning pre-workout if I am dragging a bit. I don’t like the headspace it puts me into quite as much as bromantane though.
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Bromantane (9.2/10)
Following Bemitil, Soviet scientists developed another synthetic substance called Bromantane (Ladasten) in the late 1980s. Originally, they created it as an anti-anxiety medication and later discovered its nootropic benefits. This actoprotectant works by modulating dopamine and serotonin levels. Specifically, it improves the bottleneck of dopamine production, resulting in higher levels (for a long 12-hour half-life). The result? Greater motivation, focus, and energy. It feels more physical than cognitive though. On par with other stimulants, but without the nervousness or typical side effects. It takes about 60-90 minutes to kick in and lasts throughout the day. Again, this one stacks nicely to make other ingredients more dopaminergic. It has a great safety profile and is sustainable as I don’t feel any real come down from it either. Making it among my favorite nootropics. I use it on average once per week, in the morning about 60 minutes before my workout. Note that this is a substance banned by WADA.
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Semax (9/10)
Semax is a synthetic neuropeptide derived from ACTH that was developed by the Russian Institute of Molecular Genetics in the 1980s for its potential cognitive-enhancing and neuroprotective properties. Originally, to treat neurological disorders like stroke, traumatic brain injury, and cognitive decline. It increases BDNF which helps new neurons and synapses grow and survive. It appears to have anti-inflammatory, memory, learning, immune-modulating, and mental clarity effects. It’s generally administered via nasal spray, and although the half-life is a short 1-hour, the beneficial changes it causes persist much longer. For about 4 hours after use, I notice better mood, memory, attention, and overall cognitive performance. I feel the dose within about 2 minutes, and semax quickly puts me in the zone. It’s a great overall neuropeptide and a must-have for anyone at risk of brain injury.
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N-Acetyl-Semax-Amidate (5/10)
N-Acetyl-Semax-Amidate (NA-Semax-Amidate or “NASA”) is a more potent modified version of Semax. It’s believed to have a more pronounced effect on BDNF levels and provide stronger neuroprotective properties. With better bioavailability and longer-lasting effects. In theory, it’s also better for mood, mental clarity, stress reduction, and focus. I’ve used this one about eight or nine times. Each time, I’ve felt next to nothing. I’ve experimented with a wide range of dosages too. Shame, as this one looks great on paper. If this works for your neurochemistry, it can be a potent nootropic. It also doesn’t have the same breadth of research or safety data as the original semax.
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P-21 (7.1/10)
P21 is a synthetic peptide developed by Dr. Joseph Wu at Stanford University in the early 2000s. It’s a modified version of a potent complex of neuropeptides and amino acids called Cerebrolysin. Now, Cerebrolysin is among the most legendary neuropeptide products and is widely considered one of the holy grails of brain health. The issue? Cerebrolysin requires injection. P21 is believed to work by modulating neurotrophic brain growth factors like brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDN). It was designed to have greater neuroprotective and cognitive effects compared to Cerebrolysin, while at the same time being far easier to administer. Imagining it as a more potent semax, I looked forward to improved learning and memory formation and retrieval. But after about seven usages, I didn’t feel much other than sleepy. Plus, it lacks the historical usage and safety data of Cerebrolysin. Perhaps it’d work better post-stroke or TBI. Since it’s expensive, however, I don’t love it.
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Dihexa (8.7/10)
Dihexa (PNB-0408) is a small six-amino acid synthetic peptide derived from angiotensin IV and developed in the early 2000s by Dr. Gary Arendash at the University of South Florida. It’s claimed to be 7X more potent than BDNF [R] and also enhances hepatocyte growth factor (HGF). Dr. Seeds believes it also exerts some neuro-anti-inflammatory benefits too. Dihexa users often report better thinking, learning, memory, creativity, and problem-solving. Interestingly, some influencers also advocate this one for improving athletic performance. Personally, I like to use it transdermally with DMSO to boost the results of my neurofeedback sessions. My data shows faster progress, quicker recovery between training sessions, and the training subjectively feels easier. This one warrants some caution, as the half-life is a whopping 12+ days [R]. Again, there isn’t as much safety data as I’d like. Only about 16 total studies so far [R].
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Nootropics I Haven’t Taken
Obviously, there are a ton of nootropics and I surely haven’t used all of them.
For different reasons.
The substances below I’ve either:
- Never taken
- Take but not in isolation
- Haven’t used it in a very long time
We’ll start with the naturals.
Bacopa
Ancient Ayurvedic medicine used the herb Bacopa monnieri as a cognitive enhancer (among other things). The primary active ingredients within it are called bacosides. This family of compounds protects your brain from free radical damage and helps the hippocampus better process memories. Bacopa appears able to accelerate information processing speed and improve memory and reaction times. It takes months of daily supplementation to notice a difference. Bacopa may also have a slight sedating effect. I don’t see any reason to take this one in isolation for several months at a time. So I use it as a part of stacks.
Ginkgo
Another ancient herbal, this time used by Traditional Chinese Medicine, Ginkgo biloba tree extracts also possess nootropic benefits. In fact, it’s among the best-selling herbals. Ginkgo is believed to work by promoting blood circulation in the brain and offering antioxidant protection. The general cognitive benefits also include reduced stress, better memory, and improved mental processing. One study even showed that it helps reduce nervousness [R]. Ginkgo biloba naturally contains neurotoxins, so you’ll want to make sure the brand you’re using has intentionally removed these. I don’t use Ginkgo by itself, because I already consume it in other nootropic stacks.
Selank
Selank, developed by the same Russian Institute of Molecular Genetics in the 1980s, is a derivative of a naturally occurring peptide called tuftsin. It’s regarded as Semax’s sibling nootropic, with special anxiolytic properties that translate into mood enhancement. It too modulates neurotransmitters and alters the expression of BDNF. Users administer Selank through nasal spray too. I’ve never been that interested in Selank, because I already have Semax and plenty of other anxiolytics. Although it does have significant other potential benefits too. So several recent podcast guests of mine have convinced me to try it.
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Adrafinil (6.4/10)
Adrafinil is a grey-market synthetic compound that’s metabolized in the body to produce modafinil (a pro-drug of it). It’s mainly used because it’s cheaper and far easier to get than modafinil itself. There’s debate over whether it causes liver damage (hepatotoxicity) in humans. It takes longer to kick in and doesn’t feel quite like modafinil. I used this about ten times before I completely shelved it.
Mescaline Micro-Dose
Mescaline is a naturally occurring psychedelic substance found in some cacti species (especially the Peyote and San Pedro cacti). There’s a much smaller community of mescaline users and even fewer micro-dosers. Several friends have mentioned that it is similar to micro-dosing LSD but longer-lasting and more stimulating. It also seems much harder to find, harder to do, and is illegal in many places
Methylphenidate
A central nervous system stimulant drug used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy. It works by modulating dopamine and norepinephrine in the brain. It seems to have similar effects to the amphetamines but may change personality even more. Methylphenidate also has higher abuse potential and thus is a Schedule II controlled substance. I don’t have any plans to use it.
Nick Urban’s Nootropic Ingredients Rated & Reviewed
Nootropics are a special class of dietary supplements that impact one or more facets of brain health or function.
Over the last decade or so, I’ve tested over 200 different nootropic ingredients, products, and complexes.
I’ve formulated products—personally and professionally.
Although there’s a technical definition difference, in this post I shared my own personal experience and thoughts on a wide variety of botanicals, nootropics, and smart drugs.
So that you can find your ideal brain ingredients.
I’ve also tested and written in more depth about dozens of other brain supplements.
The most popular nootropics today are:
- Nootopia (read review and save 10% with code URBAN)
- Thesis (read review and save 10% with code URBAN)
- Qualia Mind (save 10% with code URBAN)
- DIY (this post reviews & compares the best brain supplement vendors)
What about you? Which nootropics do you love?
Questions or comments on any of this? Drop a comment below and let me know!
I personally read and respond to each comment.
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