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Photographic Memory: Nootropics and Mnemonic Devices 101

Photographic memory, or eidetic memory, is the ability to vividly recall images after seeing them for a short period of time. A Google search shows over 16.000 results for “photographic memory nootropics”. Of all the articles I read, no one of them answer the fundamental question: Does photographic memory exist, and is it possible to achieve with a combination of mnemonic techniques, training, and nootropics?

What is Photographic Memory?

According to the Merriam-Webster dictionary[1]

Eidetic is the technical adjective used to describe what we more commonly call a photographic memory. The word ultimately derives from the Greek noun eidos, meaning “form.” The ability of certain individuals to recall images, sounds, or events with uncanny accuracy is a subject of fascination for researchers in the field of psychology. Among notable people who were reputed to have eidetic memories is the late television comic Jackie Gleason, who reportedly was able to memorize an entire half-hour script in a single read-through.[2]

There are only two case studies of eidetic memory in scientific research. Let’s take a quick look at them.

Case 1: The Mind of a Mnemonist

The first case study of a subject with an “incredible” (photographic?) memory was published in a Russian medical journal in the 1960s by psychologist Alexander Luria.

Alexander Luria was a famous Russian psychologist active in the mid-1900s. In the early days of his career, he met a young man named Solomon Shereshevsky. Shereshevky, — or simply ‘S.’, the acronym used in Luria’s writings — was a Russian reporter working for a local newspaper. Each morning the editor would meet with the staff to hand them a rather long list of assignments. Solomon was able to memorize the entire list by looking at the sheet of paper just once.

Solomon Shereshevsky Photographic Memory Nootropics
Solomon Shereshevsky

Even though he was not a brilliant student due to his shy nature, when S. was a schoolboy he could memorize every single thing he read without ever taking notes. Intrigued, Luria took S. to his lab and, over the course of several months, tested his memory using all kinds of complex mathematical formulas and rare languages. Once, he read him the first four lines of Dante’s La Divina Commedia in Italian, a language he could not understand, and he was able to recite it in a matter of seconds.

On the basis of the research’s findings, Luria diagnosed S. with a rare form of synesthesia, called ideasthesia.

Ideasthesia is a phenomenon in which letters, numbers, and other visual objects evoke a “perception”-like experience. Since humans are hardwired to memorize visual concepts more efficiently than letters or numbers, an individual with ideasthesia can memorize characters, numbers, and symbols after viewing them for a couple seconds

The theory of this phenomenon closely resembles the idea behind the Method of Loci (more on that later), a technique used by mnemonists to memorize many different chunks of information that would otherwise be difficult to memorize.

So what kind of visual perceptions did the Divine Comedy evoke?

The first line, Nel mezzo del cammin di nostra vita, he rendered into images this way: Nel, Nel’skaya, a ballerina; mezzo, she is together with (Russian vmeste) a man; del, there is a pack of Deli cigarettes near them; cammin, a fireplace (Russian kamin) is also close by; di, a hand is pointing toward a door (Russian dver); nos, a man has fallen and gotten his nose (Russian nos) pinched in a doorway (Russian tra); vita, the man steps over a child, a sign of life — vitalism; and so on, for 48 syllables.[3]

In 1968, after S.’s death, Luria published a book of his findings, The Mind of a Mnemonist. He wrote it for a non-scientific audience and I recommend it to anyone. The translated version can be easily found on the web with a quick Google search.

Case 2: The Girl with Eidetic Memory

Fast forward to the 1970s. A Harvard scientist named Charles Stromeyer III publishes a paper about a girl with an incredible ability. He gave her a sheet of paper with a pattern of 10,000 random dots, and the next day another random pattern with a different layout.

The girl was able to fuse the pattern in his mind and form a stereogram, which she saw as a three-dimensional image floating above the surface. A couple of days later, when questioned by the researcher, she could draw each pattern with astonishing accuracy.

The case study of Elizabeth – this is the name of the girl – was published in Nature. However, in a comical turn of events, the researcher later married the girl, and she was never tested again.

dot pattern photographic memory
A random dot pattern like the one given to Elizabeth

A couple of years later, in 1979, a researcher named John Merrit published the results of an eidetic memory test he had placed in magazines all over the country. After seeing Elizabeth results, he had hoped that someone might come forward and prove, once and for all, the existence of photographic memory. He figured that over 1 million people had tried the test. However, of the 30 people that were able to correctly figure it out, he went on to visit 15 of them, and nobody could repeat the experiment with the scientist looking over his/her shoulders.

So how was Elizabeth able to succeed in the test? Did she have some weird memory superpower?
Some say that the Elizabeth study was not real, but rather a silly prank between friends that got out of hand. nthomas from the Straight Dope forum explains it:[4]

When I was in a graduate seminar on the psychology of memory (about 16 years ago, at a major university) I was told by the professor, an expert in the field, that the “discovery” was, in fact, a hoax. As he told the story, “Elizabeth” was actually the girlfriend of the researcher, who had been talking to her about his interest in eidetic imagery. He had a reputation, however, for being rather gullible, and, for a joke, she, and a group of his other friends, cooked up a fake demonstration of her amazing eidetic powers. He was completely taken in, and became very excited at his amazing “discovery”. But before “Elizabeth” and her friends had the time (or maybe the heart) to let the victim in on the joke, things had got out of hand, and the discovery was already well known, and, before long, published.
The etiquette of scientific publication would make it difficult to get a story like this into the formal record, and, anyway, psychologists probably do not want it too widely known how easily they can be taken in. (Perhaps, also, people were reluctant to ruin the career of the poor, duped but not dishonest, researcher.)
[…]I got the impression from my professor that the hoax story was quite well known amongst memory researchers. Furthermore, my impression is that psychological opinion over whether eidetic imagery (as distinct from the ordinary, relatively unreliable, memory imagery, that nearly everyone experiences) really exists, is still much more divided than Cecil seems to believe. It may be the majority opinion that it is real, but a respectable minority of researchers have their doubts. The amazing abilities of “Elizabeth” do still occasionally get mentioned in the reputable psychological literature, however. Some serious scientists do seem to believe it. I myself am no longer sufficiently close to the “in group” of memory psychologists to have heard the hoax story again, or to check out how widely it is known or believed.

So there you have it: the only recorded case of a genuine photographic memory among ordinary human beings is, very likely, a hoax.

Kim Peek Super Memory
Kim Peek

That’s not to said that there aren’t folks with a really good memory. Kim Peek, the famous savant who was the inspiration behind Rain Man, could supposedly memorize each page of a 9,000+ page book, reading at a rate of 8 to 12 seconds per page (with each eye reading its own page). This has not been thoroughly tested, however.

The American actress and author Marilu Henner, on the other hand, can supposedly remember every day of his life. Again, this has not been tested in a clinical setting, and may just be a symptom of an obsessive-compulsive disorder.

Another savant, Stephen Wiltshire, has been called the “human camera” for his ability to draw objects around him several minutes (to hours) after having seen them for the first time. However, again, as precise he is, he takes liberties, so it is not clear if he truly has a “photographic” memory, but he’s the closest to it.

Stephen Wiltshire Eidetic Memory
Stephen Wiltshire

How to Develop Photographic Memory

Solomon, Kim, and Stephen are truly fascinating cases, but they are not normal guys – they have very rare abilities. So, can a normal human being develop photographic memory or the closest thing to it?

The answer is No. Photographic memory can’t be achieved, not even with nootropics. However, by taking nootropics and learning a few techniques, we can develop an exceptional memory. Let’s see how.

Memory: What is It, How to Improve it

There are several stages of memory formation: memory acquisition/encoding, working memory/short-term memory, long-term memory/consolidation, memory retrieval, and reconsolidation.

Five major pathways are essential for the formation, retrieval and reconsolidation of memory: dopamine, choline,AMPA, norepinephrine and adrenergic receptors, and neurotrophic factors (BDNF, GDNF, NGF).

  • Choline is essential for short-term memory and memory consolidation
  • Dopamine helps focus, motivation and general cognition[5]
  • Norepinephrine is a memory modulator[6] and it’s essential for memory retrieval[7]
  • AMPA improves synaptic plasticity and strengthen synapses
  • BDNF is important for long-term memory[8], learning, and synaptogenesis[9]

NGF is also important for neurons health and memory — but only in old subjects, as it actually impaired memory when given to young rats[10], so we’re not going to focus on it too much. Same for norepinephrine and adrenergic receptors, GDNF, Sigma, cAMP, PKA, CRE, CREBs and other minor neurotransmitters/neuromodulators.

References   [ + ]

Biohacking Tutorials

The Ultimate Guide To Hair Loss: A Scientific Approach

Male-pattern hair loss, also known as androgenic alopecia, or male-pattern baldness (MPB), is a very common condition, affecting 70% of males and an ever-increasing number of females at some point in their life. A British research poll conducted on males ages 18 to 30 asked the question, “what do you fear the most?” The number one answer was hair loss,[1], surpassing erectile dysfunction, sexually transmitted disease and a number of other rather worrying conditions. All over the web, we find remedies — frequently without any scientific basis — on how to “cure” ourselves of this annoying condition. This is the reason why I’ve decided to take a scientific approach to treating hair loss.

What is Androgenic Alopecia?

hair areas regions hair lossAndrogenic alopecia (AGA) is a condition in which the hair follicles progressively miniaturize due to the effects of androgenic hormones. The reason why it is more frequent in males is that the male scalp has regions that are highly sensitive to DHT (dihydrotestosterone), a potent androgenic hormone that has an adverse effect on hair. These sensitive areas are the vertex (crown) and the frontal regions. While hair recession on the temples is a normal part of the aging process of men, recession of the vertex and the midscalp is caused by androgenic alopecia.

Thinning Hair Treatments

Before we venture into the wild world of MPB treatments, it is important to point out that growing back completely miniaturized hair follicles (i.e. totally bald areas) is extremely unlikely and that treatment should be started as soon as possible.

That said, I don’t recommend taking DHT inhibitors (e.g. finasteride, dutasteride) if you are less than 23 years old, as DHT is important for developing the male body. If that’s the case, I recommend taking natural DHT inhibitors such as saw palmetto together with minoxidil until you feel safe about taking a heavy-duty DHT inhibitor. We’ll talk more about that later.

norwood hamilton hair loss scale
The Hamilton-Norwood scale, introduced by Dr. James Hamilton and revised by Dr. O’Tar Norwood, is used as a measurement scale in male pattern baldness.


Since its introduction in the 1980s, Minoxidil has been used by millions of people all around the world. Everything that could be said on Minoxidil has been talked about many times over throughout the internet. However, it is worth summarizing the vast amount of info we can find on the web in a small recap.

Minoxidil is a drug that was developed as a blood pressure medication due to its vasodilating properties. The drug was effective but had a number of side effects. One of these effects was unexpected hair growth. The increase of hair growth became so obvious that dermatologists began prescribing minoxidil for androgenic alopecia without it having been approved by the FDA. The researchers thus quickly repurposed minoxidil as a hair loss treatment, and the rest is history.

Minoxidil is, as of today, the most effective drug to stimulate hair growth and it is frequently used by transgenders to stimulate beard hair growth. You can buy a 6 months supply for around 26$, which is slightly more than 4$ a month. Side effects may include black circles, body hair growth, wrinkles and faster skin aging. The last two can be prevented with retinoids (more on that later).


Finasteride (Proscar) is a 5-alpha reductase inhibitor (5-ARI). Basically, it inhibits 5-AR, an enzyme that converts excess testosterone into its more androgenic brother, dihydrotestosterone (DHT). As we’ve seen already, DHT — plus other factors, including elevated sebum production, stress, inflammation, and diet — is the ultimate hair killer, so we don’t want that.

Unfortunately, DHT is involved in many bodily processes and functions, such as muscle building, depression and anxiety, body hair (generally people with a lot of body hair are more susceptible to androgenic alopecia), height and so on. finasteride dht inhibitionThat said, the incidence of side effects in Proscar (finasteride) patients is very low and around the same rate as a placebo (sugar) pill. So, why there are people all over the internet screaming about how finasteride “shrunk their balls” or destroyed their life forever? As usual, I think the truth is somewhere in the middle. In my experience, yes, finasteride slightly lowers libido. However, the effect is not as bad as some people say, and it gets better with time.

Some of the complaints may come from the fact that doctors are prescribing a higher dose than needed. The dose for hair loss is 1 mg a day (and 5 mg for prostatic hyperplasia), but according to several studies, a single dose of finasteride will lower DHT for almost a week. In fact, one study demonstrated that 0.05 mg of finasteride was nearly 50% as effective as 100 times the dose of 5 mg in reducing serum DHT after a single dose. Not only that but with daily dosing it was almost 90% effective as 1 mg!

My recommendation thus is — if you choose the oral route — to take between 0.25 to 0.5 mg every other day (or every day if your DHT levels are really high).

Topical Finasteride

One question that always struck my mind about finasteride is why the scientists that were developing it never thought about going by the topical route. I’m not a scientist but it just seems more logical to me to apply a hair loss drug directly on the hair follicle rather than taking it orally, don’t you think?

Clinical Studies

Fortunately, in the last decade, we’ve seen more and more studies being done with topical finasteride. In a study conducted in India last year[2], the researcher switched patients aged 20 to 40 years old from oral finasteride to a solution of 5% minoxidil and 0.1% finasteride. Of the 45 patients that underwent treatment, 84.44% of them maintained a good hair density with the minoxidil-finasteride combination.[3] Five of them stopped the treatment for a period of 8-12 months and then resumed it. Of those five that stopped the treatment, 4 of them had a good improvement when they resumed treatment.[4]

A Swiss study[5] compared the efficacy of topical vs oral finasteride. The results were clear: 1 mg of topical finasteride once a day reduced DHT levels in the scalp more effectively than 1 mg of oral finasteride.[6] The former reduced DHT levels by 71% while the oral finasteride only reduced them by 51%. Both administrations reduced DHT blood levels, so if you get side effects with Propecia, you will likely get side effects with topical finasteride. They also tried 0.5 mg of topical finasteride twice a day, but that only reduced scalp DHT levels by 47%.

To obtain a topical finasteride solution you need to crush Proscar (or generic finasteride) tablets in your Minoxidil solution. You should try to obtain between 0.05 and 0.1% of finasteride. Start at 0.05% twice a day and work your way up.

Black Castor Oil + Peppermint Oil

Castor oil has been used as hair growth tool since early times, but only recently has it been rediscovered as a scientifically-proven hair growth oil.

Prostaglandin D2
Prostaglandin D2

Before we go any further, we need to point out the discovery in 2012 by dermatologist Luis A. Garza and his team, that men with androgenic alopecia have high levels on the scalp of the enzyme prostaglandin D2 synthase (PTGDS) and its product prostaglandin D2.

Yin & Yang: Prostaglandin D2/E2

Prostaglandin E2
Prostaglandin E2

During a normal hair cycle, the levels of PTGDS increase immediately before a regression phase. The researchers thus assume that PTGDS and PD2 have an inhibitory effect on hair growth and that prostaglandin D2 inhibitors can, therefore, be used to stimulate hair growth.

On the other hand, we have prostaglandin E2 (PGE2) that stimulates hair growth.[7] Bimatoprost, a PGE2 analog, is currently being researched as a hair loss treatment.

“That’s cool and everything,” you may say, “but what does it have to do with Castor or Peppermint oil?”

  • Castor oil contains ricinoleic acid, a fatty acid with anti-inflammatory and analgesic activity that activates the EP3 prostanoid receptor for prostaglandin E2.[8] Unfortunately, it is terribly understudied, which is quite strange since castor oil has been a popular hair treatment for years, particularly in Jamaica.
  • Peppermint oil in a 3% solution stimulated hair growth in mice[9] through an increase in IGF-1 mRNA expression. The results were similar to those obtained with Minoxidil.
  • By combining these two oils with Minoxidil and topical finasteride, we can achieve incredible hair growth. I personally have achieved hair growth in remarkably “difficult” areas such as the temples. It’s important to start as early as possible before the hair follicles miniaturize completely.
    I personally use June Milnrow Peppermint Jamaican Black Castor Oil which combines flaxseed, peppermint, and black castor oil together, but it can be a bit expensive to buy it in the US, so here’s another one manufactured in the USA.
  • There are other oils that may aid hair growth. One of these is pumpkin seed oil (PSO), which is a well-known 5-AR. A 2013 study compared the effect of pumpkin seed oil to placebo in 76 patients suffering from mild to moderate androgenic alopecia. Half of them were assigned to the treatment group (400 mg of pumpkin seed oil capsules) and the other to the placebo group. The patients were instructed to not take any hair loss treatments (both topical and oral) for the 3 months prior to the study. The Mean Hair Count in the treatment group increased by 40%, whereas in the placebo group it increased by 10%. The study did not address the topical use of PSO nor the (common) combination of pumpkin seed oil with other natural 5-alpha reductase inhibitors (like in saw palmetto complex).

Dermaroller and Dermapen™


A dermaroller is a skin needling device. The concept behind it is that by penetrating the skin with small needles, you can stimulate collagen production without leaving scars. A dermapen is pretty much the same; the only difference is that by removing the rolling process it is more gentle on the skin, which should theoretically heal faster and have better results. It is also a hundred times more expensive, so unless you have a lot of money to throw away, I recommend going with the dermaroller.

Which Dermaroller Should I Use?

There are dermarollers of all (needle) lengths, ranging from 0.2 to 3 mm. Generally, the lengths used to stimulate hair growth are between 0.2 to 1.5 mm. So which one should you buy? The answer is: it depends.
There are two ways of doing this:

  • If you’re a minoxidil user, I recommend a 0.25 mm dermaroller to be used every other day (or every day if your skin tolerates it) before applying minoxidil. This will increase minoxidil absorption — and thus, efficacy — a lot. At this length, however, it is not able to stimulate collagen production, and its only purpose is to boost the absorption of topical products.
  • If you do not use minoxidil, or you use it but are willing to go the extra mile to regrow hair, then choose with a 1 to 1.5 mm dermaroller to be used once a week.
Skin penetration of different dermaroller needle lengths

A 2013 study[10] compared a group of patients taking 5% minoxidil twice a day to another group taking 5% minoxidil and using a weekly dermarolling regimen (the dermaroller chosen had 1.5 mm needles). The mean change in hair count after twelve weeks was significantly better in the dermaroller group compared to the minoxidil only group (91.4 vs. 22.2 respectively).[11].


Tretinoin (Retin-A), is a vitamin A (retinol) derivative. Retinoids are terribly understudied as hair loss treatments, but according to a clinical review,[12] they are important for hair growth, especially when paired with minoxidil[13] and used on females.[14] A study showed that tretinoin and 5% minoxidil once a day was as effective as 5% minoxidil twice a day.[15]

I think tretinoin 0.025% (or even just retinol itself), is a good addition to my hair loss regimen but it is not as important as the other compounds. They are important, however, to make once a day dosing of minoxidil/topical finasteride possible. So, in the end, I’ll probably keep using it (or resort to retinol should tretinoin get too expensive).

Putting It All Together

Now that we have discussed some of the most effective and convenient treatments for combating hair loss, we can use this information to develop a treatment regimen.

Regimen A


  1. wake up
  2. do a 0.25 dermaroller routine on the scalp alternating a day on and one off (or 1.5 mm once a week)
    go back and forth each roll
    dermaroller technique
  3. apply minoxidil-finasteride 5%/0.1% solution on dry hair
  4. apply a thin film of tretinoin or retinol on the hair line and vertex


  1. apply castor oil on the hair line, vertex and other balding areas

Regimen B


  1. wake up
  2. split a 1 mg tablet of finasteride and take half of it (every other day)
  3. do a 0.25 dermaroller routine alternating a day on and one off (or 1.5 mm once a week)
    go back and forth each roll
    dermaroller technique
  4. if the skin is not bleeding, apply 5% minoxidil solution, otherwise wait for it to stop bleeding


  1. apply 5% minoxidil
  2. apply castor oil on hairline and vertex

Do not dermaroll if skin if hasn’t healed yet and follow the instructions on the box closely.

Other Useful Tips for Thinning Hair

  • I recommend a complete head shave when starting the regimen. The reason is simple: doing so will allow the dermaroller (and thus the minoxidil/finasteride) to penetrate deep into the skin and strengthen the hair follicle significantly. After that you can grow your hair normally.
  • Avoid wearing hats or other constrictive headwear, they will speed up hair loss and cause more problems such as traction alopecia or scalp folliculitis.
  • To stimulate hair growth, use shampoos or creams containing caffeine[16] [17], copper peptides or miconazole (the -azoles have a synergistic effect with minoxidil).
  • Supplementing Biotin, Copper, Zinc, MSM and the amino acids L-Cysteine, L-Methionine, and L-Lysine will also stimulate hair growth. A good overall supplement is Country Life Maxi-Hair Plus
  • In my experience, N-Acetylcysteine (NAC), a more bioavailable form of the amino acid Cysteine in high doses (600 mg twice a day) will significantly stimulate hair and beard growth.
  • Blocking DHT with finasteride will increase estradiol (estrogen), a female hormone. To avoid that, consider buying a diindolylmethane supplement, which is a compound found in cruciferous vegetables that reduces the levels of estrogen.
  • Other supplements to help reduce or eliminate Propecia’s side effects are zinc and grape seed extract. The latter is a strong aromatase inhibitor, a substance that inhibits the conversion of testosterone to estrogen.
  • Aromatase inhibitors may reduce finasteride efficacy — particularly the pharmaceutical ones — so keep that in mind should you consider taking one.

So that’s it for now, folks! For any questions or suggestions leave us a comment and we’ll get back to you!

References   [ + ]

Nootropics Tutorials

Nootropics: A Beginner’s Guide To Cognitive Enhancers

The realm of nootropic substances (aka cognitive enhancers or smart drugs), at the time around its conception, was reserved for the very select few who had access to these novel cognition-enhancing drugs. In recent years, nootropics have gained more widespread recognition, and are more accessible to average individuals than ever before, thanks to the rising number of online vendors and communities who make these substances accessible for all.

The term “nootropic” has been consistently more and more searched on google ever since 2011 (the year when the film Limitless was released) , and people’s interest in the subject will certainly continue to rise. Although nootropics still maintain a type of “fringe” status in the world of drugs, their infiltration into the mainstream is undeniable.

Nootropic Trend - Google searches of keyword "nootropics"

What is a Nootropic?

nootropic brainCorneliu E. Giurgea, the Romanian chemist who first synthesized piracetam, developed the concept of nootropic substance in 1972.[1] It is a combination of the Greek words “νους” (nous) meaning “mind”, and “τρoπoς” (tropos) meaning “bend” or “change”. This is what nootropics do. Essentially, they positively alter the way in which your mind works.

Nootropic drugs are a specific subtype of psychoactive substances. According to Giurgea, in order for a drug or supplement to be considered a nootropic, it must adhere to the following criteria:[2]

  1. Enhances learning and memory
  2. Enhances resistance of learned behaviors to conditions that will disrupt them
  3. Protects the brain against physical of chemical injuries (such as concussions or neurotoxic drugs)
  4. Increases the efficacy of cortical/subcortical control mechanisms of the brain (such as improving reaction time)
  5. Typically lacks negative side-effects (i.e. sedation), and possesses low toxicity

Though these criteria lay out the foundation for what a nootropic is, most modern definitions are much more general. As a more common definition, nootropics are chemical substances or herbal supplements that enhance cognition and mental function.


If we think in terms of this general definition, there is about a 90% chance you use a pseudo-nootropic substance regularly. Caffeine, the most popular drug in the world, is commonly classified as a nootropic, due to the fact that it is stimulatory and enhances attentiveness linked to cognition, learning, and memory. [3] [4]

Certain substances that don’t explicitly enhance cognition are still sometimes grouped in with nootropics. This would include substances that improve mood, reduce anxiety, or promote an overall feeling of wellbeing. Some examples of these substances are phenibut, sulbutiamine, and ashwagandha. Even if these supplements don’t have mechanisms that directly improve cognition, their mood-improving capabilities will tend to lead to an enhanced ability to focus and think clearly.

Who Uses Them?

Giurgea coined the term “nootropic” after he synthesized piracetam, which is, under Giurgea’s definition, the first substance to display purely nootropic properties. Piracetam has cognitive enhancing and neuroprotective capabilities while also possessing relatively few side effects. [5] Because of this, piracetam is commonly used to improve cognition in individuals who are experiencing the cognitive decline that comes with old age, dementia, or Alzheimer’s.

With the development of piracetam, other nootropic substances were investigated and researched for their applications in those who experience cognitive decline. Many drugs derived from piracetam (referred to as racetams) have been developed in hopes that they would yield even more benefits than piracetam. For instance, phenylpiracetam displays stimulant properties in addition to cognitive enhancement. [6] Likewise, aniracetam works as an anxiolytic. [7]

Modafinil is wakefulness-enhancing nootropic used by college students as a safer alternative to Ritalin and Adderall

Up until the past decade, these kinds of cognitive-enhancing drugs were only used extensively in clinical applications, such as treating cognitive illnesses. However, the past few years have seen tremendous growth in the use of nootropics among younger healthy individuals in hopes that they could improve their performance in work or academic studies. For example – modafinil (Provigil), a wakefulness-promoting nootropic substance, has seen increased usage among college students as an alternative to Adderall, due to the fact that it aids the brain in focusing on tasks for extended periods of time without fatigue. [8]

Many nootropic substances, such as the racetams and tianeptine (an antidepressant nootropic), are prescription drugs in Europe but are unscheduled in the United States. This has led to many of them being sold online by nootropic vendors, making them readily available for those who wish to purchase them.

Not surprisingly, Russia, the country that has developed a large number of nootropics (including Phenibut, Picamilon, Phenylpiracetam, Selank, Semax, Cerebrolysin, Emoxypine and so on), it’s the place where the keyword “nootropic(s)” is most popular in 2016[9], according to Google.

The increasing number and growth of online communities, such as the nootropics subreddit, has attracted the attention of younger individuals who seek to improve their cognitive performance and preserve their youthful cognitive capabilities. These online communities are extremely valuable sources of information on all things related to nootropics. They are open forums where anyone can ask questions about smart drugs and cognitive enhancement and engage in valuable discussion. Many newer nootropic substances have not been extensively tested in clinical settings, but anecdotal user reports can be found within these online communities.

Where Do I Begin?

If you are determined to make a go at nootropic supplementation, then logically the smart thing to do is implement the smartest ways to use smart drugs. You do not have to be a brain surgeon to begin effectively supplementing with nootropics, but understanding at least the bare bones of the foundations of a few related fields like neuroscience, neurology, and drug metabolism, is vital to getting the most out of them.

Ideally, you want a good working understanding of all the major mechanisms of action, including receptor systems involved in memory, mood and cognition (dopamine, GABAacetylcholineserotonin, etc).learning memory nootropics Attempting anything other could end up as catastrophically as fiddling with the kernel of your operating system without knowing how it works. The best way to go about it is to learn what happens to drugs inside the body, how the classic nootropics work (like Piracetam and Aniracetam), and what are some of the basic nootropic stacks.

Even though it can be a bit daunting at first, you will also want to learn how to access & read scientific researchwhat is acetylcholine (the learning and memory neurotransmitter), how it works, how the brain produces it and what is a choline precursor. Learning the major neurotransmitters, understanding the difference between excitatory and inhibitory neurotransmitters, all these are great places to start.

When first getting into the world of cognitive enhancement, the sheer number of substances out there can be very intimidating. Here is a short list that outlines some of the most popular and proven nootropics for beginners.

Wakefulness and Motivation

  • Caffeine and L-Theanine – Promotes wakefulness and is stimulating in general. The addition of L-theanine helps reduce the negative side effects of caffeine, such as anxiety. Additionally, L-theanine also improves cognition.
  • Modafinil, Armodafinil, and Adrafinil – These three compounds are chemically related. Armodafinil is the active isomer of modafinil and is thus generally more potent. Adrafinil is a prodrug to modafinil. In other words, it is metabolized into modafinil by the body. All three of these are used to promote wakefulness and reduce fatigue.
  • Rhodiola Rosea – A herb that acts as an adaptogen, meaning it aids the body in reacting positively to stressful stimuli. It typically reduces feelings of fatigue and is slightly stimulatory. It is also sometimes used to lessen the effects of caffeine withdrawal.

Note: Prescription drugs such as Adderall (amphetamine) and Ritalin (methylphenidate) are especially effective at increasing feelings of motivation. However, they carry additional side effects and risks of dependency, and should be used with caution.

General Cognition

piracetam nootropic adhd

  • Piracetam – The original racetam, was originally developed as a sleep-aid because of it’s GABA structure, when given to rats it improved their memory and cognition.
  • Noopept – Is chemically similar to piracetam but is active at a fraction of the dose (10 mg vs 1000 mg), and also increases the production of NGF and BDNF, two neurotrophic factors that promote the survival and differentiation of neurons. It typically provides an increase in cognitive ability along with mild stimulation.
  • Aniracetam – Provides cognitive effects that are similar to Noopept, but is also anxiolytic in nature. It is especially helpful in helping the brain associate different thoughts and piecing them together to form the “bigger picture.”
  • Phenylpiracetam – Similarly aids cognition like noopept and aniracetam, but it noticeably more stimulatory. It is also known to be more neuroprotective, and aids in preventing cognitive decline. It is a good alternative to Modafinil.

Note: Because racetams and noopept work through modulation of acetylcholine, they should be supplemented alongside a choline source, such as alpha-GPC or CDP-choline.

Mood Improvement

  • Tianeptine – Chemically a tricyclic antidepressant, tianeptine is novel in the fact that it improves mood while also serving as a neuroprotectant and cognitive enhancer.
  • Phenibut – an anxiolytic compound that may enhance cognition in stressful situations (like exams or a public presentation) through means of reduced anxiety.


  • Bacopa monnieri – Bacopa has been found to improve the formation, retention, and acquisition of memory. It is an adaptogen and is often taken for its anxiolytic properties
  • Huperzine A – an acetylcholinesterase inhibitor (a compound that prevents the breakdown of the neurotransmitter acetylcholine) extracted from the plant Huperzia Serrata.

What To Expect

Most nootropics rarely display immediate or noticeable acute effects on cognition and well-being (the only exception being stimulant nootropics like Modafinil and Phenylpiracetam) . In fact, they are typically used for long-term neuroprotection, and may not display immediate or noticeable results from use. The psychoactive effects of nootropics are more subtle than the effects of recreational drugs but are ultimately more beneficial. By definition, the daily use of nootropic substances should be far more sustainable than that of recreational drugs.

Nootropics are meant to be safe to use indefinitely though not all drugs sometimes referred to as “nootropics” will meet these criteria. For instance, phenibut, a GABAergic anxiolytic, is sometimes discussed as having nootropic capabilities related to anxiety reduction. However, phenibut has a fairly high risk of causing dependency or withdrawal, and should not be used on a daily basis.

coffe and modafinil pure nootropics
Modafinil is used by college students as a safer alternative to Ritalin and Adderall

Many people supplement multiple nootropics at once to maximize their cognitive benefits. These combinations of substances are referred to as “stacks”. For instance, one might stack caffeine and L-theanine because L-theanine is known to reduce the jitters and anxiety that come with caffeine. [10] When taking multiple nootropics, it is extremely important to research any potential negative interactions between substances. is an invaluable resource for researching nootropics and their possible interactions.

Nootropics can certainly be of great benefit to those who wish to improve their cognitive function and protect their minds from degradation. However, nootropics will likely be far more beneficial when they are used in combination with exercise, a proper diet, and meditation.[11] Nootropics can only do so much, and are certainly not an excuse to neglect these other primary health factors.
In addition to this, nootropics should not be used to treat mental disorders unless under the direction of a trained health professional. It may seem tempting to use promising and novel nootropics to treat something like depression, but there is still some amount of risk involved with doing so, especially given the fact that many of the newest nootropics still require a great deal of research before they can be used clinically.

Even if “old” nootropics like racetams are totally safe, it is still a good idea to check out interactions if you’re taking prescription medications.

Up Next

References   [ + ]


What Happens to Drugs Inside the Body?

The wise nootropic user knows two things: his goals with nootropic use, & how to use nootropics to achieve those goals. The latter is an area not well explored by many nootropics users. Knowledge of how individual agents work guides the design of stacks. Certain drugs may work synergistically (both together produce a greater effect than either alone), additively (both agents work in combination), or antagonistically (counteract each other). Thus, it is essential to understand what exactly happens after a drug is ingested.

The science of pharmacology serves to explain how the ultimate pharmacodynamic effect is produced (the end result of a drug, e.g. improved long-term memory). This is accomplished by studying two aspects of what happens to drugs within the body: mechanisms & pharmacokinetics.


The most common way in which all drugs work is by modulating a receptor. The body is full of thousands of different types of receptors. These receptors are usually small proteins embedded in the surface of cells. There are 3 types of receptors:

  • Enzyme-linked receptors include enzymes & receptors that lead to the direct activation of enzymes.
  • Ion channel-linked receptors are regulated by concentrations of positively & negatively charged ions, such as Ca2+ & Cl. Na+ channels play a central role in neurotransmission.
    • Lidocaine, a Na+ channel blocker, suppresses conduction of action potentials between neurones, resulting in nullification of pain signals, hence its use as a local anaesthetic.
Receptors exhibit selectivity for ligands like locks & keys. The degree of compatibility between a ligand & a receptor is referred to as affinity.
  • G-protein-coupled receptors (GPCRs) receive signals by binding with ligands.
    • A ligand is something that binds to a receptor & produces an effect. Some examples are hormones, neurotransmitters, & drugs. When a ligand binds a receptor, it can produce any of 4 effects:
      • A receptor agonist is a ligand which produces stimulatory effects upon binding, triggering or potentiating a biochemical pathway ultimately leading to a response in the body.
        • When histamine binds H1 receptors, it triggers the immune system in such a way that symptoms of an allergic reaction are produced.
      • A receptor antagonist is a ligand which does not exert an effect upon binding, leading to the extinguishment of a somatic response as the stimulating ligand is unable to make contact with the occupied receptor. Antagonists can be competitive (meaning they reversibly bind to the receptor) or non-competitive (irreversibly bind receptors). Non-competitive receptor antagonists are more potent.
        • Aspirin is an irreversible COX-enzyme antagonist. Its inhibitory effects on platelets are permanent– following discontinuation, normal platelet function does not return for ~10 days- the lifespan of a platelet. For this reason, aspirin should be held for at least 1 week prior to major surgeries.
      • A partial agonist is a ligand which has properties of both an agonist & an antagonist ultimately producing a mild stimulatory effect.
        • Aripiprazole (Abilify) is an antipsychotic with partial agonist activity. Aripiprazole’s mild modulation at the D2 receptor produces modest reductions in some psychotic symptoms but avoids undesirable side effects due to over-antagonism of dopamine activity caused by other antipsychotics.
      • An inverse agonist is a ligand which exerts the opposite effect upon binding to a receptor, reversing a somatic process.
        • When an antihistamine drug such as diphenhydramine (Benadryl) binds H1 receptors, it does not merely occupy the receptor, preventing histamine from binding, but actually promotes the opposite biochemical pathway, actively countering the allergic reaction.

Visualised dose-response curves for various ligand-receptor interactions.
Visualised dose-response curves for various ligand-receptor interactions.



Pharmacokinetics (PK) refers to what happens to the drug after it has been ingested in the body. It is divided into 5 major areas, denominated by the acronym ADME-Tox:

  1. Absorption is the first phase of pharmacokinetic interest. Here we consider aspects of the drug’s transit into the bloodstream.
    • The route of administration (oral, sublingual, inhalation, intravenous, etc.)
    • Foods, as well as most drugs that are taken by mouth, are absorbed in the small intestine
    • How long a drug takes to be absorbed
    • The maximum amount that is absorbed (peak concentration, CMAX) & the time it takes to achieve CMAX (TMAX)
    • The onset, which is the time it takes for drug’s effects to begin
  2. Distribution is where we examine where the drug goes in the body.
    • The bioavailability (F), which refers to the concentration of the drug at the site of action (for nootropics, this would be the brain)
    • The volume of distribution (VD) which represents the degree of absorption into fat tissue. This is important because the amount of available drug is that which is present in the blood
    • Protein binding refers to the amount of drug in the blood that is bound to proteins such as albumin where it is inactive. These proteins act as carriers of the drug, preventing it from degradation. When drugs compete for binding proteins, or chronic malnutrition leads to decreased production of plasma proteins, there is a potential for increased levels of drug in the blood
  3. Metabolism has to do with biochemical pathways of breakdown or altering the structure of the drug molecule.
    • The liver is the major site of drug metabolism
    • Cytochrome P450 is a key group of enzymes in the liver that is responsible for the degradation of many drugs. Individual enzymes include 2C9, 2D6, 3A4, & so on. When 2 drugs happen to compete for the same enzyme, there is potential for a drug interaction. Understanding CYP450 is understanding the majority of drug interactions (will be covered later!)
    • Other drugs are able to undergo alternate pathways of hepatic (via the liver) metabolism (e.g. oxidation) or non-hepatic metabolism (e.g. proteolysis)
    • Prodrugs are parent compound which are inactive when ingested but become activated when undergoing metabolism. Usually, this is through the cleavage of a portion of the molecule. Active compounds, too, may have active metabolites. Keep these in mind as the metabolites can continue to contribute to the pharmacodynamic effect of the drug.
  4. Elimination is how the parent compound of the drug & its metabolites are removed from the body. There are two major pathways of elimination: hepatic (faecal) & renal (via the kidneys; urination).
    • Dysfunction of either system could lead to accumulation of drugs that are excreted by that pathway, possibly worsening side effects
    • Some drugs can be excreted via alternate pathways if the major pathway of removal is compromised
The ideal dosage of a drug achieves levels above the MEC but does not exceed the MTC.
The ideal dosage of a drug achieves levels above the MEC but does not exceed the MTC.
  • Toxicology is the propensity of a drug to cause harm & via which mechanisms.
    • «The dose makes the poison»: every agent has the ability to cause harm given the correct amount.
    • The minimum toxic concentration (MTC) is the level at which a drug’s toxicity becomes clinically significant. This is often compared with the minimum effective concentration (MEC), where a drug’s desired effects start to work. The difference between MTC & MEC is the therapeutic range. The narrower the therapeutic range, the higher the risk of toxicity.
    • Some mechanisms by which antidotes can work include binding the toxic molecule, preventing it from triggering receptors or promoting recovery processes (e.g. antioxidants)

Pharmacokinetic pathways & major organs.



  • Mechanisms are how drugs produce their effect. Most drugs work by affecting a receptor.
  • Pharmacokinetics is the study of the changes that happen to the drug after it is introduced into the body. It is broken down into 5 major areas: absorption, distribution, metabolism, elimination, & toxicology.
  • Pharmacodynamics is the outcome effect of a drug, such as reduced depressive symptoms.
  • An understanding of mechanisms & pharmacokinetics of drugs can be useful in designing stacks which exploits the characteristics of each agent for an optimised pharmacodynamic effect.

How to Understand Clinical Research, Part II: Quality of Evidence

The ability to critically understand & judge the data from a study is crucial in making decisions on whether a new drug is safe & effective. As we will see with studies regarding nootropics, the answer is not always clear. Understanding concepts of validity, bias, & limitation can help in the evaluation of any study.

Internal validity

Internal validity is analogous to the inner workings of a clock
Internal validity is analogous to the inner workings of a clock– a study with strong internal validity will produce results that truly reflect what the investigators sought to explore, like how a clock with well-adjusted inner workings will accurately display the time.

Internal validity is the strength of the study’s purported causal or associative relationship.

Higher level studies, such as randomised controlled trials & meta-analyses, seek to demonstrate a causal relationship (e.g. drug A causes improved cognitive function). Lower level studies, such as cohort studies & case-control studies provide evidence that demonstrates an association between a cause & effect (not as strong of an assumption: drug A is associated with improved cognitive function). The tighter the study’s internal validity, the more reliance we can have that drug A does indeed cause or is associated with improved cognitive function, rather than any other conclusion (i.e. has no effect on, worsens cognitive function).


Bias comprises confounding factors which may compromise a study’s internal validity.

For example, consider a study with 2 treatment groups testing the effect of a new drug on cognitive function. The group that receives the drug is generally more educated, while the group that receives placebo is generally less educated.

How much faith would you have if the investigators concluded that the drug significantly improved cognitive function?

This is an example of sample selection bias. We will introduce more forms of bias later that could impair internal validity & thus the ability to truly believe that a study’s results are relevant to the study question.

External validity

External validity is the generalisability of a study’s findings to populations beyond the study sample.

External validity should only be assessed after a study is found to be internally valid. If a study is not found to be internally valid, then its findings could not be said to truly answer the study question; & thus there would be no reason to evaluate whether its results should be generalised to others.While internal validity is susceptible to bias, external validity is counterbalanced by limitation. These are characteristics of the study sample which add to & restrict the population to whom the results may be generalised.

Always consider the type of people who were enrolled in the study
Always consider the type of people who were enrolled in the study & whether what worked (or didn’t work) for them would work for you.

Consider the previous example of a study, but with both groups comprising generally older subjects otherwise comparable at baseline. Absent other confounding variables, the study could be said to be internally valid: if the investigators reported a significant improvement in cognitive function, then this result would be probably accurate. However, whether we could assume that this drug would work for younger individuals would be up for question as it has not been tested in this population. This limitation of generalisability applies to other demographic information such as race, sex, & even geographic location, & may include comorbidity (the presence of other health conditions), diet, & other factors depending on how the data is to be used. Including more diverse individuals within a study may decrease limitations & increase external validity, but possibly at the expense of internal validity (without randomisation). Conversely, creating a more uniform sample could increase internal validity but introduce more limitations.

Other forms of bias

Other forms of bias that could impair internal validity include:

  • Sample selection bias is when the treatment groups are not equal at baseline due to demographic differences.
  • Intervention selection bias is present if different forms of the experimental variable are used. This is a risk when the study protocol is ambiguous; for this reason study protocols are usually very detailed so as to prevent deviation. Consider the previous study with 2 treatment groups. Assume the groups are balanced at baseline. However, among the individuals in the group receiving the study drug, two different manufacturers of the drug are used. This could potentially produce variation in the results, providing an imperfect picture of how well the drug actually works. To limit this type of bias, it would be more prudent to select one manufacturer or have two treatment groups (one for each manufacturer).
  • Measurement bias is when there exist variations in how outcomes are measured. If the study drug group took an easier cognitive test than the placebo group, then the results would show that they performed better, when in fact the comparison was not equal.
  • Outcome bias occurs if the selected endpoints do not correspond to the desired outcome of interest. For instance, if the researchers claiming to measure cognitive performance instead administered a personality test.
  • Attrition bias is when more subjects from one group leave the study than in the other. Although the two groups may have been equal at baseline, attrition may result in unequal groups later on in the study which can result in confounding due to imbalanced characteristics (e.g. if all the young subjects left from one group) or simply due to number (sample size too small to detect a difference).

When cognitive tests are administered to a group of subjects, two possible biases could confound the results:

  • Statistical regression to the mean is a type of bias wherein on the second administration of the same test to the same subjects, the worst performers from the first administration tend to perform better & the best performers tend to perform worse on the second exam. They regress to the mean.
  • The testing effect is when subjects who take the same test become familiar with the style & better at taking the test. Although they might perform better on subsequent applications of the same cognitive test, it may not be because the study drug resulted in cognitive improvement.
  • Other forms of biases which are less commonly implicated but could still undermine a study’s findings include maturation bias & history bias.


  • Validity, bias, & limitations are key aspects of study designs to consider when researching & evaluating clinical data. The strength of evidence is best with high internal & external validity, & low risk of bias.
  • Internal validity is the strength of a study design to determine a causal or associative relationship. Studies with highly controlled experimental methodology (which we will discuss in depth later) exhibit tight internal validity minimizing the effect of biases.
  • External validity is the extent to which findings from internally valid studies may be generalized to populations beyond the study sample. Being aware of limitations to external validity guides the extrapolation of study data.

If you are interested in reading more about validity & bias, & how to apply them when reading an article, I highly recommend the Cochrane Foundation’s tool for bias risk assessment. It has since been widely used in meta-analyses when deciding whether to include articles.

Biohacking Caffeine Modafinil Nootropics Tutorials

Hacking Sleep How-To: Sleep Less, Do More (or How I Survived 48h Hackathons)

I started out in an Engineering program at a Canadian University a couple years ago. Shortly thereafter I decided I wanted to be a programmer. Totally reasonable life choices, that came with some slightly less reasonable time demands.

You see when you’re in an engineering program pulling all-nighters to get work done start becoming fairly normal. And then if you want to become a programmer you now need to digest thousands of lines of documentation and code, which definitely doesn’t help you get all the schoolwork done in a nice timely manner. And then we compound that with the recent phenomenon of hackathons. Hackathons are 24-48hr long programming meetups where you, alone or in a team, write code hoping to create something interesting, like a mobile app, or program. As it currently stands, getting employed at a top tier tech firm is nigh nearly impossible for an undergraduate student without hackathon experience.

So this led me to try and find some way to make it easier for myself to stay awake, and get work done.
University students are often familiar with ADHD medication of some sort or the other. These include Ritalin, Adderall, Vyvanse, Biphentin and many others. But they’re only so effective and have some undesirable side effects.
But hey, I’m not trying to tell you to not take drugs here, drugs are bad, you know this from the millions of dollars spent by many governments vilifying them under one undiscriminating umbrella term. No, I’m going to teach you how to intelligently use drugs to get the results you desire.

A brief primer on the brain

Hackathons are great learning experiences, you get to try new frameworks and tools with minimal risk. You see, to build something in programming, you need to understand the tools and solutions that exist in that space. To engineer a better bridge, you need to understand how bridges work and are built. So we need to understand the human brain a little bit.

Most of you should know that a human brain is a biological electrochemical system consisting of cells called neurons. Neurons connect to each other and basically store you. Who you are, your memories, your ability to add numbers, everything is stored as connections in a dense mesh of cells in your cranium. Neurons communicate via signals triggered by electrical charges that cause chemical messengers to be released into a tiny gap in between them and accepted by another neuron on the other side.
So to hack it, we will either have to use electromagnetic phenomenon or chemicals.

Although transcranial direct current stimulation has been noted to positively influence wakefulness [1] wearing a magnet and electrical equipment on my head doesn’t seem too attractive so instead let us enter the wonderful world of neuropsychopharmacology.

synapseRight so about those chemical messengers.
Well, they’re called neurotransmitters. There’s oh so many of them. Their release is usually mediated by voltage differentials in the neuron itself (keep this in mind, it’ll come up later).
The place where two neurons connect is called a synapse, and there’s a tiny gap between them.
After crossing the tiny gap, which is also called the synaptic cleft, these little guys fall into receptor sites. Think of it as a jigsaw puzzle, a specific shape of receptor goes with a specific shape of neurotransmitter. But there are man-made chemicals as well that can fit into the receptor and cause interesting effects since they have somewhat similar shapes to the neurotransmitters. Not all these neurotransmitters lock into receptors, some are sucked back into the neurons via recovery vents. This is called reuptake.

The neurons also have some receptors along their bodies, which allow them to judge and react to the environment. For example slowing down if the environment tells them the person is tired or trying to go to sleep. Though these aren’t actively used to send messages along.

Well now we know a bit about the brain but what about sleep?
Sleep has a myriad of purposes, so I do not recommend long periods of severe sleep deprivation.
These include muscle recovery and repair.
Formation of long-term memories.
The brain also does housekeeping and maintenance, flushing out by-products of cellular function and rearranging neuron formations.[2]
At the end of the day, sleep is necessary, but that doesn’t mean we can’t engineer around having to sleep every night. But not sleeping at all for an extended period can have dire consequences, even death.

Wakefulness and receptors

Well, there are 3 main receptor types that I’ve identified that have something to do with wakefulness. Since many chemicals can affect the same receptor and the receptors often have subtypes these 3 receptor types provide a nice framework to reason about hacking sleep and chemical targets. I came to this hypothesis by looking at the mechanisms of actions of a plethora of drugs which are known to affect wakefulness.

These are the adrenergic, dopaminergic and adenosine receptors.
But I should mention that sleep is complex, so is the human brain, and other neurotransmitters like serotonin and glutamate also play a part. For a purely curious mind I recommend reading “Neuropharmacology of sleep” on NCBI.

Dopamine receptors


Ah yes dopamine, many of you have probably heard of it. It is responsible for reward-motivated behavior. If you study hard and get those grades for yourself and it makes you feel good, well it’s the dopamine. Too much dopamine and you’ll be lazy and not want to do anything, too little and you’ll get bored, yawn, maybe fall asleep(anyone else have 8 am engineering lectures?). It plays a very real role in sleep.[3][4]

You will usually have too little dopamine trying to pull all-nighters. We’ll be looking at drugs that increase dopamine concentrations in the brain and supplements that are easily metabolized to it to prevent depletion. You also want to block its reuptake to maximize signaling strength. Dopamine reuptake inhibitors, precursors or anything that increases dopamine transporter activity causing it to release more is your friend.

Adenosine receptors


Fewer people have probably heard of this one, but almost all of you have exploited this poor guy in the past. Ever drink coffee? Green tea? Energy drinks? This is the main target for all of those.

You see as you get sleepier, this pesky little molecule called adenosine builds up in your brain as a breakdown product of ATP (your cells generate energy via the ATP->ADP reaction). It binds to its namesake receptor, which in turn triggers some very calming effects like slowed heart rate, reduction in dopaminergic signalling, muscle relaxation etc. All effects we don’t want. So we drink coffee, which blocks these receptors, preventing adenosine in our brain from getting in and triggering its effects. So what you need are adenosine antagonists.

Adrenergic receptors


These guys are responsible for triggering your adrenal system. The whole fight or flight response.
If you overstimulate them well you’ll be panicky, anxious, paranoid your heart will explode from the excessive beating. But a small amount can do wonders for alertness and wakefulness.
One should note that drugs that target the dopamine and adrenergic receptors can sometimes be found under the category of monoaminergics on online retail sites.


Alright, time for the fun stuff. I didn’t just almost put you to sleep droning on about receptors and what-not for nothing. Time to teach you how to hack around the biological need for regular sleep. I can’t talk about all the drugs since new ones come out pretty often, but you can identify drugs that’ll work based on the receptors and underlying systems they target. For the best results, we want drugs that have different mechanisms of actions on these systems stacked together.


AdderallRemember those drugs kids at school take we talked about earlier? Adderall etc.
They’re amphetamines or amphetamine derivatives, all of them, and share similar mechanisms of actions. They work mainly on the dopamine and adrenaline systems.

By increasing DAT (dopamine transporter) activity, they cause your neurons to dump more dopamine into the presynaptic cleft.
It works in the same way on the adrenergic system and also triggers similar effects on a myriad of other neurotransmitters like acetylcholine, glutamate, and serotonin.
But there are other drugs that can be acquired cheaper and without legal restrictions which have the same mode of action. They can often be found in supplements for weight lifting as stimulants or pre-workouts.

For example one drug that is rather easy to get at bodybuilding and supplement stores is Ephedrine. It’s similar to amphetamine in structure and affects the dopaminergic and adrenergic systems just like the most popular ADHD medication. It doesn’t work quite as well, though.

But these amphetamine derivatives also have a dark side.

First off if you take too much your neurons will fry themselves. Remember how I mentioned neurotransmitter based transmission is triggered by electric currents in the cells? When a super excited neuron dumps a ton of dopamine, the tiny electric charge causing it is enough to damage it, permanently. But then it cascades, and the next neuron in queue attempts to pass on the signal, frying itself in the process and so on and on. Don’t worry, there’s millions of them, or actually do worry a little bit. Neurons are easily excited, and like a very very old man with a myriad of health problems, too much excitement can and does kill it.[5]

Secondly, regular use of ADHD medication can and does cause a dependency. So you’ve effectively given yourself ADHD and can’t really function without it.[6]

Third, amphetamine use severely drains your neurotransmitters. You need to replenish them. Keep reading and I’ll tell you how.
They also cause stress and fatigue in the underlying systems, namely the adrenergic and dopaminergic systems and to a lesser extent the serotonergic system.
So if you feel burnt out afterwards, try taking half the dose or less the next time. a 10% constant boost is better than a 20% boost followed by a 80% degradation.

The brotherhood of Modafinil


Now let’s consider a slightly more exotic drug. Modafinil. This guy been around for a long time and the militaries around the world love it. I just found out my home nations (India) air force includes it in contingency plans. Brilliant! Soldiers that don’t need to sleep. Now if only they could find planes that didn’t fall out of the sky on a regular basis.[7]

Modafinil works via the dopaminergic and adrenergic systems.[8]
It works as a dopamine reuptake inhibitor, which means stronger signals due to more dopamine in the presynaptic cleft, and it increases norepinephrine levels in the synaptic cleft in a similar way to amphetamines.

An important factor to keep in mind is that it’s a low-affinity binder, which means:

  • It works slowly (expect 2 hrs)
  • Its mild (you won’t necessarily feel it, but trust me, when it’s 4am and you look around and everyone but you is yawning, you’ll know it worked)
  • It won’t prevent you from falling asleep if you really want.

You can buy Modafinil and Armodafinil, an improved analog of Modafinil, at ModafinilXL.



This guy gets metabolized to modafinil in the liver. A strange queasiness might be felt in the liver as the enzyme activity increases. Not as effective as modafinil since a lot of it is destroyed in the metabolic process.



Some people absolutely love this stuff. The name is a marketing play and the molecule itself doesn’t have much in common with modafinil.[9] Though common criticisms are that it looks funny, clumps easily, has a very short duration of effect and it’s as effective as Modafinil.



AKA CRL-409,40 (or Bisfluoromodafinil), current heavyweight champion of the modafinil alternatives world. Basically modafinil with two fluorine atoms added to it. This increases the bio-availability of the drug by increasing its lipophilicity (it crosses the blood brain barrier easier since it’s more fat soluble)[10]

Recommended dose is 50-100 mg, up to 200mg if you plan on staying up for 48hrs.



AKA CRL-409,41 (or Bisfluoroadrafinil) I recommend you do not take this. It’s basically adrafinil with two fluorine molecules and all anecdotal reports say it doesn’t work very well. If you do try it, write to us and tell us how it went!

Modafinil and it’s derivatives is a lot safer than amphetamines and stimulants like Adderall, but still don’t take a massive dose. I can tell you from personal experience that staying awake for 3 days in a row isn’t fun.

Good ol’ cuppa joe


So far we’ve targeted the dopaminergic and adrenergic systems. Let’s look at adenosine real quick.
Your best bet (and cheapest) is to simply drink a cup of coffee.
Many in the nootropics community love a little bit of l-theanine with their coffee, feel free to try that if coffee makes you too jittery.

But don’t drink too much coffee. It’ll backfire.
If you drink large amounts of coffee continuously, your brain reacts by upregulating adenosine receptors on the neuron heads and by increasing the amount of adenosine in your brain, and this causes you to be constantly sleepy, tired and to need coffee to barely function. If you’re at a hackathon, hold up on the coffee till it’s near the end and you absolutely can’t function without it.

I found myself continuously getting addicted to coffee, requiring it to just stay awake and then going through a painful withdrawal/cleanse, so I switched to green tea.
There are more powerful and targeted adenosine receptor blockers though they aren’t very well known or easily found. These belong to the Xanthine family of molecules. Write to us if you have any hands on experience with them, we’d love to interview you.


“But I feel like shit after pulling all-nighters or going to hackathons!”

Well duh, what’d you expect to feel like? A million bucks?

Here’s what happened, your brain depleted a ton of its neurotransmitters thinking your thoughts. Energy stores are also depleted. I highly recommend taking a dopamine precursor afterward or even as part of your drug stack.

N-Acetyl-L-Tyrosine, better known as NALT, is a crowd-pleaser in that category. The main part of those four letters is the T, and it stands for tyrosine. Tyrosine is an amino acid that is readily metabolized to dopamine. Dopamine is further metabolized to norepinephrine which you depleted stressing your adrenergic system. Bam! Two birds, one stone.
Mice treated to have extra dopamine also have a stronger reaction to modafinil and caffeine and ended up recovering better from sleep deprivation than untreated mice.[11]

So what about the adenosine we blocked?
Well, there isn’t much you can do about that. Take a nap, even if it’s a quick 10-30-minute nap or you just close your eyes and think about stuff during your waking stint. It’ll flush some of the adenosine out of your brain. It’ll also help you get over writers block if you feel incredibly fatigued before you can afford to sleep properly.

And finally, eat something, even if you’re not hungry from all the stims in your body. I’m not going to go into dieting and what proper foods are. But hopefully, you know this part.

Best of luck with your endeavors, whatever they may be.
And remember I’m not a doctor and even if I was, you take advice from a stranger on the internet at your own risk.

References   [ + ]


How to Understand Clinical Research, Part IV: Sample Data

In previous articles, we have learned how to access & read journal articles, how to interpret validity as a measure of the strength of evidence, and the various types of studies. With this foundation, we should have a basic idea of what to look for in a study. The next step would be developing our skills of interpreting the actual data from the article, which can be expressed as charts, tables, graphs, or text. The next two articles will be focused on the two major types of results in studies: sample data & endpoint data.

Sample Data


Sample data are information about the subjects who participated in the study. Although not what most people think of when they think of study results, sample data can profoundly influence one’s interpretation of endpoint data.

The first thing to consider in sample data is the sample size (n), or how many people participated in the study. Ideally, studies should enrol enough individuals to detect a treatment effect. For example, drug A may slightly improve cognitive function, but perhaps only in 15% of people. If only 50 patients are enrolled in the study, & 25 receive the study drug while the other half receives placebo, then only 3.75 individuals will likely experience the slight improvement in cognitive function. This small change is unlikely to be detected, especially when tested against a placebo effect.

How many subjects are needed, then, in order to truly detect a treatment effect? There exist statistical tests which guide investigators in all aspects of study design, including calculating the minimum sample size needed to detect a treatment effect. This process usually involves:

  1. estimating the magnitude of the treatment effect based upon previous studies,
  2. estimating the number of subjects needed to truly see that treatment effect, &
  3. minimizing the effects of chance & randomness

The first two parts should seem fairly intuitive after the previous example. The third requirement is a new concept, & is based on the following components (This is an area of biostatistics that gets a little complicated with over-thinking, but can be understood with enough time. Comment if you have questions!):

  • The hypothesis (H1) is what is predicted to happen in the experiment. It should be explicitly defined, such as: drug A shortens rapid recall time in comparison to placebo.
  • The null hypothesis (H0) is the opposite of the hypothesis- it is what is predicted to happen if there is no treatment difference: drug A does not affect rapid recall time in comparison to placebo.

Next we have the concepts of true positives/negatives & false positives/negatives. This is usually discussed in terms of the null hypothesis, which can sometimes be confusing if you overthink it.

Screen Shot 2015-09-21 at 18.39.04

The leftmost column represents the real result. If drug A really shortens rapid recall time, then in the best case scenario, the researchers will detect this difference & claim a treatment difference. This means rejecting the null hypothesis & accepting the hypothesis. If they fail to detect this difference (maybe because they did not enrol enough participants) then we would see the false negative scenario.

On the other hand, if drug A really is ineffective, then we would either see the true negative scenario or a false positive scenario. Both the false positive & false negative scenarios emerge out of chance & confounding (e.g. some subjects on the placebo have a good day while taking the recall test, or some start taking phenylpiracetam without telling the investigators, or some subjects in the treatment group take the recall test after a night of heavy drinking; these are all examples of biases that could compromise internal validity).

  • A false positive is called a type I error. The chance of a type I error happening is denoted as α (alpha).
  • A false negative is called a type II error. The chance of a type II error happening is denoted as β (beta).
  • When β is subtracted from 1 (1 – β), this difference is called the power of a study. The power is the chance of finding a true treatment effect (true positive). To bring the discussion back to prior to this talk on hypotheses, true & false results, & errors, power is a key component in determining what sample size we need to detect a treatment effect. The standard power in a study is 80% (1 – β = 0.80). At 80% power, we have an 80% chance of correctly rejecting the H0 & claiming that there is a treatment difference when, in fact, there is one. We achieve sufficient power by enrolling enough subjects, as power & sample size are proportionally related (⊕ n → ⊕ 1 – β ).

*Although power higher than 80% is possible, usually it is not done because:

  • Initial increases in sample size lead to higher increases in power than further increases, as shown in the following graph.
  • Enrolling many subjects requires a lot of funding.
  • α & β are inversely proportional- that means that as you increase your power (1 – β) & β decreases, then α will increase- meaning there is a higher risk of a false positive. At 80% power, there is a 20% chance of a false negative & a 5% chance of a false positive. 80% power is considered a balance between the type I error rate & the type II error rate.
Initial increases in sample size lead to more substantial increases in power than later increases. Select a sample size where power ≥ 0.8 for the best chance of detecting the treatment effect- here it is a little less than 120 patients. Enrolling fewer patients would lead to a higher risk of a false positive.

So, we have established that power is a key driver of how many patients to enroll. We need to enroll enough patients so that the treatment effect does emerge & we can reliably detect it, with minimal concern for confounding & chance.

A few other odds & ends to consider in sample data:

  • Ideally, all treatment groups will be equal or similar in size
  • All treatment groups should remain similar throughout the study- if more subjects drop out of one group than another, that could lead to attrition bias. If a disproportionate amount of patients drops out from the study drug group, that should be a warning sign– investigate why they dropped out (side effects?).
  • Baseline characteristics are traits of the subjects in the study at the beginning before the study drug or placebo has been administered. These data, as previously mentioned, are typically presented in a standard table 1. It is important to skim this table for (1) significant differences between the groups & (2) generalisability/external validity- whether the results could be applied to you.
modafinil vs placebo
Discussion of power in a small RCT comparing modafinil vs. placebo. [1]


  • Sample data describe the characteristics of participants in a study.
  • Sample size (n) is the amount of subjects that are enrolled in a study. It is far from an arbitrary number– the determination of how many people are needed in a study is predicated upon the anticipated magnitude of the treatment effect, the number of subjects needed to have that effect emerge, & minimising «statistical noise» by reducing the risk of false positives (α) & false negatives (β).
  • Power (1 – β) is the chance of a true positive. Researchers typically prefer 80% power as it balances the chance of a false negative with the chance of a false positive (both error rates cannot be controlled simultaneously). Power is achieved by increasing the number of patients in a study. For those interested, power & its determinants can be mathematically expressed as: ⊕ Δ , σ, ⊕ n → ⊕ δ → ⊕ ( 1 – β ) where Δ is the true difference between groups, σ is the standard deviation, n is the sample size, & δ is the non-centrality parameter. An equation form would be δ = ( Δ ÷ σ ) √ ( n ÷ 2 )
  • Other key sample data to consider are the baseline, interim, & final sample sizes between the groups as well as the baseline characteristics.

References   [ + ]

Nootropics Tutorials

Parachuting: How To Avoid The Bad Taste of Bulk Nootropics (Tutorial)

Buying powdered Nootropics in bulk is the most economical option for many users. While it’s easy to toss and wash many, you may run across some that taste pretty awful. If you don’t have a capsule machine or are looking for a quick alternative, you may want to make small parachutes.


  1. Rolling papers (possibly “king size”)
    or Toilet paper
  2. Scissors
  3. Scale
  4. Scoop

How to Make a Basic Parachute

Here’s how to avoid the bad taste of nootropics by making a parachute:

  1. Measure the dose for your Nootropic according to manufacturer recommendations. (pic 2)
  2. Place the desired amount onto your rolling paper and fold the paper around the bulk of your supplement. (pic 3)
  3. Twist the ends together then snip off the excess paper. (pic 4)
  4. Place the supplement in your mouth and wash down with water.
  5. Done!

How to Understand Clinical Research, Part III: Types of Studies

In clinical research, there exist different types of studies which serve particular purposes. These studies are distinguished based on their experimental design (how the study is conducted) & the kind of data they produce– from the way a study is designed, we can draw certain expectations about the grade of evidence it produces.

Experimental designs can be described in several ways. A basic division of study designs can be made on how test subjects are enrolled, which significantly determines the study’s strength in describing a relationship between a cause (an experimental variable such as a drug to be tested) & an effect (an outcome such as cognitive performance). This particular way of classifying studies results in two main families of studies: observational studies & assignment studies.

Observational Studies

Observational studies are conducted in order to determine associations between certain prior exposures (e.g. a drug) & outcomes of interest (e.g. death).

Here, participants are selected based on exposure or outcome, depending on the type of observational study. These are more prevalent in research on nootropics as randomised controlled trials (RCTs) are generally conducted with larger samples requiring more funding. Small observational studies build up a body of evidence which provide the grounds for an RCT, a process called «hypothesis-generating» (as opposed to hypothesis-testing). Cohort studies & case-control studies are two major types of observational studies, both of which involve following a group of patients over a period of time.

Subjects in cohort studies are selected based on their having received a particular exposure, then they are followed prospectively (forward in time) until a certain outcome of interest (e.g. death) occurs. RCTs are also prospective.

Depiction of observational studies. Prospective cohort studies work from the perspective of the left viewer, while retrospective case-control studies work from the perspective of the right viewer.

In a case-control study, subjects are selected based on their exhibiting a certain outcome & tracing their history back (retrospectively) to find out whether they have had a certain exposure (e.g. used a particular drug). Retrospective case-control studies are especially useful when studying rare diseases.

Assignment Studies

Assignment studies enroll subjects to either test or control groups.

Assignment studies are subdivided based on (1) whether the allocation of subjects into test groups is randomised & (2) whether a control group is present.

Randomised controlled trials (RCTs) are generally considered to be the gold standard of clinical evidence for their strong internal validity, & are used to demonstrate causal relationships between experimental variables & outcomes. Randomly assigning patients to either treatment or control groups theoretically establishes equal groups, as any differences in age, race, comorbidity, or other features are equally distributed (eliminates sample selection bias). Prospective follow-up & the presence of a control group allows for comparison of the experimental variable (e.g. a new drug) against a standard treatment (to demonstrate a better treatment effect) or placebo (to demonstrate a treatment effect).

Mohamed AD, Lewis CR. Modafinil increases the latency of response in the Hayling Sentence Completion Test in healthy volunteers: a randomised controlled trial. PLoS One. 2014 Nov 12;9(11):e110639.
Standard CONSORT diagram depicting enrolment, allocation, follow-up, & analysis of subjects from an RCT comparing modafinil vs. placebo.

Synthetic Studies

Systematic reviews & meta-analyses critically evaluate the literature by consolidating the results of several studies focused on the same topic.

Synthetic studies are more recent study designs that have been developed out of a need to draw from the existing evidence on a topic. Prior to the rise of systematic reviews & meta-analyses, studies were selectively cited which led to bias (e.g. selecting only the studies which supported the use of a drug & either intentionally or unwittingly omitting the others which found significant side effects). Nowadays, both are considered the highest forms of clinical evidence, producing strong inferences of treatment effects. Synthetic studies are part of the trend of comparative efficacy analyses (CEAs): gathering data on several major drugs used for the same purpose & determining which are superior. Collecting findings from multiple RCTs & observational studies can produce a more complete picture of a drug’s safety & efficacy- in other words, considering the ‘big picture’. However, before drawing conclusions, one must be cognisant of differences between the studies that have been gathered (e.g. study protocol, different doses used, different sample characteristics).

Systematic reviews present findings from a pre-defined, reproducible search of the literature- that is, the authors exhaustively describe the methods they used to search databases & how they selected which studies to include in their systematic review, usually with a pre-defined criteria set. The importance of reproducibility is to reduce bias from selective inclusion of studies– this is a weakness of narrative reviews, in which the author performs a search & simply chooses which studies to include.

Meta-analyses are systematic reviews where the gathered data is then combined, producing an estimate of the true treatment effect from the pooled data. This is commonly expressed in what’s called a Forest plot, which shows the individual trials included in the systematic review as well as a diamond representing the estimate of the true efficacy or safety measure of the drug (how to read & interpret different tables & graphs will be covered later!).

An example Forest plot, with included trials listed on the left & their findings on the right. The findings are also plotted, with the diamond representing the composite of the studies’ results.


As we have seen, the design of a clinical trial can provide a quick way to judge its findings.

  • Observational studies produce evidence of associations by following patients over a period of time. Patients are selected based on a specific previous exposure in the case of prospective cohort studies or for a certain outcome in the case of retrospective case-control studies.
  • Assignment studies produce evidence of causal relationships by assigning patients to multiple groups including a comparator arm. The most prominent example of an assignment study is the randomised control trial, which has become the standard for clinical data.
  • Synthetic evaluations of the literature, such as systematic reviews & meta-analyses, draw on existing studies to better approximate treatment effects of drugs of interest.
  • Other experimental designs which are less commonly relevant to the area of nootropics include cross-sectional observational studies & non-randomised controlled trials.
Biohacking Nootropics Tutorials

Microdosing Psychedelics For Cognitive Enhancement

Most drugs used for nootropic purposes are far different from drugs that are used recreationally. However, a handful of substances with “no accepted medical use” in countries like the United States hold great promise as cognitive enhancers and therapeutic agents. Case in point: psychedelics

It has been common knowledge since the 1960s that psychedelic drugs, such as LSD, psilocybin and mescaline, are potent enhancers of creativity and divergent thinking. However, at common recreational doses, this boost in creativity is often accompanied by feelings of intoxication, rendering the user incoherent and unable to get any “serious” work done.

That said, a new trend in psychedelic usage has emerged in the past few years that seeks to reap the creative and cognitive benefits of these drugs, while still leaving the user sober and able to function normally. This method, known as microdosing, is the practice of consuming a psychedelic substance at a dosage lower than the threshold of noticeable effects, in order to produce subtle yet effective increases in cognition and creativity. Because the dosage consumed is below the threshold of recreational effects for the substance, the user does not experience the inebriating effects of the substance. The hope is to maximize cognitive enhancement while minimizing any effects that would impair the user as they go about their day.

Microdosing with psychedelic substances is by no mean a new concept, with Albert Hofmann (the creator of LSD) himself having used microdoses of LSD frequently and having called microdosing a regretfully “under-researched” area of psychedelics.[1] However, microdosing has not seen substantial popularity until very recently, and it appears to be an emerging trend in 2015.

How Does it Work?

Microdosing, in the form discussed here, is performed by using psychedelic drugs that act on serotonin receptors, such as LSD, psilocybin, mescaline, 2C-B, and many others . The impact that psychedelics have on cognition has not been extensively researched due to government restrictions on research of illegal drugs. However, as the scientific community continues to push more and more against research limitations, more studies are being published that give us a glimpse into how psychedelic substances affect human cognition.

Enhancement of associative learning produced by the 5-HT2A agonist LSD under different experimental conditions.

The psychedelics most commonly used for microdosing work by acting upon serotonin (5-hydroxytryptamine, or 5-HT) receptors. Thus, in order to understand microdosing, one must first recognize that the serotonergic system regulates cognition and the way in which we learn. There are numerous unique serotonin receptors within the nervous system, collectively regulating everything from mood to gastrointestinal motility. The receptors most involved with learning, memory, and cognition, however, are the 5-HT1A, 5-HT2A, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors, with 5-HT2A being the most acted upon by psychedelics.[2]

In the sober individual, serotonin molecules bind to these receptors, stimulating the receptors and their respective neurons, which is partially responsible for learning, cognition, and memory acquisition. The cognitive boosts that come from microdosing psychedelics are thought to be due to their action of agonists at the 5-HT2A receptor. Although this is an oversimplification, it provides the basis for understanding why microdosing does what it does.

A 2003 study[3] conducted by John A. Harvey at Drexel University explored these effects on cognition by administering LSD to rabbits and recording their performance on cognitive tests. The doses used in this study were equivalent to about 1 µg/kg in humans, which amounts to 80-100 µg in the average human, which is a common recreational dosage for LSD. When the rabbits were given LSD, they performed significantly better on learning and cognitive tests than those that has not been given LSD.[4]

There is also relevant research that was conducted by Willis Harman and James Fadiman before the FDA placed a moratorium on psychedelic research. In one study[5] conducted in 1966, researchers gave 200 mg of mescaline (equivalent to 100 µg of LSD) to a group of 27 professionals who worked in high-level occupations, such as engineers and mathematicians. Each subject came to the experiment with a particular problem from their occupation that they were having trouble solving. All but four subjects, after they had worked on these problems under the influence of psychedelics, were able to make significant progress on the problems they had been struggling with, many of which turned out to be innovative solutions.[6]

Which Substances Can Be Used?

Microdosing can potentially be carried out with any serotonergic psychedelic, but some are more popularly used and tested than others. Typically, the most popular choices are LSD and Psilocybin. As long as the threshold dose of the drug is known, it can be effectively microdosed, although results will certainly vary from person to person. The following is a tentative list that includes common microdosage amounts of various psychedelics.

Drug Dose Threshold Duration Note
LSD 10 – 30µg 20µg 8 – 12h
AL-LAD 10 – 30µg >20µg 6 – 8h
Psilocybin 2 – 5mg 0.25g 4 – 6h dry weight with uniform blending; corresponds to 0.15 – 0.4g Psilocybe Cubensis
Mescaline 50 – 150mg 100mg 6 – 10h dry weight with uniform blending; corresponds to 4.5 – 13.5g L. williamsii or 10 – 25g T. pachanoi
DMT 2 – 6mg ~3.5mg 5 – 20m
4-AcO-DMT 1 – 4mg 2.5mg 4 – 6h
2C-B 2 – 6mg ~3.5mg 4 – 6h
2C-E 2 – 6mg ~3.5mg 4 – 9h
2C-I 2 – 6mg ~3.5mg 5 – 8h
2C-D 2 – 6mg ~3.5mg 3.5 – 5h

(Table taken from /r/microdosing)

The Potential Effects of Microdosing Psychedelics

As with the usage of any drug, microdosing psychedelics can have both positive and negative effects. Due to the lack of clinical and experimental evidence dealing with psychedelics, most of this information is anecdotal, and must be regarded of as such. Users must proceed with caution in order to find if microdosing is of benefit to them.

Some of the purported benefits of microdosing include:

  • Increases in energy and wakefulness
  • Enhanced creativity and cognition
  • Enhanced concentration and motivation
  • Increased ability to learn new material
  • Positive changes in mood
  • Empathy when interacting with others
  • Better stamina and performance in athletic activities

Some negative side effects of microdosing include:

  • Headaches (due to increase in blood pressure)
  • Problems falling asleep, or poor quality of sleep
  • Stomach discomfort
  • Anxiety and irritability
  • Permanent personality changes (can be both negative or positive)

Addiction or withdrawals may be a concern with certain psychedelics, but the most commonly used psychedelics, including LSD, have not displayed addictive properties. It is also important to note that while psychedelic drugs have the ability to enhance cognition, they can also induce effects that make it harder to think clearly and analytically.

Some might find it harder to focus on tasks while microdosing (especially if the dose is too high), and the introspective nature of many psychedelics might cause some users to focus on their own internal problems rather than external ones. Although microdosing seeks to prevent these effects with lower (and less impairing) doses, it is not guaranteed that they will not occur. In some circumstances, users might find microdosing to be of little to no benefit to their cognition. As stated before, results will vary for each individual.


Microdosing psychedelics for cognitive enhancement is far from a traditional nootropic, and must be regarded as such. Because there is not much solid clinical evidence to attest to its efficacy, it must be used cautiously. However, most common psychedelics are considered very safe to use, especially in lower doses that are not as physically and mentally impairing. Due to the illegal status of psychedelics in most of the world, it is advised that you proceed with caution and remain aware of the drug laws where you live.

Microdosing may hold a significant amount of promise for some nootropic users. As the use of psychedelics becomes more and more accepted by society, in general, we can expect to see an increase in scientific research on the subject, giving us a more detailed glimpse into how psychedelics affect our minds.

References   [ + ]