What if you could take a pill to enhance your cognitive abilities?  What if this pill could help you ace a test, get more work done efficiently, and truly multitask?  For entrepreneurs in Silicon Valley and executives on Wall Street, the answer to these questions is a resounding “Yes!”  In these high stake environments, the use of nootropics, or “smart drugs,” by normal healthy people has become commonplace.  But what exactly are the compounds that are claimed to improve brain function?  And are they safe?

For centuries, people have used substances to improve their cognitive functions.  Ancient civilizations used hallucinogens in an effort to better communicate with their gods.  Today, caffeine is commonly consumed to increase alertness.  Over the past decade, people have been experimenting with stimulants and glutamateThe principal excitatory neurotransmitter in the nervous sys... More activators to explore their cognitive enhancing abilities.  This is the main hypothesis of neuroenhancement: if a drug works to improve cognitive abilities in people with cognitive and motor function difficulties, such as in disorders like Alzheimer’s, Parkinson’s, Huntington’s, or ADHD, then wouldn’t they make normal, healthy people have even more enhancements in cognitive abilities, like memory, creativity, motivation, and executive functions?

The movie Limitless brought nootropics to the mainstream when it showed the power of a smart drug to unlock the brain’s potential.  Of course, there is no such pill that can transform you into a financially prosperous, cognitive superman.  But, as evidenced by the over 70,000 subscribers in the nootropic subreddit, there is intense interest in figuring out how to do just that – enhance brain function.  In this and other pseudo-underground communities, adventurous biohackers share their experiences sourcing obscure substances and running self-medicated experiments.  Sure, these personal experiences are interesting, but with a sample size of n = 1, it is impossible to generalize their observations and anecdotal evidence into anything too useful.  So what is the science behind nootropics?  Honestly, there isn’t much!  Only a handful of studies have investigated the use, effect, and functioning of cognitive enhancers in the daily life of healthy individuals.

Nootropic_KnowingNeurons

Perhaps the most well-known example of a pharmacological nootropic is methylphenidate, more commonly known as Ritalin.  This psychostimulant is typically prescribed to treat individuals with ADHD (attention deficit-hyperactivity disorder) to stay focused on a task.  However, it is also used by healthy students as a study and test-taking aid.

So how does methylphenidate work? It blocks the reuptake of dopamineA monoamine neurotransmitter. Dopamine is involved in many b... More and norepinephrine into the presynaptic neuronThe functional unit of the nervous system, a nerve cell that... More.  You see, normally, after dopamine has been released, it is transported back into the presynaptic neuron for subsequent release; when reuptake is inhibited, dopamine builds up in the synaptic cleft, and it continues to bind to postsynaptic receptors.  So, when a person takes Ritalin, they experience the effects of increased dopamine and norepinephrine neurotransmission much longer than normal, which include increased alertness, decreased fatigue, and improved attention – exactly the effects that a person with ADHD would benefit from.

But what are its effects on a normal brain?  Numerous animal studies have shown that effects depend on the dosage.  High doses of methylphenidate in healthy adult rats caused increased locomotor activity and impaired attention skills; moderate doses improved cognitive abilities and reduced motor activity; and very low doses increased attention skills without affecting motor activity (Mehta et al., 2001).

What could account for these variations in efficacy?  Well, the answer has to do with how well dopamine and norepinephrine bind to their receptors.  When the levels are optimal, dopamine binds to their D1 receptors and norepinephrine binds to their α2 receptors with high affinity in the prefrontal cortex, where it efficiently aids in executive functions.  At higher levels, dopamine starts to bind to D2 receptors and norepinephrine binds to α1 and β receptors, which together decrease the ability of neurons in the prefrontal cortex to do what they need to do (Arnsten and Li, 2005).

OK, so you find the sweet spot in dosage, and you’re good to go, right?  Wrong.  The long-term side effects of using methylphenidate can be quite profound, especially in young adults and teens, who are the common misusers of this drug, and where prolonged drug use can cause permanent brain changes.  Studies in young rats have shown that prolonged treatments with methylphenidate can permanently reduce the activity of excitatory neurons in the prefrontal cortex (Urban et al., 2012).

In the era of “cosmetic neurology,” where people try to make good brains better, the risks of using drugs like methylphenidate as cognitive enhancers is often overlooked or determined to outweigh the immediate benefits.  While the use of many “cognitive enhancers,” like Adderall (dextroamphetamine) and Provigil (modafinil), are controversial, most nootropics are often concoctions of more socially acceptable supplements and stimulants, such as the components of chocolate and coffee.  These nootropic stacks aim to increase specific functions, like alertness, focus, or cognition.  Many companies, including truBrain, Nootrobrain, and Nootroo, sell pre-packaged mixtures of nootropics, but there are lots of people who make their own mixtures and share their effects on message boards all over the Internet.

The risk of using supplements as nootropics is that they are largely unregulated.  You might think the FDA (the U.S. Food and Drug Administration) would have some rules regulating these types of “smart drugs,” since they have really strict guidelines for other types of drugs, but these rules do not apply to supplements. And this lack of oversight can create problems.  Last year, a test by the New York State Attorney’s General Office found that four of five herbal supplements at GNC, Target, Walgreens, and Walmart contained none of the herbs on the label.  None!  Sure, they were pulled from shelves once they were caught, and a few companies have started using DNA sequencing to make sure the components of their products is what they say it is, but this is not a hard and fast rule, and the FDA still doesn’t have much control in this area.

Risks aside, do they even work?  At this time, the brain enhancing effects of nootropics are still generally unproven, but a few clinical studies have shown that certain compounds can increase short-term memory, reduce reaction time, and improve spatial awareness.  For example, studies have shown that theanine, an amino acid commonly found in green tea, may be neuroprotective (reviewed by Kakuda, 2011) and could enhance the effects of caffeine on speed and accuracy of information processing.  Still, it is unclear if the main effects felt by these concoctions are simply a placebo effect.

Clearly, more vigorous research needs to be done to determine the efficacy and safety of smart drugs – and quickly, as more and more people become enamored with the potential for cognitive enhancement that nootropics offers.

Nootropic_KnowingNeurons_2

~

Images by Jooyeun Lee

~

References:

Arnsten AF, Li BM Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. 2005. Biol Psychiatry. Jun 1; 57(11):1377-84.

Mehta M.A, Sahakian B.J, Mavaddat N, Pickard J.D, Robbins T.W, Solanto M.V, Arnstenand A.F, Castellanos F.X. Stimulant Drugs and ADHD: Basic and Clinical Neuroscience. New York: Oxford University Press; 2001. Comparative psychopharmacology of methylphenidate and related drugs in human volunteers, patients with ADHD and experimental animals; pp. 303–331.

Urban KR, Waterhouse BD, Gao WJ Distinct age-dependent effects of methylphenidate on developing and adult prefrontal neurons. 2012. Biol Psychiatry. Nov 15; 72(10):880-8.

Additional sources:

Battleday, R. M., and A-K. Brem. “Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: a systematic review.” European Neuropsychopharmacology 25.11 (2015): 1865-1881.

Frati, Paola, et al. “Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology.” Current neuropharmacology 13.1 (2015): 5.

Healthcare Triage. “Update on Supplements: Healthcare Triage News – 04/03/2015” YouTube.

Kakuda, T. “Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction.” Pharmacological Research 64.2 (2011): 162-168.

Woo, G and Brant, M. “Nootropics Aren’t Just For Tech Millionaires.” Techcrunch (2015)

Kate Fehlhaber

Kate graduated from Scripps College in 2009 with a Bachelor of Arts degree in Neuroscience, completing the cellular and molecular track with honors. As an undergraduate, she studied long-term plasticity in models of Parkinson’s disease in a neurobiology lab at University of California, Los Angeles. She continued this research as lab manager before entering the University of Southern California Neuroscience graduate program in 2011 and then transferring to UCLA in 2013. She completed her PhD in 2017, where her research focused on understanding the communication between neurons in the eye. Kate founded Knowing Neurons in 2011, and her passion for creative science communication has continued to grow.

Latest posts by Kate Fehlhaber (see all)

Kate Fehlhaber

View posts by Kate Fehlhaber
Kate graduated from Scripps College in 2009 with a Bachelor of Arts degree in Neuroscience, completing the cellular and molecular track with honors. As an undergraduate, she studied long-term plasticity in models of Parkinson’s disease in a neurobiology lab at University of California, Los Angeles. She continued this research as lab manager before entering the University of Southern California Neuroscience graduate program in 2011 and then transferring to UCLA in 2013. She completed her PhD in 2017, where her research focused on understanding the communication between neurons in the eye. Kate founded Knowing Neurons in 2011, and her passion for creative science communication has continued to grow.

3 Comments

  1. “Risks aside, do they even work?”

    Then goes on about the barely proven effects of a specific amino acid in green tea.

    The answer is yes, they work, often quite well. Modafinil and certain racetams have been studied relatively well and there is little to no evidence that they can cause harm in the long run. Amphetamine (dexedrine, methylphenidate) based drugs are more likely to cause long term harm.

  2. Hello, thanks for the post. I have tried a couple of brands and i noticed some good effects. Maybe not that excellent effects they promise, but there are not placebo. They work well on improve your concentration, this also boost the memory abilities.

Leave a Reply