# data[].attributes.attachment_link.readable_text
The use of drugs by people hoping to boost mental performance is rising worldwide, finds the largest ever study of the trend. In a survey of tens of thousands of people, 14% reported using stimulants at least once in the preceding 12 months in 2017, up from 5% in 2015.

The non-medical use of substances - often dubbed smart drugs - to increase memory or concentration is known as pharmacological cognitive enhancement (PCE), and it rose in all 15 nations included in the survey. The study looked at prescription medications such as Adderall and Ritalin - prescribed medically to treat attention deficit hyperactivity disorder (ADHD) - as well as the sleep-disorder medication modafinil and illegal stimulants such as cocaine.

The work, published in the International Journal of Drug Policy in June, is based on the Global Drug Survey - an annual, anonymous online questionnaire about drug use worldwide. The survey had 79,640 respondents in 2015 and 29,758 in 2017.

US respondents reported the highest rate of use: in 2017, nearly 30% said they had used drugs for PCE at least once in the preceding 12 months, up from 20% in 2015.

But the largest increases were in Europe: use in France rose from 3% in 2015 to 16% in 2017; and from 5% to 23% in the United Kingdom (see 'Quest for cognitive enhancement'). An informal reader survey by Nature in 2008 found that one in five respondents had used drugs to boost concentration or memory.

The latest analysis is impressive in its size, says Barbara Sahakian, a neuroscientist at the University of Cambridge, UK, who was not involved in the work. There is an increasing 'lifestyle use' of cognitive-enhancing drugs by healthy people, which raises ethical concerns, she says.

Cultural factors, the prevalence of ADHD diagnoses and availability all influence which drugs are used for PCE and the rate of use, says Larissa Maier, a psychologist at the University of California, San Francisco, who led the study.

In the United States, where ADHD diagnoses are high and medication is a common treatment, 22% of respondents said they had used amphetamine-combination drugs such as Adderall for PCE. Those drugs are not approved in the European Union, where methylphenidate - sold under various trade names, including Ritalin - is more commonly used.

The study suggests that the spread of US-style practices in ADHD treatment is driving the trend and making drugs more available: countries with higher rates of ADHD diagnoses, such as the United States, Canada and Australia, have higher rates of non-medical prescription-drug use for cognitive enhancement.

"The increased diagnoses of ADHD and their prescription drug use is creating a substantial population of young pharmacologically medicated persons whose underlying problems may very likely be located in their social world," says Steven Rose, a neuroscientist at the Open University in Milton Keynes, UK.

Nearly half (48%) of people said they obtained the drugs through friends; 10% bought them from a dealer or over the Internet; 6% obtained them from a family member; and 4% said that they had their own prescriptions.

Debate continues over whether the non-medical use of prescription drugs boosts brain performance. Data suggest that some people benefit from certain drugs in specific situations, - for example, surgeons using modafinil - but larger population-wide studies report lesser gains, and conflicting results.

Maier notes that respondents to the Global Drug Survey are more likely than the general population to be interested in drug use, which could bias results. But she says that similar rates of non-medical use of smart drugs are seen in studies of the general population, suggesting that the findings are robust.
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# data[].attributes.attachment_link.description
The use of drugs by people hoping to boost mental performance is rising worldwide, finds the largest ever study of the trend. In a survey of tens of thousands of people, 14% reported using stimulants at least once in the preceding 12 months in 2017, up from 5% in 2015.

# data[].attributes.attachment_link.title
Study Puts Smart Drugs Back in Spotlight

# data[].attributes.attachment_link.description
This Medical News article explores the nonmedical and medical uses of cognition enhancing drugs.

# data[].attributes.attachment_link.title
The Public Health Consequences of Performance-Enhancing Substances

# data[].attributes.attachment_link.description
The nonmedical use of performance-enhancing substances, particularly androgens and related drugs, has been a global public health problem for several decades.1,2 A meta-analysis of 271 studies published between 1970 and 2013 estimated lifetime prevalence rates of 6.4% among males and 1.6% among...

# data[].attributes.attachment_link.readable_text
Dr Ruairidh Battleday and Dr Anna-Katharine Brem from the University of Oxford and Harvard Medical School evaluated all research papers on cognitive enhancement with modafinil from January 1990 to December 2014. They found 24 studies dealing with different benefits associated with taking modafinil, including planning and decision making, flexibility, learning and memory, and creativity.

Unsurprisingly, they found that the performance-enhancing capacity of modafinil varied according to the task. What emerged was that the longer and more complex the task tested, the more consistently modafinil conferred cognitive benefits.

Modafinil made no difference to working memory, or flexibility of thought, but did improve decision-making and planning. Very encouragingly, the 70% of studies that looked at the effects of modafinil on mood and side effects showed very little overall effect, although a couple reported insomnia, headache, stomach ache or nausea (which were also reported in the placebo group).

Ruairidh McLennan Battleday said: 'This is the first overview of modafinil's actions in non-sleep-deprived individuals since 2008, and so we were able to include a lot of recent data. Interestingly, we found that the type of test used to assess modafinil's cognitive benefits has changed over the last few decades. In the past, people were using very basic tests of cognition, developed for neurologically-impaired individuals. In contrast, more recent studies have, in general, used more complex tests: when these are used, it appears that modafinil more reliably enhances cognition: in particular 'higher' brain functions that rely on contribution from multiple simple cognitive processes.'

Anna-Katharine Brem, a researcher at both the University of Oxford and Harvard Medical School, said: 'We ended up having two main conclusions: first, that, in the face of vanishingly few side effects in these controlled environments, modafinil can be considered a cognitive enhancer; and, second that we need to figure out better ways of testing normal or even supra-normal cognition in a reliable manner. However, we would like to stress the point that with any method used to enhance cognition, ethical considerations always have to be taken into account: this is an important avenue for future work to explore.'

Professor Guy Goodwin, President of the European College of Neuropsychopharmacology (ECNP) commented: 'This overview suggests that, on current evidence, modafinil enhances cognition independent of its known effects in sleep disordered populations. Thus, the authors say that 'modafinil may well deserve the title of the first well-validated pharmaceutical nootropic agent'. In other words, it's the first real example of a 'smart drug', which can genuinely help, for example, with exam preparation. Previous ethical discussion of such agents has tended to assume extravagant effects before it was clear that there were any. If correct, the present update means the ethical debate is real: how should we classify, condone or condemn a drug that improves human performance in the absence of pre-existing cognitive impairment?

'As the authors point out, modafinil is not licensed for this use, and it will not be because it would be outside the current terms of reference of regulatory bodies. The non-medical use of mind altering drugs has hitherto broadly conflicted with the work ethic of many societies, has been very popular but leads to a range of demonstrable harms. Regulation has been and remains problematic. We cannot know either if demand for modafinil in the same societies will actually be significant, whether society will be more accepting and how regulation will then be framed.'

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Review of 'smart drug' shows modafinil does enhance cognition | University of Oxford

# data[].attributes.attachment_link.description
The drug modafinil was developed to treat narcolepsy (excessive sleeping), but it is widely used off-licence as a 'smart drug' to promote cognitive enhancement, where qualities such as alertness and concentration are desired to assist someone with, for example, exam preparation.

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Dor Abelman

Student use of off-counter stimulants for studying purposes is becoming an increasingly challenging issue as more students use them to study and negative health effects becoming increasingly reported. Recent studies suggest that more than 1 in 20 North American university students have engaged in the use of ADHD treatment drugs such as Adderall, Ritalin, Concerta, or Focalin for studying purposes in the past year [ Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey, Cognitive Enhancement in Canadian Medical Students, Nonmedical ADHD Stimulant Use in Fraternities, College Undergraduate Ritalin Abusers in Southwestern California: Protective and Risk Factors]. While most students who use them recreationally do not experience detrimental health issues, severe cardiac effects, addiction, anxiety, and psychosis have been reported.

My new article in BioMed Central's Harm Reduction Journal hopes to address this issue through the evaluation of fifty studies. Through my literature review, I found that many students are using these drugs to cope with underlying issues such as low self-esteem, high reliance on external audiences for validation, few sources of meaning in their lives, limited parental attention, and potentially mental health issues.

When one takes a step back to see a large sample of those who use the substances and looks for trends, they can begin to notice risk factors, which can be used to design effective risk-reduction campaigns. For example, among students who used study drugs, more pre-existing issues of alcohol abuse, other mental health issues, or low self-esteem were reported than among students who do not use study drugs.

Theories in addiction that describe drugs to be coping mechanisms for deeper issues can be applied. Thinking of drug use in this way helps address underlying risk factors for use that may be overlooked, and helps the individual to reduce their drug use and improve health outcomes in a more effective way. While not all students who used study drugs experienced these underlying issues, helping those who do can help improve outcomes for many who use drugs and reduce harms.
In my article, I recommend that postsecondary institutions implement education campaigns in their orientation weeks to teach about the dangers of using study drugs, provide psychological services to all students to help them feel comfortable reaching out for help when they need, encourage participation in extracurricular activities to help students find more meaning and feelings of self-efficacy in their lives, and promote campaigns encouraging students with ADHD to feel comfortable taking their medication without the pressure to share it with others. The largest access to recreational use of stimulants as study drugs come from students who are prescribed them for their ADHD and share them with others.

Helping to reduce the pressure students face - such as through providing more academic support, providing opportunities for students to find more meaning and enjoyment in their studies, and challenging misperceptions that 'everyone else is doing it' - can help reduce the risk factors that lead some students to want to use the potentially hazardous drugs in the first place.

Finally, I encourage policies that ban study drugs to not be implemented, in order to help students who use them feel more comfortable reaching out for help. As many students who use the drugs are experiencing other issues at the same time and banning drug use has been ineffective at optimizing health outcomes in other similar cases, reducing stigma associated with use can be more effective in helping those who need it the most.

This framework of helping to improve outcomes for students who use drugs follows the principles of harm reduction. Harm reduction is based on the recognition that many people will continue to use drugs despite efforts to prevent drug use, that many drug users do not need treatment, and that there are things that can be done to help drug users achieve more favourable health outcomes. This is not to say that prevention efforts are not necessary, just that a combined approach with harm reduction targeting the many individuals who already use potentially harmful substances may be more effective.

With a focus on harm reduction and acknowledgement of the social determinants of health, we can help students to have better and more favourable health outcomes at a critical and memorable point in their lives.

Read more: Mitigating risks of students use of study drugs through understanding motivations for use and applying harm reduction theory: a literature review by Dor David Abelman in the Harm Reduction Journal.

# data[].attributes.attachment_link.title
Why are students using study drugs, and what can we do about it?

# data[].attributes.attachment_link.description
Dor Abelman Student use of off-counter stimulants for studying purposes is becoming an increasingly challenging issue as more students use them to study and negative health effects becoming increasingly reported.

# data[].attributes.attachment_link.readable_text
Phenibut is a GABA analog, which has anxiolytic effects.

[/FLOAT_LEFT] β-Phenyl-γ-aminobutyric acid (phenylGABA) one of the minor tranquilizers is a drug used for the treatment of anxiety and its related psychological and physical symptoms. Anecdotal evidence suggests Phenibut to be a nootropic displaying improve neurological functions.

Phenibut is derived from gamma-Aminobutyric acid. GABA is a primary mammalian central nervous system inhibitory neurotransmitter.

Using Phenibut
Phenibut is a GABA derivative that was developed in the Soviet Union. It has a wide array of uses. Some of these uses include anxiolytic, nootropic, sleep-inducing, mood-enhancing, recreational, and growth-hormone manipulating effects. It is usually taken orally at doses ranging from 500 mg to 10 grams and above. Like all drugs, it can be extremely beneficial or extremely dangerous depending on the dosage, frequency of usage, and purity of the product. Its beneficial effects can range from neuroprotective, cardioprotective, antidepressant, and nootropic effects; and its negative effects can range from minor drowsiness to full blown addiction and seizures when usage is abruptly discontinued. It does have minor recreational potential and can be considered a drug of abuse.

Ways of Administration

Swallowing Phenibut
Phenibut is usually administered orally from doses ranging from as low 500mg to as high 10grams - sometimes even more in chronic users. Phenibut HCl is slightly acidic so capsules may be preferred for some to avoid the taste. Insufflation would not be recommended as the dose would need to be very high and the acidity would cause nasal pain.

Snorting Phenibut
Snorting Phenibut is not advised since it burns mucus membranes, and it would take too much powder to be effective.

Injecting Phenibut
Injecting Phenibut HCl is definitely not recommended at all because its acidity can cause severe vascular damage and pain. If still insisted, one should obtain the free amino acid form (less common and usually sold as "phenibut FAA"), which has a more neutral pH, and make sure to read up on all the warnings and possible interactions on injecting Phenibut. Here's a good thread/warning for someone who tried to IM Phenibut.

https://drugs-forum.com/forum/sh...d.php?t=220576

Plugging Phenibut
Plugging Phenibut HCl is definitely not recommended because its acidity can cause severe tissue damage and pain. If still insisted, one should obtain the free amino acid form (Phenibut FAA), which has a more neutral pH, and make sure to read up on all the warnings and possible interactions on plugging Phenibut.

Effects of Phenibut
Reputed Positive Effects:
- Anxiolysis
- Euphoria
- Improved Cognitive Functioning
- Improved Mood and Increase in Energy
- Muscle Relaxation

Neutral Effects:
- Drowsiness
- Confusion and Dizziness
- Somnolence
- Rapid Development of Tolerance

Negative Effects and Withdrawal Symptoms:
Like most GABAergic drugs, tolerance develops quickly and there can be withdrawal symptoms after cessation of consistent usage for extended periods of time. Some of these symptoms can be:
- Rebound Anxiety
- Panic Attacks
- Tremors or Shaking Hands
- Muscle Spasms
- Seizures
- Insomnia
- Restlessness and inability to feel comfortable
- Cravings
- Cognitive deficits
- Irritability and Rage
- Paradoxical effects

Combinations with Phenibut

Different Uses for Phenibut
- Phenibut is commonly used as a sleep-aid for those with insomnia or trying to induce a state of relaxation and calmness to allow for an easier transition into sleep.

- Phenibut has a reputation for being a nootropic. It is reported to enhance cognition, focus and concentration, motivation to work, and minor dis-inhibition to allow for unrestrained creativity. Its anxiolytic properties also allow for cognitively demanding tasks to be undertaken with reduced stress.

- It has often been used as an anxiolytic. It has been used by people generalized-anxiety disorders, panic-disorders, and other anxiety provoking situations.

- In the bodybuilding community Phenibut is widely used as it is suggested to increase human-Growth-Hormone (hGH) production. However its efficacy in this area is under dispute.

- It is used in the treatment of alcoholism

- In the treatment of PAWS ( Post Acute Withdrawal Syndrome)

- Used for the treatment of a irregular heartbeat

- Used to treat depression

- Improving memory and cognitive performance

Pharmacology of Phenibut
Phenibut is known to act primarily as a non-selective agonist at the GABAb metabotropic receptor in the central nervous system. It also acts to a lesser extent at the GABAa ionotropic receptor site. Phenibut is also a dopamine receptor agonist (although it is unclear exactly how phenibut's mechanism works on the DA system and what specific areas of the dopaminergic system is acts upon) and an antagonist of the neuromodulator and anxiogenic beta-phenethylamine in the central nervous system.

GABA itself is bio-synthesized in vivo in the mammalian brain from glutamate acid undergoing decarboxylation. Exogenous GABA however cannot pass through the blood-brain-barrier very well due to high hydrophilicity. With Phenibut, the additional phenyl-ring allows greater blood-brain-barrier permeability and attaching to the designated site (the GABA receptor complex).

LD ₅₀ (mg/kg) (as the hydrochloride) [1]:
Mice : 900 intraperitoneally
Rat : 700 intraperitoneally

Chemistry of Phenibut

Column 1

Column 2

Systematic (IUPAC) name:

( RS)-4-amino-3-phenylbutanoic acid

Synonyms:

β-(aminomethyl)benzenepropanoic acid, β-(aminomethyl)hydrocinnamic acid, 4-amino-3-phenylbutyric acid, β-Phenyl- γ-aminobutyric acid, fenibut, phenibut, phenigamma, phenygam, PhGABA

Molecular Formula:

C ₁₀H ₁₃NO ₂

Molar mass:

179.22 g/mol, 260.13 g/mol (hydrobromide), 215.68 g/mol (hydrochloride)

CAS Registry Number:

1078-21-3, 103095-38-1 (hydrobromide), 3060-41-1 (hydrochloride)

Melting Point:

250-253°C (with decomposition), 114°C (hydrobromide)

Boiling Point:

no data

Flash Point:

no data

Solubility:

no data

Additionnal data:

none

Notes:

Hydrobromide aspect : irregular patelets; crystallized from benzene

[1]

Structure - Phenibut structurally related to the amino-acid and inhibitory neurotransmitter GABA (γ-Aminobutyric acid). It only differs from GABA structurally by having a phenyl group attached to the third carbon of butyric acid.

The Dangers of Phenibut
Long-term phenibut use can lead to dependence. Abruptly discontinuing a phenibut habit can cause highly unpleasant withdrawal symtoms, similar to benzodiazapine drugs, so it is recommended to taper off.

In addition, phenibut dehydrates you, so it's recommended to drink plenty of water. Those who use phenibut to help with sleep often put water by their bedside.

Producing/Growing Phenibut

Forms of Phenibut
Phenibut is sold in two forms currently, the HCl and Free Amino Acid. It is also sold in raw powder or dispensed in capsules for easier dosing.

Legal Status of Phenibut

United Nations

USA
Phenibut is legal and uncontrolled in the U.S..

EU
Phenibut is uncontrolled in the United Kingdom.

Other Countries
Currently (7/30/13) Phenibut is unscheduled in Canada and is available without a prescriptions. There are no legislative parameters placed on Phenibut.

History of Phenibut

Popularity of Phenibut over time

More Phenibut Sections

References

http://www.webmd.com/vitamins-supple...tName=PHENIBUT

http://www.deadiversion.usdoj.gov/sc...c_cs_alpha.pdf

http://www.legislation.gov.uk/ukpga/1971/38/contents
[1] Merck Index, fifteenth edition (2013)

The Latest Phenibut Threads

This page has been seen 132,636 times.

Created by

on

Last updated by

on

Contributors:

Phenibut is a GABA analog, which has anxiolytic effects.

[/FLOAT_LEFT] β-Phenyl-γ-aminobutyric acid (phenylGABA) one of the minor tranquilizers is a drug used for the treatment of anxiety and its related psychological and physical symptoms. Anecdotal evidence suggests Phenibut to be a nootropic displaying improve neurological functions.

Phenibut is derived from gamma-Aminobutyric acid. GABA is a primary mammalian central nervous system inhibitory neurotransmitter.

Using Phenibut
Phenibut is a GABA derivative that was developed in the Soviet Union. It has a wide array of uses. Some of these uses include anxiolytic, nootropic, sleep-inducing, mood-enhancing, recreational, and growth-hormone manipulating effects. It is usually taken orally at doses ranging from 500 mg to 10 grams and above. Like all drugs, it can be extremely beneficial or extremely dangerous depending on the dosage, frequency of usage, and purity of the product. Its beneficial effects can range from neuroprotective, cardioprotective, antidepressant, and nootropic effects; and its negative effects can range from minor drowsiness to full blown addiction and seizures when usage is abruptly discontinued. It does have minor recreational potential and can be considered a drug of abuse.

Ways of Administration

Swallowing Phenibut
Phenibut is usually administered orally from doses ranging from as low 500mg to as high 10grams - sometimes even more in chronic users. Phenibut HCl is slightly acidic so capsules may be preferred for some to avoid the taste. Insufflation would not be recommended as the dose would need to be very high and the acidity would cause nasal pain.

Snorting Phenibut
Snorting Phenibut is not advised since it burns mucus membranes, and it would take too much powder to be effective.

Injecting Phenibut
Injecting Phenibut HCl is definitely not recommended at all because its acidity can cause severe vascular damage and pain. If still insisted, one should obtain the free amino acid form (less common and usually sold as "phenibut FAA"), which has a more neutral pH, and make sure to read up on all the warnings and possible interactions on injecting Phenibut. Here's a good thread/warning for someone who tried to IM Phenibut.

https://drugs-forum.com/forum/sh...d.php?t=220576

Plugging Phenibut
Plugging Phenibut HCl is definitely not recommended because its acidity can cause severe tissue damage and pain. If still insisted, one should obtain the free amino acid form (Phenibut FAA), which has a more neutral pH, and make sure to read up on all the warnings and possible interactions on plugging Phenibut.

Effects of Phenibut
Reputed Positive Effects:
- Anxiolysis
- Euphoria
- Improved Cognitive Functioning
- Improved Mood and Increase in Energy
- Muscle Relaxation

Neutral Effects:
- Drowsiness
- Confusion and Dizziness
- Somnolence
- Rapid Development of Tolerance

Negative Effects and Withdrawal Symptoms:
Like most GABAergic drugs, tolerance develops quickly and there can be withdrawal symptoms after cessation of consistent usage for extended periods of time. Some of these symptoms can be:
- Rebound Anxiety
- Panic Attacks
- Tremors or Shaking Hands
- Muscle Spasms
- Seizures
- Insomnia
- Restlessness and inability to feel comfortable
- Cravings
- Cognitive deficits
- Irritability and Rage
- Paradoxical effects

Combinations with Phenibut

Different Uses for Phenibut
- Phenibut is commonly used as a sleep-aid for those with insomnia or trying to induce a state of relaxation and calmness to allow for an easier transition into sleep.

- Phenibut has a reputation for being a nootropic. It is reported to enhance cognition, focus and concentration, motivation to work, and minor dis-inhibition to allow for unrestrained creativity. Its anxiolytic properties also allow for cognitively demanding tasks to be undertaken with reduced stress.

- It has often been used as an anxiolytic. It has been used by people generalized-anxiety disorders, panic-disorders, and other anxiety provoking situations.

- In the bodybuilding community Phenibut is widely used as it is suggested to increase human-Growth-Hormone (hGH) production. However its efficacy in this area is under dispute.

- It is used in the treatment of alcoholism

- In the treatment of PAWS ( Post Acute Withdrawal Syndrome)

- Used for the treatment of a irregular heartbeat

- Used to treat depression

- Improving memory and cognitive performance

Pharmacology of Phenibut
Phenibut is known to act primarily as a non-selective agonist at the GABAb metabotropic receptor in the central nervous system. It also acts to a lesser extent at the GABAa ionotropic receptor site. Phenibut is also a dopamine receptor agonist (although it is unclear exactly how phenibut's mechanism works on the DA system and what specific areas of the dopaminergic system is acts upon) and an antagonist of the neuromodulator and anxiogenic beta-phenethylamine in the central nervous system.

GABA itself is bio-synthesized in vivo in the mammalian brain from glutamate acid undergoing decarboxylation. Exogenous GABA however cannot pass through the blood-brain-barrier very well due to high hydrophilicity. With Phenibut, the additional phenyl-ring allows greater blood-brain-barrier permeability and attaching to the designated site (the GABA receptor complex).

LD ₅₀ (mg/kg) (as the hydrochloride) [1]:
Mice : 900 intraperitoneally
Rat : 700 intraperitoneally

Chemistry of Phenibut

Column 1

Column 2

Systematic (IUPAC) name:

( RS)-4-amino-3-phenylbutanoic acid

Synonyms:

β-(aminomethyl)benzenepropanoic acid, β-(aminomethyl)hydrocinnamic acid, 4-amino-3-phenylbutyric acid, β-Phenyl- γ-aminobutyric acid, fenibut, phenibut, phenigamma, phenygam, PhGABA

Molecular Formula:

C ₁₀H ₁₃NO ₂

Molar mass:

179.22 g/mol, 260.13 g/mol (hydrobromide), 215.68 g/mol (hydrochloride)

CAS Registry Number:

1078-21-3, 103095-38-1 (hydrobromide), 3060-41-1 (hydrochloride)

Melting Point:

250-253°C (with decomposition), 114°C (hydrobromide)

Boiling Point:

no data

Flash Point:

no data

Solubility:

no data

Additionnal data:

none

Notes:

Hydrobromide aspect : irregular patelets; crystallized from benzene

[1]

Structure - Phenibut structurally related to the amino-acid and inhibitory neurotransmitter GABA (γ-Aminobutyric acid). It only differs from GABA structurally by having a phenyl group attached to the third carbon of butyric acid.

The Dangers of Phenibut
Long-term phenibut use can lead to dependence. Abruptly discontinuing a phenibut habit can cause highly unpleasant withdrawal symtoms, similar to benzodiazapine drugs, so it is recommended to taper off.

In addition, phenibut dehydrates you, so it's recommended to drink plenty of water. Those who use phenibut to help with sleep often put water by their bedside.

Producing/Growing Phenibut

Forms of Phenibut
Phenibut is sold in two forms currently, the HCl and Free Amino Acid. It is also sold in raw powder or dispensed in capsules for easier dosing.

Legal Status of Phenibut

United Nations

USA
Phenibut is legal and uncontrolled in the U.S..

EU
Phenibut is uncontrolled in the United Kingdom.

Other Countries
Currently (7/30/13) Phenibut is unscheduled in Canada and is available without a prescriptions. There are no legislative parameters placed on Phenibut.

History of Phenibut

Popularity of Phenibut over time

More Phenibut Sections

References

http://www.webmd.com/vitamins-supple...tName=PHENIBUT

http://www.deadiversion.usdoj.gov/sc...c_cs_alpha.pdf

http://www.legislation.gov.uk/ukpga/1971/38/contents
[1] Merck Index, fifteenth edition (2013)

The Latest Phenibut Threads

This page has been seen 132,636 times.

Created by

on

Last updated by

on

Contributors:

# data[].attributes.attachment_link.description
Phenibut is a GABA analog, which has anxiolytic effects. [/FLOAT_LEFT] β-Phenyl-γ-aminobutyric acid (phenylGABA) one of the minor tranquilizers is a drug used for the treatment of anxiety and its related psychological and physical symptoms. Anecdotal evidence suggests Phenibut to be a nootropic displaying improve neurological functions. Phenibut is derived from gamma-Aminobutyric acid.

# data[].attributes.attachment_link.description
This section collates various resources to help improve clinical practice in the management of harms resulting from the use of club drugs and novel psychoactive substances.

# data[].attributes.attachment_link.keywords[]
1 psychoactive smart drug nootropic supplement; index list

# data[].attributes.attachment_link.description
Information on a variety of smart drugs including research, legislation, media coverage, bibliographies and links.

# data[].attributes.attachment_link.readable_text
The dose makes the poison, according to the old adage. And a recent study on microdosing with magic mushrooms suggests this might be true.

Research led by Luisa Prochazkova of Leiden University in the Netherlands indicates that ingesting tiny amounts of magic mushrooms could enable people to experience their reputed creativity-boosting effects, without the risk of 'bad trips' associated with higher doses.

Prochazkova and her colleagues set 36 people three tasks before and after giving them a dose of 0.37g of dried mushrooms. The tasks assessed the subjects' convergent thinking (the identification of a single solution to a problem), their fluid intelligence (the capacity to reason and solve new problems) and their divergent thinking (the ability to recognise multiple solutions).

After taking the mushrooms, the participants' convergent thinking improved, they were more flexible in their approaches to finding solutions, and had more ideas about how to complete the divergent thinking task. Their intelligence scores and general analytical abilities didn't change, however, suggesting that the effect is limited to the creative elements of the brain.

These findings correlate with anecdotal evidence from tech workers in Silicon Valley, where there's a trend developing for microdosing LSD in the belief that it can enhance productivity.

Prochazkova hopes that the findings from her study will stimulate further research into the effects of microdosing psychedelics. "Apart from its benefits as a potential cognitive enhancement technique, microdosing could be further investigated for its therapeutic efficacy to help individuals who suffer from rigid thought patterns or behaviour, such as depression or obsessive-compulsive disorder," she explains.

WARNING: Psilocybin (the psychedelic substance in magic mushrooms) and LSD are Class A drugs according to UK law. Anyone caught in possession of them will face up to seven years in prison, an unlimited fine, or both. More information and support for those affected by substance abuse problems can be found at bit.ly/drug_support

Follow Science Focus on Twitter, Facebook, Instagram and Flipboard

# data[].attributes.attachment_link.title
Small doses of psychedelics might help you solve problems

# data[].attributes.attachment_link.description
The dose makes the poison, according to the old adage. And a recent study on microdosing with magic mushrooms suggests this might be true. Research led by Luisa Prochazkova of Leiden University in the Netherlands indicates that ingesting tiny amounts of magic mushrooms could enable people to experience their reputed creativity-boosting effects, without the risk of 'bad trips' associated with higher doses.

# data[].attributes.attachment_link.title
The Joe Rogan Experience - Sleep Expert and Neuroscientist Dr. Matthew Walker - Podcast Notes

# data[].attributes.attachment_link.description
Matthew Walker is Professor of Neuroscience and Psychology at the University of California, Berkeley, and Founder and Director of the Center for Human Sleep Science. Check out his book "Why We Sleep: Unlocking the Power of Sleep and Dreams" on Amazon.

# data[].attributes.body
Ease of accessibility.

# data[].attributes.attachment_link.readable_text
If you're curious about how to buy Modafinil in the UK - then you've come to the right spot.

In this detailed guide, I talk about everything you need to know about getting the world's most popular smart drug while living in the United Kingdom.

While I'm not from the UK, I certainly know how to order Modafinil online while living in the country. Luckily, it's not too difficult these days.

After buying nootropics online for nearly a half decade, I've found out which vendors will send your legit smart drugs with fast shipping.

These online Modafinil pharmacies will also guarantee your order. You'll get your smart drugs or you'll get your money back. No questions asked.

When ordering from these online Modafinil vendors, there's no risk for you! Buying Modafinil in the United Kingdom has never been easier.

In this guide, we'll talk about:

Feel free to click any link above and skip ahead to the information you're looking for.

This United Kingdom Modafinil guide is comprehensive to ensure anything and everything you need to know is included.

I wanted to make sure every question about Modafinil and the UK was answered.

Of course, I've gotta hit you with a quick disclaimer before we dive in...
I am not a doctor or a lawyer. This is not legal or medical advice. This article or guide is strictly for entertainment. Always consult a medical professional before consuming any nootropic, like Modafinil. Always abide by the laws in the United Kingdom. As well, please read my disclaimer page.
What is Modafinil?

Now, you might just want to know where you can buy Modafinil online in the U.K. - which is perfectly fine.

But some of y'all may want a little more information about what Modafinil is and why so many successful individuals use the smart drug.
Because Modafinil works.
As the world's most popular smart drug, Modafinil has gained popularity for one reason. Why?

The smart drug is the premier cognitive enhancer on the market for a reason. If you take Modafinil, you will find benefits like:

They say coffee is the lifeblood of champions, but I'm of the opinion that Modafinil is.

Overall, Modafinil will help you crush the day like nothing else. You'll feel like you can accomplish anything and everything you want to.

Now, Modafinil isn't the "Limitless" pill in real life. You won't write a full novel in one day. But it's pretty darned close.

In the late 1980s, French researchers were working to create a wakefulness agent to treat common ailments like ( Source):

The pharmaceutical drug was named Provigil and quickly made its way to the United States, the land of overuse and abuse.

It didn't take long for CEOs and grad students to see the value of Modafinil. In the blink of an eye, every hustler on the east coast of the U.S. was taking Modafinil to gain an advantage over the competition.

The smart drug craze had officially begun.

Why?

Because it's easy to beat the competition when you can pop one pill and focus for upwards of 12-15+ straight hours.

There's a reason you're curious how to get your hands on Modafinil in the United Kingdom.

Is Modafinil Legal in the UK?

You should know I'm not a lawyer. Certainly no legal scholar. Just a dude who knows way too much about smart drugs and how they benefit people looking to achieve more.

With that in mind, this section about Modafinil in the UK and legalities should be taken as hyperbole. Nothing less. Nothing more.

So, is it legal to buy Modafinil in the United Kingdom? Well, yes and no.

Modafinil, whether generic or Provigil, is a prescription-only medication (POM) in the U.K. (Source). This means a few things. First, you can only legally buy Modafinil from the pharmacy in the United Kingdom if you have a prescription from a British doctor (Source).

It's a bit of a grey area. Here's how I'll break it down:

So, you cannot get the smart drug for off-the-label uses, like cognitive enhancement, from a pharmacy in the United Kingdom. You'd have to prove you have narcolepsy or sleep apnea to a doctor within the country.

However, what about ordering online? Are there legal issues to worry about when buying Modafinil online and shipping it to the United Kingdom?

Well, I don't believe so.

If you're buying online...

Possession of a POM is only illegal in the United Kingdom if the pharmaceutical drug is the on UK Misuse of Drugs Act 1971 (Source). Currently, Modafinil is not on this list. As such, possession of Modafinil is not considered a punishable offense.

Here's why:

Basically, since Modafinil is not listed on the Misuse of Drugs Act, it's not illegal to possess the substance for personal use - even if you don't have a prescription.

In practical terms, this means that you can order Modafinil online in the United Kingdom and have little issue receiving the product.

Even if import controls "catches" your smart drugs, there are no legal repercussions you need to worry about.

The worst that happens? Your package gets confiscated by import controls and customs destroys it.

If that happens, your online Modafinil pharmacy will issue you a refund or reshipment. Whatever you want.
Is Modafinil legal in the UK?
No harm. No foul.

In my opinion, it's legal enough to order online without worry. But, I'm no lawyer and you'll have to make that choice for yourself.

If you're looking to buy Modafinil in the United Kingdom, you're in the right spot. Below you'll find the best online Modafinil vendors that ship to the country.

After working with over a half dozen pharmacies throughout the years, I've found the vendors below to be the absolute best.

All my preferred Modafinil sellers offer:

But enough with the ado, let's get into things and see where you can buy Modafinil online in the UK.

Here are my favorite sellers:

If you're buying Modafinil in the UK, I'd start with Afinil Express. These guys rock. Seriously, if you're looking for quick shipping times, you found them with this online Modafinil pharmacy.

Afinil Express orders arrive in the UK within 4-10 days!

You read that right. If you order smart drugs from these guys, they'll be at your front door in as little as four days.

That's quick.

Along with fast shipping, Afinil Express is known for great customer service, low prices, legit products, and some of the best discounts in the industry.

You can save up to 30% on your order from this vendor with their Bitcoin and return customer coupons.

Overall, Afinil Express has been around for awhile and is a trustworthy Modafinil seller.

If for some reason your package doesn't arrive, you'll get a full refund or reshipment. Whatever you prefer.

Highly recommended!

Now, Buy Moda is a newer Modafinil vendor.

They haven't been around as long as Afinil Express, but I've been incredibly impressed with these guys so far.

If you're buying Modafinil in the United Kingdom, I'd recommend taking a look at these guys.

Their customer service is impeccable, the pricing is low, and their Bitcoin discount is solid.

Modafinil orders in the UK from BuyMod.org will arrive within 6-10 days, with most orders arriving within a week. Overall, pretty quick shipping!

Like all legitimate Modafinil vendors, BuyMod.org offers guaranteed delivery. You either get your order or they'll send you a full refund or a reshipment. It's your choice.

As one of the only Modafinil vendors that hold stock in Europe, ModaPharma is one of the best places to buy Modafinil in the UK.

Your Modafinil order will arrive in 3-7 days when ordering from these guys in the United Kingdom.

That's fast.

Plus, all products from ModaPharma are tested for purity in Europe. As such, you're guaranteed to get legit stuff from these guys.

The only issue? You'll pay a little more when ordering Modafinil from ModaPharma. Their product tends to be more expensive than other vendors on this list.

The vendor also offers solid Bitcoin discounts, guaranteed deliveries, and more.

Overall, this is an impressive Modafinil seller. If you need to get smart drugs quick in the UK, then this is the Modafinil pharmacy to order from.

Another vendor who holds stock in Europe is Eufinil.

In fact, these guys only ship to Europe. It's what they do. It's their specialty. So you know they do it well.

While I prefer the vendors above for larger orders because they're generally cheaper, I found one heck of a use for Eufinil.

If you're looking to buy Modafinil in the United Kingdom, but don't want to spend tons of cash...

Eufinil allows you to make small orders.

You can order as low as 20 servings of Modafinil from these guys - which equates to less than $50 Euro with shipping.

Not a bad deal.

Eufinil also offers fast shipping to the UK because they hold stock in the country, guaranteed delivery, and great customer services.

Overall, they're an ideal option for anyone looking to test Modafinil out.

I've been a fan of Modafinil Star for a while now. Some hate on these guys, but I've found their products legit and their customer service impeccable.

But that's not why I included Modafinil Star on the list of best places to buy Modafinil in the UK.

No. I included these guys because of their Bitcoin discounts.

If you're buying Modafinil with BTC, you'll save a ton of money by ordering from Modafinil Star!

Your order will arrive within 7-14 days in the United Kingdom. Plus, they offer legit generic Modafinil and guaranteed delivery, too.

Adrafinil in the UK, Prescription-Free Alternative

I'm of the opinion that ordering Modafinil in the United Kingdom from an online vendor shouldn't be an issue.

However, I know a few of you may have concerns.

If that's you, there's also viable Modafinil alternatives to consider. These nootropics are 100% legal and offer decent cognitive benefits.

One of my personal favorites? Enter Adrafinil.

Adrafinil is a 100% legal nootropic that's available over-the-counter.

It works like Modafinil because the body essentially converts Adrafinil to the active ingredients in Modafinil upon ingestion ( Source).

As such, it takes a little longer for Adrafinil to kick in when compared to Modafinil. Plus, this stuff isn't as strong as Modafinil.

But it works! You'll find cognitive benefits from Adrafinil.

If you're looking to get your hands on over-the-counter smart drugs, like Adrafinil, this is my favorite vendor.

How to Buy Modafinil in the UK | Verdict

That wraps it up, mate.

Everything you need to know about how to buy Modafinil in the UK. The details you need to get the good stuff.

We talk about if Modafinil is legal in the United Kingdom, where you can buy it online, and so much more.

If you have any questions about buying Modafinil in the UK, feel free to sound off in the comments below.
More Modafinil Content:
I'll get back to you with a detailed answer.

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Buy Modafinil in the UK - Ultimate Guide | 2019 Edition

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If you're curious about how to buy Modafinil in the UK - then you've come to the right spot. In this detailed guide, I talk about everything you need to know about getting the world's most popular smart drug while living in the United Kingdom.

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Abstract

New drugs that enhance cognition in cognitively healthy individuals present difficult public policy challenges. While their use is not inherently unethical, steps must be taken to ensure that they are safe, that they are widely available to promote equality of opportunity, and that individuals are free to decide whether or not to use them.

New drugs to treat Alzheimer's disease and other cognitive deficits also may improve cognition in healthy individuals. This hope presents both opportunities and challenges. This article explores the ethical, legal, and public policy implications of these interventions. After reviewing the potential benefits and detriments, it considers and rejects ethical objections to their general use and concludes with policy recommendations to promote safety and efficacy, fairness and equality, and voluntariness.

New Discoveries and Future Prospects

The war on Alzheimer's disease and other cognitive ravages of aging is stimulating an intensive effort to develop drugs to improve cognitive functioning. The U.S. Food and Drug Administration already has approved a number of these drugs, including donepezil (Aricept®), rivastigmine tartrate (Exelon®), galantamine HBr (Reminyl®), and memantine (Namenda®). In addition, the new psychostimulant modafinil (Provigil®) improves alertness, a key factor in cognitive performance.

Two aspects of these drugs are noteworthy. The first is that they improve cognition in healthy individuals, not merely in people with Alzheimer's and other diseases. Modafinil is being tested for use by the military and has been shown to improve the simulator performance of helicopter pilots ( Caldwell et al. 2000). Preliminary results from federally funded and industry-supported randomized trials on the performance of airline pilots in flight simulators suggest that donepezil improves performance even in highly functioning individuals ( Yesavage et al. 2002).

Second, these drugs may not simply maintain wakefulness or improve recall. Some of them may also improve executive function, "the orchestration of basic cognitive processes during goal-oriented problem solving" ( Welsh and Pennington 1988, 202).

The use of drugs and other techniques to enhance cognition is not new, of course. Caffeine has been used as a stimulant for at least a thousand years and is often consumed in extremely high dosages. (The popularity of Starbucks, for example, may be due in part to the fact that a 16-ounce serving of its coffee contains 550 milligrams of caffeine, five times the amount in a regular cup of coffee or in a single No Doz® tablet [see Center for Science in the Public Interest 2003].) Nicotine promotes cognitive abilities ( Rezvani and Levin 2001). One study at Duke University, for example, found that nicotine patches significantly improved age-associated memory impairment ( Romain 2003). Amphetamines were widely employed by the armed forces in World War II and the Korean War ( Stoil 1990) and are still being used by the U.S. military today. Indeed, they have been blamed for friendly fire incidents in Afghanistan ( Shankar and Duenwald 2003). Students have long used amphetamines as a study aid ( Schrage 1985), with methylphenidate (Ritalin®) being the current cognitive enhancement drug of choice on U.S. college campuses ( Babcock and Byrne 2000; Farah 2002; Zielbauer 2000).

The new crop of cognitive enhancement drugs may not raise substantially greater ethical, legal, or social concerns than these more familiar interventions. Modafinil does not appear to be significantly more effective at promoting wakefulness than large doses of caffeine ( Wesensten et al. 2001). In addition, the currently available Alzheimer's drugs have side effects that may discourage their use for enhancement purposes. (Aricept®, for example, can cause nausea, diarrhea, insomnia, fatigue, vomiting, muscle cramps, and anorexia [see Pfizer 2004].) The Olympics and other sports organizations already have testing regimes designed to prevent the use of stimulants ( World Anti-Doping Agency 2003).

But the new enhancement drugs are only a first step. The federal government alone is spending more than $480 million a year to combat Alzheimer's disease ( NIH 2004), which is bound to lead to the development of more effective and safer modalities that produce enhancement effects in healthy individuals. Scientists have only just begun to understand and manipulate the genetics of cognitive performance. Researchers at the University of Pennsylvania, for example, announced in 1999 that they had genetically engineered mice to improve memory and learning ( Tang et al. 1999). Accordingly, it is entirely possible that far more powerful and highly selective cognitive enhancement interventions will become available in the near future.

Promises and Pitfalls

These discoveries could yield enormous social benefits in addition to their impact on disease and aging. Students could become better learners. Improved memory and problem-solving skills could make workers safer and more productive. Scientific researchers could achieve breakthroughs more quickly. Policymakers could respond more effectively to crises. Yet the development of more powerful cognitive enhancements poses serious public policy challenges as well.

Health Risks

Future enhancement drugs, like some of their current counterparts, may be accompanied by deleterious side effects, including toxicity and physical or psychological dependence. These risks may be exacerbated by long-term use, which may be necessary to achieve or maintain the desired enhancement effect. Exotic interventions like genetic engineering could produce especially unusual types of damage. The genetically altered "smart mice" at Penn, for example, are reported to be unusually sensitive to pain ( Tang, Shimizu, and Tsien 2001; Wei et al. 2001).

Concerns about the safety of cognitive enhancements will be exacerbated by the lack of safety data. The Federal Food, Drug, and Cosmetic Act requires manufacturers to show that drugs are safe for their intended purposes (21 U.S.C. §355[b][1]). Manufacturers may decide to obtain approval from the U.S. Food and Drug Administration (FDA) for enhancement claims for drugs initially developed to treat cognitive disorders, and if they do so, they will have to submit data showing that the drugs are safe and effective for enhancement use. For example, Allergan originally obtained FDA approval to market Botox® for blepharospasm, strabismus, and cervical dystonia but then submitted data to substantiate a labeling claim for cosmetic use "for the temporary improvement in the appearance of moderate to severe glabellar (frown) lines" ( Allergan 2004).

The law permits physicians to prescribe drugs approved for one purpose for any other purpose, even though the manufacturer has submitted no safety or efficacy data to the FDA substantiating the so-called off-label use. Organized medicine has staunchly defended this prerogative as an exercise of professional autonomy within the practice of medicine, a realm that the FDA has long acknowledged lies outside the scope of its authority ( Kessler 1989). Many drugs are widely used for off-label, nontherapeutic purposes, including drugs that improve cognition. According to the manufacturer's own data, for example, almost 350,000 prescriptions for the alertness drug modafinil are being written in the United States every year, even though the only condition for which it was approved until recently was narcolepsy, which affects only about 135,000 people ( Cephalon 2003). The law restricts the ability of manufacturers to promote drugs for off-label uses, but the recent case in which Warner-Lambert agreed to pay $430 million to settle charges that it promoted Neurontin® for unapproved uses ( U.S. Department of Justice 2004) demonstrates that the practice nevertheless takes place.

Physicians might be counted on to refrain from prescribing unsafe or ineffective cognitive enhancements to their patients, and consumers might avoid using risky drugs on their own, but this presupposes that physicians and the public knew the risk/benefit profiles of the products when they were used as enhancements. Some general safety information about the drugs will be available from studies to support approved uses, but special risks could arise if they were used for enhancement purposes. Unless manufacturers were forced to conduct clinical studies on off-label uses or the government financed trials of its own, these risks would not be known until people started using the products as enhancements. The FDA does require manufacturers to notify the agency of adverse events caused by drugs, regardless of the purpose for which the drug was being used, but these events are believed to be significantly underreported ( Lazarou, Pomeranz, and Corey 1998). Physicians might be sued for malpractice if patients were injured by off-label drugs they prescribed, but the burden is on the plaintiff to establish that the physician behaved unreasonably, and this would be difficult to prove in the absence of data from which a jury could conclude that a reasonable physician should have known that the drug was unsafe or ineffective. Persons who were injured by drugs used for off-label enhancement use might file product liability suits against the manufacturers, but a recent clarification of the rules of products liability law, which declares drugs unsafe in design only if they are not safe for any group of patients ( American Law Institute 1998), may reduce the future likelihood of success.

Another reason that safety data may be lacking is that some cognitive enhancements, like gingko biloba, may be sold as dietary supplements. The Dietary Supplement Health Education Act (21 U.S.C. §321) permits products to be marketed without safety data so long as they do not claim to treat a specific disease, bear a disclaimer on the label that they are not approved by the FDA, and are taken by mouth (21 U.S.C. §321[ff][1]). Unlike drugs, whose sponsors bear the burden of proving that their products are safe and efficacious before they may be marketed, the burden is on the FDA to show that a dietary supplement is unsafe before it can stop the product from being sold. Moreover, the law does not require dietary supplement manufacturers to report adverse events, and there is little voluntary reporting ( U.S. General Accounting Office 2001).

Even if safety data are available, the experience with performance-enhancing drugs in sports demonstrates that individuals may employ cognitive enhancements notwithstanding the risks if they expect that the benefits will be great enough. Athletes use anabolic steroids, for example, despite claims that they can cause serious adverse effects such as heart attacks and liver cancer ( NIDA 2002). One writer reported that more than half of the 200 world-class athletes he interviewed told him they would take a drug that would enable them to win every competition for five years and then kill them ( Amateur Athletic Association Newsletter 2003).

Individuals who are willing to trade health risks in return for cognitive benefits are especially vulnerable to unscrupulous entrepreneurs who misrepresent the effectiveness of their cognitive enhancement products. Even if ineffective substances are not harmful, their purchase transfers wealth, often from those least able to afford it, to hucksters and frauds. The Federal Trade Commission has the authority to punish advertisers who make false or deceptive claims, but its resources are extremely limited, especially considering the ease with which products can be hawked on the Internet.

Pressures and Inducements to Use Performance-Enhancing Drugs

The experience with performance-enhancing drugs in sports reveals another problem with cognitive enhancements. One reason that athletes take performance-enhancing drugs is pressure from trainers, coaches, teammates, and competitors. When sprinter Ben Johnson was stripped of his 1988 Olympic gold medal, his coach repeatedly stressed that athletes could not succeed in highly competitive environments without using drugs ( Starkman 1991). Similarly, individuals may feel that they are unable to refuse to use cognitive enhancements. Business journals already speculate that employers will require employees to take smart pills on the job ( Schrage 1999). The military may issue enhancement drugs to soldiers in combat. A naval flight surgeon manual states that although pilots cannot be required to use amphetamines, those who refuse may be denied the opportunity to fly combat missions ( U.S. Navy 2000). Schools under pressure to improve standardized test scores might distribute pills to pupils. Parents may give them to their children. Even if the use of cognitive enhancements is not explicitly mandated, people may feel that they must do so in order to succeed or just to stay where they are in competitive endeavors.

Access

Another concern raised by cognitive enhancements is the unfairness that would result if they were not widely available and if only some people could get their hands on them. The supply may be limited because of the FDA's restrictions on the shipment of experimental drugs or the Drug Enforcement Administration's controls on the amount of controlled substances that may be produced. Even if a sufficient supply existed, the FDA would likely require that new Alzheimer's drugs be available only by prescription, and many people, especially those with low incomes, do not have access to a personal physician ( Gold and Kuo 2003). Even if individuals do have access to a physician willing to prescribe a drug for enhancement use, the cost may be prohibitive. The retail cost of Aricept, for example, is about $1,500 per year ( Senior Market Advisor 2002). Obviously, a black market would emerge, but even the street price might be too steep for many to afford.

Conceivably, the cost of cognitive enhancements might be borne by health insurance. Physicians might be willing to prescribe therapeutic drugs for cognitively healthy patients and submit claims for treating cognitive impairment. Moreover, it may be hard to distinguish between therapeutic and enhancement use ( Buchanan et al. 2000; Parens 1998; Whitehouse at al. 1997). Assuming for the sake of discussion that IQ is a valid measure of cognitive capacity, would a drug that increased IQ be "therapeutic" for everyone whose IQ was below the population mean? For everyone who had less than the maximum measurable IQ? Since cognitive performance appears at least in part to be a function of one's genetic endowment, should suboptimal cognitive ability be considered a genetic defect? Moreover, many people suffer mild cognitive degradation as they age. This has led to a diagnostic category, "mild cognitively impaired" (MCI), which has been arbitrarily defined as someone whose performance on neuropsychological tests is greater than 1.5 standard deviations from age-associated norms ( Petersen et al. 1999). This automatically makes approximately 1,750,000 people in the United States into sufferers of MCI. Moreover, there is evidence that age-associated cognitive deterioration begins around age 30 ( Victoroff 2000). If so, then everyone beyond that age might be regarded as cognitively impaired.

Health insurers might be willing to accommodate this diagnostic creep and cover cognition-improving drugs for a large percentage of their insureds. But the cost might be so great that plans might refuse to expand their coverage beyond a narrow set of extreme cases or refuse to cover certain modalities at all, just as some plans do not pay for Viagra® ( Klein and Sturm 2002). Although persons suffering from cognitive dysfunction might be deemed to have a disability as defined in the Americans with Disabilities Act, the courts have interpreted the law to allow insurers to decline to cover entire classes of individuals with disabilities (e.g., Doe v. Mutual of Omaha, 179 F.3d 557 [7th Cir. 1999]). State legislatures might respond by enacting so-called state mandates-state laws requiring insurers to cover certain services, such as breast reconstruction after mastectomies-but because of preemption by the Employee Retirement Income Security Act (ERISA), these laws do not apply to employers' self-insured health plans, through which most people get private health insurance. In short, many people who have health insurance may not have coverage for expensive cognitive enhancement drugs. And this does not take into account the 40 million or so Americans who lack health insurance altogether.

Imagine, then, a society in which the only people who could obtain the powerful new cognitive enhancements were those with access to amenable physicians and the resources to bear the cost out-of-pocket. Cognitive enhancements would be available only to the wealthy, or, if their cost were modest enough, to everyone but the poor. Those who were already relatively better off would gain the advantage of cognitive enhancement. The less well-off would fall further and further behind.

Nonetheless, our system tolerates other sources of inequality. Why should we worry about cognitive enhancement when we permit people to profit from advantages like natural talent and good luck-including the good luck of inheriting wealth or gaining social connections through one's family? One answer is that cognitive enhancement could be so powerful a determinant of social success that it would undermine the foundations of our liberal, democratic society ( Mehlman 1999, 2000, 2003). But even if we could accommodate the social inequalities that resulted from cognitive enhancements, the question is whether we should.

Is Cognitive Enhancement Ethically Acceptable?

The answer to this question is best approached by returning to the analogy with performance-enhancing drugs in sports. Opponents of drug use in sports object not only to the health risks and the unfairness if only some athletes can obtain them but also to the fundamental incompatibility between drugs and sports. According to this view, sports values only certain inputs: determination, effort, natural talent, and luck. An athlete who wins because she is driven to succeed spends endless hours in training and practice, has an innate athletic ability, and enjoys the good fortune, say, of having wealthy, supportive parents and avoiding injury is entitled to her medal. Her victory is deserved, worthwhile, "authentic." Conversely, a medal won by an athlete who uses drugs is not deserved; her accomplishment is "inauthentic."

A related argument is that drug use is against the rules of sports. Therefore, athletes who use drugs are cheating, just like the baseball player who "corks" his bat or the marathon runner who begins her race by slipping onto the course at the halfway mark. Moreover, it does not matter why the rules prohibit drugs. The organizers and participants may be worried about the safety hazards of drugs, concerned that some athletes may not have access to them, believe that drug-induced achievements are inauthentic, or just not like the idea of people using drugs for nontherapeutic purposes. The point is that the rules of a sport can be, and often are, completely arbitrary. Why does baseball only permit nine players on the field, instead of five or 11? Even rules that are premised on safety turn out to be highly arbitrary, since it is hard to explain why athletes should be allowed to accept the risk of injury that is inherent in a sport but are not permitted to take comparable risks from drugs. Yet it is entirely appropriate, indeed necessary, for a sport to enforce its rules, since a sport must be played within the rules for it to have meaning as a sport.

As a child, you may have tried to play a game in which the individual players made up the rules to suit them as they went along; no doubt you quickly abandoned it in frustration at its pointlessness. Think of the Queen of Hearts' croquet game in Alice in Wonderland.

The rules of sports and games can take a similarly arbitrary stance when it comes to cognitive enhancements. It is entirely up to the international Olympic movement to decide to prohibit amphetamines at the same time that it allows motivational counseling, or for the Spanish Chess Federation to forbid the use of high levels of caffeine at the same time that it continues to allow the inhalation of unlimited amounts of aromatic nicotine outside the playing hall ( Associated Press 1999; World Chess Federation 2004). Indeed, it might be interesting to see whether a fully enhanced human chess player could beat the most powerful computer.

But what about outside sports and games? Should cognitive enhancements be prohibited in other competitions in which their use might be advantageous, such as school exams and entrance tests or in the workplace? Should the rules arbitrarily forbid people from voluntarily obtaining an advantage from taking relatively safe, widely available enhancement drugs while at the same time allowing them to profit from remedial and test preparation courses or tutors or to send their children to private schools?

One answer might be that cognitive enhancements can be singled out for objection because they are not natural, customary, or traditional. But clearly, the fact that something is naturally occurring does not mean that it is good or desirable. Many scourges of humanity, from floods and famine to Alzheimer's disease and cancer, are naturally occurring phenomena, yet we do not object to measures to combat them like sandbags, humanitarian food aid, Aricept®, or effective chemotherapy. Similarly, the fact that something does not occur in nature does not make it bad, or we would eschew everything from shoes to the wheel. Moreover, some substances used as cognitive enhancements, such as caffeine, gingko biloba, and nicotine, do occur in nature. The view that cognitive enhancement drugs are bad because they are not customary or traditional also is not persuasive. Caffeine has been used for centuries. Nor is there any obvious reason why something that has been around for a while-like speed reading courses-should be accepted, but a new pill-say, one that replicates the effect of such courses-should be regarded as evil.

A second objection to cognitive enhancement drugs simply might be to the fact that they are "drugs." This argument associates performance-enhancing drugs with illegal "recreational" drug use and drug abuse. But as noted earlier, cognitive enhancement drugs may be perfectly legal (because they are dietary supplements, have FDA approval for an enhancement indication, or are prescribed for off-label use). Obviously there is nothing inherently "abusive" about people wanting to improve their cognitive performance, and except for someone, for example, who takes a cognitive enhancement drug merely to complete the New York Times crossword puzzle, cognitive enhancement use would not be recreational (assuming there is something wrong with recreation). Like some types of illegal drugs, these drugs might be objectionable if they were unsafe or habit forming, but this is not true of all drugs, nor is there any reason to believe that it is true of, or inherent in, cognitive enhancement drugs in particular. A concern might be raised if taking cognitive enhancement drugs led to the use of more abhorrent drugs, but this is another empirical claim rather than a necessary characteristic of cognitive enhancements.

A third objection to cognitive enhancement drugs is that accomplishments achieved through their use are unearned and therefore not worthy of reward. Something can be earned in a number of ways, including hard work, self-sacrifice, or kindness to others. If cognitive enhancement drugs avoided the need for these, the argument goes, then the achievements produced with their help would not be merited.

This argument has a number of flaws, however. First, purchasers may have acquired the money to buy cognitive enhancements through hard work and self-sacrifice. Second, the user must decide what tasks to undertake, and so the decision to do something praiseworthy, rather than, say, to use the drugs to commit crimes or for other forms of ill-gotten gain, confers merit. Third, individuals are likely to have to expend some effort to produce results even if they take enhancement drugs. Athletes who take steroids, for example, must still work very hard to be competitive. Fourth, we reward accomplishments that result from natural talent and luck that are unearned (except in the minds of people who believe that they are rewards from God for good works and clean living).

Apart from sports and games, there seems to be only one other realm in which the use of cognitive enhancements might be objectionable. That is art, in which how it is produced (its artistry) may be as significant as the outcome. Some people value an object because it is handmade, for example, even if it looks and functions the same as one made by a machine. Assuming a computer could write a good book, the fact that it was written by a computer might repel some people. Listeners may criticize a musician who uses propranolol, a beta blocker drug that reduces performance anxiety ( Brantigan, Brantigan, and Joseph 1982), even if the drug is used outside of competition.

If cognitive enhancement drugs have a positive effect on artistic ability, as may well be the case, they might be accused of corrupting the aesthetic value of the art that is produced.

But this brings us to a key point: Outside of sports, games, and perhaps the arts, cognitive accomplishments are valued primarily for the social benefits they confer, not for the manner in which they are achieved. If there is an aesthetic dimension to cognitive achievements, any loss of aesthetic value is easily outweighed by the social value of the accomplishment. A gifted composer who dashes off a beautiful symphony in a jiffy, or a child prodigy who produces a charming sonata with little formal training, produces just as treasured a piece as does someone who took years of music lessons or labored over the score for half a lifetime. The inventor of a pollution-free automobile engine reaps the same financial rewards from her patent if her breakthrough occurred by accident than if it followed from painstaking experimentation. Short of misappropriating someone else's work, the value of the results is what counts. Nor is this an objectionable case of the ends justifying the means; no harm is produced by exceptional ability or serendipitous discovery, except perhaps envy, which arguably is generated by any achievement, including one that is earned by hard work.

The question, then, is whether outside of sports, games, and art, the use of cognitive enhancement drugs is analogous to socially unacceptable stealing or to socially rewarded natural talent or luck. The answer seems clear: You deserve to win a Nobel Prize if you discover the cure for cancer, whether or not you do so with the aid of cognitive enhancement drugs. Outside the realm of certain games, sports, and arts, there is nothing inherently wrong with cognitive enhancements.

This does not mean, however, that powerful, new cognitive enhancement drugs will be readily accepted. They will change a fundamental aspect of American society by adding to the recipe for social success a fourth ingredient, in addition to natural talent, luck, and exercises of the will like effort and self-sacrifice. The new regime will be especially disorienting because of the singular role that the old formula has played in the development of American society. Instead of the older aristocratic recipe for success based largely on lineage, America from the time of its Revolution embraced a reward structure based on "merit." A farmer's son could become president. In Horatio Alger's books, anyone who tried hard enough could become rich. The merit-based reward structure revolutionized American society, enabled the nation to absorb and profit from its waves of immigrants, and became the framework for Western liberal democracy, which Francis Fukuyama called "the final form of human government" ( Fukuyama 1989, 4).

There nevertheless are a number of compelling reasons why we should alter the formula for success to accommodate cognitive enhancements. The first is that it would be too difficult to prevent their use. As discussed earlier, under current law, some may be sold as dietary supplements or, if prescription drugs, approved for enhancement uses or prescribed for unapproved enhancement uses. Cognitive enhancements as a class could be subjected to special prohibitions. An amendment to the Federal Food, Drug, and Cosmetic Act that Congress enacted in 1994, for example, makes it a federal felony to distribute human growth hormone "for any use in humans other than the treatment of a disease or other recognized medical condition" (21 U.S.C. §333). Congress also could preclude the sale of cognition-enhancing drugs as dietary supplements. Any changes in the law, however, would have to overcome powerful dietary supplement and physician lobbies. Like anabolic steroids, cognitive enhancement drugs could be classified as controlled substances, and physicians could be prohibited from prescribing them for nonmedical, enhancement purposes. But the Controlled Substances Act permits the government to designate therapeutic drugs as controlled substances only if they have a potential for abuse and could lead to physical or psychological dependence (21 U.S.C. §812). Even if the repeated use of a drug to achieve or maintain improved cognitive performance might qualify as psychological dependence, it might not lead to physical dependence, and some drugs might be taken to boost cognition only occasionally, rather than repeatedly. Moreover, the government would have difficulty maintaining that enhancing cognition was an abuse, especially given the legality of caffeine and nicotine. In any event, these highly restrictive approaches require physicians and law enforcement officials to be able to distinguish readily between lawful therapeutic and unlawful enhancement uses of the same substances; yet as pointed out earlier, this distinction is extremely elusive. The government might try to designate an arbitrary cutoff, so that only people below a certain performance level could lawfully employ enhancements, but politicians would find it hard to sustain such an arbitrary determination against political pressure and constitutional challenge, particularly if these drugs contributed significantly to cognitive achievement. The only way to avoid having to distinguish between therapeutic and enhancement uses would be to ban enhancing substances altogether-that is, for both enhancement and therapeutic uses. But given the fact that most of these substances will be developed in the first place to treat dread diseases like Alzheimer's, this is politically unthinkable.

In any event, a law that prohibited cognition-improving products would be virtually unenforceable. A black market is certain to arise. The government could attempt to interdict the manufacture, distribution, and possession of these products in the same way that it tries to halt drugs like marijuana and cocaine, but it is likely to enjoy the same dismal record of success. Furthermore, the last thing the rule of law in this country needs is for an enormous portion of the population to be converted into criminals because they try to become more productive at work or to do better in school. Finally, since a main motivation for banning relatively safe cognitive enhancements would be to prevent people from obtaining an unfair or unearned advantage when they competed with nonusers, the law would have to prevent not only the manufacture, distribution, and possession of these products but also their use in competitive situations. In other words, the government would have to operate a drug-testing program like the Olympics, only vastly more widespread and expensive.

Besides the fact that it would be practically impossible to prevent, there is an even more compelling reason why society should permit the use of cognitive enhancements. If they were truly safe and effective, they would produce significant societal gains. We want our cancer researchers to have access to whatever will help them find a cure, our pilots to react better to sudden emergencies, and our soldiers to be better able to protect themselves and to carry out their missions. A ban on cognitive enhancements would be bad policy because it would deprive society of immeasurable benefits.

The key question, then, is how to maximize the benefits from cognitive enhancements but minimize the harms.

Promoting Safety and Efficacy

As described earlier, loopholes in current law allow cognition-enhancing drugs to be marketed as dietary supplements or to be prescribed for off-label enhancement use without adequate safety and efficacy data. To plug these loopholes, manufacturers could be required to establish the safety and efficacy of their products for these uses before the products were marketed. Essentially this would convert dietary supplements into full-fledged drugs and transform potential off-label uses into actual labeling claims. But since this would trigger intense opposition from the dietary supplement industry and it might be difficult for regulators to predict the off-label uses of drugs before the drugs were introduced into the market, a more likely approach would be to focus on these safety and efficacy concerns after the products began to be sold.

Targeting safety, Congress could authorize the FDA to require dietary supplement manufacturers to report adverse events to the FDA, so that the agency could remove dangerous products, like ephedra, from the market. The FDA also could be given the authority to require drug manufacturers to submit safety data for unapproved uses of their products that generated substantial sales. Except under the Oregon Death with Dignity Act, which requires physicians to inform pharmacists that they are providing drugs for patient suicides (Ore. Rev. Stat. §127.815[3.01]), there is no current method for determining whether a prescription is being written for an approved or unapproved use. To avoid privacy objections, the FDA could conduct confidential physician and consumer surveys and require manufacturers to produce safety profiles for major off-label uses of approved drugs that the surveys identified. These profiles could be based initially on adverse event reports from physicians and hospital emergency rooms, with the manufacturers providing compensation for the administrative costs of reporting. If these reports identified a potential safety problem, the FDA could be empowered to require manufacturers to conduct clinical trials to demonstrate safety. Monetary penalties for noncompliance could be calculated to strip the manufacturer of the economic gain from the off-label sales of the product. (Removing the product from the market would be an inappropriate sanction, since it would deprive patients of the benefits from approved uses.) Moreover, the courts could interpret product liability law to make manufacturers who failed to conduct safety studies liable for consumer injuries.

Safety information is only half the equation, however. No drug is completely safe. Regulatory determinations about whether or not to permit a drug to be tested or marketed, professional judgments about whether to recommend or prescribe it, and individual decisions about whether or not to use it all entail a balancing of risks and benefits. In addition to information about safety, people therefore need information about efficacy.

Yet full-scale clinical trials are enormously expensive. Congress has authorized the FDA to accept less-than-complete efficacy data, such as data from only phase I and II investigations, in order to accelerate the availability of drugs to treat AIDS and other serious illnesses, and this approach might be extended to dietary supplements and off-label uses of approved drugs on the theory that otherwise they would lack efficacy data altogether. But this would encourage manufacturers to seek FDA approval only for easy-to-establish labeling claims and leave more problematic indications to the less rigorous process for proving the efficacy of off-label uses. A better option might be to require manufacturers to conduct postmarketing efficacy studies of the enhancement uses of only those drugs or dietary supplements that had been shown by adverse event reports to present a high risk of injury. At the same time, the Federal Trade Commission could be given additional resources to investigate and take action against false or unsupported efficacy claims.

Absent some calamity, it is unlikely that concerns about the safety and efficacy of cognitive enhancement products alone would stimulate a significant shift in the law. But the development of these products is part of the growth of "lifestyle medicine" in general. Collectively, concerns about these products may be enough to overcome industry opposition to the need for more safety and efficacy data.

A separate question beyond how to generate the safety and efficacy data necessary to balance risks and benefits is who should do the balancing. In the case of therapeutic interventions, the traditional approach has been to assign this task in the first instance to regulators and health care professionals and to permit consumers to do their own balancing, such as deciding whether to participate in a medical experiment or to employ a particular treatment, only in the case of options that make it past this initial expert review. Such a paternalistic decision-making model may be harder to justify for enhancement interventions, however, since a physician arguably has no greater expertise than a lay person when it comes to ascertaining whether the benefits of enhancing cognitive performance outweigh the risks. Consumers, therefore, may be entitled to considerable autonomy in deciding whether to use a cognition-enhancing drug despite its risks or when its risks or benefits are uncertain or unknown.

Promoting Fairness and Equality

The availability of powerful cognitive enhancements only to those with enough money or connections raises challenging issues of distributive justice. Already privileged individuals could gain significant advantages in a wide variety of competitive social endeavors.

One solution would be for the government or private philanthropies to provide cognitive enhancements to those in need. But who would this be? It would not be persons who were retarded or otherwise regarded as having cognitive deficits, since presumably they would be entitled to cognition-improving products as therapy. Instead, it would be people whose native cognitive abilities, while within the "normal" range, were lower than those of other people.

At first blush, this idea might seem appealing. Cognitive enhancements would compensate for the undeserved disadvantages of lack of talent and bad luck. They would make everyone more equal, creating a society in which there was greater equality of opportunity. By strengthening the role of effort and self-sacrifice as determinants of social reward, they would make the nation more truly a meritocracy.

But the approach is problematic. To begin with, suppose cognitive enhancements gave people a certain boost in their cognitive ability-say, made them 20 percent smarter. Suppose further that cognitive enhancements were given to all those in the lower half of the "normal" range. These individuals, along with those with below-normal cognitive ability who received the interventions therapeutically, would move up 20 percentage points. But people in the upper half of the population range who obtained enhancements on their own would move up as well. The entire population would move upward in terms of cognitive ability, but the disparities created by natural talent and luck would remain. More realistically, however, due to people's genetic and environmental differences, cognitive enhancement drugs are likely to affect people differently, to be more efficacious in some and more hazardous in others. Some users might see a 40 percent improvement in cognitive ability; others, only a 5 percent improvement. Cognitive enhancements, therefore, could make social success even more a product of undeserved factors than it is now. This could be avoided if enhancements raised everyone's cognitive ability to the same ceiling or if some way were found to handicap those who gained greater cognitive abilities from enhancement than others. But neither of these scenarios is realistic: the former as a matter of biology and the latter because we are unlikely to force people to relinquish the cognitive advantages they obtain from natural talent and luck, even assuming we could design and operate the elaborate, intrusive testing and handicapping system that would be necessary ( Vonnegut 1968).

A better approach would be to permit cognitive enhancements to be available on the open market for those who can afford them and to subsidize access to them for those who cannot. This would avoid the economic and social costs of attempting to ban these products, which ultimately would be futile, or of having government or some other party try to identify and distribute enhancements only to persons with a cognitive need. By making these products widely available, society would gain the benefits of the achievements they made possible and reduce or at least refrain from exacerbating the inequalities that stemmed from differences in wealth. Cognitive enhancements would be subsidized only if they were approved by the FDA as safe and efficacious, thereby promoting the development of safer and more effective products and generating safety and efficacy data to inform individual decision making. Both the government and the private sector could subsidize access, the former through Medicare and Medicaid and the latter through private health insurance. Public- and private-group purchasing programs could drive down the costs of the products. If they were safe enough that physicians were not required as decision-making intermediaries, the products ultimately could be sold cheaply over-the-counter.

This approach is not as radical as it may sound. Medicaid and private insurers no doubt already are paying for enhancement uses of drugs like Ritalin®. More important, many private insurers pay for Viagra®, which is widely used for enhancement purposes, and in 1998, the federal government ordered state Medicaid programs to cover the drug ( Goldstein 1998). To ensure the widest possible coverage by private third-party payers and avoid ERISA preemptions of state mandates, Congress could make coverage of cognitive enhancements a federal mandate, similar to the requirement that all third-party payers pay for at least a 48-hour hospital maternity stay ( Newborns' and Mothers' Health Protection Act 1996). Obviously this would still leave those without public or private health insurance to rely on their own financial resources, but Congress could take the same approach it adopted in 1972 to cover kidney dialysis under the Medicare End Stage Renal Disease Program and make cognitive enhancements available to everyone under Medicare. The government also would have to force down the price of the drugs. If the drugs cost the same as the current retail price of Aricept® and every American took them, the total cost would be approximately $350 billion a year.

Reducing Pressures and Inducements to Use Performance-Enhancing Drugs

The more effective cognitive enhancements prove to be, the more pressure people will feel to use them to gain or retain socioeconomic advantages. So long as resources remain scarce and continue to be apportioned to such a large extent competitively, this type of inducement will persist. As discussed earlier, since the only ways to reduce this pressure-banning cognitive enhancements or discounting the achievements they facilitate-would be highly impractical, the best response would be to ensure that the substances were as safe as possible.

Since no drug is completely safe, however, the question remains whether individuals can be compelled to take cognition-enhancing drugs. The strongest case can be made for persons whose cognitive performance could have a substantial impact on public safety, such as transportation workers or nuclear power plant operators. Instead of requiring these individuals to take drugs, minimum cognitive qualifications could be established for these jobs, which drug use could enable individuals to meet.

In non-safety-critical employment settings, the primary purpose of enhancement drugs would be to increase productivity. To the extent that drug use resembles other techniques to increase productivity, such as employee-training programs, employers might seem entitled to mandate use of the drugs. But drugs are biomedical interventions. A better analogy, therefore, might be employees' wellness programs. Presumably because these programs affect employees' health and bodily integrity, the rules of the Equal Employment Opportunity Commission prohibit employers from requiring employees to participate in them or punishing employees if they refuse ( EEOC 2000). Since cognition-enhancing drugs are likely to be accompanied by greater health risks than wellness programs, it would seem even less appropriate for employers to require their use. This does not mean that employers will have to forgo the productivity gains from the use of these drugs, however, but only that they will have to allow employees to use the drugs voluntarily.

What about the military? Military service can subject individuals to extraordinary risks, even death. But there are limits to the extent of these risks. For example, in the absence of special circumstances and a presidential order, soldiers cannot be required to participate in medical experiments (10 U.S.C. §1107[f]). Yet the exigencies of combat probably justify requiring soldiers to use cognition-enhancing drugs unless they are highly dangerous.

Should parents be allowed to give cognitive enhancement drugs to their children? Note that they already are, since no law prohibits parents from feeding their kids caffeinated colas or coffee. If the new enhancement products were deemed safe enough to be sold over-the-counter or added to foods, parents should have the right to give them to their children as well. In fact, the law currently seems to give parents much greater leeway: Clearly, some of them are giving Ritalin® to their children for enhancement purposes, yet Ritalin® is classified as a Schedule II controlled substance, meaning that it has a high potential for abuse and may lead to severe psychological or physical dependence (21 U.S.C. §812[b][2]).

Even if enhancement drugs were extremely safe, control over use by minors should remain with their parents (or, as with caffeine, perhaps with the minors themselves). Although enhancement use might facilitate classroom learning or improve test scores, schools should not be permitted to require children to use them. There is currently a considerable backlash against schools' pressuring parents to give Ritalin® to pupils perceived to be disruptive ( Strawn 2003). In a culture in which children are at risk from illicit drug use, requiring children to use enhancement drugs is likely to be viewed as morally objectionable.

Conclusion

This article has argued that for the most part, competent adults should be free to decide whether or not to use cognition-enhancing drugs, and if these drugs are sufficiently safe and effective, the government should subsidize access to them. It thus is important that the public have valid and reliable safety and efficacy data for these products. The greater the safety hazards are, the greater should be the justification required for anyone, including the government, employers, or parents, to mandate their use.

Some cognitive enhancement products may be so dangerous that society would be justified in outlawing their use in certain cases. Giving them to children, for example, could be deemed child abuse and neglect. However, given the potential societal benefits from cognitive enhancements, the difficulties of interdicting them, the traditional rights of adults to accept risks as long as they do not impose undue costs on third parties, and the liberty of parents to raise their children as they see fit, the government should bear a heavy burden before imposing highly restrictive regulatory prohibitions.

Acknowledgments

The author would like to thank Eric Juengst, Peter Whitehouse, and Dale Nance for their helpful comments.

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New drugs that enhance cognition in cognitively healthy individuals present difficult public policy challenges. While their use is not inherently unethical, steps must be taken to ensure that they are safe, that they are widely available to promote equality ...

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'Smart drug' modafinil may not make you brainier

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'Smart drug' modafinil may not make you brainier

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'Smart drug' modafinil may not make you brainier

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"Smart drug 'may help improve creative problem solving'," is the headline in The Daily Telegraph. The media reports have been prompted by a new study on the effects of modafinil...

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Cognitive enhancement by drugs in health and disease

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Cognitive enhancement by drugs in health and disease

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Abstract

Attempts to improve cognitive function in patients with brain disorders have become the focus of intensive research efforts. A recent emerging trend is the use of so-called cognitive enhancers by healthy individuals. Here, we consider some of the effects - positive and negative - that current drugs have in neurological conditions and healthy people. We conclude that, to date, experimental and clinical studies have demonstrated relatively modest overall effects, most probably because of substantial variability in response both across and within individuals. We discuss biological factors that might account for such variability and highlight the need to improve testing methods and to extend our understanding of how drugs modulate specific cognitive processes at the systems or network level.

Uses of cognitive enhancement

In the last decade, pharmacological treatments aimed at improving cognitive function across a range of brain disorders have been explored and have even become established in clinical practice [1]. In developmental conditions such as attention deficit hyperactivity disorder (ADHD), drugs acting on the noradrenergic and dopaminergic systems, such as methylphenidate and atomoxetine, are now in widespread use [2-4]. For neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, acetylcholinesterase inhibitors (AChEIs) and memantine [an N-methyl-D-aspartate (NMDA) receptor antagonist] are now standard treatments [5-9].

In chronic mental disorders such as schizophrenia, cognitive deficits are a separable feature from positive (e.g. hallucinations and delusions) and negative (e.g. blunted affect, poverty of speech) symptoms, with current antipsychotic treatments having little, if any, impact on cognitive impairments. A wide range of compounds is therefore being assessed for cognitive enhancement in this disorder [10]. Similarly, attempts to ameliorate cognitive deficits following stroke are being actively explored [1,11-13], although none have been established. Many such cognitive enhancers target neuromodulatory systems - cholinergic, dopaminergic, noradrenergic and serotonergic - ascending from brainstem nuclei to innervate both cortical and subcortical systems ().

Table 1

Cognitive enhancer

Neuromodulatory mechanism

Cognitive functions improved

Known brain systems most affected

Currently recommended clinical use

Although most of the reported positive effects of such drugs have been modest in magnitude overall and are highly variable across individuals, they have had an enormous impact, stimulating interest in cognitive enhancement not only for patients with brain disorders, but also for healthy individuals. Compounds such as methylphenidate and modafinil are used by students in pursuit of better grades, military personnel who need to remain awake for long missions, elderly individuals afraid of cognitive decline and even university academics keen to maintain their performance [14-17].

Here we focus on what aspects of cognition are enhanced, the magnitude of these effects and possible mechanisms underlying variations in response across individuals. Our aim is to highlight key common themes across studies of clinical populations and healthy individuals, using examples that highlight these principles. Other recent reviews provide excellent discussions of ethical issues in cognitive enhancement [18] and illustrate the complexity of physiological, cellular and computational mechanisms underlying such effects [19-22].

What is enhanced?

What exactly do cognitive neuromodulators do? It might be tempting to assume a selective one-to-one mapping between a specific neurotransmitter system and a particular cognitive function. For example, dopamine has been strongly linked with working memory (WM) and attention [19], whereas serotonergic drugs have been prominently associated with affective processes [23,24]. However, serotonergic modulation can also influence WM [25], as can noradrenaline and acetylcholine. Conversely, dopamine influences affective processing [26,27]. A simple mapping between a specific neurotransmitter and a particular cognitive function described at a very general level - such as WM - therefore seems untenable. However, subtle but important differences in the precise processes modulated might provide some discriminating value: for instance, dopamine has an established role in reinforcement learning in response to rewards [28,29], whereas serotonin seems to modulate reinforcement learning for aversive stimuli [20,23].

To add to the complexity, neurotransmitters act via a suite of different receptor systems. Thus, dopamine acting at D1 receptors can have very different - even opposing - effects to that of its actions at D2 receptors [19,30]; for serotonin there are 17 different receptor systems. In addition, dopamine can have very different effects at different brain regions, even within different regions of the human basal ganglia [31]. Its release can also be modulated in a highly specific regional manner by other neurotransmitters, such as glutamate within the nucleus accumbens [32]. Thus, interactions between neuromodulatory systems are also a probable mechanism by which some of their effects are modulated. For instance, dopamine, noradrenaline and acetylcholine release is under histaminergic H3 heteroreceptor control [33], whereas noradrenaline and dopamine can interact to modulate spatial WM neuronal responses in prefrontal cortex in a synergistic fashion [19,21]. Again, these considerations suggest that simple conceptualizations linking a specific neurotransmitter to a single cognitive function are unlikely to be helpful.

Finally, there is increasing evidence that several neurotransmitters might have different modes of action when released in a tonic, sustained manner compared to phasic release [29,34,35]. For instance, baseline firing of noradrenergic cells in the locus coeruleus varies with different states of alertness or arousal. Optimal responses to environmentally important events seem to be linked to phasic firing of these cells, but this occurs only when tonic levels of activity are moderate [35]. Thus, alteration of global concentrations of a neurotransmitter might modulate the ability to respond to external events mediated by phasic firing.

How do drugs currently used as enhancers produce their beneficial effects? Is it through multiple effects on several different cognitive processes or do they enhance one cognitive mechanism - such as arousal or improved sustained attention - through which they lead to better performance across a battery of tests? For studies in clinical populations, the difficulty is that many standard cognitive test batteries used in clinical trials are very unlikely to be sensitive enough to answer questions on the specificity of cognitive modulation ( Box 1).

Box 1

In clinical studies of neurodegenerative conditions - such as Alzheimer's disease, Parkinson's disease with dementia (PDD), dementia with Lewy bodies (DLB) and vascular dementia - the gold standard outcome measure has become the ADAS-Cog (Alzheimer's Disease Assessment Scale) [91]. This is a relatively short battery of cognitive tests covering memory, orientation, language, visual construction and limb praxis skills measured on a 70-point scale.

Drugs approved for use in these clinical conditions have demonstrated efficacy in changing this measure in the context of a randomized controlled trial (RCT), in which patients are randomly assigned either to drug or to placebo. Many trials have also revealed changes in CIBIC-plus (Clinician's Interview-Based Impression of Change) [92], ADAS-CGIC (Alzheimer's Disease Assessment Scale-Clinical Global Impression of Change) [92] or Neuropsychiatric Inventory (NPI) scores [93]. These scoring systems attempt to capture more global function or psychiatric effects of drug interventions.

For example, the CIBIC-plus is a semi-structured instrument that attempts to evaluate four areas: general, cognitive and behavioural functions and activities of daily living, based on the clinician's observations of the patient at interview, together with information supplied by a caregiver. By contrast, the NPI evaluates delusions, hallucinations, dysphoria, anxiety, agitation or aggression, euphoria, disinhibition, irritability or lability, apathy, aberrant motor activity, and night-time behaviour disturbances. It also relies on a structured interview with a caregiver who is familiar with the patient.

The problem with such scoring systems is that they are relatively crude and subjective. Many of them were developed for Alzheimer's disease and might not be as appropriate for other neurodegenerative conditions or for individuals performing in the normal range, but at risk of developing Alzheimer's disease. For example, fluctuations in attention or vigilance are a prominent feature of PDD and DLB whereas impairments in speed of information processing are common in vascular dementia. These aspects of cognition are not measured well by batteries such as ADAS-Cog.

Such scoring systems also often lack dynamic range and can be affected by ceiling or floor effects. Alternative measures comprising computerized batteries have therefore been used [36,94]. These can give more sensitive cognitive indices and reaction time measures can avoid saturation effects. However, they might be time-consuming to perform and require some degree of expertise to administer and interpret.

Similar issues also pertain to treatment studies of developmental disorders such as ADHD. Here, rating scales are also used as outcome measures, with trials showing relatively modest effects compared to placebo [90,95]. In ADHD too, experimental measures using reaction time indices, for example to assay response inhibition using the STOP signal reaction time task, might be more sensitive measures of the efficacy of drug interventions [96,97].

For example, AChEIs such as rivastigmine and donepezil are now widely used to treat Parkinson's disease dementia (PDD) and the related condition of dementia with Lewy bodies (DLB). Many clinical trials have reported modest global beneficial effects of such drugs on bedside cognitive screening tests [5-7]. More detailed assessment using sensitive computerized cognitive tests has revealed widespread improvements in the domains of attention, WM and episodic memory [36-38]. However, these positive effects of AChEIs might all be mediated via a common process such as elevated arousal [39,40]. In fact, the very same issue pertains to the modulatory effects of AChEIs in healthy subjects [41]. For example, in young volunteers, donepezil improves episodic memory, whereas healthy elderly subjects show improvements in verbal memory [42]. Is it possible that these effects could be due simply to a generalized improvement in arousal? Studies demonstrating that donepezil attenuates decline in short-term memory and visual attention induced by sleep deprivation [43,44] raise the possibility that this might indeed be the case.

Similar considerations as for AChEIs also apply to modafinil, which has become a popular drug for cognitive enhancement in healthy individuals. Although its precise mechanism of action remains to be established, modafinil is used as a wake-promoting agent for the treatment of narcolepsy, a disorder associated with excessive daytime somnolence. Analysis of the effects of modafinil in healthy subjects has revealed improvements in attention, memory and executive function in sleep-deprived individuals [17]. However, this might simply be due to improved wakefulness or arousal induced by the drug [17], just as caffeine can improve performance on a variety of measures, including vigilance, and on incidental learning and WM tests [45]. However, it is also important to appreciate that 'arousal' need not be a unitary process: there is evidence of different arousal systems that might be selectively modulated by different types of pharmacological intervention [46].

It is possible that neuroimging studies might contribute to identification of the mechanisms underpinning improvement on cognitive tests, including arousal. Although early studies assessed changes in brain activity on drug administration [47-49], more recent investigations have begun to examine the modulatory effect of compounds on brain networks. For example, the beneficial effects of reboxetine on visuomotor control are associated with strengthening of coupling between selective regions in posterior and anterior regions of the right hemisphere () [50]. Approaches to characterize the effects of drugs at a network level in brain disorders are also being applied in patient groups ( Box 2). Finally, it is also crucial to appreciate that non-cognitive factors such as alterations in mood, anxiety, motivation or apathy induced by a drug can have indirect effects on cognition. Hence, it is useful to control for these factors if at all possible.

Box 2

Although a great deal of work has been performed on furthering our understanding of the actions of several cognitive enhancers at a cellular level, it is likely that this level of explanation will be insufficient, on its own, to account for the effects of drugs on cognitive performance in both healthy humans and those with brain disorders. Instead, more insight might be obtained from an understanding of the modulatory effects of drugs on large-scale brain networks underlying cognitive skills at the systems level. Early studies demonstrated how drugs such as AChEIs and methylphenidate might modulate visual attention and WM via effects on parietal, frontal and extrastriate occipital regions [47-49].

More recent investigations have focused on the effects of drugs on functional connectivity across a brain network. For example, reboxetine, a noradrenergic reuptake inhibitor, improved performance on a visuomotor task, an effect that was associated with enhanced effective connectivity between right hemisphere parietal and frontal regions, as well as their influences on left hemisphere regions [50]. Such approaches have also been used to examine more challenging effects, such as that of modafinil on the noradrenergic locus coeruleus, a very small nucleus located in the pons [98].

A different approach, applied to clinical populations, has been to examine brain metabolic network deficiencies associated with neurodegenerative conditions, such as motor and cognitive deficits in PD, using fluorodeoxyglucose PET [99]. Researchers have also started to use this methodology to investigate the effects of treatment at the network level, raising the possibility of producing a network-level account of how a drug might modulate function in a particular brain disorder. Importantly, different neurodegenerative diseases seem to have characteristically different effects on the resting-state functional connectivity across brain network nodes, as indexed by fMRI [100].

How effective are the benefits?

A major issue in assessing cognitive enhancement studies is the problem of effect size. First, in studies of healthy subjects, there is no universal, standard battery of tests that has been agreed on, so comparisons across studies are not easy. It is not possible to compare effect sizes for different drugs if the tests used differ in the level of difficulty or method of measurement (e.g. reaction time vs error rate). Overall, however, the effects of cognitive enhancers such as methylphenidate, modafinil and AChEIs in healthy individuals seems to be quite modest according to recent systematic reviews [17,41]. Second, many experimental investigations in healthy subjects have used single-dose assessments aimed primarily at assessing mechanisms rather than establishing optimal cognitive enhancement. Very few studies have examined the effects of repeated doses or long-term effects, which might be far more revealing and representative of the overall costs and benefits of taking cognitive enhancers on a regular basis. Third, as we have seen, although clinical trials in patients often use standardized bedside batteries, they might be hampered by their insensitivity and limited range of measurement ( Box 1).

Nevertheless, even for these relatively crude measures, studies in clinical populations have revealed significant effects of long-term drug use that have led to changes in practice. For example, one of the remarkable changes in the management of neurological conditions in the last decade has been the advent of treatment for cognitive deficits in neurodegenerative conditions, initially in Alzheimer's disease with AChEIs [7]. These studies stimulated clinical trials in other conditions such as PDD and DLB, with two major placebo-controlled studies involving over 650 patients demonstrating significant positive effects of the AChEI rivastigmine on cognition and neuropsychiatric measures such as apathy, anxiety and visual hallucinations [5,6].

Although these trials have now led to widespread clinical use of rivastigmine, it is important to keep the effect size in perspective. In the larger study, rivastigmine produced only a mean 2-point improvement on the ADAS-Cog battery ( Box 1), which has a 70-point range [6]. Similar degrees of change have been observed in Alzheimer's disease and vascular dementia trials with AChEIs (a).

Of course, effect sizes vary across individual patients. Indeed ∼40-80% of PDD or DLB patients might not show a response to treatment on such clinical measures, but other individuals show a very strong improvement [5,6]. Overall, therefore, this means that positive effects have been moderate, at best, when results are examined at the group level - at least using this currently accepted method for measuring cognition in neurodegenerative clinical trials. Similar conclusions have been reached in schizophrenia, for which there is currently no established treatment for cognitive enhancement [10]. Thus, interindividual variability might be one potential reason for small overall effect sizes (see below).

By contrast, a first glance might indicate far more substantial effect sizes in treatment trials of ADHD, for which several drugs that target the catecholaminergic system are used in clinics. For example, a recent study using high levels of the α2 noradrenergic agonist guanfacine demonstrated a 12-point mean improvement compared to placebo on a rating scale with a range of 54 points (b). However, these effects were based on ratings by parents or caregivers, and not on cognitive tests. These might be very valid measures to rate the behavioural effects of a drug, but the point is that when considering effect size it is crucial to bear in mind the nature of the assessments. It is also important to question whether there might be negative effects of taking a compound.

The downside of cognitive enhancers

Like all drugs, those used with the aim of enhancing cognition can have side effects via body systems other than the brain. Thus, both AChEIs and methylphenidate frequently cause gastrointestinal upset or nausea, sometimes leading patients to discontinue medication altogether. These effects have the potential to offset any positive effects of the drug on overall performance, and also need to be borne in mind by anyone contemplating use of such drugs for non-medicinal purposes. More important from a cognitive neuroscience perspective is the ability of some drugs to impair certain aspects of cognition while simultaneously enhancing others in the same individual.

Thus, rivastigmine in healthy elderly subjects can improve learning on a motor task and making associations between symbols and digits, but can at the same time impair verbal and visual episodic memory [51]. Similarly, the dopamine agonist bromocriptine can enhance spatial WM while simultaneously impairing probabilistic reversal learning in young participants [52]. This finding echoes results in patients with PD: dopaminergic medication improves their performance on WM and task-set switching tasks, but degrades reversal learning [53,54]. It has been hypothesized that such opposing effects are due to 'overdosing' of ventral striatal areas involved in the latter, but replenishment of dopamine in dorsal striatal areas required for the former [53,55]. Thus, doses of dopaminergic medication sufficient to ameliorate motor function and some aspects of cognition in PD have the potential to worsen others.

Indeed, this conclusion might well be applicable to recent reports that some PD patients on dopaminergic agonists developed impulsive behaviours such as gambling, compulsive shopping and hypersexuality [56,57]. It has been reported that such behaviour in PD is often associated with the presence of dyskinesias, involuntary movements due to excessive dopaminergic stimulation [58], consistent with the notion that such impulse control disorders might indeed be associated with 'overdosing' of some basal ganglia regions. Importantly, reducing the dose of dopaminergic drugs often leads to reductions in impulsivity. These findings show that dopamine agonists in PD can have a spectrum of effects, both beneficial and harmful, on cognition and behaviour.

Who benefits from cognitive enhancers?

A major theme that has emerged from studies of neurological patient groups is that there is a great variability of response, with many individuals not responding to treatment on (relatively crude) clinical measures, whereas others show a very strong improvement, for example in response to AChEIs [5,6]. Thus, although this group of patients demonstrates a modest average cognitive change overall, the effect is likely to be diluted by the fact that many individuals show very little benefit.

The same issue has arisen in investigations in healthy individuals: some subjects respond, whereas others might show little or no benefit. As we discuss below, recent investigations have begun to question whether such differences in outcome might depend on genotype and/or the baseline level of cognitive function. These considerations also raise concerns about what has become the standard method of performing clinical drug trials. Large-scale randomized controlled trials offer protection from false positive findings, but they also have the potential to discard the fact that some subgroups might benefit from a compound, whereas others might not.

What might be the cause of such variations in response? Several studies on the effects of dopaminergic drugs on WM in healthy volunteers support the conclusion that those who benefit most are low performers, such as those with low WM capacity or span. Thus, methylphenidate or dopamine receptor agonists such as bromocriptine improve WM updating or retrieval in people who were low performers on study entry, but can actually impair performance in participants with high baseline WM spans [47,59-62].

One possible explanation for such contradictory effects might reside in the classic inverted U-shaped relationship between cognitive performance and dopamine receptor (particularly D1 receptor) stimulation (). Such effects have been known for a long time, with investigations in experimental animals revealing that both low and excessively high levels of D1 receptor stimulation in the prefrontal cortex can impair WM [63-65]. For optimal performance, a baseline level between these two extremes is required.

However, until recently, direct evidence in favour of this concept has been lacking in humans. New findings reveal that dopamine synthesis capacity in the caudate nucleus of the basal ganglia is lower in individuals with low WM spans compared to those with high spans [66]. Participants in this study were also investigated after taking bromocriptine or placebo. Ability to update reward predictions on a reversal learning task was improved by bromocriptine far more in individuals with low baseline dopamine synthesis capacity in the basal ganglia. Indeed, high-synthesis subjects were actually impaired in their performance [67].

More recently, it was demonstrated using radioligand positron emission tomography (PET) imaging that individuals with small levels of dopamine release induced by methylphenidate improved on a reversal learning task [31]. By contrast, participants with larger dopamine release in the caudate nucleus were impaired by the drug. Importantly, the authors also found that the most impulsive subjects (as indexed by their score on an impulsivity scale) were more likely to improve with methylphenidate. Thus, both baseline trait impulsivity and methylphenidate-induced dopamine release affected response to drugs.

The effects of methyphenidate on spatial WM in healthy subjects are also most prominent in individuals with the lowest performance [47]. In ADHD it has similarly been reported that children with the poorest sustained attention or highest baseline motor activity are most likely to respond to methylphenidate treatment [68]. The effects of baseline performance might also be evident for cholinergic modulation: whereas beneficial effects of donepezil on cognitive function were evident in healthy participants whose performance declined after sleep deprivation, those who were not much affected by sleep loss tended to deteriorate after donepezil intake [43,44]. Modafinil also seems to have the most prominent cognitive effects on attention and WM in subjects who have low baseline performance [69,70]. Interestingly, recent studies using magnetic resonance spectroscopy suggest that levels of GABA in specific brain regions predict differences in individual performance on cognitive tasks [71,72]. Thus, one reason for baseline performance modulation of response to drugs might be the baseline level of a neurotransmitter in a critical brain region or network.

Effects of genotype on response to drugs

Genetic predictors of individual variability in response to treatments aimed at improving cognitive function would clearly be beneficial in effective targeting of therapeutic strategies. These effects might result directly from variations in efficiency of drug targets or indirectly via metabolic pathways or other risk genes. Several studies have suggested a role for polymorphisms in the catechol-O-methyltransferase (COMT) enzyme-coding region on chromosone 22 in WM [73]. COMT degrades catecholamines, including dopamine, at the synapse. Polymorphisms of the COMT gene seem to be associated with variability in human WM performance and associated brain activity, presumed to be via its putative influence on cortical dopamine levels [73].

Amphetamine responses might interact with COMT activity. When performing a test of cognitive flexibility - the Wisconsin Card Sorting Test - those with the higher-activity COMT Val-Val genotype improved, whereas those with the lower-activity Met-Met genotype deteriorated after a single dose of amphetamine. An inverted-U relationship between predicted cortical dopamine levels and performance is consistent with these findings ().

Variations in COMT and the dopamine transporter gene (DAT) are both obvious candidates for modulation of response to psychomotor stimulant treatment in a condition such as ADHD. DAT is a major target of methylphenidate and amphetamine, and many treatments for ADHD, including the noradrenaline transporter inhibitor atomoxetine, are thought to increase cortical dopamine levels [74], consistent with a role for COMT. An association between good clinical response to methylphenidate and carriers of the high-activity Val polymorphism also suggests a role for cortical dopamine in mediating treatment response [75,76]. However, the influence of variable number of tandem repeats in the DAT gene on methylphenidate response seems to be mixed [77-79].

Apoliprotein E4 ( apoE4), an allele of apolipoprotein E, which is involved in lipoprotein processing in cells, increases the risk of developing dementia later in life. Perhaps paradoxically, young healthy carriers of this genotype, who have a higher risk of cognitive decline later in life, actually show better performance on decision-making and prospective memory tasks compared to their apoE3 counterparts [80]. Moreover, nicotine - but not dopaminergic drugs - potentiate the advantage in apoE4 carriers, producing greater cognitive benefits in these individuals than in apoE3 carriers on these tasks [80]. The reasons for this are unclear, but the findings suggest that some genetic variations influence the integrity of specific neurotransmitter systems, limiting the potential to improve function in response to drugs acting on the same systems.

For the AChEIs, extensive metabolizers of drugs as defined by gene variations in cytochrome P450 (a family of degradative enzymes) might show greater response to donepezil and rivastigmine [81,82]. This has been demonstrated using the Mini Mental State Examination (MMSE), which is a relatively crude bedside test of cognition; selective cognitive tasks have not been used to elucidate process-specific advantages.

Drug effects and behavioural training

One area that is likely to develop in cognitive enhancement research is investigation of the interaction between drugs and behavioural approaches to improve cognition. There has been a great deal of recent interest in the potential for cognitive training, for example on WM tasks, to improve performance not only on these paradigms but also to generalize to other tasks in healthy people, as well as those with brain conditions such as ADHD [83,84]. fMRI studies in healthy participants have revealed alterations in activity across parietal and frontal regions during such training [85]. Intriguingly, radioligand PET imaging demonstrated associated changes in dopamine D1 receptor binding in parietal and frontal areas [86]. Thus it might be possible to visualize alterations in neurotransmitter systems as a function of cognitive training using brain imaging.

An important question for future studies will be whether there can be synergistic effects of behavioural training and cognitive-enhancing drugs. Such synergism has been demonstrated for learning of new material and levodopa in healthy subjects [87]. Whether such combined intervention might also be useful for cognitive deficits in brain disorders has yet to be explored in detail. However, there is emerging evidence of such effects. For example, both memantine and speech therapy improved dysphasia in stroke patients, but the combination of the two led to enhanced outcomes [88]. Demonstrations of network-level interactions for drug and cognitive training in this type of context would be an important way to investigate the mechanisms underlying such synergistic effects. Taking the effects of genotype, baseline cognitive performance and the nature of brain disorder in patients into account is likely to be an important factor in understanding such synergies.

Concluding remarks

It would probably be fair to say that we are still in the first generation of studies to examine the potential for cognitive enhancement in humans. In both healthy individuals and many patient groups, the overall effects of drugs generally seem to be modest. However, there is evidence that there might be more significant effects in subgroups, such as those whose baseline performance is poorest or individuals with a particular genotype. Moreover, new drugs aimed at enhancing the phasic response of neurotransmitter systems, such as direct nicotinic agonists for the cholinergic system [34], might prove to have greater effects than existing modulators that globally increase levels of a neurotransmitter in a tonic fashion. The neurobiology underpinning the effects of cognitive enhancers and the mechanisms that determine responsiveness across individuals promise to be the focus of research in health and brain disorders in the future ( Box 3).

Box 3

* Can we improve outcome measures used to study the effects of drugs in clinical populations?

* Is it possible to improve prediction of which healthy individuals or patients might respond to a particular cognitive-enhancing drug?

* How do different neurotransmitter systems interact to modulate a particular cognitive function? Animal studies provide evidence of such interactions but there are few investigations in humans.

* Is there a role for combined treatments for neurological disorders, targeting different neurotransmitter systems?

Acknowledgments

We thank Dr Alex Leff for helpful comments on the manuscript. This work was funded by The Wellcome Trust and the NIHR CBRC at UCL/UCLH.

Glossary

Acetylcholinesterase

enzyme that breaks down acetylcholine at synapses.

Cholinergic system

nervous system pathways that use acetylcholine as a neurotransmitter. This includes cholinergic neurons in the basal forebrain that project to the cerebral cortex.

COMT (catechol- O- methyltransferase)

enzyme that degrades catecholamines, including dopamine, at synapses.

DAT (dopamine active transporter)

membrane-spanning protein that pumps dopamine from the synapse back into the cell, thereby reducing its synaptic concentration.

Dementia with Lewy bodies (DLB)

form of dementia characterized by the presence of Lewy bodies (consisting of α-synuclein and ubiquitin proteins), closely related to Parkinson's disease with dementia (PDD).

Dopaminergic system

neurons that use dopamine as a neurotransmitter have cell bodies located in the midbrain. The mesolimbic pathway and mesocortical pathway originate in the ventral tegmental area to innervate the limbic system and cerebral cortex, respectively, whereas the nigrostriatal pathway projects from the substantia nigra to innervate the caudate and putamen.

Glutamate

ionized form of the amino acid glutamic acid; acts as an excitatory amino acid transmitter.

Heteroreceptors

receptors on axons that are specific for neurotransmitters released by other cells at axon-axon synapses.

Histaminergic system

neurons that use histamine as a neurotransmitter have cell bodies in the hypothalamus and project to brain regions including the cerebral cortex.

NMDA receptor

class of glutamate receptors activated by N-methyl-D- aspartate.

Noradrenergic system

neurons that use noradrenaline as a neurotransmitter project from cell bodies in the locus coeruleus in the pons to innervate the cerebral cortex.

Nucleus accumbens

part of the basal ganglia. Its inputs include dopaminergic neurons from the ventral tegmental area via the mesolimbic pathway.

Serotonergic system

neurons that use serotonin as a neurotransmitter project from cell bodies in the brainstem (notably in the raphe nucleus) to the cerebral cortex.

Working memory

process whereby information is held in mind for brief periods.

References

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Cognitive enhancement by drugs in health and disease

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Attempts to improve cognitive function in patients with brain disorders have become the focus of intensive research efforts. A recent emerging trend is the use of so-called cognitive enhancers by healthy individuals. Here, we consider some of the effects ...

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Universities must do more to tackle smart drugs, say experts.

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Universities must do more to tackle smart drugs, say experts.

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Universities must do more to tackle use of smart drugs, say experts

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Academics call on institutions to consider measures such as drug testing to stem UK rise of drugs used to cope with exam stress

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The 14 Best Nootropics and Smart Drugs Reviewed

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The 14 Best Nootropics and Smart Drugs Reviewed

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The 14 Best Nootropics and Smart Drugs Reviewed.

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The 14 Best Nootropics and Smart Drugs Reviewed.

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Comprehensive list of both natural and synthetic

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Nootropics and smart drugs are natural or synthetic substances that can be taken to improve mental performance in healthy people.

They have gained popularity in today's highly competitive society and are most often used to boost memory, focus, creativity, intelligence and motivation.

Here's a look at the 14 best nootropics and how they enhance performance.

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Caffeine is the most widely consumed psychoactive substance in the world ( 1).

It's naturally found in coffee, cocoa, tea, kola nuts and guarana and added to many sodas, energy drinks and medications. It can also be taken as a supplement, either on its own or in combination with other substances ( 2).

Caffeine works by blocking adenosine receptors in your brain, making you feel less tired ( 3).

A low to moderate caffeine intake of 40-300 mg increases your alertness and attention and decreases your reaction time. These doses are especially effective for people who are fatigued ( 4, 5, 6).

Summary Caffeine is a naturally occurring chemical that increases your alertness, improves your attention and reduces your reaction times.

L-theanine is a naturally occurring amino acid found in tea, but it can also be taken as a supplement ( 7).

Several studies have shown that taking 200 mg of L-theanine has a calming effect, without causing drowsiness ( 8, 9).

Taking even just 50 mg - the amount found in roughly two cups of brewed tea - has been found to increase alpha-waves in the brain, which are linked to creativity ( 9).

L-theanine is even more effective when taken with caffeine. For this reason, they're often used together in performance-enhancing supplements. What's more, they are both naturally found in tea ( 7, 10).

Summary L-theanine is an amino acid found in tea that can increase feelings of calmness and may be linked to increased creativity. Its effectiveness is even greater when combined with caffeine.

Creatine is an amino acid, which your body uses to make protein.

It's a popular bodybuilding supplement that promotes muscle growth but is also beneficial for your brain.

After it's consumed, creatine enters your brain where it binds with phosphate, creating a molecule that your brain uses to quickly fuel its cells ( 11).

This increased availability of energy for your brain cells is linked to improved short-term memory and reasoning skills, especially in vegetarians and highly stressed people ( 12, 13, 14).

Studies show that it's safe to take 5 grams of creatine per day without any negative effects. Larger doses are also effective, but research on their long-term safety is unavailable ( 15).

Summary Creatine is an amino acid that can improve short-term memory and reasoning skills. It's most effective in vegetarians and people who are stressed. Doses of 5 grams per day have been shown to be safe in the long term.

Bacopa monnieri is an ancient herb used in Ayurvedic medicine to enhance brain function.

Several studies have found that Bacopa monnieri supplements can speed up information processing in your brain, reduce reaction times and improve memory ( 16, 17, 18).

Bacopa monnieri contains active compounds called bacosides, which protect your brain from oxidative stress and improve signaling in your hippocampus, an area of your brain in which memories are processed ( 19).

The effects of Bacopa monnieri are not felt immediately. Therefore, doses of 300‒600 mg should be taken for several months for maximum benefit ( 20, 21).

Summary Bacopa monnieri is an herbal supplement that has been shown to improve memory and information processing when taken for several months.

Rhodiola rosea is an adaptogenic herb that helps your body handle stress more effectively.

Several studies have found that Rhodiola rosea supplements can improve mood and decrease feelings of burnout in both anxious and highly stressed individuals ( 22, 23).

Taking small daily doses of Rhodiola rosea has been shown to reduce mental fatigue and increase feelings of well-being in college students during stressful exam periods ( 24).

More research is needed to determine optimal dosing and better understand how the herb causes these effects.

Summary Rhodiola rosea is a natural herb that may help your body adapt to periods of high stress and reduce associated mental fatigue.

Panax ginseng root is an ancient medicinal plant used to boost brain function.

Taking a single dose of 200-400 mg of Panax ginseng has been shown to reduce brain fatigue and significantly improve performance on difficult tasks like mental math problems ( 25, 26, 27).

However, it's unclear how Panax ginseng boosts brain function. It may be due to its strong anti-inflammatory effects, which help protect your brain from oxidative stress and enhance its function ( 28).

Some longer-term studies have found that your body may adapt to ginseng, making it less effective after several months of use. Therefore, more research is needed on its long-term nootropic effects ( 29).

Summary Occasional doses of Panax ginseng may help improve mental function, but more research is needed on its long-term effectiveness.

Extracts from the leaves of the Ginkgo biloba tree may also have positive effects on your brain.

Ginkgo biloba supplements have been shown to improve memory and mental processing in healthy older adults when taken daily for six weeks ( 30, 31, 32).

Taking Ginkgo biloba before a highly stressful task also reduces stress-related high blood pressure and decreases levels of cortisol, a type of stress hormone ( 33).

It's hypothesized that some of these benefits may be due to increased blood flow to the brain after supplementing with Ginkgo biloba ( 34).

While these results are promising, not all studies have shown beneficial effects. More research is needed to better understand the potential benefits of Ginkgo biloba on your brain ( 35).

Summary Some research suggests that Ginkgo biloba can improve memory and mental processing and may be beneficial in stressful situations. Yet, more research is needed.

Nicotine is a naturally occurring chemical found in many plants, especially tobacco. It's one of the compounds that make cigarettes so addictive.

It can also be consumed through nicotine gum or absorbed through your skin via a nicotine patch.

Studies show that nicotine can have nootropic effects, such as improved alertness and attention, especially in people with naturally poor attention spans ( 36, 37).

It has also been found to improve motor function. What's more, chewing nicotine gum is linked to better handwriting speed and fluidity ( 38).

However, this substance can be addictive and is lethal in high doses, so caution is warranted ( 39).

Summary Nicotine is a naturally occurring chemical that boosts alertness, attention and motor functions. Nonetheless, it's addictive and toxic in high doses.

Noopept is a synthetic smart drug that can be purchased as a supplement.

Unlike some of the natural nootropics, the effects of Noopept can be felt within minutes, rather than hours, days or weeks, and typically last for several hours ( 40, 41).

Animal studies have shown that Noopept speeds up how quickly the brain forms and retrieves memories by boosting levels of brain-derived neurotrophic factor (BDNF), a compound that promotes the growth of brain cells ( 42, 43, 44).

Human research has found that this smart drug helps people recover more quickly from brain injuries, but more studies are needed to understand how it might be used as a nootropic in healthy adults ( 45, 46).

Summary Noopept is a fast-acting, synthetic nootropic that may improve memory by increasing BDNF levels in your brain. However, more human-based research is needed.

Piracetam is another synthetic nootropic molecule that's very similar to Noopept in structure and function.

It has been shown to improve memory in people with age-related mental decline but does not seem to have much benefit in healthy adults ( 47, 48).

During the 1970s, a few small, poorly designed studies suggested that piracetam may improve memory in healthy adults, but these findings have not been replicated ( 49, 50, 51).

Though piracetam is widely available and promoted as a smart drug, research on its effects is lacking.

Summary Piracetam is marketed as a nootropic supplement, but research supporting its effectiveness is lacking.

Phenotropil, also known as phenylpiracetam, is a synthetic smart drug that is widely available as an over-the-counter supplement.

It's similar in structure to piracetam and Noopept and helps the brain recover from various injuries like stroke, epilepsy and trauma ( 52, 53, 54).

One study in rats found that phenotropil slightly enhanced memory, but research to support its use as a smart drug in healthy adults is unavailable ( 55).

Summary Phenotropil is marketed as a smart drug, but research showing memory-enhancing benefits in healthy adults is unavailable.

Commonly sold under the brand name Provigil, modafinil is a prescription drug that is often used to treat narcolepsy, a condition that causes uncontrollable drowsiness ( 56).

Its stimulating effects are similar to those of amphetamines or cocaine. Yet, animal studies suggest it has a lower risk of dependence ( 57, 58).

Several studies have shown that modafinil significantly reduces feelings of fatigue and improves memory in sleep-deprived adults ( 59, 60, 61).

It also enhances executive functioning, or the ability to properly manage your time and resources to accomplish your goals ( 60).

While modafinil appears to have strong nootropic effects, it's only available via prescription in most countries.

Even when prescribed, it's important to use this drug responsibly to avoid negative side effects.

Though modafinil is generally considered non-addictive, instances of dependence and withdrawal have been reported at high dosages ( 62, 63).

Summary Modafinil is a prescription drug that can reduce drowsiness and improve brain function in healthy adults, particularly those who are sleep deprived. However, it should only be taken as prescribed.

Adderall is a prescription medication that contains highly stimulating amphetamines.

It's most commonly prescribed to treat attention deficit hyperactivity disorder ( ADHD) and narcolepsy, but it's increasingly taken by healthy adults to improve attention and focus ( 64).

Adderall works by increasing the availability of the brain chemicals dopamine and noradrenaline within your prefrontal cortex, an area of your brain that controls working memory, attention and behavior ( 65).

The amphetamines found in Adderall make people feel more awake, attentive and optimistic. They also reduce appetite ( 66).

A review of 48 studies found that Adderall significantly improved people's ability to control their behavior and enhanced short-term memory ( 67).

Depending on the dose and type of pill prescribed, the effects last up to 12 hours ( 68).

It's important to note that these drugs are not without side effects.

Adderall is widely abused on college campuses, with some surveys indicating that up to 43% of students use stimulant drugs without a prescription ( 69).

The side effects of Adderall abuse include anxiety, low sex drive and sweating ( 70).

Recreational Adderall abuse can also cause more severe side effects, such as heart attack, especially when mixed with alcohol ( 71, 72, 73).

Evidence that Adderall enhances mental performance is strong, but it should only be taken as prescribed.

Summary Adderall is not available without a prescription but does appear to improve brain function in healthy adults and those with ADHD.

Ritalin is another prescription drug used to manage symptoms of ADHD and narcolepsy.

Like Adderall, it's a stimulant and increases dopamine and noradrenaline concentrations in your brain. However, it does not contain amphetamines ( 74).

In healthy adults, Ritalin improves short-term memory, information-processing speed and attention ( 75, 76).

It's typically well tolerated, but may have the opposite effect and impair thinking if an excessive dose is taken ( 77).

Like Adderall, Ritalin is widely abused, especially by people aged 18-25 ( 78).

The most common side effects of Ritalin include insomnia, stomach ache, headache and loss of appetite ( 79).

It can also cause hallucinations, psychosis, seizures, heart arrhythmias and high blood pressure, particularly when taken in high doses ( 79, 80, 81, 82).

Ritalin is a powerful stimulant that should only be taken as prescribed and monitored closely for abuse.

Summary Ritalin is a smart drug that enhances information processing, memory and attention. It's only available with a prescription.

Nootropics and smart drugs refer to natural, synthetic and prescription substances that enhance mental function.

Prescription smart drugs, such as Adderall and Ritalin, have the strongest and most significant effects on memory and attention.

Synthetic nootropic supplements like Noopept and piracetam are widely available, but research on their effectiveness in healthy adults is lacking.

Many natural nootropics are used in alternative medicine, but their effects are typically more subtle and slower acting. They're sometimes taken in combination to boost their effectiveness.

The use of nootropics and smart drugs is on the rise in today's society, but more research is needed to better understand their benefits.

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The 14 Best Nootropics and Smart Drugs Reviewed

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Nootropics and smart drugs are natural or synthetic substances that can be taken to improve mental performance in healthy people. They have gained popularity in today's highly competitive society and are most often used to boost memory, focus, creativity, intelligence and motivation. Here's a look at the 14 best nootropics and how they enhance performance.

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Photograph courtesy of the author

This article originally appeared on VICE Colombia

Originally synthesised in France in the 1970s, Modafinil was approved by the US's Food and Drug Administration (FDA) as a treatment for narcolepsy and other sleep disorders in 1998. Recently, however, totally healthy people have began using it to stay awake for extended periods of time and to increase their cognitive performance. Medications such as Adderall and Ritalin - originally prescribed for attention deficit disorder (ADD) patients - and Ampakine - used for Alzheimer's - are also being used to improve the brain function of people studying and working. These drugs are known as nootropics, or smart drugs.

I decided to give Modafinil a try and see how it would affect my work. I had a good look at the side effects and, after making as certain as possible that I wouldn't just drop dead after taking it, I swallowed the neon orange capsule.

Arriving at work at 9AM, I began thinking it was funny that no one around me had a clue that I was on a drug taken by war pilots, ER doctors and Silicon Valley millionaires. They all take the drug for the same reason: to give their concentration a kick up the arse. After a couple of hours sitting at my desk, I was getting impatient. Was anything ever going to happen? Around 11:30AM, I noticed that I hadn't taken a cigarette break yet. I mean, I had plenty of cigarettes on me and knew that some of my colleagues were already outside the office smoking but, because of the pill, I didn't feel like it.

The kick arrived with all certainty at about noon. I was hungry for work and agreed to take on an extra task that my editor was trying to get done. For the next hour, I was completely engrossed in it, too. I was so into my work that I wasn't even that interested in getting lunch when my colleague asked if I felt like pizza, which was quite unusual for me. I still ordered some though.

Truth is, no one really knows how this drug works. It sounds absurd, especially considering you can buy it over the counter in Colombia where I live, but it's the same with widely used substances like general anaesthetics. It's broadly accepted that general anaesthetics are effective and safe (at least compared to chloroform), but science is still at a point where anyone who tries to explain how it works, will probably be proven wrong.

Some say that Modafinil stimulates the brain so it releases a hormone called histamine. You've probably heard of antihistamine, a compound that inhibits the production of histamine found in those anti-allergy medications that make you really drowsy. So, it makes sense: by increasing the production of histamine, Modafinil causes the opposite effect. It makes you way less drowsy.

However, other studies suggest that Modafinil affects the brain similarly to things like amphetamines and cocaine. They claim it increases people's levels of dopamine - the hormone we release when we eat, have sex or run into a friend. If this theory is true, it would mean that Modafinil use could lead to abuse and addiction. Something that - due to a lack of long-term research - nobody has been able to prove yet.

Back at the office, it took more than 45 minutes for the delivery guy to bring a pizza to my colleague Camila, but I couldn't have cared less. The thought of pepperoni was probably causing Camila's brain to flood with dopamine but mine had already received a shot of it in the form of that funny coloured pill. A few days later, I asked Camila whether or not I was acting normally during that lunch break.

"You were cool," she said.

Once I ate my pizza, there was no "walk around the block to digest lunch", no "let's have dessert to kill the pepperoni taste", not even the sacred "after lunch cigarette". I just sat right back down to finish my work. By the time my editor returned to his desk, it was done. "Already?" my boss asked with his eyes wide open. I nodded casually, as if it was completely normal for me to finish my assignments early.

Aside from Modafinil's effects - and side effects -, there is a rather interesting ethical debate behind medications that increase cognitive performance. Was using that pill unfair on my colleagues? According to an article by Rob Goodman, published in the Kennedy Institute's Ethics magazine, the use of medication to improve cognitive performance is acceptable, as long as it doesn't put someone else's job in jeopardy. Last year, employees at the Australian Department of the Treasury admitted (anonymously) to having had used the medication to help complete the nation's budget on time.

The debate surrounding drugs like these is full of ethical grey areas. Sure, as a website editor, if I took those pills on a daily basis I could probably churn out more articles per week. Something that wouldn't necessarily affect the other reporters' work, but it would pressure them into upping their productivity. Especially if I never mentioned that I was taking the pills. That said, I could argue that I'm free to take whatever medication I want because it's a part of my private life. Besides, unlike me, many of my colleagues consume energy drinks all day long.

According to Professors Mirko Garasic and Andrea Lavazza, if you choose to take these medications, the ethically correct thing to do is to be honest about it and tell your coworkers and bosses. You could also simply not take them but that's apparently pretty unrealistic. According to Vince Cakic, Psychology Professor at the University of Sydney, we could learn something by looking at how hard it's been to control doping in sports. He has called on academics to start focusing on researching these drugs and informing people about their side effects, rather than declaring war on them.

My suspiciously productive workday began to crumble when I drank a cup of coffee. Almost immediately after, my heart began racing and I started feeling pressure in my chest. The mental effects were even more worrisome. I began getting extremely angry anytime my coworkers asked me for a synonym, sent me a video or showed me a meme. The casual desk chat that I usually enjoy and promote suddenly seemed offensive - not against me, but, even worse, against my work. I found myself wondering why they couldn't all just be full of drugs, too.

I got it into my head that the desk I shared with six others wasn't a healthy work environment and I chose to head over to Bogota's Pontifical Xavierian University library. On my way, my bike wheel punctured and I was forced to take a detour and swing by the closest mechanic. The artisanal process of fixing a tire had never been so infuriatingly slow. When the chap was done, I raced towards the university as if my life depended on it. Right before walking into the library - and several hours later than usual - I had my first cigarette of the day. My heart, the only object in the universe that seemed to be able to keep up with my newfound rhythm, began racing again. I sat myself down in front of a computer in a quiet, dark room and somehow managed to enter my password incorrectly a bunch of times. I was sweaty and my hands were shaking but, as soon as I saw my screen loading, I was filled with the same satisfaction and enthusiasm that usually fills me when I complete a task.

According to Dr. Scott Vrecko, nootropics might not increase a person's ability to receive, remember or process information; instead, they will have a positive effect on a person's mood while performing these tasks. Vrecko spent a few weeks at an American university collecting testimonies from students that took Adderall and many said that the pill made them feel more capable of performing their tasks - even before they got started. Another study points out that Modafinil could induce a state of excessive confidence.

My second task of the day was to transfer data mapping out the effects of robbery in Bogotá (by time and location) from a PDF file into an Excel worksheet. That's exactly the kind of mechanical task that usually sends me - an easily distracted person - straight to Facebook. But this time, it was different. Typing cold, flat figures became the highlight of my day and I felt better and better as I inserted numbers into that worksheet. Before long, I stopped sweating and my shivers all but disappeared. I won't lie: I did login to Facebook a couple times, but when I did, something inside me convinced me to get back to the task at hand.

The pill works, there's no doubt about it. But, at what cost? Doctors Kimberly Urban and Wen-Jun Gao fear that we could see long-term damage in healthy individuals under 30. Apparently, Modafinil can fuck up a thing called brain plasticity. Brain plasticity refers to the brain's ability to adapt to different situations and different contexts across a period of time.

What worries doctors are the effects of increasing the amount of dopamine in a developing brain. Modafinil and other smart drugs can affect brain receptors that consolidate short-term memory and regulate brain flexibility when it comes to responding to diverse stimuli - such as social situations. Researchers suspect that, in the long term, young individuals that take Modafinil - and similar medications - may end up with an increased ability to concentrate for longer periods of time but their short-term memory could decrease. Something that would lead to a disadvantage in social situations or when it comes to performing tasks that require cognitive flexibility - like being a journalist or driving a car. However, Urban and Gao's research is filled with speculation, not-yet-proven hypotheses and, just like every study about Modafinil, has a distinctive lack of long-term studies.

The day after my initial experiment, I decided to take another pill. The effects were basically the same - pleasure and well-being in the library. Sweating outside. I even decided not to buy a water bottle at the cafeteria because I couldn't stand waiting in line. I had another mishap with my bike: this time I just left it and walked to college. Usually, I love walking but because of the drug, it suddenly seemed like a complete waste of time. Getting home after a long day, turning off the light, smoking a joint and watching a comedy show didn't give me half as much pleasure as it usually does either.

Modafinil may be the least fun drug there is (at least of the ones I've tried) but in the rat race that is modern day life, it's sort of the only one that makes sense. It's weird, isn't it? The same generation that enthusiastically welcomed love drugs like MDMA and pills, are now into taking things like Modafinil - which, ironically, only makes you love work.

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Taking the 'Smart Drug' Modafinil Made Me Love Work but Hate People

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Photograph courtesy of the author This article originally appeared on VICE Colombia Originally synthesised in France in the 1970s, Modafinil was approved by the US's Food and Drug Administration (FDA) as a treatment for narcolepsy and other sleep disorders in 1998.

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how to beat brain fog and boost cognition naturally

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Do you frequently walk into a room and forget why you're there?

Do you have a hard time staying focused?

Or do you just not have the same mental endurance you used to in college?

The good news is, you are not alone.
I see dozens of patients a week, in their 30s, 40s, and 50s, who complain of a lack of mental energy, brain fog, and cognitive issues they can't chock up to a "senior moment".
The not-so-good news is, despite its growing prevalence, this is NOT normal for young to middle-age adults.
But there is a LOT you can do to fix it without resorting to drugs, sugar, or other stimulants.
Get ready to clear your mental cobwebs and boost your brain power, and reset your memory with today's tips on natural ways to improve cognitive function.

Brain Fog Tip #1: Take a nature break at least once a day every day

There have been a lot of studies surfacing lately about the beneficial effects of nature and greenspace for children with attention and other cognitive disorders.

The same rings true for adults.

This peer-reviewed, published study completed by two professors of psychology proved that time spent immersed in nature improved cognition by increasing the creative problem solving abilities of their subjects by a whopping 50%!

Likewise, this report from the University of Michigan demonstrated the restorative benefits of brief encounters in nature, or looking at pictures of natural landscapes, to cognitive function and control.

But the benefits of time spent in greenspace don't stop there. For a full look at all the proven benefits of taking "nature breaks", check out this article from the University of Washington.

Brain Fog Tip #2: Reduce these inflammatory foods
Chronic inflammation is a leading cause of cognitive issues in adults, children, and seniors.
What better way to feed and nourish your brain than cutting back on the foods that add inflammatory fuel to the fire?
Here's a list of the worst inflammatory foods to restrict in your diet

Refined sugar-sugar binds to amino acids in your body to form compounds called advanced glycation end products, or "AGEs" for short, that cause premature aging.

Plus it feeds the "bad" bacteria in your gut which contributes to the "brain fog" so many experience daily.

Refined grains and white potatoes-some people find reducing ALL grains helps them immensely

Alcohol-depresses your memory, immunity, and causes the same effects as sugar

Excess caffeine-coffee and green tea are rich in antioxidants and a cup a day, or a couple cups of green tea is fine, but don't go nuts

Processed foods-are loaded with mind-altering chemicals, loads of sugar, and other unsavory ingredients. Limit them as much as you can.

High-fat foods-as in the ones with refined oils. Instead, stick to moderate amounts of healthy fats like avocados, coconut oil, olive oil, and pastured butter.

Brain Fog Tip #3: Take up a mindfulness practice

I've shared before about how learning mindfulness is what saved me during my health crisis in college.

Mindfulness, the practice of calming and focusing your mind and intention on the task or experience at hand, has been practiced since the beginning of time.

And modern psychological science is starting to catch up to its cognitive benefits.

A variety of published studies prove mindful meditation helps with improving memory, reducing anxiety, increasing focus and concentration, and increasing productivity.

In addition, this study from the American Journal of Hypertension proved mindfulness meditation helps reduce blood pressure. This is significant as imbalances in blood pressure can negatively affect your cognition, no matter what your age.

Brain Fog Tip #4: Grab the right type of nap

I mentioned in a previous post "Help and Hope for the Sleep Deprived" how even a 6-minute nap can improve you long-term memory.

But what's the right type or ideal length of a nap?

Research suggests healthy adults keep their power naps under 30 minutes to maximize the benefits of improved learning, wakefulness, and enhanced overall performance.

Brain Fog Tip #5: Try these brain-boosting supplements

Though there are a lot of products that claim to improve memory and boost cognitive function, these are some of the ones I frequently recommend:

Bacopa-though most of us think "Ginkgo" when it comes to herbs for memory, the Ayurvedic herb Bacopa is backed by an impressive body of research on its ability to enhance cognition by nourishing and protecting our neurons.

Again, just because brain fog is common (especially during the parenting years) doesn't make it normal.

Don't spend years and years functioning at sub-optimal brain power when you could be out living your dreams and changing the world.

With so many easy, natural, and affordable ways to naturally improve your memory, enhance your focus, and boost cognitive function there is no reason to miss out on your best self...

...or keep forgetting why you walked into the kitchen (-:.

-Dr. Alex

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How to Beat Brain Fog and Boost Cognition Naturally - Nourish Medicine

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Do you frequently walk into a room and forget why you're there? Do you have a hard time staying focused? Or do you just not have the same mental endurance you used to in college? The good news is, you are not alone. I see dozens of patients a week, in their 30s, 40s, and ...

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'My heart was racing all night. It felt like a comedown so I knew something was wrong.'

With most drugs, you rarely know the purity of what you're taking. It might be cut with something, it might be a different drug entirely, or it might be a bad batch of whatever you've got.

But there's a certain assumption that study drugs will be safe. Study drugs help you focus and boost your memory, making them ideal for use in the weeks leading up to exams or essay deadlines, or even during a stressful period at work. The most common drugs used in the UK are Modafinil, Ritalin and - if you're feeling more adventurous - the Russian powder Noopept. They're all available to legally buy online, via a prescription.

Sarah, a Pharmacology student at a top London university, regularly buys Modafinil online. She usually buys a batch from a supplier in India, but her last delivery was different. After taking it, she later discovered it had been mixed with PMA, a substitute for MDMA which has killed several people over the past few years.

"My normal Modafinil experience involves a clear mind, focus, a normal heart rate and a normal night sleep at the end of it," Sarah said. "The stuff that came through from India gave me a slight euphoria. The first effects were that I became anxious and started to feel hot.

"It gave me a dry mouth and my heart was racing all night. I didn't get any sleep and it felt like I had a comedown feeling - so I knew something was wrong."

Sarah heard from a friend who had gone through a similar experience when buying Modafinil online. They reported similar palpitations and a feeling that they were over-heating, which they likened to the effects of taking MDMA. Similarly, one of their housemates had concerns about a study drug which she bought from someone inside their student union.

"We wanted to do some detective work so we bought an EZ drug testing kit online for a fiver," Sarah explained.

After running the test, she discovered the 'Modafinil' she had been taking actually contained PMA - often used by dealers as a substitute to MDMA in pill form. Despite having similar effects, it is more poisonous and can kill at lower doses.

She said: "The trouble is that when the Modafinil - or drug you think you bought - doesn't kick in, you take more. This is what happened to me.

"It seems vendors are cutting their Modafinil, arModafinil and Noopept with PMA to maximise their yield. That's certainly what we found out."

Wanting to spread awareness about dangerous batches of Modafinil, Sarah explained: "If a person feels abnormally hot, or stressed, [experience their] heart racing, [or get a] comedown, they've probably been taking PMA/PMMA cut with smart pill."

She added: "Looking into it, PMA has a delayed fuse and kicks in all at once hours later and lasts for a very long time. Serotonins run away, and I could have overheated and died.

"We have since flushed the tablets down the toilet."

---

Names in this article have been changed at the request of the student.
If you've had a drug experience you want to talk about, email [email protected]

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My Modafinil horror story: 'It had been cut with deadly chemical PMA'

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'My heart was racing all night. It felt like a comedown so I knew something was wrong.' With most drugs, you rarely know the purity of what you're taking. It might be cut with something, it might be a different drug entirely, or it might be a bad batch of whatever you've got.

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Microdosing means regularly taking very small doses of psychedelic substances such as LSD or psilocybin (magic mushrooms) over a period of weeks or months. The practice has made countless headlines over the past couple of years, with claims it can improve health, strengthen relationships, and increase productivity.

These claims are surprising because microdosers take doses so small there are no noticeable effects. These can be just 1/20th of a typical recreational dose, often every three or four days. With such small amounts, microdosers go about their daily business, including going to work, without experiencing any typical drug effects.

Previous research suggests microdosing may lead to better mood and energy levels, improved creativity, increased wisdom, and changes to how we perceive time.

Read more: LSD 'microdosing' is trending in Silicon Valley - but can it actually make you more creative?

But these previous studies have mainly involved asking people to complete ratings or behavioural tasks as one-off measures.

Our study, published today in PLOS One, tracked the experience of 98 users over a longer period - six weeks - to systematically measure any psychological changes.

Overall, the participants reported both positive and negative effects from microdosing, including improved attention and mental health; but also more neuroticism.

What we did

As you would expect, there are many legal and bureaucratic barriers to psychedelic research. It wasn't possible for us to run a study where we actually provided participants with psychedelic substances. Instead, we tried to come up with the most rigorous design possible in the current restrictive legal climate.

Our solution was to recruit people who were already experimenting with microdosing and to track their experiences carefully over time, using well validated and reliable psychometric measures.

Parker Byrd

Each day we asked participants to complete some brief ratings, telling us whether they had microdosed that day and describing their overall experience. This let us track the immediate effects of microdosing.

At the beginning and end of the study participants completed a detailed battery of psychological measures. This let us track the longer-term effects of microdosing.

In a separate sample, we explored the beliefs and expectations of people who are interested in microdosing. This let us track whether any changes in our main sample were aligned with what people generally predict will happen when microdosing.

What we found

There are five key findings from our study.
1. A general positive boost on microdosing days, but limited residual effects of each dose.
Many online accounts of microdosing suggest people microdose every three or four days. The thinking is that each microdose supposedly has a residual effect that lasts for a few days.

The daily ratings from participants in our study do not support this idea. Participants reported an immediate boost in all measures (connectedness, contemplation, creativity, focus, happiness, productiveness and wellness) on dosing days. But this was mostly not maintained on the following days.

However, there was some indication of a slight rebound in feelings of focus and productivity two days after dosing.

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2. Some indications of improvements in mental health
We also looked at cumulative effects of longer term microdosing. We found that after six weeks, participants reported lower levels of depression and stress.

We recruited people who were not experiencing any kind of mental illness for the study, so levels of depression and stress were relatively low to begin with. Nevertheless, ratings on these measures did drop.

This is an intriguing finding but it's not clear from this result whether microdosing would have any effect on more significant levels of mood disturbance.
3. Shifts in attention
The microdosers in our study reported reduced mind wandering, meaning they were less likely to be distracted by unwanted thoughts.

They also reported an increase in absorption, meaning they were more likely to experience intense focused attention on imaginative experiences. Absorption has been linked to strong engagement with art and nature.
4. Increases in neuroticism and some challenging experiences
Not everyone had a good time microdosing. Some participants reported unpleasant and difficult experiences. In some cases, participants tried microdosing just once or twice, then didn't want to continue.

Overall, participants reported a small increase in neuroticism after six weeks of microdosing, indicating an increase in the frequency of unpleasant emotions.
5. Changes do not entirely match people's expectations
People have strong expectations about the effects of microdosing. But when we looked at the specific variables participants most expected would change, these didn't match up with the changes actually reported by our microdosers.

Two of the biggest changes microdosers expected were increases in creativity and life satisfaction, but we found no evidence of shifts in these areas. This suggests the changes we found were not simply due to people's expectations.

What does it all mean?

This complex set of findings is not what's typically reported in media stories and online discussions of microdosing. There are promising indications of possible benefits of microdosing here, but also indications of some potential negative impacts, which should be taken seriously.

Read more: Opening up the future of psychedelic science

It's important to remember this was an observational study that relied heavily on the accuracy and honesty of participants in their reports. As such, these results need to be treated cautiously.

It's early days for microdosing research and this work shows that we need to look more carefully at the effects of low dose psychedelics on mental health, attention, and neuroticism.

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Does microdosing improve your mood and performance? Here's what the research says

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Microdosing means regularly taking very small doses of psychedelic substances such as LSD or psilocybin (magic mushrooms) over a period of weeks or months. The practice has made countless headlines over the past couple of years, with claims it can improve health, strengthen relationships, and increase productivity.