Maldarizzi Clara, Vibi Gisella
Definition
Neuroenhancement refers to the use of drug medication to enhance certain brain processes in healty persons who do not have any mental illness. Neuroenhancement drugs are not specifically designed to improve cognitive performance of healthy individuals, but are used to treat patients with mental disorders and are being abused by normal individuals.
The abuse of neuroenhancement drugs without clinical consent poses a pressing issue. Today, we do not have enough information to conclusively say that neuroenhancements drugs have a positive effect on healthy individuals.
Neuroenhancers' classification
Cognitive doping can include lifestyle drugs, prescription drugs and illicit substances; most of them are primarily designed and used for the treatment of some diseases.
- Lifestyle drugs:
- Coffee;
- Energy drinks, containing substances such as caffeine, B vitamins, ginseng, ginkgo biloba, L-carnitine and antioxydants;
- Omega-3 fatty acids.
The advantage of this classification is twofold. Firstly it allows for a much more faceted view of the phenomenon, secondly it allows for describing multiple neuroenhancement substance abuse. This is relevant, as lifestyle drugs may pave the road for later prescription drugs or illicit substances. In fact, compared to non-users, lifestyle drug users were more likely addicted to the polydrug use.
(Subjective stressors in school and their relation to neuroenhancement: a behavioral perspective on students’ everyday life “doping”, 2013)
Molecular mechanism
Neuroenhancers exert their therapeutic effects especially increasing dopamine and norepinephrine levels in the synapses. These neurotransmitters play essential roles in attention and thinking. It may be an artifact to attempt to attribute unique functions to each neurotransmitter since they collaborate in facilitating many cognitive and affective functions. Both agents contribute to maintaining alertness, increasing focus and motivation. Norepinephrine and Dopamine are structurally very similar, differing only in the presence of a hydroxyl group.
(Functional Roles of Norepinephrine and Dopamine http://www.medscape.org/viewarticle/523887)
Dopamine is a neurotransmitter that plays an important role in higher cognitive function and has essential action on prefrontal cortical function.
It is synthesized in brain cells and adrenal cells from the precursor L-DOPA. In brain cells, it is transported to synaptic sites and packaged into vesicles for release after an action potential, which occurs during synaptic transmission. Once in the synapse, dopamine binds to and activates dopamine receptors, which can be located either on postsynaptic target cells or on the membrane of the dopamine-releasing cell itself. After release, the dopamine molecules quickly become unbound from their receptors and dopamine is either reabsorbed into the presynaptic terminal for reuse, or broken down by the enzymes "Monoamine oxidase" (MAO) or “Catechol-O-methyl transferase” (COMT), producing a variety of degradation metabolites.
Studies find that the effect of neuroenhancers like Metilphenidate, Modafinil and Cocaine on the central nervous system is the blockage of the dopamine transporter protein called DAT, which normally removes dopamine from the presynaptic neuron, in this way they operate as Dopamine reuptake inhibitors (DRI). It is also proved that Methylphenidate stimulates the release of this neurotransmitter into the synapse. Accordingly, it leads to an increase in extracellular and thus synaptic concentrations of dopamine.
(Fisiologia Medica - Fisiologia degli organi e dei sistemi; Autore: Grassi; Curato da: Conti Fiorenzo; Editore: Edi. Ermes; Volume: 1; Data di Pubblicazione: 2010
Dopamine http://en.wikipedia.org/wiki/Dopamine)
Norepinephrine is a catecholamine with multiple roles, including as a hormone and a neurotransmitter. It is the hormone and neurotransmitter most responsible for vigilant concentration and cognitive alertness, as its most chemically similar hormone, dopamine. As a stress hormone, norepinephrine affects parts of the brain, such as the “Amygdala”, where attention and responses are controlled. Norepinephrine also underlies the fight-or-flight response, along with epinephrine, directly increasing heart rate, triggering the release of glucose from energy stores, increasing blood flow to skeletal muscle and increasing the brain's oxygen supply. Norepinephrine is synthesized from dopamine by “Dopamine β-hydroxylase enzyme” in the secretory granules of the medullary chromaffin cells, during the transformation, norepinephrine is transported into synaptic vesicles. This is accomplished by "vesicular monoamine transporter" (VMAT) in the lipid bilayer. It is released from the adrenal medulla into the blood as a hormone, and is also a neurotransmitter in the central nervous system and sympathetic nervous system, where it is released from noradrenergic neurons.
The actions of norepinephrine are carried out by the binding to adrenergic receptors. To perform its functions, norepinephrine must be released from synaptic vesicles.
An action potential reaches the presynaptic membrane, which changes the membrane polarisation, Calcium ions thus enter, resulting in vesicular fusion, releasing norepinephrine. Norepinephrine performs its actions on the target cell by binding to and activating adrenergic receptors.
In mammals, norepinephrine is rapidly degraded to various metabolites. The principal metabolites are:
- Normetanephrine (by the enzyme “Catechol-O-methyl transferase”, COMT)
- 3,4-Dihydroxymandelic acid (by “Monoamino oxidase”, MAO)
- Epinephrine (by “Phenylethanolamine N-methyltransferase”, PNMT)
- Vanillymandelic acid or VMA (by MAO), the major metabolite of catecholamines in the periphery, excreted unconjugated in the urine.
Studies find that Neuroenhancers are Norepinephrine reuptake inhibitors (NRI) by blocking the action of the norepinephrine transporter NET. This in turn leads to increased extracellular concentrations of norepinephrine and therefore an increase in adrenergic neurotransmission.
In fact, Neuroenhancers are commonly used in the treatment of conditions like ADHD and narcolepsy due to their psychostimulant effects, many drugs of abuse such as Cocaine and Methylphenidate possess NRI activity, though it is important to mention that NRIs properties, without combined "Dopamine reuptake inhibitor" (DRI), are not significantly rewarding and are considered to have a negligible abuse potential. However, Norepinephrine has been implicated as acting synergistically with dopamine when actions on the two neurotransmitters are combined to produce rewarding effects in psychostimulant drugs abuse.
(Fisiologia Medica - Fisiologia degli organi e dei sistemi; Autore: Grassi; Curato da: Conti Fiorenzo; Editore: Edi. Ermes; Volume: 1; Data di Pubblicazione: 2010
Norepinephrine http://en.wikipedia.org/wiki/Norepinephrine
Adrenergic Receptor http://en.wikipedia.org/wiki/Adrenergic_receptor)
Side effects
Since most of the information on neuroenhancements and its capabilities are drawn from research experiments, the best way to determine adverse effects are subjective ratings as no other method exists to measure the adverse effects. Each type of neuroenhancer has its own side effects.
The adverse effects of lifestyle drugs are:
- Anxiety
- High blood pressure, associated with an increase in strokes, and cerebral vascular diseases;
- Reduced control of fine motor movements (e.g. producing shaky hands);
- Increased cortisol secretion;
- Insomnia;
- Headache.
In the drug trials, participants reported the following adverse reactions to the consumption of prescription drugs:
- Nausea;
- Headache;
- Dizziness;
- Nightmares;
- Anxiety;
- Drowsiness;
- Nervousness;
- Restlessness;
- Sleep disturbances;
- Insomnia.
The sides effects of illicit drugs are various; in case of cocaine they include:
- Lethargy;
- Psychosis;
- Depression;
- Akathisia;
- Itching;
- Tachycardia;
- Hallucinations;
- Paranoid delusions;
- Hyperthermia;
- High blood pressure;
- Arrhythmias;
- Death.
Ethical and Social Issues
A common concern raised is an unfair advantage of people who consume enhancing drugs over people who don’t. Many people, however, feel that the only way to compete with people that take performance enhancing drugs is to take those as well. Students, in particular, often feel that cognitive neuroenhancers are acceptable.
Parents and healthcare providers however are concerned about the safety of those that consume neuroenhancers. When asked if children under the age of 16 should be restricted from taking these drugs, most respondents (86%) said that they should. But one-third of respondents said they would feel pressure to give cognition-enhancing drugs to their children if other children at school were taking them. These numbers strongly suggest that even if policies restricted their use by kids, pressure would be high for parents.
Some people think that it would be useful to submit students before a test to blood and urine analysis to find out if they have taken any neuroenhancers.
(Poll results: look who's doping, 2008)
Students and Neuroenhancement
Prescription drugs used in the treatment of brain disorders, including Alzheimer's disease, attention deficit hyperactivity disorder (ADHD) and narcolepsy, boost dopamine, norepinephrine and acetylcholine in the brain, improving alertness and attention. This could give these "plus" students an unfair advantage. However, the majority frowned on their use in competitive situations, such as university entrance exams. Competition seems to cloud student’s judgment, and push them to a point where it seems "immoral" not get any and every possible advantage.
(Brain doping, 2007)
In 2008, the Medical journal "Nature" launched an informal survey into readers' use of cognition-enhancing drugs. The study found a wide use and a mix of attitudes towards the drugs.
They asked specifically about three drugs: Methylphenidate, Modafinil and Beta blockers. Respondents who had not taken these drugs were directed straight to a simple questionnaire about general attitudes. Those who revealed that they had taken these drugs for non-medical purposes, were asked several additional questions about their use. Here's what the study found out: among the students, one in five used drugs for non-medical reasons to improve concentration, focus or memory. In fact, household surveys suggest that stimulant use is highest in people aged 18–25 years, and in students.
For those who choose to use, Methylphenidate was the most popular: 62% of users reported taking it, 44% reported taking Modafinil and 15% said they had taken Beta blockers.
| Drug | % |
|---|
| Methylphenidate | 62 |
| Modafinil | 44 |
| Beta blockers | 15 |
Furthermore, all participants who took part in the survey were asked 10 questions about their attitudes towards neuroenhancing drugs. Almost all respondents (96%) thought people with neuropsychiatric disorders should be given cognition-enhancing drugs. But a high four-fifths thought that healthy adults should be able to take the drugs if they want to. And 69% reported that they would risk mild side effects to take such drugs themselves.
Another research found out that also others mild neuroenhancers are used widely, for example, coffee is used by 53.2% of the students, and energy drinks by 39% of the students.
(Poll results: look who's doping, 2008)
References
- Poll results: look who's doping, 2008
- Brain doping, 2007
- Subjective stressors in school and their relation to neuroenhancement: a behavioral perspective on students’ everyday life “doping”, 2013
- Neurologist: Test students for smart drugs, 2010
