Utilization Of Pharmacology To Enhance Intelligence

Introduction

Cognitive Enhancement has been an eternal pursuit by mankind. Like William Shakespeare quoted in Hamlet, “There’s Rosemary, that’s for remembrance…” it is well known that ancient Greek scholars would wear wreaths of Rosemary to improve their memory while taking exams. In fact, research by Nematolahi et al. from Kerman University of Medical Sciences has shown that Rosemary, in small doses, can boost prospective and retrospective memory.

Enhancing intelligence is no more just science fiction. As we keep on learning more and more about how our brain works, it is very likely for mankind to develop drugs that enhance our cognitive functions. Well, such pharmacological fixes, or in simpler terms, drugs, do exist. They go by many names – Smart Drugs, Nootropics or Neuroenhancers. Drugs that are mainly prescribed for dementia in Alzheimer’s and for ADHD disorders, are sought by intellectually intact to enhance their learning and memory. These drugs increase concentration and attention and hence should inevitably lead to better learning. Need to complete that 2000-word essay of ‘Can Pharmacology make you smarter’ by morning? Need to memorize every cardiovascular drug and its side effects? Then pop Ritalin (methylphenidate) or Adderall (amphetamine) or Provigil (modafinil). If not, you can always rely on the trusted companion – caffeine! We live in a world where we must be bigger, better and faster, making it inevitable for many people to fall back on CNS stimulants. However, enhancing learning and memory is one thing. But does it make us smarter? Smartness is more associated with how much ease one can contemplate complex ideas rather than the more common academic parameters like IQ or SATs. But haven’t we frequently confused ‘smarter’ as ‘faster’?

How does memory work?

One of the most complex structures in the universe, the human brain, is the seat of memory. There are different types of memories like the ‘Long-term memory’ or the ‘Short-term memory’ or ‘Sensory memory’. These three types of memory form the basis of a widely acknowledged Atkinson – Shriffin Model (The Stage Theory) that proposes that the information is processed and stored through these three stages. The cerebral cortex plays a key role in memory, thought, language and attention. The parietal, occipital and temporal lobes are responsible for integrating sensory information from external stimuli while the frontal lobe plays an important part in processing short-term memories and retaining long-term memories. Deep inside the medial temporal lobe lies the Hippocampus, Amygdala, Thalamus, Hypothalamus which are of particular importance to processing of memory. Information transmission (during memory encoding or retrieval) in the brain generally takes place by electro – chemical signals. Neurotransmitters like Glutamate, GABA, Acetylcholine, Dopamine, Serotonin, and etc. relay signals. Dementia, clinically opposite to neuro-enhancement, is caused by degeneration of the neurons. For example, in Alzheimer’s, widespread degeneration and damage is seen in the hippocampus – which is essential in memory formation.

For Alzheimer’s disease, most medications are directed towards increasing acetylcholine at the sites where neurons transmit messages – drugs known as acetylcholinesterase inhibitors prevent enzymes from breaking down acetylcholine. It is exactly such drugs, that when taken up by healthy individuals, result in cognitive enhancement.

Neuroenhancers and their mechanism of action

A variety of drugs come under the category of Neuroenhancers. The main aim of these drugs is cognitive enhancement by improvising a person’s memory, attentiveness or concentration. Most of these drugs are prescribed for Attention Deficit Hyperactivity Disorder or Alzheimer’s disease. For example, methylphenidate, commonly known as Ritalin, is prescribed for ADHD or similarly Adderall, which is a combination drug of two forms of amphetamines. One possible reason for the growing use of these drugs is that they may improve cognitive abilities such as learning and executive functions through their effects on catecholamine neurotransmission.

Amphetamines/Mixed Amphetamine Salts (MAS)

Noradrenaline (NA), one of the most important members of the catecholamine family, is responsible for alertness, readiness for action and vigilance. Administering Amphetamine results in release of NA and it effectively prevents it’s uptake. Being structurally similar to NA, Amphetamine enters the nerve terminal via the NA transporter (NET) and further enters the synaptic vesicles via vesicular monamine transporter (VMAT), in exchange for NA. The NA, thus, accumulates in the cytosol, which then escapes the nerve terminal via NET in exchange of amphetamine - the released NA acts on postsynaptic receptors. Amphetamine also inhibits the uptake of NA via NET.

A study by Irena Ilieva, J. Boland and M. Farah, on the cognitive enhancing effects of MAS on healthy individuals showed that there was no overall enhancing effect of MAS on cognitive performance. The selected dose was a standard clinical dose of MAS that is commonly used for cognitive enhancement. The cognitive enhancement effects of MAS were tested on 13 tasks like face recognition, word recall, SAT verbal and SAT math amongst others. The test had sufficient power to detect any medium-sized effect on MAS on cognitive performance. However, the study did not find enhancement on any of the 13 measures tested.

Methylphenidate

Methylphenidate acts by blocking NET and Dopamine Transporter (DAT) resulting in inhibition of NA and dopamine uptake and hence, elevated concentration of these neurotransmitters in the synaptic cleft. Unlike Amphetamine, it does not enter the nerve terminals.

Despite the increasingly widespread use of Methylphenidate as a cognitive enhancer, the evidence of the same has been difficult to establish and researchers have had contradicting results for the same. C. Klinge, et al. , carried out a study to understand the effects of Methylphenidate on implicit learning (learning that occurs without a person’s awareness; for e. g. , naturally occurring language acquisition). Implicit cognitive tests included a priming task (wherein prior exposure to a stimulus influences response to a later stimulus) and a contextual cueing task (which involves locating a target stimulus from ‘distractor’ stimuli) amongst others. The study showed that a low dose of methylphenidate (10mg) enhanced implicit learning; however, there was no evidence to show that there was enhancement in any of the explicit learning measures that were tested.

Furthermore, S. Batistela, et al. , also studied the cognitive enhancing effects of methylphenidate on healthy young people. The study was carried out on doses of 10mg, 20mg, 30mg & 40mg and the subjects were tested for

1. ‘Visual Attention Test’ (includes selective attention, divided attention – to respond to multiple stimuli and sustained attention),
3. ‘Digit – Span – Forward’ (temporary storage of acoustic information),
5. ‘Corsi Blocks’ (temporary storage of visual and spatial information)
7. ‘Operational Span task for words’ (relates the contents of the working memory to the already stored long – term memory) amongst other tests.

The study also carried out analysis of Bodily Symptom Scale (BSS) that corresponds to different bodily symptoms and participants are asked to mark an appropriate score on the scale based on how they were feeling before and after taking the drug.

No significant difference was observed between the placebo and the drug groups for all the tests measured and all the groups exhibited a similar response. However, higher doses of methylphenidate (30mg & 40mg) seemed to improve the general wellbeing of the participants by a marginal score.

A study by Volkow et al. showed that Methylphenidate decreases the amount of glucose needed by the brain to perform a cognitive task by as much as 50% resulting in a more efficient brain. However, this effect is visible when the neuronal resources are non – optimally distributed i. e. focused elsewhere or are adversely affected as in ADHD or in healthy individuals after sleep deprivation. However, the authors concluded that there was no benefit of the drug if the neuronal resources were already optimally distributed i. e. in healthy and intellectually intact individuals.

Modafinil

Modafinil is an approved drug to treat excessive sleepiness, in case of narcolepsy. Modafinil works by inhibiting the dopamine uptake by DAT and hence ensuring increased extracellular dopamine levels. Franke et al. studied the effects of Modafinil on healthy individuals for cognitive enhancement in chess – a game requiring highly advanced cognitive skills. The evaluation was carried out on two scales – the score of each game (win/loss/draw) and the time required for each game. The study found that Modafinil increased the average reflection time as compared to the placebo during the middle phase of the game (the most complex phase). Increased reflection time led to a much better quality of the game (slower, but accurate responses) suggesting that the players were willing to spend more time on decision making. However, this came at a cost – time constraint. The average reflection time decreased again towards the end of the game as players feared to lose the game over time restrictions. The authors, thus concluded that Modafinil may enhance performance when there is no time limit, but it could be detrimental when a task has time constraints.

Muller et al. studies the effects of Modafinil on non – verbal cognition, task enjoyment and creative thinking on healthy volunteers through certain neuropsychological tests from the CANTAB (Cambridge Neuropsychological Test Automated Battery – a computer based cognitive assessment system which examines various functions like general learning, working memory, visual memory, attention and reaction time and decision making). The study reported a clear performance improvement in the most difficult stages of the test, which suggested towards the fact that Modafinil improved alertness in healthy individuals. However, it did not improve the performance in creativity tests.

Donepezil

Donepezil, an acetylcholinesterase inhibitor, was the first drug to gain widespread patient use. It is indicated for mild to moderate Alzheimer’s disease (AD). Donepezil inhibits acetylcholinesterase enzyme which otherwise breaks down Acetylcholine (Ach). The increased concentration of Ach in the synaptic cleft is thought to increase cognition in AD patients.