study drugs

Question 1

What are study drugs?

Answer 1

Prescription-based psychostimulants used to enhance aspects of cognitive function in healthy individuals.

Question 2

What is the definition of psychostimulants?

Answer 2

A broad class of psychoactive substances that can increase, for example, wakefulness and aspects of cognitive performance (e.g. attention, working memory).

Question 3

Name some examples of psychostimulants.;

Answer 3

Drugs of abuse (cocaine, methamphetamine) as well as prescription drugs (Ritalin).

Question 4

What are some natural substances that fall under the category of psychostimulants?;

Answer 4

Caffeine and coca leaves (used for increasing wakefulness).

Question 5

What is caffeine primarily used for?

Answer 5

Increasing wakefulness and performance enhancement.

Question 6

What are some traditional uses of caffeine?;

What are some modern uses of caffeine?;

What is coca primarily used for?

Answer 6

Used in coffee for thousands of years for its stimulant effects.

Now used in newer products such as gum to improve cognitive performance.

; Stimulant effects.

Question 7

What were some common uses of cocaine in the 19th century?

Answer 7

In the west, cocaine was widely used in the second half of the 19th century in coca wines, cigarettes, medicines, and even coca cola.

Question 8

What is Khat used for in Yemen?;

When does the usage of Khat date back to?

Answer 8

It is used as a social mainstay and even given to children to help them study.

The usage of Khat dates back to at least the 11th century.

Question 9

What is the traditional usage of Ephedra in Chinese medicine?;

What was Ephedra used for in the early 1900s?;

Answer 9

Ephedra has been used in traditional Chinese medicine for around 500 years.

It was used to fight fatigue and prevent sleep deprivation-related performance in US fighter pilots.

Question 10

What is the modern association of Amphetamines?

Answer 10

Amphetamines have a modern association with performance enhancement.

Question 11

Why was Benzedrine synthesized in the early 1900s?;

Answer 11

Benzedrine was synthesized as an alternative to Ephedra.

Question 12

what did a worldwide survey on study drugs users reveal?;

How does the trend of study drug use vary between age groups?;

Answer 12

-The survey revealed that a vast majority of people had never used study drugs, but among those who did, more used it for cognitive enhancement rather than medical purposes.

-The trend of study drug use varies between age groups.

 62% of all users reported taking Ritalin, 44% reported taking Modafinil, 15% reported taking beta blockers (propranolol)
 The most common alternative study drug was Adderall
 Most popular reason for taking the drugs was to improve concentration
 A close second was improving focus for a specific task – although difficult to distinguish from concentration
 A range of other reasons were also provided, including managing jet lag

Question 13

what did the UK survey assess

Answer 13

 Large-scale survey of pharmacological cognitive enhancement (PCE) among 877 students in the UK and Ireland

 Showed relatively low number of uses of the study drugs investigated (methylphenidate, modafinil, Adderall and caffeine pills)

Question 14

What dopaminergic pathways do study drugs target

Answer 14

• Mesocortical pathway: cognitive control, motivation and emotion
• Mesolimbic pathway: reward
• Both project from VTA and to the frontal cortex (mesocortical) or to regions of the limbic system
  (mesolimbic)

 Study drugs also target the Noradrenaline pathway
- Fight or flight, energy and focus

Question 15

what does the inverted U-shaped dose-effect curve represent?; T

Answer 15

The inverted U-shaped dose-effect curve is a graphical depiction of the cognitive effects of psychostimulants – also termed the optimal arousal theory (see image)

 Increasing cognitive activation as psychostimulant dose increases, initially produces wakefulness and cognitive enhancement

 As dose increase, a sense of power and euphoria can ensue, these are the effects addicts seek and are accompanied by cognitive deficits

 Higher doses can result in overdose, psychosis, coma and eventual circulatory collapse

 This shows that moderate arousal is beneficial to cognition but too much arousal leads to cognitive impairment

Question 16

1. METHYLPHENIDATE (RITALIN)

Answer 16

 First introduced in 1957 to treat a number of ailments e.g. sleepiness, nasal congestion

 Today it is primarily used as a treatment for ADHD but can also be used as a treatment for narcolepsy

 Leads to a non-competitive block in DAT and NET = dopamine and noradrenaline not taken up into pre-synaptic neurone = accumulate in the synaptic cleft = post-synaptic receptor activation

Question 17

What are the human and rodent studies on this

Answer 17

***Rodent studies:
 Showed dose-dependent increase in extracellular levels of dopamine and noradrenaline in prefrontal cortex
 Higher doses increase dopamine in nucleus accumbens
 Other studies have shown that lower doses improve cognitive performance, whereas higher doses impair cognitive performance – specifically spatial working memory
 This can be reversed with D1 receptor antagonist or a2-receptor antagonist – suggests that Ritalin improves performance by increasing availability of DA and NA which stimulates D1 and a2 receptors

***Human studies:
 PET studies support dopamine and noradrenaline as critical to the mechanism of action of Ritalin
 Accordingly, Ritalin blocks DAT and causes an increase in extracellular dopamine concentration
 Dose leading to 70% DAT occupancy causes more than 80% NET occupancy which supports the importance of noradrenaline in therapeutic effects of the drug

Question 18

2. ADDERALL

Answer 18

 A combination of amphetamine and dextroamphetamine salts (isomers)

 Prescribed for ADHD in the US but not in the UK
 Adderall is competitively reuptaken by DAT, NET and less commonly SERT

 It then accumulates in the presynaptic terminal and degrades the pH gradient needed for dopamine and noradrenaline transport

 Leads to the accumulation of the neurotransmitters in the presynaptic terminal
 This can cause the reversal of the transporter (due to a switch in concentration gradient) and/or the removal of the transport from membrane – done by the interaction of Adderall/amphetamine with trace amine-associated receptor 1 (TAAR1)

Question 19

what are the rodent studies on adderall

Answer 19

Rodent studies:
 Studies using amphetamine on rodents to measure their freezing behaviour in response to a buzzer sound
 Results showed that lower doses can improve cognitive performance whereas moderate-high doses can impair cognitive performance; specifically, associative memory

Question 20

What does modanafil do

Answer 20

 First used as a treatment for narcolepsy in the UK but used for obstructive sleep apnoea and shift-work sleep disorder in the US
 Tested for other conditions including ADHD and depression
 A clear mechanism yet to be established but primary action is thought to effect dopamine and noradrenaline signalling
 May directly interact with D1/2 postsynaptic receptors but primary evidence suggests that its primary action is through inhibition of DAT
 This was supported by a study showing that Modafinil reduces the spontaneous firing rate of dopamine neurones in control mice whilst not affecting dopamine neurones of mutant mice insensitive to DAT blocker cocaine
 Acts on subcortical structures – thalamus, hypothalamus, amygdala – involved in the activation and maintenance of wakefulness
 Has been shown to increase extracellular levels of serotonin, glutamate, histamine and orexin and decrease extracellular levels of GABA

Question 21

How can we evaluate the effectiveness of study drugs?

Answer 21

 It has been proposed that cognitive performance is at its highest based upon optimal concentrations of dopamine and noradrenaline in the brain
 Individual differences in baseline dopamine levels effects how the drug impacts your cognitive performances

see image

Question 22

What did the metanalysis show on modanafil

Answer 22

 Meta-analysis has shown that Modafinil has an overall positive effect on attention for well-rested individuals – done by Repantis in 2010
- Also showed that Modafinil maintains wakefulness, memory and executive functions to a significantly higher degree in sleep deprived individuals than placebo
- However, repeated doses of Modafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation through maintaining wakefulness

Question 23

What did the metanalysis show on ritanil

Answer 23

 Same study also looked at Ritalin and the meta-analysis showed that Ritalin has an overall positive effect on memory performance – particularly spatial working memory but no other consistent evidence for other enhancing effects were found (e.g. attention)
 However, other meta-analyses conducted by Linssen in 2014 have shown that the effects of Ritalin are less clear on specific aspects of cognitive performance
- Single doses of Ritalin showed an improvement in cognitive performance in the health population in the domains of working memory (65%) and speed of processing (48%), with potential improvements in verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%)
- No effect reported on visual learning and memory
- All effects are dose-dependent and differ between cognitive domains