**Influence of Drugs on Cognitive Functions**

**Influence of Drugs on Cognitive Functions**

DOI: 10.5772/intechopen.71842

Claudia Juárez-Portilla, Tania Molina-Jiménez, Jean-Pascal Morin, Gabriel Roldán-Roldán and Rossana Citlali Zepeda Jean-Pascal Morin, Gabriel Roldán-Roldán and Rossana Citlali Zepeda Additional information is available at the end of the chapter

Claudia Juárez-Portilla, Tania Molina-Jiménez,

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.71842

#### **Abstract**

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Disorders related to the misuse of certain drugs represent not only a worldwide public health problem, but also an economic and social issue. Adolescents and children represent the most vulnerable population for drug consumption and addiction. At this early stage in life, a crucial phase of the neurodevelopmental process, substance abuse can induce brain plasticity mechanisms that may produce long-lasting changes in neural circuitry and ultimately behavior. One of the consequences of these changes is the impairment of cognitive functions, with academic negative impact in the acquisition of new knowledge. In this chapter, we will describe the effects of illicit substances of abuse, both stimulants and depressants as well as prescription drug misuse and its influence of on learning and memory processes. Recent evidence on the new so-called smart drugs is also discussed.

**Keywords:** abuse, cognition, performance, nootropic, smart, stimulants, depressant, memory, impairment, adolescent

#### **1. Introduction**

According to United Nations Office on drugs and Crime, in 2015, around a quarter of a billion people used drugs, and approximately 29.5 million showed drug use disorders, including dependence [1]. Drug abuse produces health disruption. Disorders related to the use of certain drugs are associated with an important worldwide rate of morbidity. A wide range of druginduced neurobiological modifications have been described; some of which can affect learning and memory functions. Stimulant drugs, like nicotine and amphetamine, improve cognitive function at lower doses but impair memory performance at higher doses. Depressant drugs, like alcohol, can cause long-term effects on prefrontal cortex function, disrupting cognitive abilities.

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

Several studies have suggested that the influence of psychoactive drugs on learning and memory might be explained, at least in part, because of the shared neurobiological mechanisms involved in learning and memory processes and the drug-induced structural and functional changes in the brain. Anatomically, there is an important overlap between the neural substrates of learning and memory and those of addiction. Some of the areas that show overlap include the cerebral cortex, hippocampus, amygdala and striatum [2]; all of them are components of the mesolimbic dopaminergic system.

Adolescence is a sensitive period in brain development characterized by a decrease in gray matter and an increase in white matter. The diminution of gray matter is thought to be due, at least in part, to the process of synaptic pruning, which is the developmental refinement of brain circuits by removal of superfluous synapses [3]. Early drug exposure is associated with frontal lobe damage, low cognitive performance and emotional learning, as well as other behaviors. Moreover, it has been demonstrated that adolescent exposure to both prescription and social drugs impairs cognition, as well as other behaviors, in the adulthood [4].

There is a clear bidirectional relationship between abuse of drugs and poor academic achievement. It has been suggested that cognitive deficits could make adolescents more vulnerable to substance abuse than others; conversely, other proposals argue that substance abuse is the source of cognitive impairments [5–7]. Of course the two possibilities are not mutually exclusive; teenagers with poor academic performance may be more prone to abusing illicit drugs, which may impair their results at school even further. While the several social science theories have been proposed to try to explain each of these phenomena [6], in the following text, we will focus on the cognitive consequences of adolescent substance abuse on the functioning of the nervous system that may have a deleterious impact on cognitive abilities, academic achievement and long-term satisfaction with life in general.

> When nicotine is administered acutely, it produces positive effects improving cognitive functions, including sustained attention, vigilance, visuospatial selective attention, spatial working memory and associative memory, both in animal models [10] and in humans [11]. Conversely, a vast amount of literature has showed that chronic nicotine use leads to tolerance, and 1 h after cessation of nicotine exposure, nicotine withdrawal syndrome emerges and it is characterized by mild cognitive deficits. In other words, nicotine tends to improve cognitive function at lower doses and impair performance at higher doses [12]. Furthermore, heavy smokers under acute abstinence from smoking experience decreased neurocognitive functions, including impairments in sustained attention, working memory and response inhibition [13]. Strong activation of memory-related brain regions that include the dorsolateral prefrontal cortex and hippocampus has been correlated with smoking-related cues in adult heavy smokers [14].

**Effect Model Reference**

Monkey Rat Mice Zebrafish Human

Influence of Drugs on Cognitive Functions http://dx.doi.org/10.5772/intechopen.71842

> Human Rat

[10, 11]

61

[13, 25–27, 29]

Human [37, 38, 41,

Human [39, 61–67]

55–57]

Improving selective visuospatial attention, spatial working memory and associative

Mild deficits in memory and inhibition

Disruption in prospective and visual memory, verbal ability, reasoning and decision making

Facilitation in working memory, verbal fluency

Impaired working memory, verbal fluency and

Disruption in working and episodic memory, consolidation memory, attention and memory

Some reports have shown that nicotine and nicotinic agonists, as mecamylamine, evoked cognitive enhancement by potentiating the release of dopamine [12, 15]. Working memory is critically reliant on dopaminergic neurotransmission. In addition, rodent studies have revealed a direct relationship between dopamine release in the prefrontal cortex and on memory task accuracy [16]. Moreover, cholinergic systems and nicotinic receptors are essential for cognitive processes and have been implicated in diseases associated with cognitive impairment [17].

These areas are involved in emotional learning and reward-related learning.

**Drug Cognitive** 

Stimulant drugs Attention

Depressant drugs Attention

**process**

Vigilance Memory

Memory

*Acute*:

memory

*Chronic*: Tolerance

response

*Acute/low doses*:

and executive functions

Also, presence of blackouts

executive functions

*Chronic/high doses*:

**Table 1.** Effects of the stimulants and depressant drugs in cognitive functions.

Withdrawal syndrome

## **2. Stimulant drugs**

Memory is the natural counterpart of learning; both are necessary for behavioral change that precedes survival of species. Substance abuse has been demonstrated to exert detrimental impact upon learning and memory. According to the United Nations Office on Drugs and Crime through World Drug Report 2017, 29.5 million people globally suffer from drug use disorders [8]. Cognitive impairment is a well-established consequence of long-term substance abuse, with stimulants as nicotine, methamphetamine (MA) and cocaine leading deficits in the area of executive function. Stimulants are a class of illicit drugs that can have negative impact on individuals who use them, although this impact might be masked by the believed benefits (**Table 1**) [9].

#### **2.1. Nicotine**

Nicotine is the main psychoactive component of tobacco and the responsible agent of tobacco dependency. According to the World Health Organization, despite its severe health consequences, about one billion people smoke worldwide.


**Table 1.** Effects of the stimulants and depressant drugs in cognitive functions.

Several studies have suggested that the influence of psychoactive drugs on learning and memory might be explained, at least in part, because of the shared neurobiological mechanisms involved in learning and memory processes and the drug-induced structural and functional changes in the brain. Anatomically, there is an important overlap between the neural substrates of learning and memory and those of addiction. Some of the areas that show overlap include the cerebral cortex, hippocampus, amygdala and striatum [2]; all of them are

Adolescence is a sensitive period in brain development characterized by a decrease in gray matter and an increase in white matter. The diminution of gray matter is thought to be due, at least in part, to the process of synaptic pruning, which is the developmental refinement of brain circuits by removal of superfluous synapses [3]. Early drug exposure is associated with frontal lobe damage, low cognitive performance and emotional learning, as well as other behaviors. Moreover, it has been demonstrated that adolescent exposure to both prescription

There is a clear bidirectional relationship between abuse of drugs and poor academic achievement. It has been suggested that cognitive deficits could make adolescents more vulnerable to substance abuse than others; conversely, other proposals argue that substance abuse is the source of cognitive impairments [5–7]. Of course the two possibilities are not mutually exclusive; teenagers with poor academic performance may be more prone to abusing illicit drugs, which may impair their results at school even further. While the several social science theories have been proposed to try to explain each of these phenomena [6], in the following text, we will focus on the cognitive consequences of adolescent substance abuse on the functioning of the nervous system that may have a deleterious impact on cognitive abilities, academic

Memory is the natural counterpart of learning; both are necessary for behavioral change that precedes survival of species. Substance abuse has been demonstrated to exert detrimental impact upon learning and memory. According to the United Nations Office on Drugs and Crime through World Drug Report 2017, 29.5 million people globally suffer from drug use disorders [8]. Cognitive impairment is a well-established consequence of long-term substance abuse, with stimulants as nicotine, methamphetamine (MA) and cocaine leading deficits in the area of executive function. Stimulants are a class of illicit drugs that can have negative impact on individuals who use them, although this impact might be masked by the believed

Nicotine is the main psychoactive component of tobacco and the responsible agent of tobacco dependency. According to the World Health Organization, despite its severe health conse-

and social drugs impairs cognition, as well as other behaviors, in the adulthood [4].

components of the mesolimbic dopaminergic system.

achievement and long-term satisfaction with life in general.

quences, about one billion people smoke worldwide.

**2. Stimulant drugs**

60 Health and Academic Achievement

benefits (**Table 1**) [9].

**2.1. Nicotine**

When nicotine is administered acutely, it produces positive effects improving cognitive functions, including sustained attention, vigilance, visuospatial selective attention, spatial working memory and associative memory, both in animal models [10] and in humans [11]. Conversely, a vast amount of literature has showed that chronic nicotine use leads to tolerance, and 1 h after cessation of nicotine exposure, nicotine withdrawal syndrome emerges and it is characterized by mild cognitive deficits. In other words, nicotine tends to improve cognitive function at lower doses and impair performance at higher doses [12]. Furthermore, heavy smokers under acute abstinence from smoking experience decreased neurocognitive functions, including impairments in sustained attention, working memory and response inhibition [13]. Strong activation of memory-related brain regions that include the dorsolateral prefrontal cortex and hippocampus has been correlated with smoking-related cues in adult heavy smokers [14]. These areas are involved in emotional learning and reward-related learning.

Some reports have shown that nicotine and nicotinic agonists, as mecamylamine, evoked cognitive enhancement by potentiating the release of dopamine [12, 15]. Working memory is critically reliant on dopaminergic neurotransmission. In addition, rodent studies have revealed a direct relationship between dopamine release in the prefrontal cortex and on memory task accuracy [16]. Moreover, cholinergic systems and nicotinic receptors are essential for cognitive processes and have been implicated in diseases associated with cognitive impairment [17].

#### **2.2. Methamphetamine (MA)**

MA abuse represents a serious public health issue associated with a high likelihood of relapse. By 2008, nearly 25 million people worldwide were estimated to have used MA, with abuse being among younger age groups [18]. MA used is mainly for recreational purposes and it is known to induce a variety of desirable effects, including increased energy levels, positive mood, euphoria, reduced appetite, weight loss, enhanced mental acuity and social and sexual disinhibition [19]. In addition, MA-dependent individuals often claimed enhancement of cognitive function and ability to focus following drug administration. However, this drug induces long-term changes in the brain structure and function, changes in synaptic plasticity, cell death via apoptosis and neurotoxicity, and consequently, it causes dependence and withdrawal syndrome [20].

control tasks in cocaine addicts [30]. These brain areas may be involved in the maintenance and relapse of drug use [31]. Individuals with cocaine abuse and dependence show higher insula, frontal and/or striatum activation in response to cocaine-related cues, reflecting heightened attention in response to this drug [32, 33]. Furthermore, imaging data have revealed that gray matter volume loss over time is twice as fast among cocaine addicts as in healthy individuals. Given that gray matter volume in prefrontal cortex has been related to working memory performance, these findings are in keeping with the idea that long-term cocaine use may cause

Influence of Drugs on Cognitive Functions http://dx.doi.org/10.5772/intechopen.71842 63

Adolescence is the critical period for initiation of alcoholic beverage consumption. Epidemiologic studies reveal that alcohol use is remarkably common among teenagers, with increasing rates of alcohol abuse in the US including heavy episodic drinking [33]. After alcohol and tobacco, marijuana is the social drug most frequently consumed by this cohort. Additionally, a high percentage of alcohol abusers also consume marijuana [34]. Several studies have shown that both alcohol and marijuana tend to alter the structure and function of the brain and are associated with impaired decision-making, memory and impulsivity in young adults and adolescents

Evidence shows a direct correlation between early onset of alcohol intake and alcohol-related problems in adulthood, suggesting that adolescent exposure to the reinforcing properties of this drug increases the probability of its abuse later [35]. However, as for other addictive substances, the effect of exposure to alcohol depends to a great extent on how much and for how

Acute alcohol intake has a biphasic effect on brain activity, causing excitation and euphoria at low blood concentration and depression as it increases [36]. However, regarding cognitive functions, experimental data have been inconsistent using a variety of cognitive tests. Thus, low or moderate doses of alcohol, relative to placebo, produced facilitation [37, 38], deficits [39] or no change [40] in memory performance at subtoxic amounts (<65 mg/dl). Moreover, it apparently does not produce adverse effects and may even slightly improve working memory in nonproblem drinkers, regardless of sex [41]. However, as the dose of alcohol increases, confusion, loss of awareness and selective attention begin to occur, significantly diminishing the execution of working memory and its long-term consolidation. The effect of alcohol on long-term memory formation is much greater than its impact on the capacity to remember previously consolidated memories or to retrieve short-term memory. It is well known that if subjects are asked to repeat newly acquired information following short delays (seconds) after its presentation while intoxicated, they often do fine [42]. Likewise, they are able to retrieve information acquired before acute intoxication. On the contrary, subjects perform very poorly using delays longer than 20 min, particularly if they are distracted between the

sustained deleterious effect on working memory.

**3. Depressant drugs**

(**Table 1**).

**3.1. Ethanol**

long it is consumed.

stimulus presentation and testing [43].

Anatomically, MA has a preferential neurotoxic effect on the frontostriatal systems that contributes to both emotion dysregulation and neurocognitive impairment [21]. For instance, MA addicts showed impaired performance on tests of cognitive flexibility, which measures the ability to modify behavior when presented with new information or changing outcomes. These deficits may impair MA addicts from altering their habitual drug abuse behavior, leading to an inability to initiate abstinence or resist relapse [22]. Cellular mechanism of this MA impairment has been associated with long-term downregulation of dopamine transporters, suggesting that there are structural changes in some of the dopamine nerve terminals [23]. Other findings suggest that MA use causes changes in the metabolism of the insula and striatum [24]. In a study in humans, MA-dependent participants had significantly lower results than control participants on memory tasks, including prospective memory and visual memory [25]. Accordingly, studies in young adult MA abusers have shown impaired verbal ability, deficits in psychomotor processing [26], reasoning deficits reflecting problematic decisionmaking abilities as well as retrospective memory task impairment [27].

The evidences pointed that acute administration of MA improves cognitive functions, while chronic consumption of MA deteriorates them.

#### **2.3. Cocaine**

Cocaine has long been one of the most common recreational stimulants, especially for adolescents. A recent estimate indicates that half a million of United States habitants use this drug weekly; in this sense, cocaine addiction represents a substantial burden for societies worldwide, linked to adverse outcomes such as violence, suicide and disability, as well as high rates of chronic relapse [28]. In the brain, crack cocaine use has been shown to cause toxic effects, particularly in the prefrontal cortex. These abnormalities are associated with neuropsychological impairments.

Abundant evidence has shown that cocaine withdrawal induces memory decline after its chronic use. It has been reported that chronic cocaine users showed significant harm on verbal memory and fluency as well as deficits in cognitive flexibility, but not in spatial memory, after acute withdrawal. Further, Briand and colleagues observed that object recognition was disturbed after withdrawal from chronic exposure to cocaine by an object recognition task in 2-week abstinent rats [29]. Several reports have shown that the insular and prefrontal cortices, involved in cognitive control, show reduced activity on selective attention and inhibitory control tasks in cocaine addicts [30]. These brain areas may be involved in the maintenance and relapse of drug use [31]. Individuals with cocaine abuse and dependence show higher insula, frontal and/or striatum activation in response to cocaine-related cues, reflecting heightened attention in response to this drug [32, 33]. Furthermore, imaging data have revealed that gray matter volume loss over time is twice as fast among cocaine addicts as in healthy individuals. Given that gray matter volume in prefrontal cortex has been related to working memory performance, these findings are in keeping with the idea that long-term cocaine use may cause sustained deleterious effect on working memory.
