Running head: EFFECTS OF METHAMPHETAMINE 1

12EFFECTS OF METHAMPHETAMINE

Neurological, Psychological, and Social Effects of Methamphetamine AbuseKristen BrownNortheastern University

Authors NoteThis paper was prepared for the Honors course in Foundations of Psychology

Abstract

Methamphetamine is an addictive psychostimulant whose popularity has grown in recent years in part due to the lasting high it produces. The drug, however, has also been found to negatively impact several aspects of its users lives. A surge of research on the effects of methamphetamine has been conducted in the past decade to investigate the consequences of meth abuse. Particular areas of interest include methamphetamines mechanism of action, its impact on the body and brain, its psychological impact, and the effects it has on meth users children. This research has uncovered new knowledge, but more time is necessary to assess whether the consequences are lasting.

Neurological, Psychological, and Social Effects of Methamphetamine Abuse

In the past few decades, methamphetamine has surged past cocaine and heroin in popularity, with 25 million people abusing the psychoactive stimulant worldwide (Panenka et al., 2012, p.168). Meth is widely used because it is relatively cheap, can be made at home, and produces a high that can last for days. There are, however, numerous negative consequences associated with meth abuse beyond its addictiveness. These consequences are not yet fully understood, but meth is known to impact mental health, brain functioning, multiple organ systems, and behavior of the user. Furthermore, it affects the children of parents that abuse or manufacture the drug in their homes (Abar et al., 2013, p.1). With meth use on the rise and the rescue of dozens of children from clandestine methamphetamine labs across the United States, recent research has focused on meths mechanism of action, lasting effects on the brain and body, psychological effects, and impact on unborn and living children of meth abusers. Though some questions remain, researchers have learned much about the way methamphetamine interacts with the body to produce pleasurable feelings. After ingestion through inhalation, injection, or digestion, meth quickly crosses the blood-brain barrier because it is lipophilic (Rusyniak, 2011, p.263; Vocci & Appel, 2007, p.101). It then binds to transporters of norepinephrine, dopamine, and serotonin in neurons cell membranes, which pump it into the neuron (Rusyniak, 2011, p.263). Inside the neuronal cytoplasm, meth interacts with the vesicular monoamine transporter 2 (VMAT2), a protein that helps store the neurotransmitters dopamine, serotonin, and norepinephrine in secretory vesicles. This interaction causes the secretory vesicles to release their contents into the neuronal cytoplasm, with norepinephrine released most efficiently, then dopamine, followed by serotonin (Panenka et al., 2012, p.168). Meth also competitively inhibits the reuptake of these monoamines back into the vesicles, which increases their concentration in the synapse and cytosol (p.169). The membrane dopamine transporter can send dopamine into the synaptic cleft by reverse transport, which activates the mesolimbic brain reward system that causes users to feel high (Vocci & Appel, 2007, p.98). By releasing and blocking reuptake of neurotransmitters, meth produces various cognitive effects that can be observed in a users behavior. These effects include increased arousability, intensified emotions, inhibition of cues that control behavior, and interference with interactive communication (Sommers, Baskin, & Baskin-Sommers, 2005, p.1475). Sommers et al. (2005, p.1469) suggest that these changes make meth users more prone to committing acts of violence, but the context of the situation plays a role as well. Meth also results in increased energy, euphoria, and confidence; decreased appetite; and heightened libido (Panenka et al., 2012, p.171). Improved attention and concentration can also result from low to moderate doses of meth (p.171). Because of its 12-hour half-life, meths psychological effects last for hours (Rusyniak, 2011, p.264).Higher doses cause excessive stimulation to occur, which can produce dysphoric feelings with symptoms of restlessness and anxiety that are manifested as tremors and dyskinesia (Panenka et al., 2012, p.171). When users binge for a period of a few days, the euphoric effects diminish while the dysphoria and compulsive behavior increases; bingeing can also cause sleeplessness, hallucinations, and paranoia that are associated with irritability and aggression (p.171). They may exhibit punding, which is focused, repetitive behavior that lacks purpose (p.171). Large, continuous doses of meth can lead to psychosis-like psychological changes, with overlapping schizophrenic symptoms of splendor, delusions, suspiciousness, and hallucinations (p.171). Compared to schizophrenic patients, meth users were more anxious, depressed, and hostile but were less disorganized and socially withdrawn (p.171). With repeated meth use, the brains stores of dopamine are depleted, and dopamine and serotonin nerve terminals are damaged; users may then experience anhedonia, which is an impaired ability to feel pleasure without the drug (Rusyniak, 2011, p.264).People who abuse methamphetamine may also experience deficits in episodic memory, motor function, and executive function (p.264). They become impulsive and easily distracted; they act inappropriately to social cues, lack purpose, and prefer smaller, immediate rewards to greater, delayed ones (p.265). One common delusion is parasitosis or formication, when the person believes that bugs have infested their body and are biting them, known as meth mites; this can cause them to continuously pick at their skin, which leads to scars and greater risk of skin infection (p.266). The combination of teeth grinding, decreased saliva production, and poor oral hygiene causes tooth erosion and dental carries (meth mouth) (p.269). Meth mouth, meth mites, and weight loss combined can dramatically change a meth abusers appearance in a short amount of time, as publicized by anti-meth campaigns before and after images. Meth can certainly influence an abusers cosmetic appearance, but its impact on their internal organ systems can be even more devastating, and perhaps fatal. Meth elicits the release of epinephrine from the adrenal glands, which stimulates the sympathetic nervous system (Panenka et al., 2012, p.169). The heart and lungs must work harder as vasoconstriction and bronchodilation occur (p.169). Muscles prepare for action due to an increase in blood sugar and the dilation of blood vessels within skeletal muscle (p.169). A 200% increase in the stress hormones cortisol and adrenocorticotropic hormone happens, and these elevated levels remain for hours after meth administration. In the long term, this extreme stress on the body can result in chronic hypertension and cardiovascular disease, such as angina, arrhythmias, valve disease, hemorrhagic and ischemic strokes, and a higher incidence of heart attack (p.170). The body loses its ability to maintain normal health because of this allostatic load (p.169).Lung problems, such as bronchitis and pulmonary hypertension, may also result from smoking meth (Panenka et al., 2012, p.170). Meth abuse can damage the liver, which leads to an increase of ammonia, the neurotoxic waste product of protein breakdown, in the body and in the brain (Halpin, 2013, p.3). Malnourishment may also occur because of decreased appetite (Panenka et al., 2012, p.170). Users who inject meth are more likely to contract infectious diseases like HIV and hepatitis C due to needle sharing, risky sexual behavior, and immune system degradation (Frohmader, 2010, p.93; Panenka et al., 2012, p.170). Many users also consume other substances and have confounding psychiatric issues (Panenka et al., 2012, p.171). A large quantity of research has been conducted in the past decade to investigate the lasting effects of methamphetamine abuse on the brain. According to Yu, Chang, & Gean (2013, p.72), repetitive drug taking brings about long-lasting changes in the brain. It also causes the user to compulsively pursue the drug, which they propose is a result of enduring drug memory that prevents the user from cognitively controlling their motivated behavior (p.72). Similarly, Miyazaki et al. (2012, p.1341) reported that chronic exposure to meth causes elements in various parts of the brain to change slowly, which results in drug dependence, sensitization, and psychosis. Adaptive changes in the nucleus accumbens, the link between motivation and action, bring about behavioral sensitization to meth and are responsible for its rewarding effects (p.1341). They found that the synaptic input from dopaminergic and glutamatergic terminals plays an important role in the sensitization and pleasure caused by meth, and that the activation of these systems might be associated with addiction and changes in the brain (p.1348). Figure 1: How Methamphetamine Use Results in Dependence (Miyazaki et al., 2012, p. 1348)

Other studies have demonstrated that heavy methamphetamine use can leave a lasting impact on the structure of the brain itself. Panenka (2012, p.172) and Aoki (2013, p.356) both reported a loss of gray matter in the frontal cortices of meth users when magnetic resonance images of meth users brains were compared to the brains of non-users. In subjects who used meth for 10 years, Panenka also wrote of reduced hippocampal volume, which may explain why meth users experience memory problems (2012, p.174). One study saw an increase in white matter in chronic meth users (p.172). Aoki et al., on the other hand, saw a reduction in white matter volume in the orbitofrontal area of meth users; they suggest that this decrease and the cortical gray matter loss are associated with antisocial traits (2013, p.358). Aoki also found volume decreases in gray matter of the left perisylvian area of the brain (the posterior inferior frontal gyrus and anterior superior temporal gyrus), which is a structural trait seen in schizophrenic patients that could indicate a shared pathophysiology between schizophrenia and methamphetamine abuse (p.358). Additionally, Jernigan et al. (2005, p.1466) witnessed significant increases in all three segments of the basal ganglia, namely the caudate nucleus, lenticular nucleus, and nucleus accumbens, in meth-dependent subjects. Unlike Aoki and Panenka, Jernigan et al. found an increase in the volume of the cerebral cortex, but the only significant increase was in the parietal cortex (p.1467). Another recent study conducted on monkeys by Groman et al. (2013, p.531) saw an increase of gray matter in the right putamen with exposure to meth, and the degree in gray matter change correlated with change in reversal-learning performance, which they believe proves a functional impact of brain structural alteration on inhibitory control. They hypothesized that inflammation caused these changes in gray matter, but did not suggest an exact mechanism for this (p.536). According to Groman et al., the structural integrity of the striatum also experienced lasting changes (p.527). Ahmadlou et al. (2013, p.1122) noted that chronic meth use disrupted the normal Small-World brain network, which interfered with cognitive tasks and information transmission among brain networks.Methamphetamine abuse also alters blood glucose metabolism in the brain, which is a marker of brain function and can be observed by positron emission topography (PET) (p.1129; Volkow et al., 2001, p.383). Halpin et al. (2013, p.3) observed that meth produced a high demand for energy and caused increases in the metabolism of energy in brain regions. They saw evidence of compromised energy metabolism to meet the demand, as well as depletion of energy stores (p.3). Halpin also found that meth induced mitochondrial damage, which caused an even greater negative impact on energy metabolism (p.3). Researchers in another study observed that the whole brain metabolism in meth users was 14% greater than that of non-users, with the parietal cortex most affected (Volkow et al., 2001, p.383). Meth increased the amount of glutamate receptors in the parietal cortex, making it more susceptible to glutamate excitotoxicity (p.387). The thalamus, on the other hand, showed a significantly lower metabolism with a 17% difference, as did the striatum (p.384). Yet another meth-induced change in the brain seen in multiple studies is the damage and loss of nerve terminals (Halpin et al., 2013, p.4; Panenka et al., 2012, p.174; Rusyniak, 2011, p.268). Panenka et al. (2012, p.172) witnessed a 50-61% reduction in levels of dopamine throughout the striatum, as well as decreased levels of dopamine transporters and receptors, also seen by Northrop & Yamamoto (2013, p.956). The caudates levels of dopamine were depleted as severely as seen in some Parkinsons disease patients (Panenka et al., 2012, p.172). Serotonin nerve terminals were also damaged in multiple regions of the brain (p.174; Rusyniak, 2011, p.264). According to Rusyniak (p.264), meth damages neurons because of oxidative stress, neuroinflammation, and excitatory neurotoxicity caused by increases in dopamine concentrations inside and outside of the cell. In addition to terminal damage, meth use can also produce cell death, as seen by Halpin et al. (2013, p.2) in the prefrontal cortex and striatum. Another study looked at the combined impact of meth abuse and stress, discovering that stress exacerbates the terminal damage caused by meth and also produces inflammation in the brain (Northrop & Yamamoto, 2013, p.96). Chronic unpredictable stress also increased meth-induced depletions of monoamines in the hippocampus and striatum (p.97).As previously mentioned, a variety of psychological effects result from the changes methamphetamine causes in the brain, which can manifest into social issues. Panenka et al. (2012, p.172) wrote of the executive function impairment brought about by meth use, which results in poor coping skills, a disorganized lifestyle, and difficulties interacting with other people. Compared to users of other drugs, chronic meth users can also be more impulsive, aggressive, and irritable, with impairments in memory and attention (p.173). They can lose their ability to suppress irrelevant task information and have poor attentional processing (p.172). Similarly, they are less capable of shifting their attention away from formerly relevant, but currently irrelevant stimuli (Marshall & ODell, 2012, p.540). This cognitive impairment does not appear to be permanent, as it can improve over time (Panenka et al., 2012, p.174). Meth is also associated with long-term motor deficits brought about by striatal dopamine innervation loss, and users have deficits in the decision-making process (Chapman et al., 2000, p.520). In response to pleasant stimuli, meth-dependent people had lower brain activation than control individuals, which demonstrates their impaired reward processing (May et al., 2013, p.238). Chronic psychosis similar to schizophrenia, as well as other mental illnesses like anxiety and depression, may also result from abuse of methamphetamine (Rusyniak, 2011, p.262). Individuals with meth-induced psychosis, however, tend to exhibit more anti-social behavior and immorality than schizophrenics (Aoki et al., 2013, p.356). Meth is also associated with a heightened risk of developing Parkinsons disease (Halpin et al., 2013, p.4) and involuntary, uncontrollable movements called choreoathetoid movements (Rusyniak, 2011, p.269). Compared to users of other psychoactive drugs, meth abusers had the highest risk of schizophrenia, and there is a genetic overlap between meth-induced psychosis and schizophrenia (Ikeda et al., 2013, p.1864). Meth-dependent individuals showed considerable impairment in tests of everyday functional ability, mainly in comprehension, finance, transportation, communication, and medication management (Henry et al., 2010, p.593). Interestingly, in one study, meth use appeared to have the least impact on school, work, and finances while 50% of participants reported problems with spouses, lovers, or friends instead (Sommers et al., 2005, p.1474). Meth users are also at risk of other psychosocial issues, including medical and legal problems, risky behaviors that can exacerbate the situation (such as acquiring HIV), and loss of familial support (Panenka et al., 2012, p.167). In a survey of prisoners entering correctional facilities in Wyoming, researchers found a surprising trend that countered their expectations (Roussell, Holmes, & Anderson-Sprecher, 2009, p.1037). Anticipating that more socially disorganized conditions (higher poverty, residential instability, and ethnic diversity) would facilitate more abundant meth use, they actually found that social organization (relatively wealthy, stable, and ethnically homogenous conditions) contributed more to meth use (Roussell et al., 2009). They saw that meth users tended to be young, white, and single, living in houses and typically having a legitimate source of income; users in more rural areas with sparser populations had more severe problems of meth use (p.1038). Roussell et al. (p.1038) hypothesized that meth was more available to them because of the stable social networks and meth suppliers that existed. A different study that analyzed identity management in meth circles of young adults (Green & Moore, 2013, p.695) found that users typically associated their drug consumption with control, responsibility, and autonomy, and distanced themselves from the notion that they were addicts or junkies. Green & Moore (p.698) wrote that the stigmatization of meth may deter young adults from seeking out help because they are ashamed, and it may even cause them to deny that they have a problem.The highest rates of methamphetamine abuse are seen in individuals aged 20 to 29, who often have children (Haight et al., 2005, p.951). According to child welfare workers, children of meth-abusing parents are brought into a rural drug culture with antisocial beliefs and practices, as well as environmental danger, neglect, abuse, isolation, and chaos (p.958). Influenced by their drug-abusing parents, children may start lying, stealing, using drugs, and behaving violently p.961). The children may also be victims of physical, sexual, and emotional abuse; maltreatment is associated with disruptive behavior disorders, attention problems, anxiety disorders, and mood disorders (p.952). They are at higher risk of dropping out of school, early pregnancy, and criminal involvement (p.952). If their home is used as a lab to manufacture meth, they are also at risk of explosions, fire, and exposure to toxic chemicals (p.958). More than half of children removed from home-based meth labs were found to have toxic levels of chemicals in their bodies (Messina et al., 2006, p.2). Another area of related research is the impact of meth on a developing fetus. A pregnant woman who uses meth imparts on her baby a higher risk of spontaneous abortion, premature birth, low birth weight, smaller head circumference, cerebral infarction, and congenital abnormalities (p.5; Haight et al., 2005, p.951). Meth use while pregnant has also been associated with perinatal maternal death (Vearrier et al., 2012, p.59). These problems may result from meths anorexic effect on mothers and the vasoconstriction that interferes with placental blood flow and nutrient delivery to the fetus (Abar et al., 2013, p.7). Affected newborns may show neurologic and physiologic abnormalities, such as poor feeding, tremors, disruptive sleep patterns, decreased arousal, poor quality of movement, and lower grasping scores (Smith et al., 2010). Studies looking at meth-exposed neonates brains saw increased incidence of intraventricular hemorrhage and greater white matter density (Smith et al., 2007, p.26). Chang et al. (2004, p.105) found smaller brain volume in the putamen, globus pallidus, and hippocampus, which is associated with memory and attention deficits. Not much is known about the lasting impact of prenatal meth exposure in the long term, but one study reports significant decrements in cognitive, language, and behavioral functioning in 3-6 year olds (Messina et al., 2007, p.6). Finally, a comparison of meth-exposed infants living in the United States versus New Zealand indicated that children in New Zealand fared better, which Abar et al. (2013, p.1) suggest is due to the countries differing health care systems and philosophies. The recent global increase in methamphetamine use has sparked a great deal of research into its effects on the brain and the body, both physically and psychologically. Much has been uncovered about the immediate and short-term changes meth brings about, but questions remain about its lasting impact on the brain and on children of meth-abusing parents. With time and continued effort, this area of research will hopefully acquire more answers.

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