Substance Abuse and Chemical Changes in Human Body
According to the National Survey on Drug Use and Health (NSDUH, 2014), one in every ten American adults above the age of 12 had abused illegal drugs within a period of 4 weeks preceding the research. This in turn translated to 27 million people who had abused drugs, representing more than 10% of the total American population (Center for Behavioral Health Statistics and Quality, 2015). The increase in the incidences of drug abuse in the USA is driven by the continued abuse of marijuana and nonmedical injection of prescription drugs meant to stimulate the endocrine system. Dopamine is one of these essential chemical substances in the brain that is a chemical messenger of the brain responsible for sending pleasure signals. Dopamine also plays a critical part in the process of acquisition of information, memory formation, and abilities of coordination and attention functions. This research presents the how substance abuse influences the chemical changes in the human body.
The highest percentage of those found out to have used drugs in 2014 was because of the continued increase in the use of marijuana as compared to other illicit drugs (Center for Behavioral Health Statistics and Quality, 2015). During the same period, more than 66 million US citizens aged 12 and above were reported as current abusers of tobacco products with the greatest number being the cigarette smoking. On the other hand, more than 139 million people were found out to have abused alcohol within the past month with the binge alcohol users representing more than 80% of the total population sampled. Drug abuse indices chemical compounds in the body that have the potential of interacting with the naturally secreted chemicals in the brain and substances that alter the mind especially those involved in the reward processing center and pathway (Hardey et al., 2020).
Substance abuse is considered as one of the biggest problems in the USA and the rest of the world, considering that it can alter the function of naturally occurring chemicals in the body. When they are induced into the body either through injection or orally, drugs causes the brain to adjust the production of essential chemicals to the level that the normal brain function cannot be possible without the substance, a situation known as dependence. Drug abuse therefore causes chemical imbalance in the brain, resulting in symptoms such as depression, irrational thoughts, swinging moods, and instability in the emotions of the drug abuser. Substance abuse impacts almost all organs in the human body with side effects including the weakened immune system, increased strain in the liver, and problems related to memory. All drugs including marijuana, nicotine, cocaine, alcohol, and alcohol tend to negatively impact the reward circuit of the brain that is the broader component of the limbic system. This area of the brain affects the moods and instincts of the individual. Once drugs target the limbic system, they trigger the flooding of dopamine to the brain, a chemical that functions by regulating the emotions and feelings of pleasure in the brain.
Drug use is always involuntary at the initial stages alters the chemistry of the brain, marked by initiating changes to the ways in which the brain functions, thus interfering with the ability of the individual to make decisions. Drug use often leads to the intense levels of craving and compulsivity, where this behavior turns to dependency of the drug upon consistent use.
Alcohol as one of the illicit drugs has short and long-term effects on the communication pathways in the brain, which in turn adversely affects the cognitive function, moods and the behaviors exhibited buy the user. Lack of alcohol induced-nutrition tends to cause brain damage, while the exposure to alcohol among pregnant women can negatively impact the reward circuit of the brain of the unborn child. Regular abuse of drugs initiate the process of production, absorption, and transmission of less dopamine in the brain, which leads to the consequent chemical imbalance. Before drugs are induced to the brain among addicts, dopamine levels are known to drop to the levels that the individual feels uncomfortable withdrawal symptoms with high levels of craving for the drugs. At this stage, dependence takes precedence, while the user often forced to maintain the high levels in a bid to increase the dopamine levels to avoid these negative withdrawal symptoms.
Addiction occurs quickly with the victim losing control over the dosages as the brain adopts a new normal in the sense that it cannot operate normally without the influence of the drugs. The adverse effects to the brain can heal over time with consistent abstinence, even though some of the damages might not heal completely. Dopamine is a neurotransmitter in the brain, whose normal balance in the brain is highly affected by virtually all drugs in as much as there are other chemical messengers in the brain that might as well be affected. Drugs have both effects of inhibiting the absorption of the chemical messengers and stimulating their production in specific regions of the brain. In nature, these chemical messengers can either be excitatory or inhibitory, which implies that they can stimulate the nervous system or its consequent depression.
Drugs that stimulate the nervous system such as cocaine, methamphetamine, and amphetamines hijack the normal production of the neurotransmitters, leading to their overproduction, while drugs such as ecstasy (3,4-methalynedioxymethamphetamine) inhibit the normal transmission models of these chemical messengers like serotonin. On the other hand, drugs like heroin, opioids, and marijuana that are illegally traded mimic the functioning of the brain chemicals by binding to the receptor sites, causing the activation of neurons in abnormal ways with the eventual result being the disruption of the natural production and transmission of the brain chemicals. Many side effects of drugs on the chemical functioning of the body are turned around whenever the non-prescription drugs are processed from the body within lengthy periods. Most of the drugs present long-lasting impacts to the brain chemistry with the damage to the cells producing dopamine and the nerve cells containing serotonin being the common adverse effects following chronic exposure of the brain to the chemical compounds in the drugs.
The receptors in the brain of humans recognize these natural or endogenous chemicals released in the brain including noradrenaline, serotonin, and dopamine and other unnaturally synthesized chemicals that cross the barrier between blood and brain when induced like antidepressants. These non-endogenous chemicals released from drugs work by mimicking the natural chemistry of the body to the level that the brain can recognize and respond to their action. The following figure shows the binding action of endogenous chemicals and non-endogenous chemicals:
Figure 1: Binding action of endogenous chemicals and non-endogenous chemicals. Source
In the figure above dopamine and cocaine are shown to be bounded to the central cavity of the dopamine transporter shown as the gray surface. On one hand, dopamine is released in the brain following the perception of rewar-related behaviors, while on the other, cocaine works as a blocker of the re-uptake of dopamine in such a way that the dopamine is reserved in the brain to maintain the reward feeling. Following its repeated intake of the dopamine reuptake inhibitor, the brain becomes responsive by releasing lower levels of dopamine, where more cocaine will now be required to attain the same reward feeling. Loss of secretion of dopamine is associated with mental diseases like Parkinson’s disease.
Dopamine belongs to the catecholamine family of neurotransmitters in the brain and acts as a precursor to noroadrenaline and adrenaline. The chemical substance is synthesized when the dehydroxyphenyllalanine undergoes decarboxylation, where it is mediated through the myocardial beta-1 adregernic receptors to influence processes such as increase in the heart rate and force levels with the consequent increase in the levels of cardiac output. The chemical structure of dopamine is as shown below:
In the synthesis of the amine above, a carboxyl group is removed from a molecule of its precursor chemical levodopa and 1-3,4-dihydroxyphenylalanine, and amino acid that is synthesized in the normal brain and is synthesized from phenylalanine, and essential amino acid. Dopamine is readily available in the food consumed, even though it does not have the ability of crossing the blood-brain barrier surrounding and protecting the brain. Its synthesis is therefore relegated to the brain, where it performs its neurological functions. The following is the general synthetic pathway that happens in the brain during the synthesis of dopamine.
Figure 3: Sythesis of dopamine. Source: https://www.barnardhealth.us/human-brain/i-anatomical-distribution-in-the-central-nervous-system.html
Several dopamine-containing pathways are located in the central nervous system. The cells that secrete dopamine convert tyrosine as a non-essential amino acid found in food to L-DOPA in the presence of the rate-limiting enzyme tyrosine hydroxylase (TH), with the L-DOPA being converted to dopamine. Under basal conditions the enzyme TH is saturated by tyrosine. However, the intake of drugs tends to block the activity of the enzyme at greater levels, which in turn affects the dopamine levels at extracellular levels in a rate limiting step for the dopamine synthesis.
Drugs lead to dopamine inactivation, which is a process that is reached through the combination of steps such as enzymatic catabolism and reuptake. Dopamine reuptake depends on energy as well as the presence of sodium and chloride. Cocaine and other stimulants of the brain exert their effect through increasing the levels of dopamine by inhibiting the reuptake of dopamine, where high levels of dopamine accumulate in the synaptic cleft. The following figure shows how cocain blocks dopamine transportors, which in turn results in the inhibition of the reuptake of the chemical compound in the brain with the reported increased levels.
Figure 4: How cocaine blocks the dopamine transporters
Dopamine transporters are membrane-spanning proteins with the ability of pumping the neurotransmitter dopamine out of the synaptic cleft into the cytosol. The reuptake of this dopamine via the dopamine transporters us the major process in which the dopamine can be cleared from the synapses (Heard et al., 2008). The functioning of the dopamine transporters calls for the binding of the co-transport and two Na+ ions and a single Cl– sequentially with the substrate of dopamine. The force of drive in the reuptake of this is the gradient of ion concentration that is generated by the plasma membrane. Cocaine influences the gradient of ion concentration along the plasma membrane by binding to the proteins such as the voltage gated ion channels.
The cocaine affinity is varied for each target protein and can be assigned quantities that are quantified by Ki for the transporters and Kd for the binding proteins. The quantities of the target protein and their concentration have significant meanings with low levels of Ki or Kd implying that the protein has high levels of affinity of the cocaine (Heard et al., 2008). On the other hand, the concentrations near Ki or Kd implying that the concentration-binding curve slope is steep in the sense that small alterations in the concentration might result in large alterations in the amount of cocaine under interaction with the protein. Whenever the concentrations become more than 10-fold below the Kd, there will be limited sites that would be occupied with the maximum effect for the receptor occurring. The table below shows the interactions between the concentration and activity for drug:
Figure 5: Curve portraying the relationship between the concentration and activity for a drug.
The determination of Ki and Kd values is in vitro, where it is not translatable to in vivo occupancy of the receptor and they tend to allow a room for making comparisons of the receptor occupancy at any stipulated concentration of the drug (Heard et al., 2008).
References
Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: results from the 2014 National Survey on Drug Use and Health. HHS Publication No. SMA 15-4927, NSDUH Series H-50. Retrieved from https://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf. Accessed: [27 June, 2019).
Hardey, S., Thomas, S., Stein, S., Kelley, R., & Ackermann, K. (2020). Drug Abuse and Chemical Imbalance in the Brain: Dopamine, Serotonin & More. New York: American Addiction Center . Retrieved from https://americanaddictioncenters.org/health-complications-addiction/chemical-imbalance Accessed: [27 June, 2020].
Heard, K., Palmer, R., & Zahniser, N. R. (2008). Mechanisms of acute cocaine toxicity. The open pharmacology journal, 2(9), 70. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703432/ Accessed: [27 June, 2019).