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The effect of addiction drugs on Neurotransmitters and Cardiac Enzymes levels in Thi-Qar Province

Ali Jabbar Hasab Al-Sadawy1, Mohannad Abdul Razzaq Gati2

1-2Thi-Qar University, College of science, Iraq Email: [email protected]

Abstract

The current study aims to study the effect of the anesthetic drug Captacon on the neurotransmitters (Acetylcholine and Epinephrine) and cardiac enzymes (Troponin and Creatine kinase). Where the research took a study of groups of young people present in popular cafes, in addition to another group of people detained in the Department of Drugs and Psychological Account in Nasiriyah and accused of using and consuming narcotic substances. A total of 128 samples were taken, as the sample collection period extended from November 2020 to March 2021 in Thi Qar province, Where they divided into two groups, the first group was divided into adults and adolescents, their number 88 drug users distributed among 60 adults and 28 adolescents. And the second group is not users of any kind of narcotic their number 40 control group. Blood samples were collected from the abused subjects and the control, where the ELISA test was performed on the serum to check the levels of acetylcholine and epinephrine in the abusers and Control, The tests were also conducted on cardiac enzymes, which are both troponin and creatine kinase the results showed that there are significant differences in the abused people, and this explains that the drug Captacon affects the neurotransmitters and cardiac enzymes directly.

Keywords: drugs, Neurotransmitters, Cardiac Enzymes levels

Introduction

Addiction is defined as a chronic, relapsing disorder characterized by compulsive drug seeking and use despite adverse consequences. It is considered a brain disorder, because it involves functional changes to brain circuits involved in reward, stress, and self-control [1].

Drugs can be categorized by the way in which they affect our bodies:

Depressants: slow down the function of the central nervous system.

Hallucinogens: affect your senses and change the way you see, hear, taste, smell or feel things.

Stimulants: speed up the function of the central nervous system.

Narcotics or opioid: are drugs that are used medically for pain relief but that have strong addictive potential

Some drugs affect the body in many ways and can fall into more than one category. For example, cannabis appears in all 4 categories [2]. Stimulants speed up the messages between the brain and the body. This can cause: your heart to beat faster, your blood pressure to go up, your body temperature to go up leading to heat exhaustion or even heat stroke, reduced appetite, agitation, sleeplessness, you can feel more awake, alert, confident or energetic.

Larger doses can cause anxiety, panic, seizures, stomach cramps and paranoia. Examples include: amphetamines (speed and ice), caffeine, cocaine, ecstasy (MDMA), nicotine (tobacco) [3]. Amphetamine is a powerful stimulator of the central nervous system.

It is used to treat some medical conditions, but it is also highly addictive, with a history of abuse [4]. Amphetamines are prescribed for the treatment of conditions such as narcolepsy (a sleep disorder) and Attention Deficit Hyperactivity Disorder (ADHD), while these are legal forms of amphetamine, the misuse or recreational use of these medications is illegal [5].

Long-term misuse of amphetamines can lead to serious problems, including changes to the brain, cardiovascular damage, malnutrition and anxiety and paranoia [6], amphetamine a group of drugs whose principal members include amphetamine and methamphetamine.

However, a range of other substances also fall into this group, such as methcathinone, fenethylline, ephedrine, pseudoephedrine, methylphenidate and MDMA or ‘Ecstasy’ an amphetamine-type derivative with hallucinogenic properties [7]. Fenethylline (captagon) is in the family of drugs known as amphetamines. These drugs are human-made but are

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chemically related to natural neurotransmitters like dopamine and epinephrine (adrenaline).

When a person takes Captagon, their metabolism breaks the drug down to amphetamine (24.5%), as well as to theophylline(13.7%), a molecule that naturally occurs in small amounts in tea and that also has cardiac stimulating activity (Ghiabi, 2018). Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of 'captagon' [8]. Stimulants like captagon have profound effects on the and cardiovascular system; they may lead to congestive cardiomegaly, cardiac chambers and valvular fibrosis, effects of captagon include vascular hypertrophy, interstitial fibrosis, microvascualr changes (hypertrophy) of the tunica media of the arteries, Accelerated atherosclerosis has also been observed in relation to captagon use [9]. Captagon stimulates the central nervous system, increasing alertness, concentration ability, and physical performance while providing a feeling of well‐being and appetite suppression, due to its fenethylline structure and its chemical resemblance to natural neurotransmitters, like Acetylcholine and adrenaline. It causes dilation of bronchial vessels, and elevation of heart rate, body temperature, respiration, and blood pressure in small to moderate doses [10]. The present study to study the effect of Captagon on some neurotransmitters (Acetylcholine and Epinephrine) and cardiac enzymes (Troponin and Creatine kinase) in addicted and compare it with healthy group.

Materials and methods

The study carried from November 2020 to March 2021in Thi Qar province, A total of 128 samples were a collection from of groups of young people present in popular cafes, in addition to another group of people detained in the Department of Drugs and Psychological Account in Nasiriyah and accused of using and consuming narcotic substances, Where they divided into two groups, the first group was divided into adults and adolescents, their number 88 drug users distributed among 60 adults and 28 adolescents. And the second group is not users of any kind of narcotic their number 40 control group. Urine samples were collected and vein blood samples from people suspected of taking Captagon drug where 4 ml of blood samples were drawn placed in the Gel tube. The urine samples were placed in a Blain Tube.

We began to conduct the test on urine samples, where we put the cassette for detecting the presence of drugs in the body in the urine, and if the result is positive, we run the tests on the blood samples collected and put the blood sample collected in the gel tube in the centrifuge at a speed of 3000 rpm for 10 minutes, where the serum is extracted and frozen at -20 Cº for the purpose of conducting biochemical tests (Troponin and Creatine kinase) and ELISA test (Acetylcholine and Epinephrine), but if the result appears negative, meaning that the person does not use any type of drug, the sample is ignored. The statistical package for social science (SPSS) version used in the current study to analyze data and the results expressed as (Mean±SE.). Independent sample Chi-square-test used to determine the statistical differences by consideration P-value ≤ 0.05 was statistically significant.

Results

Concentration of Acetylcholine and Epinephrine in two Categories Patients and control The current results indicated that the concentration of Acetylcholine and Epinephrine recorded non-significant differences between patients Categories (Adult and adolescents), while a significant difference between both patients groups and control at P. value < 0.05.

Table 1: Concentration of acetylcholine and epinephrine in two categories patients and control

Parameters Groups

Mean + SD

Acetylcholine Epinephrine

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Adolescent 10.8 ± 3.8b 105.7 ± 25.7b

Adult 9.87 ± 2.9b 99.3 ± 27.9b Control 2.94 ± 1.4a 22.3 ± 8.9a

P. value < 0.01 < 0.01

LSD NS / 1.38/1.15 NS / 11.3 /

9.3

Figure 1: Concentration of acetylcholine and epinephrine in two categories patients and control

Concentration of Troponin, and C. kinase, in two Categories Patients and Control The results of current study showed that their where a significant difference was detected in concentration of troponin between adolescent patient and with both adult and control, and non-significant difference was detected between adult patients and control. The C. kinase was recorded a significant difference between patient categories and with control at P. value <

0.05.

Table 2: Concentration of Troponin and C kinase in two Categories Patents and Control Parameters Groups

Mean + SD Troponin µg/L

C. Kinase U/L

Adolescent 0.24 ±

0.15b 11.8 ± 3.8b Adult 0.10 ± 0.06a 13.9 ± 4.1c Control 0.08 ± 0.02a 8.92 ± 2.6a P. value < 0.01 < 0.01

LSD 0.04/0.04/N

S

1.65 /1.78/

1.47

Figure2: A: Concentration of C. kinase in two Categories Patients and Control

0 50 100 150

Adolescent Adult

Control 10.8 9.87

2.94

105 99.3

22.3 Acetylcholine

Epinephrine

0 2 4 6 8 10 12 14

Adolescent

Adult

Control 11.8

13.9

8.92

C. Kinase

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Figure 2: B: Concentration of Troponin in two Categories Patients and Control Discussion

Neurotransmitters

The current results indicated that the concentration of Acetylcholine recorded non-significant differences between patients groups, while a significant difference between both patients groups and control. The present study agreed with the study conducted by [11] in USA, where he studied the effect of cocaine on a group of neurotransmitters, including acetylcholine, and concluded that when cocaine is used, the concentration of acetylcholine increases. Through the results, I reached a conclusion similar to that reached by [11], as Captagon works similarly to cocaine, as he concluded that the effects of cocaine include local vasoconstriction and central nervous system stimulation. Cocaine prevents neurotransmitter (dopamine, norepinephrine, serotonin, and acetylcholine) reuptake at presynaptic nerve terminals, thereby increasing the amounts of neurotransmitters available for stimulation of sympathetic nerves, I agree with that reason because Captagon does the same job. The current results exhibited that the concentration of Epinephrine recorded a non-significant differences between patients, while a significant difference between both patients groups and control.

The present study agreed with the study conducted by [12] in Netherlands, who studied the effect of cocaine on epinephrine and concluded that cocaine has a positive effect on the level of epinephrine. Through the results, I reached a conclusion similar to that reached by [12], as Captagon works similarly to cocaine, as he concluded that hypothesize that the noradrenergic system mediates the effects of epinephrine on behavioral sensitization to cocaine.

Noradrenergic signaling would then be expected to play a critical role in behavioral sensitization to psycho stimulants, as epinephrine is rapidly secreted in response to these drugs , in support of this hypothesis, it has been shown that α-1 adrenergic receptors play a role in cocaine and amphetamine, as these narcotic substances increase the level of epinephrine.

Cardiac enzymes

The results of current study demonstrated that their where a significant difference was detected in concentration of troponin between adolescent patient and with both adult and control, and non-significant difference was detected between adult patients and control. The

0 0.05 0.1 0.15 0.2 0.25

Adolescent Adult

Control 0.24

0.1

0.08 Troponin

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cocaine on the cardiovascular system and concluded that cocaine has a positive effect on the heart and blood vessels. The current study also agreed with the study conducted by [14] in Israel, where he studied the effect of cocaine on the heart and concluded that cocaine affects positively on the heart. An elevation of troponin in adolescent may be the cause of myocardial toxicity, as Captagon drugs contains toxic chemicals that can lead to myocarditis or myocardial infarction in advanced stages, or perhaps stress and hyperactivity in adolescent can cause elevated troponin. As for adults, they may have a subclinical cardiac injury, as they may have future cardiac injuries [13]. The C. kinase was recorded a significant difference between patient categories and with control. The current study agreed with the study conducted by [15] in New York, where he studied the effect of heroin on rhabdomyolysis and concluded that heroin positively affects muscles, including cardiac muscles, and raises the level of creatine kinase. The current study also agreed with the study conducted by [16] in USA, where he studied the effect of drug use on cardiac muscles and concluded that drugs positively affect the heart muscles and raise the level of creatine kinase, and this is in line with the findings of this study. This could explain the increase in the enzyme creatine kinase, as the drug Captagon may affect the muscles, as it causes damage to the muscles, especially the cardiac muscles, and may lead in the future to myocardial infarction or rhabdomyolysis [15].

Conclusions

1- Most captagon abusers are adults, ages 18 to 35 years old.

2- Captagon increases levels of the neurotransmitters acetylcholine and epinephrine.

3- Captagon affects cardiac enzymes, troponin, and creatine kinase levels, and raises their levels.

4- Captagon does not affect blood parameters.

5- The lack of strict control and the absence of clergy and bad friends is the reason for the spread of Captagon and the difficulty of controlling its spread.

References

1. Singh, J., & Gupta, P. K. (2017). Drug Addiction: Current Trends and Management.

International Journal of Indian Psychology, 5(1).

2. Moeller, S., Huttner, H. B., Struffert, T., & Müller, H. H. (2016). Irreversible brain damage caused by methamphetamine. Alcoholism and Drug Addiction, 29(1), 39–41.

3. Koob, G. F. (2008). A Role for Brain Stress Systems in Addiction. Neuron, 59(1), 11–

34.

4. Al-Imam, A. (2017). Adverse Effects of Amphetamines on the Cardiovascular System: Review and Retrospective Analyses of Trends. Global Journal of Health Science, 9(11), 102.

5. Schifano, F., Corkery, J. M., & Cuffolo, G. (2007). Smokable (“ice”, “crystal meth”) and non smokable amphetamine-type stimulants: Clinical pharmacological and epidemiological issues, with special reference to the UK. Annali Dell’Istituto Superiore Di Sanita, 43(1), 110–115.

6. Pietschmann, T., & Publication, U. N. (2011). Amphetamines and ecstasy. United Nations Publication.

7. Alhazmi, H. A., Ahsan, W., Al Bratty, M., Javed, S. A., El-Sharkawy, K. A., Khalid, A., Alsalem, H. M., Hakami, A. M., Attafi, M. A., & Oraiby, M. E. (2020). Analysis of amphetamine and methamphetamine contents in seized tablets from Jazan, Saudi Arabia by liquid chromatography-mass spectroscopy (LC-MS/MS) and chemometric techniques. Saudi Pharmaceutical Journal, 28(6), 703–709.

8. Report, T. big old, Matfess, H., & Miklaucic, M. (2016). Beyond Congvergence:

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World Without Order. Beyond Convergence: World without Order, 275–296.

9. Al-Imam, A. (2017). Adverse Effects of Amphetamines on the Cardiovascular System: Review and Retrospective Analyses of Trends. Global Journal of Health Science, 9(11), 102.

10. Twark, C., & Suzuki, J. (2017). Fenethylline-Induced Psychosis, Fenethylline- Themed Paranoid Delusions, or Both? Psychosomatics, 58(5), 561–564.

11. Esse, K., Fossati-Bellani, M., Traylor, A., & Martin-Schild, S. (2011). Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard. Brain and Behavior, 1(1), 44–54.

12. De Jong, I. E. M., Steenbergen, P. J., & De Kloet, E. R. (2009). Behavioral sensitization to cocaine: Cooperation between glucocorticoids and epinephrine.

Psychopharmacology, 204(4), 693–703.

13. Riley, E. D., Hsue, P. Y., Vittinghoff, E., Wu, A. H. B., Coffin, P. O., Moore, P. K.,

& Lynch, K. L. (2017). Higher prevalence of detectable troponin I among cocaine- users without known cardiovascular disease. Drug and Alcohol Dependence, 172, 88–

93.

14. Shemesh-Darvish, L., Shinar, D., Hallak, H., Gross, A., & Rosenstock, M. (2018).

TV-1380 attenuates cocaine-induced changes in cardiodynamic parameters in monkeys and reduces the formation of cocaethylene. Drug and Alcohol Dependence, 188(December 2017), 295–303.

15. Abdullah, M. S., AL-Waili, N. S., Butler, G., & Baban, N. K. (2006). Hyperbaric Oxygen as an Adjunctive Therapy for Bilateral Compartment Syndrome, Rhabdomyolysis and Acute Renal Failure after Heroin Intake. Archives of Medical Research, 37(4), 559–562.

16. D’Anci, K. E., Allen, P. J., & Kanarek, R. B. (2011). A potential role for creatine in drug abuse? Molecular Neurobiology, 44(2), 136–141.

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