WHAT MAKES COCAINE SO ADDICTIVE AND DANGEROUS?

Cocaine is a psychoactive alkaloid of the coca plant; it was originally used for local surgeries as an anaesthetic but has now become a recreational drug. Unlike amphetamines, which resemble the structural formula of dopamine and noradrenaline, cocaine has a similar structure to other synthetic sedatives. Cocaine is well absorbed when administered via the mucous membranes, the GI tract and IV route. Peak concentration happens within five minutes after intravenous injection, while the peak levels from smoking are usually reached within 60 minutes. Some cocaine is excreted in urine unchanged, the majority is metabolized into benzoylecgonine, ecgonine methyl ester, norcocaine and other metabolites. Although cocaine has a short half-life, the elimination half-life of the metabolites lasts longer. Studies also show that the half-life of cocaine may increase the longer it is used.

Cocaine acts by enhancing the action of dopamine, it does this by blocking its reuptake into the nerve terminal via the transporter and thus increasing the amount of dopamine available. Dopamine is a neurotransmitter that helps control the brain’s reward and pleasure centres. Dopamine also helps regulate movement and emotional responses. It is a neurotransmitter that projects in many areas of the brain. Physiologically dopamine is involved in many essential functions, these include; cognition, movement and reward. Disruption in the dopaminergic system has been shown to lead to a wide range of symptoms. For example, Parkinson’s disease like symptoms can appear, such as tremors. These symptoms are marked by a change in cognitive function and mood. Studies show that people with low dopamine may be more prone to addiction. The presence of specific dopamine receptors is also associated with sensation seeking people (Verma, 2015).

Cocaine, like other drugs has a euphoric and sustained mood elevation effect on the individuals taking them. This is because cocaine produces its psychoactive and addictive effects on the limbic system.  The limbic system is a series of interconnected system in the brain that regulates pleasure and motivation. An initial short-term effect of taking the drug is euphoria caused by the build-up of dopamine, this causes the desire to take the drug again.  The more dopamine molecules meet the receptors the more the electrical properties of the receiving cells are altered. To keep the cells in each region of the brain functioning at appropriate intensities, neither too high or low, the dopaminergic cells continually increase and decrease the number of molecules they produce.  They further regulate the amount of dopamine by pulling some previously released dopamine into themselves.

 Cocaine interferes with this control mechanism, by tying the transporter molecule that dopaminergic cells use to retrieve dopamine from the surrounding cells. As a result of this, the dopamine that would otherwise be picked up remains in action  (Nestler, 2005). (About Glutamate Toxicity, 2011) found that changes involving genes occur in the limbic system, which is the main site for cocaine effects. The effects are enormous and long lasting and contribute significantly to the transition from drug abuse to addiction. Studies indicate that cocaine affects the expressions of several genes in the brain, including some that influence the important neurotransmitter glutamate and the body’s natural opioid like compounds (Nestler, 2005). Glutamate is a powerful neurotransmitter that is responsible for sending signals between nerve cells. Under normal condition it plays an essential role in learning and memory.

 Cocaine increases energy, self-confidence, promotes talkativeness, alleviates fatigue and enhances mental alertness. At high doses and during chronic use, feelings of euphoria may be replaced with restlessness, excitability, sleeplessness, loss of libido, nervousness, aggression, suspicion and paranoia, hallucinations, delusional thoughts, and large dilated pupils. Chronic cocaine use may lead to a range of cardiac complications. For example, acute myocardial infarction and myocardial ischemia are common. Cocaine blocks the sodium/potassium channels, which induces abnormal depressed cardiovascular profiles.  Use of cocaine together with alcohol increases cocaine levels in the blood. Cocaine stimulates the adrenergic system by binding to norepinephrine transporters. This results in an increased effects of norepinephrine effects on post synaptic receptor sites. Blocking norepinephrine reuptake induces tachycardia and hypertension.  Other studies indicate that the perpetual use of cocaine is associated with an increase of CV complications such as hypertension and coronary spasms.  Heart attack in constant cocaine use is thought to be caused by increased oxygen demand, vasoconstriction of the coronary artery, increased platelet aggregation and thrombus formation. Also, potential arrhythmias and dysrhythmias may occur (Kim & Park, 2019).

Other long-term complications include accelerated atherosclerosis, cardiomyocyte apoptosis, sympathoadrenal-induced myocyte damage, chronic arrhythmias, cardiac hypertrophy and dilated cardiomyopathy. Regular cocaine use has also been associated with many abnormalities in the vascular system of the brain, the most common are, haemorrhagic and thromboembolic strokes. Some people are more vulnerable to cocaine-induced excited delirium, symptoms include hyperthermia, extreme behavioral agitation and in some cases, violent behaviours. This may result in collapse or sudden cardiac death (Roberts, 2007).

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 Illicit use of drugs In Australia
• In 2016, around 3.1 million Australians reported using an illegal drug.
• In 2016, the most common illegal drug was cannabis, followed by misuse of pharmaceuticals, cocaine, and then ecstasy.
• While overall use of methamphetamine has decreased, use of crystal methamphetamine (ice) continues to be a problem.
• People who are using crystal methamphetamine (ice), are using it more frequently which increases the risks and harms.

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Source

Elsevier. (2018, May 31). Cocaine use alters gene expression in brain reward circuits: Study investigates transcriptome-wide alterations in response to cocaine self-administration in mice. ScienceDaily. Retrieved June 20, 2018 from http://www.sciencedaily.com/releases/2018/05/180531102706.htm

Winhusen, T. M., Lewis, D. F., Somoza, E. C., & Horn, P. (2014). Pharmacodynamics Must Inform Statistics: An Example from a Cocaine Dependence Pharmacotherapy Trial. ISRN Addiction, 2014.

About Glutamate Toxicity. (2011, June 26). HOPES Huntington’s Disease Information. https://hopes.stanford.edu/about-glutamate-toxicity/

Kim, S. T., & Park, T. (2019). Acute and Chronic Effects of Cocaine on Cardiovascular Health. International Journal of Molecular Sciences, 20(3). https://doi.org/10.3390/ijms20030584

Nestler, E. J. (2005). The Neurobiology of Cocaine Addiction. Science & Practice Perspectives, 3(1), 4–10.

Roberts, J. R. (2007). Acute Agitated Delirium from Cocaine: A Medical Emergency. Emergency Medicine News, 29(10), 18–20. https://doi.org/10.1097/01.EEM.0000296568.05338.c5

Verma, V. (2015). Classic Studies on the Interaction of Cocaine and the Dopamine Transporter. Clinical Psychopharmacology and Neuroscience, 13(3), 227–238. https://doi.org/10.9758/cpn.2015.13.3.227

What Makes Heroin So Addictive and Dangerous?

   Firstly, it is to do with the way heroin is metabolised. There are two main ways that heroin is metabolised; one of the ways is through the Hepatic First Pass. This is done via the removal of an acetyl group when taken orally. The other way is through injections. Heroin that is administered via this route will evade the Hepatic First Pass and will quickly cross the blood-brain barrier. This is because of the presence of an acetyl group that makes it more soluble to fat. Once, in the brain, the acetyl group is removed, and heroin is reduced to 3-monoacetylmorphine and 6-monoacetylmorphine.

These compounds are reduced to morphine that then bind to opioid receptors that are found in the brain. Opioid receptors are important for autonomic processes of the body such as breathing, blood pressure, pain and arousal. When heroin binds to these receptors, it reduces pain, users of the drug also report a feeling of euphoria, dry mouth and a flush of the skin accompanied with a feeling of heavy extremities (Chetna J. Mistry, 2014). An individual can also develop tolerance to the drug, meaning more quantity of the drug may be needed to achieve the desired effect.

Research indicates that the presence of 6- MAM molecules in the blood after heroin has been reduced, could account for its high metabolism. There is also a noticeable difference in alleles among different ethnic groups. The study that was done on SNPs showed the variant Single nucleotide polymorphism A118G did not show altered binding affinities to most opioid receptors and alkaloids. However, the variant receptor A118G binds beta-endorphin and endogenous opioids that activate the Mu opioid receptors more tightly than the most common receptor (Bond, Gong & Kreek, 1998)

Also, beta-endorphins are more potent at the A118G variant than at the most common allelic forms; this is in the agonist-induced activation of the G proteins that have Potassium on their channels (Ying Zhang, 2005). The study concluded that the SNPs in the Mu receptor could alter the binding and signal transduction of the Mu receptors (Chetna J. Mistry, 2014). This may affect the normal physiology of the body, can impact on the treatment protocol, and can play a part in how individuals deal with diseases.

Studies have also found that there is a common reward pathway for drug addiction and that these addictions usually occur in individuals that are vulnerable both neurologically and genetically. This pathway is in the primitive limbic system. Opioids can affect this pathway by; increasing the postsynaptic sensitivity to dopamine or by increasing the release of dopamine by the neurons (Cherie et al., 1998).

    Heroin is a very addictive drug in that, when injected or taken orally can mimic the body’s endorphin pathway of the CNS.  The endorphins normally activate the bodies opioid receptors. These receptors are found at the surface of the cell membrane, in the Limbic system (controls pain, smell and hunger) where there are numerous. The receptors that heroin binds to influences whether the ion channels will open and, in some cases, influence the excitability of the neuron.

    In addition to this, Heroin, also affect the GABA inhibitory receptors of the ventral tegmental area. When Heroin binds to these receptors, the amounts of GABA is reduced. In normal physiology, GABA reduces the amount of dopamine that is produced in the brain. Prolonged use of the drug will cause the reduction in cAMP. Cyclic AMP is one of the molecules that determine the ability of the neuron to produce electrical impulses; it has been found that the increase in these molecules is what causes cravings in heroin users (Guitart, Thompson, Mirante, Greenberg, & Nestler, 1992).

Effects on Adolescents

    Studies have shown that prolonged use of the drug may cause structural changes to the brain by shrinking or enlarging some parts of the brain. For example, structural MRI has shown that prolonged use of the drug can cause changes to the prefrontal cortex of the brain. The images revealed that the prefrontal cortex had a lower proportion of the white matter, this is also seen in the brains of individuals with psychiatric abnormalities (Fowler, Volkow, Kassed, & Chang, 2007). These findings were correlated with the fact that individuals with these changes in the brain structure had a lower score in Wisconsin’s test. This is the area of the brain that controls logical thinking, goal setting and planning. This could explain why heroin users, which are mainly teenagers, are more likely to engage in high risk behaviours, are withdrawn from society and are aggressive.

Other signs of teenage drug addictions are; cognitive difficulties, short-term memory loss, a reduction in attention span, poor information processing and poor problem-solving skills compared to non-heroin or drug users. Some of the warning signs that a teenager is using drugs are; withdraw, low self-esteem, a sudden drop in the grades at school and when they suddenly start having older friends (Lambie, 2007).

Heroin and Pregnancy

     Heroin is a lipophilic drug, hence the use of the drug in pregnancy can cause a wide range of effects, one of them is Neonatal Abstinence Syndrome (NAS). NAS is a syndrome where the foetus together with the mother become dependent on Heroin. The symptoms are; low birth weight, excessive crying, seizures, and irritability. Children that addicted to the drug also show reduced motor and behavioural developmental issues. They are also at risk of contracting hepatitis if the mother was sharing needles during pregnancy. Current treatment of heroin addiction during pregnancy is the use of methadone (Fajemirokun-Odudeyi et al., 2006). According to the Australian government of health and warfare, NAS is most likely to be found in young Australian women, unmarried and indigenous people (AIHW, 2006).

   There a lot of factors that predisposes an individual to addiction.  Recent studies have found that children from single-parent homes and teens that come from poor families are more likely to use drugs. Also, teens with poor relationships and with a family history of drug addictions are themselves more likely to suffer from drug addiction.  Addiction can also be found in families that have no interest in education and in some cases if there is a history of any abuse, depression and anxiety (CDC, 2020). https://video.wordpress.com/embed/WbZJrztZ?hd=0&autoPlay=0&permalink=0&loop=0

References 

AIHW. (2006). Statistics on drug use in Australia 2006. from http://www.aihw.gov.au/publication-detail/?id=6442467962

CHERIE BOND, K. S. L., MINGTING TIAN, DOROTHY MELIA, SHENGWEN ZHANG, LISA BORG,, JIANHUA GONG, J. S., JUDITH A. STRONG, SUZANNE M. LEAL, JAY A. TISCHFIELD,, & MARY JEANNE KREEK, A. L. Y. (1998). Single-nucleotide polymorphism in the human mu opioid receptor

gene alters b-endorphin binding and activity: Possible

implications for opiate addiction. from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC21386/pdf/pq009608.pdf

Chetna J. Mistry, M. B., Dipika Desai, David C. Marsh, Zainab Samaan,. (2014). Genetics of Opioid Dependence: A Review of the Genetic Contribution to

Opioid Dependence. Current Psychiatry Reviews.

Fajemirokun-Odudeyi, O., Sinha, C., Tutty, S., Pairaudeau, P., Armstrong, D., Phillips, T., & Lindow, S. W. (2006). Pregnancy outcome in women who use opiates. European Journal of Obstetrics & Gynecology and Reproductive Biology, 126(2), 170-175. doi: http://dx.doi.org/10.1016/j.ejogrb.2005.08.010

Fowler, J. S., Volkow, N. D., Kassed, C. A., & Chang, L. (2007). Imaging the addicted human brain. Sci Pract Perspect, 3(2), 4-16.

Guitart, X., Thompson, M. A., Mirante, C. K., Greenberg, M. E., & Nestler, E. J. (1992). Regulation of Cyclic AMP Response Element-Binding Protein (CREB) Phosphorylation by Acute and Chronic Morphine in the Rat Locus Coeruleus. Journal of Neurochemistry, 58(3), 1168-1171. doi: 10.1111/j.1471-4159.1992.tb09377.x

Lambie, G. W., & Davis, K. M.,. (2007). Adolescent Heroin Abuse: Implications for the Consulting Professional School Counselor. Journal of Professional Counseling, Practice, Theory, & Research.

Megan Wood. (2004). Illicit drug use in australia from http://www.studnets.adelaisehs.sa.edu.au/subjects/issues/illictdrugs.pdf

Ying Zhang, D. W., Andrew D. Johnson, Audrey C. Papp and Wolfgang Sadée. (2005). Allelic Expression Imbalance of Human mu Opioid Receptor (OPRM1) Caused by Variant A118G*. Journal of biological chemistry.

CDC. (2020, April 30). Data and Statistics About Opioid Use During Pregnancy | CDC. Centers for Disease Control and Prevention. https://www.cdc.gov/pregnancy/opioids/data.html