Prescription Drug Addiction

Non-Medical Abuse of Prescription Drugs
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Prescribed Pills. Image Source:

Addiction presents itself in numerous forms. In fact, there are a plethora of addictions, such as caffeine-addiction, that are already known to the public. Of these possible addictions, prescription drug addiction is a pressing matter. It is prevalent in adolescent demographics[1] (adolescents-and-addiction). In fact, prescription drug abuse is becoming a major public health issue. This matter is of vital importance due to the fact that it is predominant in the youth of society for the focal reason of possessing the characteristic of being highly accessible.[2] There is an abundance of abused drugs. Some of these drugs include opioids (i.e., Morphine), tranquilizers (i.e., Valium), as well as stimulants (i.e., Ritalin).[3] Prescription drug addiction demonstrates high relevance to society and as such, is not taken lightly in regards to its detrimental effects on the adolescent demographic.

The Death of One Adolescent and its Effect on Another
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1. Neurobiology

1.1 Of Prescription Opioids and Heroin

Opioids Explained
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Prescription opioids possess a very extensive assemblage. Of this collection, prescription opioids include Vicodin (also known as Hydrocodone), Codine, Oxycontin (also known as Oxycodone), and Morphine.[3] The molecular neurobiology of prescription opioids, as well as heroin, incorporates a specific receptor system – that of the MOP-r, KOP-r, and DOP-r receptors – as well as various neuropeptides that act within various dopaminergic systems.[4] At the MOP receptors (MOP-r), these drugs act fast and they behave as agonists.[4] As these two domains of drugs follow similar pathways, heroin will be explained in detail. Heroin is also known for its scientific name, diacetylmorphine.[4] Diacetylmorphine, upon entry into the brain, is rapidly converted (or more precisely, broken down) into monoacetylmorphine and morphine.[4] Subsequently, the two resulting compounds bind to MOP-r. A resulting dopamine release occurs as previously inhibited dopaminergic neurons are now disinhibited due to the disappearance of GABA neurotransmitters (which function for inhibition). In other words, the addictive phenomena for heroin (and also opioids) has been noted to share relation to this downstream dopaminergic activation.[4]
The neurobiology may also incorporate the HPA axis and its synonymous factor of stress.[4] Stress incorporates the HPA axis (Hypothalamic-Pituitary- Adrenal axis) through a predicted pathway. The preliminary stimulator, stress, causes the paraventricular nucleus (PVN) of the hypothalamus to release corticotropin-releasing factor (CRF), as well as arginine-vasopressin (AVP). CRF then stimulates and causes the release of adrenocorticotropic hormone (ACTH) and β-EP as CRF binds the CRF-R1 receptors and AVP binds the AVP-V1b receptors of the anterior pituitary, acting upon the adrenal cortex to release cortisol.[4] With this, it is evident that prescription opioids are, in fact, crucial factors in the control of the HPA-axis – prescription opioids and heroin display an inhibitory role in the stress response – thus explaining why peptides such as β-EP are incorporated in the addictive effects and propagation of drug abuse.[4]

1.2 Genetics of Prescription Opioids and Heroin

Genetic factors are deeply relevant and consistent with individual predispositions of becoming a prescription opioid or heroin drug addict. This, indirectly, affects one’s course of treatment and/or effectiveness of treatment methods as different individuals possess varying degrees of susceptibility.[4] One form of genetics incorporates the convention of gene polymorphisms – those occurring on the receptors and ligands.[4] With a focus on the MOP-r gene (OPRM1) in particular, it is important to note that there are two OPRM1 single nucleotide polymorphisms (SNPs) that have been researched to a moderate degree – 17C>T and 118A>G – with the 17C>T being the least researched OPRM1 variant and 118A>G being the most heavily researched.[4] The 118A>G variant of the gene, which causes an amino acid substitution (aspartic acid [A] replaces the amino acid of asparagine),[4] has been shown through various studies to show a positive correlation to various addictions including opioid addiction and heroin addiction,[4] among others. In terms of genotype, carriers of the 118G allele portray lower pain tolerance (hence, higher sensitivity to pain) and reduced pain-relieving response to opioids,[4] which represents a negative connotation. The 17C>T variant of the gene, which causes an amino acid substitution (alanine is converted to valine),[4] is also associated with higher forms of dependence on opioid drugs. However, more research is required in order to validate and form more concrete evidence to back this up.

1.3 Compare and Contrast to that of Marijuana and Alcohol

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Individuals, especially adolescents, are prone to engaging in the abuse of illicit drugs and alcohol. In fact, the age of primary abuse of marijuana and alcohol is younger than that of prescription drugs.[2] Young adults have been found to first engage in the abuse of alcohol at the age of 16.6 years, the abuse of marijuana at the age of 19 years, and the abuse of prescription opioids at the age of 21.9 years.[2] However, even though age of primary onset of such abuse occurs at a later age for prescription opioids, it has been found that prescription opioids possess an increased chance of exploitation as compared to illegal opioids such as cocaine or heroin.[2] Prescription opioids can be attained legally and thus possess a much higher accessibility rate compared to that of marijuana and alcohol.[2]
Marijuana is a very popular drug among adolescents. The central component of its addictive trait is the delta-9-tetrahydrocannabinol (Δ9-THC).[5] The Δ9-THC binds cannabinoid (CB1) receptors.[5] These receptors are implicated in several neural processes, including that of memory and cognitive processing.[5] Abuse of marijuana causes neurological and hence, functional alterations and deficits in the brain and its many functions.[5]
Alcohol, on the other hand, is more of a social drug. Due to its misuse and overuse, individuals become dependent on it and gain an increased tolerance for it.[6] Biological modifications occur as alcohol has been found to induce changes in protein translation,[6] and as such, some researchers have identified candidate proteins[6] that may contribute to alcohol addiction. For example, the proteins, pyruvate dehydrogenase E1 beta-subunit and transketolase,[7] found within the dorsolateral prefrontal cortex (PFC), may be considered candidate proteins as they are expressed differently in individuals who abuse alcohol. Further research is required however, in the domain of proteomics due to other possible confounding explanations. More probing into this area may prove beneficial and help us to better understand the intricacies of alcohol abuse.

2. Causes

Individuals journey on the addiction path for prescription opioids for a variety of reasons. Some of these reasons include:

• Self-treatment of pain[2]
• Self-medicate in response to other health conditions[3]
• To restrict heroin use[3]
• To achieve a “heroin high”[3]
• Reduce stress levels[4]
• To aid in effective socialization
• To curb withdrawal symptoms

Not only do patients/non-patients experience this addiction, surgeons are also at risk.[8] The cause for surgeons to undertake such an addiction incorporates the motives of attaining both cognitive and mood enhancements,[8][9] which inadvertently aid in deterring fatigue and stress.[8][9]
Several other specific causes are available – one of which includes the treatment of chronic non-cancer pain (CNCP).[10]

3. Methods of Prevention

With the accomplishment of a national sample of Medical Toxicologists (MTs), Perrone et al. have demonstrated the methods in which medical toxicologists choose to prescribe opioids to patients.[11] These MTs are fully mindful of prescription drug monitoring programs (PDMP’s) and they are sentient regarding the negative connotations that confound with prescribing medicine, such as overprescribing.[11] It has been established, however, that MTs refrain from putting state-based PDMPs into effect when prescribing.[11] This usually occurs as limitations are prominent. Such limitations include, but are not restricted to, time constraints and accessibility issues.[11] Medical Toxicologists, regardless of being aware of the protocols of prescribing drugs, some also face the reality of prescribing opioids as emergency medicine,[11] disregarding their preliminary dogmas.
Cases, such as the one stated above, further demonstrate that preventative methods are a crucial necessity. Few researchers are actually trying to advance their studies and research in developing abuse deterrent formulations (ADFs).[12] These researchers are hoping that these formulations will aid in preventing current and possible prescription drug abusers from extracting the active ingredients from the drugs,[12] for example, by somehow making certain drugs immune from being dissolved or crushed.[12] This, in theory would aid in abolishing the forms that abusers choose in administering the drug (such as injection or snorting),[12] however, it also creates paradoxes, as it inhibits normal administration and consumption of the drugs to patients who show no signs of addiction.

Crucial Departments/Individuals Who Need To Be Engaged in PDMPs
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3.1 Early Identification and Screening

Patient/non-patient abusers and clinicians alike, are welcome to interventions and informational/educational sessions[12] regarding prescription drug abuse in order to propagate the prevention of possible addiction and/or to stop the addiction early in the process. One method of screening, termed the Drug Abuse Screening Test (DAST),[13] is a brief method of screening for possible drug-related abuse and is composed of twenty-eight self-report items.[13] Due to it being contingent on having individuals self-report, its data cannot be considered 100% reliable as individuals are capable of falsifying what they choose to report. Another method of screening incorporates the use of the Audio-guided Computer Assisted Self Interview (ACASI)[14] Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST),[14] comprehensively known as ACASI ASSIST.[14] This screening method is also a self-report measure and possesses great reliability in re-tests.[14]

3.2 Tests and Diagnosis

Immunoassay Confirmation Rates for Drug Types
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Several methods of testing are available for detecting abuse of prescription drugs. Routine immunoassay drug tests[15] are one form of testing available. These immunoassays include those of CEDIA, EMIT, and KIMS immunoassays.[15] Standard urine tests[15] can also be performed and then compared to urine standards[15] of which are known to contain substances contained in specific drugs of interest. Another method incorporates the use of Amphetamine Class tests,[15] which have been shown to be effective as amphetamine reacts with most new drugs.[15] In addition, hair samples[16] can also be examined and their analysis aids in distinguishing which prescription drugs are being abused.

One of Many Immunoassay Analyzers
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Urine Test: Distinguishing Results From Test Strips
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1. Zosel, A., Bartelson, B. B., Bailey, E., Lowenstein, S., & Dart, R. (2013). Characterization of adolescent prescription drug abuse and misuse using the researched abuse diversion and addiction-related surveillance (RADARS(®)) system. Journal of the American Academy of Child and Adolescent Psychiatry, 52(2), 196-204.
2. Mendelson, J., et al. (2008). Addiction to prescription opioids: Characteristics of the emerging epidemic and treatment with buprenorphine. Experimental and Clinical Psychopharmacology, 16(5), 435-441.
3. Lankenau, S. E., et al. (2012). Patterns of prescription drug misuse among young injection drug users. Journal of Urban Health: Bulletin of the New York Academy of Medicine, 89(6), 1004-1016.
4. Kreek, M. J., Levran, O., Reed, B., Schlussman, S. D., Thou, Y., & Butelman, E. R. (2012). Opiate addiction and cocaine addiction: Underlying molecular neurobiology and genetics. Journal of Clinical Investigation, 122(10), 3387-93.
5. Sneider J.T., Mashhoon Y., Silveri M.M. (2013). A review of magnetic resonance spectroscopy studies in marijuana using adolescents and adults. J Addict Res Ther, Suppl 4: 010.
6. Gorini G., Roberts A.J., Mayfield R.D. (2013). Neurobiological signatures of alcohol dependence revealed by protein profiling. PLoS One, 8(12).
7. Wang, J., Yuan, W., & Li, M. D. (2011). Genes and pathways co-associated with the exposure to multiple drugs of abuse, including alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine, and/or nicotine: A review of proteomics analyses. Molecular neurobiology, 44(3), 269.
8. Franke A. G., Bagusat C., Dietz P., Hoffmann I., Simon P., Ulrich R., et al. (2013). Use of illicit and prescription drugs for cognitive or mood enhancement among surgeons. BMC Med.
9. Maier, L. J., Liechti, M. E., Herzig, F., & Schaub, M. P. (2013). To dope or not to dope: Neuroenhancement with prescription drugs and drugs of abuse among Swiss university students. PloS one, 8(11).
10. Franklin, G. M., Fulton-Kehoe, D., Turner, J. A., Sullivan, M. D., & Wickizer, T. M. (2013). Changes in opioid prescribing for chronic pain in Washington State. The Journal of the American Board of Family Medicine, 26(4), 394-400.
11. Perrone, J., DeRoos, F. J., & Nelson, L. S. (2012). Prescribing practices, knowledge, and use of prescription drug monitoring programs (PDMP) by a national sample of medical toxicologists, 2012. Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology, 8(4), 341-352.
12. Budman, S. H., Grimes Serrano, J. M., & Butler, S. F. (2009). Can abuse deterrent formulations make a difference? Expectation and speculation. Harm Reduct J, 6(8).
13. Skinner, H. A. (1982). The drug abuse screening test. Addictive behaviors, 7(4), 363-371.
14. McNeely, J., Strauss, S. M., Wright, S., Rotrosen, J., Khan, R., Lee, J. D., & Gourevitch, M. N. (2014). Test–retest reliability of a self-administered Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in primary care patients. Journal of substance abuse treatment.
15. Beck, O., Rausberg, L., Al‐Saffar, Y., Villen, T., Karlsson, L., Hansson, T., & Helander, A. (2014). Detectability of new psychoactive substances, ‘legal highs’, in CEDIA, EMIT, and KIMS immunochemical screening assays for drugs of abuse. Drug Testing and Analysis.
16. Vignali, C., Stramesi, C., Morini, L., San Bartolomeo, P., & Groppi, A. (2014). Workplace drug testing in Italy: Findings about second-stage testing. Drug Test Anal.

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