Severe opioid use disorder (OUD) involves the dependency on the drug resulting in clinically significant impairment or distress. The severe opioid condition consists of having at least six or more distressful items due to drug use based on the American Psychiatric Association DSM-5 diagnostic criteria. Opioid use disorder affects approximately 16 million people worldwide, and the United States leads with over 2.1 million addicted users ( Blanco & Volkow, 2019) . The condition causes more than 120,000 deaths annually ( Blanco & Volkow, 2019) . The severity of the condition involves the desire to obtain and take opioid drugs despite its professional and social consequences. The dependency on opioids drugs like codeine, fentanyl, morphine, and heroin contributes to the worsening physical or psychological health. The drugs interfere with the neurological systems such as basal ganglia, prefrontal cortex, and extended ganglia, and the condition can be treated using opioid maintenance or substitution drugs such as buprenorphine, naltrexone, and methanol. Severe opioid use disorder is a chronic condition that affects the patient's neurobiological components, and understanding its neurophysiology and neuroanatomy helps in the administration of an effective pharmacological plan.
Incidence, Symptoms, and Societal Impact
The dependency on opioid is a serious international crisis that affects public health and economic welfare. According to the Centre for Disease Control (CDC), the death rate caused by the dependence on opioid analgesics increased by 7% for every 100,000 people in 2015 ( Blanco & Volkow, 2019) . In the United States, opioid use disorder contributes to 47,000 deaths annually and over 120,000 worldwide ( Blanco & Volkow, 2019) . Over 2 million people globally use opioids for medication, whereas the rest consume the drug for recreational purposes. The incidence of opioid use and dependency varies by gender and age. Men account for the majority of opioid dependency disorder. Severe cases of opioid use are highest among individuals between 40 and 50 years ( Fields & Margolis, 2015) . The peak age for OUD treatment is between 20 and 35 years. If not resulting from prescribed medication, most patients diagnosed with the disorder are associated with previous high impulsivity and criminal records.
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Severe OUD symptoms include social or legal ramifications, drug-seeking behavior, and multiple opioid disruptions from different clinicians. The main symptoms that physicians observe when establishing the severity include the patient's inability to stop consuming the drug despite the worsening psychological and physical health, social and interpersonal consequences ( Blanco & Volkow, 2019) . Other symptoms are individual withdrawal indicators such as agitation, pupil dilations, sweating, inability to decrease the amount of opioid used, tolerance, and intoxication ( Volkow et al., 2019) . The leading indicators of intoxication include miosis, confusion, decreased pain perception, and euphoria.
Despite the benefits that opioid use has in pain management among patients with chronic illnesses, the drugs' dependency has contributed to significant health and economic burden to society. Opioids have led to an increase in deaths worldwide ( Lutz et al., 2020) . By 2016, it was established that relatively 11.5 million Americans misused prescription opioids, leading to more than 42,000 deaths. The statistics contribute to the annual deaths of approximately 830,652 people worldwide ( Volkow et al., 2019) . The U.S Department of Health and Human Services declared opioids use a crisis that requires public health emergency. Opioid has also contributed to the financial burden for the individuals, families, and society at large. Prescription opioids for chronic illnesses such as cancer and other life-threatening diseases have negatively impacted the quality of health and life. According to Fields & Margolis (2015) , the severity of the dependence on opioids leads to depression and poor physical health-related quality of life. Compared with the general population, individuals with severe OUD are susceptible to other illnesses such as chronic obstructive pulmonary disease, hypertension, infections like HIV/AIDS, and tuberculosis ( Fields & Margolis, 2015) . The conditions mentioned above result in diminished quality of life, a challenge that extends beyond the individual’s family. The severe OUD has also contributed to financial costs for managing the condition associated with drug use. The costs incurred are a burden to society. For instance, in 2014, severe OUD was responsible for 147, 654 patients in the emergency department, with an estimated cost of $83.7 million ( Lutz et al., 2020) . Other economic burdens associated with the dependence on opioids drugs that affect society include higher costs to the criminal justice system and foregone earnings.
Neurologic Basis of Severe Opioid Use Disorder
The severe OUD interferes with how the neurons send, receive, and process signals via neurotransmitters. Opioids drugs mimic brain chemicals ( Lutz et al., 2020) . However, its method of activating the neurons is not similar to the natural transmitter, leading to abnormal message transmissions between the neurons. OUD activates the mesolimbic reward system in the brain circuit ( Lutz et al., 2020) . The activation generates signals in the ventral tegmental area that result in the release of the chemical dopamine in the nucleus accumbens (NAs) region. The release of the chemicals causes feelings of pleasure. Repeated exposure to opioids also alters brain functions, leading to drug dependence and tolerance. Severe OUD changes the locus ceoruleus part of the brain by activating the neurons in the region to produce the noradrenaline chemical and distribute it to other parts of the brain ( Fields & Margolis, 2015) . The process leads to stimulation of general alertness, wakefulness, blood pressure, and excessive breathing. The pleasure derived from the continued use of opioids induces brain dependency and leads to daily drug use resulting in long-lasting changes in the brain's natural functioning mechanism.
Neuroanatomy of severe opioid use is associated with the disruptive nature in different parts of the brain. The alteration occurs during the onset, development, and maintenance stages of the drug. The severe OUD leads to alteration in the basal ganglia, prefrontal cortex, and extended ganglia ( Lutz et al., 2020) . The basal ganglia play the role of keeping the body movements coordinated and smooth. However, the dependency on opioids causes the dorsal striatum to form habits and routine behaviors, initiating continuous desire for the drug. The changes strengthen an individual’s substance-seeking behavior, and such practices ultimately cause its compulsive use ( Fields & Margolis, 2015) . The prefrontal cortex region controls the executive functions of the brain. It organizes an individual's activities and thoughts, impulses, actions and emotions, and time. Severe OUD leads to a deficit in the executive function of the prefrontal cortex, leading to greater reactivity to drug-related stimuli ( Fields & Margolis, 2015) . The extended ganglia regulate behavior and negative emotions such as stress, irritability, and unease. Opioid use changes extended ganglia by reducing the brain sensitivity to pleasure or reward and heightening the brain stress system's activation.
The neurophysiology of severe OUD is based on the repeated exposure of the opioid drug to the brain, causing disturbance to the neurobiological circuits. The mechanism causes the brain to undergo complex neurobiological adaptations in its major systems such as mesolimbic and locus coerulus ( Herman & Roberto, 2015) . The opioid use disorder is associated with a recurring cycle in the functioning stages of the mesolimbic system. The mesolimbic system and basal forebrain are the primary drivers for understanding the acute symptoms and the withdrawal of opioid drugs ( Herman & Roberto, 2015) . The brain region comprises major neurobiological circuits such as basal ganglia, extended amygdala, and prefrontal cortex involved in the reward system. Severe OUD affects neuroplastic and neurotransmitters of the neurons, leading to the activation of reward signals. The locus ceoruleus (LC) is the primary pathway of opioid physical dependence and tolerance. It is located in the pons and makes up the largest group of noradrenergic neurons in the brain. It gives rise to fibers that regulate the autonomic and arousal functions. For severe forms of opioid use, LC inhibits the conversion of adenylyl cyclase and adenosine triphosphate to cyclic adenosine monophosphate (cAMP) ( Herman & Roberto, 2015) . The process leads to the release of noradrenergic neurons, which signals up-regulation of the LC to normal to facilitate the maintenance of opioid homeostasis in the brain.
Treatment of the Disorder
The recommended drug for the treatment of severe opioid use is naltrexone. The medication's therapeutic action is to monopolize mu-opioid receptors in the brain ( Volkow et al., 2019) . It prevents the addictive opioid from linking up with mu and stimulates the brain's reward system by blocking euphoric, a physiological effect of the opioid. The naltrexone medication clings to the mu-opioid receptors more strongly compared to the opioid. The medication does not promote the brain process responsible for feelings of pleasure, making it suitable for addiction treatment ( Volkow et al., 2019) . An individual who uses the drug as prescribed does not obtain pleasure from the addictive opioid, making them less motivated to use it. The drug can also be used in the rapid detoxification of patients with opioid dependency. It suppresses noradrenergic neurons, which is a primary cause of withdrawal.
Conclusion
Severe opioid use disorder is a chronic condition that affects the patient’s neurobiological system. The disease's direct clinical consequences are associated with the mesolimbic and locus ceoruleus reward system, which leads to chronic opioid abuse, addiction, dependence, and tolerance. The neurophysiological processes are associated with arousal functions and autonomic regulation, which are the primary drivers of opioid tolerance and dependence. The condition's neuroanatomy involves its ability to interfere with the normal functions of the basal ganglia, prefrontal cortex, and extended ganglia. Patients with acute cases of the condition are treated using naltrexone because of its ability to monopolize muscarinic receptors.
References
Blanco, C., & Volkow, N. D. (2019). Management of opioid use disorder in the USA: present status and future directions. The Lancet , 393 (10182), 1760-1772. https://doi.org/10.1016/S0140-6736(18)33078-2
Fields, H. L., & Margolis, E. B. (2015). Understanding opioid reward. Trends in neurosciences , 38 (4), 217-225. https://doi.org/10.1016/j.tins.2015.01.002
Herman, M. A., & Roberto, M. (2015). The addicted brain: understanding the neurophysiological mechanisms of addictive disorders. Frontiers in integrative neuroscience , 9 , 18. https://doi.org/10.3389/fnint.2015.00018
Lutz, P. E., Courtet, P., & Calati, R. (2020). The opioid system and the social brain: implications for depression and suicide. Journal of neuroscience research , 98 (4), 588-600. https://doi.org/10.1002/jnr.24269
Volkow, N. D., Jones, E. B., Einstein, E. B., & Wargo, E. M. (2019). Prevention and treatment of opioid misuse and addiction: a review. JAMA psychiatry , 76 (2), 208-216. https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2716982
