_________________________________________________________________________ Opioid Use Disorder
Opioids produce reinforcement by inhibition of the GABA neurons that normally inhibit dopaminergic neurons in the ventral tegmental area. This results in a surge of dopamine in the nucleus accumbens and other mesolimbic-mesocortical brain regions [86]. The neurochemical cascade begins with activation of mu- or kappa-opioid receptors differentially dis- tributed on GABAergic cells in the ventral tegmental area and nucleus accumbens and dopamine terminals in the nucleus accumbens. This activation produces rewarding and aversive effects by increasing or decreasing dopamine release in the nucleus accumbens. Inhibition of medium spiny GABAergic neurons in the nucleus accumbens by dopamine and opioids can synergistically facilitate opioid reinforcement. Increases in glutamatergic afferents into the ventral tegmental area may facilitate opioid reinforcement by activating dopamine neurons. An increase in glutamate activity in the nucleus accumbens may decrease opioid action by activating nucleus accumbens GABAergic cells. Also, an increase in nucleus accumbens 5-HT by opioids modulates opioid reinforcement by activation of 5-HT1 and/or 5-HT3 receptors [81]. EFFECTS OF OPIOID USE DISORDER The misuse of opioids results in several acute and long-term effects. Signs and symptoms of acute opioid intoxication include drowsiness, decreased respiration, euphoria, and impaired judgment ( Table 1 ). SIGNS AND SYMPTOMS OF ACUTE OPIOID INTOXICATION Constricted pupils (or dilated pupils with meperidine) Euphoria Apathy
immunodeficiency virus (HIV) and hepatitis B [8]. Common bacterial infections include Staphylococcus aureus, cellulitis and abscesses around the injection site, pneumonia, bactere- mia, and endocarditis. Of HIV-positive persons in the United States, more than 33% have injected opioids and more than 25% report sharing needles with other users [10]. Injection drug users represented 10.6% of new HIV infections in 2021 and 13.6% of those living with HIV in 2021 [90]. ENDOCRINE/METABOLIC EFFECTS Opioid use affects multiple endocrine functions and is associ- ated with hypogonadism, adrenal dysfunction, reduced bone mineral density, and growth hormone abnormalities [91]. Hypothalamic-Pituitary-Gonadal (HPG) Axis Opioid use has been implicated in gonadal dysfunction [92]. Central hypogonadism can result from opioid receptor activation in the vicinity of the hypothalamus. Resultant diminished secretion of gonadotropin-releasing hormone can lead to decreases in gonadotropin and testosterone levels. This effect may decrease over time secondary to the development of tolerance [91]. Metabolic Effects Heroin use has been associated with abnormalities in glucose metabolism by multiple mechanisms. Fasting insulin levels can be substantially higher in heroin addicts than in control subjects, and insulin resistance stemming from opioid use may be coupled with beta cell dysfunction [93]. Heroin addicts often have lower acute insulin response than control patients evaluated by oral glucose tests and response to a standard meal. This blunted glucose response suggests an association between opioid use and abnormal glucose metabolism [91]. The use of highly active anti-retroviral therapy (HAART) for the treatment of HIV infection is also associated with a number of metabolic problems, including increased prevalence of insulin resistance, dyslipidemia, and changes in fat distribution. Because opioid use can also result in metabolic abnormalities, the presentation of patients who are both HIV-positive and opioid dependent may be complicated. Chronic heroin use may also complicate dyslipidemia, evi- denced by elevated total cholesterol levels, hypertriglyceride- mia, decreased total cholesterol and high-density lipoprotein, and elevated triglyceride levels relative to controls [91]. Hypothalamic-Pituitary-Adrenal (HPA) Axis Opioid addicts may also have impaired adrenal function, documented by a high prevalence of adrenal insufficiency and abnormal response to the cosyntropin test [92]. The action of heroin on neurotransmitters that regulate the secretion of corticotrophin-releasing factor, leading to disturbances in cortisol levels, has been hypothesized as the underlying pathophysiology. This is supported by the observation of lower plasma cortisol levels concurrent with depressed ACTH levels in heroin addicts [91].
Dysphoria Drowsiness Loss of consciousness Coma Psychomotor agitation or retardation
Decreased respiration Decreased heart rate Pulmonary edema Impaired social judgment Slurred speech
Impaired attention and memory Impaired occupational functioning Source: [87]
Table 1
INFECTIOUS DISEASE Infectious complications from opioid use generally stem from injection use, primarily of heroin, in which bloodborne patho- gens are transmitted via contaminated needles. An estimated 60% to 90% of injection users have hepatitis C virus infection [88; 89]. Other common infectious diseases include human
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MDRI2026
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