Dysphoria, opioids causing

The answer is c. (Hardman, p 527. Katzung, p 516.) Naloxone is a pure opioid antagonist at the (1, K, and 5 receptors. j,-receptor stimulation causes analgesia, euphoria, decreased gastrointestinal (Gl) activity, miosis, and respiratory depression. K-receptor stimulation causes analgesia, dysphoria, and psychotomimetic effects. 5-receptor stimulation is not fully understood in humans, but is associated with analgesia and antinociception for thermal stimuli. 

In studies of its use in treating alcohol, opioid, and nicotine dependence, naltrexone has not been reported to cause depression or dysphoria. Patients who complain of naltrexone-associated dysphoria often have co-morbid depressive disorders or depression resulting from opioid or alcohol withdrawal states (549). Co-morbid depression is not a contraindication to naltrexone. Small pilot studies have supported the use of naltrexone in combination with antidepressants for the treatment of patients with co-mor-bid depression. The risk of non-fatal overdose is significantly increased after naltrexone treatment, as a result of reduced tolerance, compared with patients taking substitution methadone (550). 

EFFECTS IN THE ABSENCE OF OPIOID DRUGS Subcutaneous doses of naloxone (narcan) up to 12 mg produce no discernible subjective effects, and 24 mg causes only slight drowsiness. Naltrexone (revia) also appears to be a relatively pure antagonist but with higher oral efficacy and a longer duration of action. At doses in excess of 0.3 mg/kg naloxone, normal subjects show increased systolic blood pressure and decreased performance on tests of memory. High doses of naltrexone appeared to cause mild dysphoria in one study but almost no subjective effect in several others. 

The second most common alkaloid in opium is codeine, at 0.5-1% of total mass. Codeine is a weak opioid, and is commonly used as an analgesic, sometimes in combination with acetaminophen. The third most common alkaloid is thebaine, at 0.3-1%. Thebaine has similar chemistry but very different biological effects than morphine or codeine, causing dysphoria and agitation in low doses and seizures in high doses. Thebaine is commonly used as a precursor for synthetic opioids. Papaverine is also about 1% of opium, and is a smooth muscle relaxant with little CNS effect. It should be noted that many specialty varieties of P. somniferum have... 

There are three families of opioid receptors mu, delta, and kappa. Each type of receptor has a different affinity for specific opioids, and specific effects when activated. Each opioid receptor can cause analgesia mu-agrafists (such as morphine) also tend to cause more dependency, while kappa-agonists such as the endogenous opioid dynorphin cause more dysphoria. 

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