Abuse factors. Tolerance and dependence can develop. When dependent rats were given a choice between water and a sweetened solution of levorphanol, they preferred the drug solution, but when the choice was between the same drug solution and sweetened water they preferred the sweet water. When experimenters offered another set of dependent rats straight water and unsweetened levorphanol solution, those animals preferred straight water. Such results imply that the drug has a low addiction potential, but an implication is not a fact. Also, animals do not always react to a substance in the same way humans do.
In humans the drug can improve spirits and even produce euphoria, and some users say they became addicted. A rat experiment demonstrated partial cross-tolerance with alcohol, suggesting that the two drugs appeal to the same kinds of people.
Some employer drug testing cannot distinguish between levorphanol and dextrorphan.
Drug interactions. Simultaneous use of levorphanol with alcohol or other depressants increases the possibility of cumulative overdose. In mice the anesthetic lidocaine boosts levorphanol's pain relief actions. Antihistamines and monoamine oxidase inhibitors (MAOIs, found in some antidepressants and other medicine) should be avoided when taking levorphanol. Levorphanol can also be dangerous when taken with alprazolam, diazepam, flurazepam, lor-azepam, phenobarbital, or temazepam.
Cancer. Levorphanol's potential for causing cancer is unknown.
Pregnancy. Mice experiments with the drug have caused pregnancy failures and birth defects. Offspring from male mice exposed to the drug weighed less than normal, were slower to mature, and had abnormal motions in water. The potential for similar outcomes with humans is unknown. Rabbit experiments show the drug passing into the fetus of a pregnant animal, reducing fetal respiration. Milk from a nursing mother who uses levorphanol is assumed to contain enough of the drug to cause unwanted effects in a nursing infant, but that possibility may be minimized by waiting long enough after a dose before nursing (the delay can allow much of the drug to wash out of the woman's body).
Additional scientific information may be found in:
Chernin, T. "Use of Opioids for Chronic Nonmalignant Pain." Pharmacy Times 65 (1999): 18-20, 23-25.
Coniam, S.W. "Withdrawal of Levorphanol." Anaesthesia 46 (1991): 518. Friedler, G. "Effects of Limited Paternal Exposure to Xenobiotic Agents on the Development of Progeny." Neurobehavioral Toxicology and Teratology 7 (1985): 739-43. Fuchs, V., and H. Coper. "Development of Dependence on Levorphanol in Rats by Oral Intake of the Drug—The Influence of Taste on Drinking Behaviour in Rats Physically Dependent on Levorphanol." Drug and Alcohol Dependence 6 (1980): 373-81.
Knych, E.T. "Cross-Tolerance between Ethanol and Levorphanol with Respect to Stimulation of Plasma Corticosterone." Life Sciences 31 (1982): 527-32.
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