Pregnancy Category C

Uses. Morphine was identified as opium's main active ingredient in the early 1800s. The body transforms a heroin dose into morphine. If stored too long in a water solution, morphine will eventually transform into other chemicals including morphine-N-oxide, a Schedule I controlled substance. Although pharmaceutical supplies of morphine come from opium harvests, mammals produce small amounts of morphine in their bodies. Thus the substance is a natural product in both the plant and animal kingdoms. The drug can also be created entirely in a laboratory.

Morphine's role in medicine did not become prominent until the hypodermic needle was introduced in the 1850s. Injection was long the main means of administration, but other delivery systems (such as absorption by the nasal lining and through rectal suppositories) have since been developed. Oral dosage formats are also available.

Morphine is widely used to sedate people and to ease anxiety. The drug is commonly given to treat acute pain from injury or surgery and chronic pain from assorted afflictions. The hurting does not actually go away, but people become less aware of it. In addition to pain control, morphine also has anti-inflammatory actions and can suppress coughing.

The drug tends to produce better pain relief in women than in men. A small study examined whether Chinese men respond to morphine differently than white men do: Doses lasted longer in the whites, interfered more with their breathing, and produced greater reduction in their blood pressure.

Drawbacks. When used to reduce continual pain in serious disease, too much morphine can increase discomfort rather than relieve it and cause a condition in which a patient experiences pain from activity that should not be uncomfortable.

Morphine can make people drowsy, so they should avoid operating an automobile or other hazardous machinery until they know how the drug affects them. Despite morphine's safety in a medical context, it can be hazardous when injected into fluid circulating through the spinal cord and brain, and if hospital staffs use this technique, they are advised to have resuscitation equipment on hand.

Nausea and vomiting are common unwanted effects from morphine. It promotes constipation and urine retention. Itching and hives can occur. The drug interferes with sexual activity by male rats and lowers testosterone levels in human males. Morphine can impede breathing and often is avoided if a person suffers from asthma. Rats dosed with morphine for six weeks developed a weakened immune system. People can experience seizures and accelerated heart activity from a strong dose.

Abuse factors. After several weeks of medical dosage a person can experience noticeable dependence with morphine. Such development should take longer with adulterated street supplies. Medical patients who were surveyed about their experience with morphine claimed to have experienced no difficulty in stopping the drug. Addiction from medical use is almost unheard of. Normally withdrawal symptoms are a mild version of the opiate withdrawal syndrome. Tolerance is normally described as evidence of drug abuse, but morphine tolerance can develop in persons receiving the drug medically for pain relief. Symptoms of such tolerance include a need to take doses more often and at a higher strength in order to produce the same amount of pain relief. This is notable because tolerance to medical effects of a drug tends to be unusual; perhaps the development indicates a substantial psychological component in morphine's pain management. Tolerance is commonly observed among addicts, but they do not continually increase their dosage. At some point they generally reach a level adequate to maintain the sensations they seek. In the 1980s a mice experiment indicated that vitamin C may prevent morphine tolerance and dependence, but judging from subsequent absence of this technique in treating humans, apparently initial hopes for the therapy have not been fulfilled.

One of the main appeals in illicit use of morphine is the drug's ability to induce calmness. People making unauthorized use of the drug for this purpose are not so much using the drug for recreation as for relieving mental suffering. In some people the drug can cause euphoria, a characteristic that can have appeal strictly for recreation but also for self-medication. In these and other respects, morphine and heroin will appeal to the same sorts of people for the same sorts of reasons.

For decades morphine addiction was portrayed as the classic kind of drug abuse. Although the substance was unwelcome in the workplace as the twenty-first century began, a century earlier some workers used the drug to increase productivity in both manual and intellectual tasks by relieving tension that otherwise diminished performance. Other pharmaceuticals later su perseded that antianxiety function of morphine. Somewhat surprisingly, given morphine's depressant actions, researchers have found the drug can improve performance on a test of response time in decision making. Other researchers have found no effect on performance in tests of memory, reasoning, muscular coordination, and various additional skills basic to everyday living. Few ill effects seem to come from chronic use of pure morphine (as opposed to adulterated street supplies). Addicts with access to the pure product have lived healthy and productive lives into old age. As drug laws tightened over the past century, use of morphine by ordinary middle-class people declined, shifting the prevalence of nonmedical morphine usage from law-abiding persons into populations with more social deviance. Consequently, illicit use of morphine became more associated with society's outcasts. That association, however, was caused by changes in laws and social attitudes (changes in setting), not by any chemical effect of the drug.

Drug interactions. Animal and human experiments show that more pain relief can come from morphine if ephedrine is taken at the same time. Dextroamphetamine can improve pain relief provided by morphine. Alcohol, tri-cyclic antidepressants, and monoamine oxidase inhibitors (MAOIs, found in some antidepressants and other medicine) can boost morphine effects. Rat experiments indicate that benzodiazepine class depressants lengthen the effect from a morphine dose. Researchers find that morphine and nicotine have cross-tolerance in mice.

Cancer. Morphine is not known to cause cancer. Some laboratory tests and some studies of human users, however, detect cell damage that could lead to cancer. Some people smoke morphine, and the smoke is suspected of causing esophageal cancer. Evidence exists that naturally occurring morphine in lung tissue may constrain development of lung cancer, that nicotine counteracts such protection, and that tobacco smokers have more naturally occurring morphine in their lung tissue than nonsmokers (perhaps because the body increases morphine production when challenged by nicotine). All this evidence, however, involves minute levels of naturally occurring morphine in the body and does not support taking the drug in hopes of avoiding lung cancer.

Pregnancy. When given in amounts exceeding normal human medical doses by hundreds of times, morphine has caused animal birth defects. Malformations involving bones and soft tissues have been observed in animals. Pregnant rats and hamsters dosed on morphine produce male offspring that exhibit feminized behavior. When morphine was routinely given to male adolescent rats, the drug seemed to interfere with sexual maturation. As their offspring reached adulthood, they appeared normal but had hormone abnormalities.

In humans no increase in birth defects has been observed in offspring of women who used morphine during pregnancy. A morphine dose quickly passes from the woman into the fetus, however, and reaches a blood level similar to the woman's. A dose lasts longer in the fetus than elsewhere in a woman's body. The drug reduces fetal motions. A baby born to a chronic morphine user can have dependence on the drug and exhibit withdrawal symptoms after birth. One study found that infants receiving morphine for medical purposes soon after birth show no ill effects five years later in conduct, muscular coordination, or intelligence.

Morphine apparently passes into a mother's milk. One case report described the amount as minimal and found no effect on the nursing infant, but another report tells of an infant receiving so much morphine from milk that dependence developed.

Additional scientific information may be found in:

Hamilton, G.R., and T.F. Baskett. "In the Arms of Morpheus, the Development of Morphine for Postoperative Pain Relief." Canadian Journal of Anaesthesia 47 (2000): 367-74.

Hill, J.L., and J.P. Zacny. "Comparing the Subjective, Psychomotor, and Physiological Effects of Intravenous Hydromorphone and Morphine in Healthy Volunteers." Psychopharmacology 152 (2000): 31-39. O'Neill, W.M., et al. "The Cognitive and Psychomotor Effects of Morphine in Healthy Subjects: A Randomized Controlled Trial of Repeated (Four) Oral Doses of Dex-tropropoxyphene, Morphine, Lorazepam and Placebo." Pain 85 (2000): 209-15. Walker, D.J., and J.P. Zacny. "Subjective, Psychomotor, and Analgesic Effects of Oral Codeine and Morphine in Healthy Volunteers." Psychopharmacology 140 (1998): 191-201.

Zacny, J.P., et al. "Comparing the Subjective, Psychomotor and Physiological Effects of Intravenous Pentazocine and Morphine in Normal Volunteers." Journal of Pharmacology and Experimental Therapeutics 286 (1998): 1197-207.

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