By David Brown
Thursday, January 14, 2010; A04
More than 200 years after it was isolated from poppies, morphine remains one of medicine's best painkillers. But that isn't its only use.
Physicians sometimes include the drug in a cocktail of medications given to people having heart attacks. It can relieve the breathlessness of pulmonary edema. It decreases diarrhea. A famous physician of the early 20th century, William Osler, once called morphine "God's own medicine."
Research published this week suggests that the compound might have at least one more use.
In a study of about 700 troops who were wounded in Iraq, those who received morphine soon after being injured were about half as likely to develop post-traumatic stress disorder as those who did not get the drug.
It is not known whether morphine's apparently protective effect arises directly from the relief of traumatic pain or indirectly by blocking the brain circuits that lay down traumatic memory.
The researchers and outside experts agreed that the effect would have to be proved virtually beyond a doubt before morphine would be routinely given to prevent the mental disorder.
"I would be very reluctant to suggest any change in clinical practice," said Troy Lisa Holbrook of the Naval Health Research Center in San Diego, who headed the study published in the New England Journal of Medicine. "We need to understand a great deal more how this appears to work."
Morphine has been used for pain relief from battle wounds as far back as the Civil War. Since World War II, medics and hospital corpsmen have carried small injectors filled with the drug.
Although it is the battlefield painkiller of choice, how commonly it is used in front-line first aid is not known. A recent survey of 114 burn patients treated at the Army Institute of Surgical Research in Texas found that 30 percent had received pre-hospital injections, according to Laura L. McGhee, a researcher there.
PTSD is characterized by intrusive thoughts and memories, a desire to avoid specific situations or stimuli, and feelings of both numbness and extreme vigilance. The disorder is common in veterans of the Iraq and Afghan wars, although its exact prevalence is also uncertain.
About 40 percent of those veterans cared for at Department of Veterans Affairs hospitals have PTSD. Repeat deployment to a war zone increases the risk of developing the disorder. PTSD can also come on slowly. In one study, 4 percent of troops had the condition; six months later, the prevalence was 12 percent.
In the new study, Holbrook and her colleagues looked at the records of 696 wounded forces. About 40 percent had been injured by improvised explosive devices, generally roadside bombs; about 20 percent by gunshots and 10 percent by mortar rounds. About 70 percent received morphine within an hour of being hurt.
Most people developed PTSD, diagnosed from one month to two years after their injuries occurred. Those who had received morphine, however, were somewhat less likely. Sixty-one percent had the disorder, compared with 76 percent of people who hadn't gotten the drug -- which researchers said translated into a 53 percent reduction in risk.
(None of the people in the study had serious traumatic brain injuries. Morphine is generally not used in such patients, as it can cloud consciousness and increase pressure in the skull, worsening the problem.)
The researchers saw no clear connection between the amount of morphine people received and their risk of PTSD, in part because the drug was generally given in a standard one-shot dose. But Holbrook would not rule out that such a connection might exist.
There are many chemical variations on morphine, some man-made, some naturally occurring, as well as numerous sites in the brain and spinal cord where the opioid compounds work.
"The next study needs to look at what is the mechanism of action in morphine that reduces PTSD," said Michael R. Galarneau, another of the San Diego researchers.
Other drugs have been tried as possible PTSD preventives. They include beta blockers (which block adrenaline) and Valium-like drugs called benzodiazepines. Generally, the results have been disappointing.
One drug that shows some protective effect is ketamine, an intravenous anesthetic known to affect memory. In one study, 27 percent of burn patients who received ketamine during treatment developed PTSD, compared with 46 percent of burn patients who did not.
Ian Black of the University of Vermont, a former Army anesthesiologist who did that study, was not surprised by the latest findings.
"The conventional wisdom now is that there is some sort of memory consolidation that happens during stress, and things you can do to interrupt or decrease stressors, like pain, may reduce the risk of PTSD," he said.