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National Institute on Drug Abuse -  NIDA NOTES
Volume 15, Number 1 (March, 2000)

Research Eases Concerns About Use of Opioids To Relieve Pain

By Robert Mathias, NIDA NOTES Staff Writer

Many physicians limit their use of powerful opioid pain medications because they think that patients may become addicted to them. Now, accumulating evidence from a series of NIDA-funded studies indicates that the abuse potential of opioid medications is generally low in healthy, non-drug-abusing volunteers. The findings from this research could help to improve the use of opioid medications to treat a variety of pain conditions.

The term "opioids" describes morphine and other natural and synthetic chemicals that are structurally similar to morphine. Opioids include codeine and meperidine and other medications that are used to treat pain, as well as heroin, an abused drug. Research has provided much information about the addictive mechanisms and mood-altering and behavioral effects of opioids in opioid abusers. However, little is known about whether non-opioid-abusers being treated for postoperative pain experience similar effects.

"There is a prevailing notion that patients can readily become addicted to opioid medications, but it is not based on scientific evidence," says Dr. James Zacny of the University of Chicago. This belief in a high risk of addiction often leads to underuse of opioid medications for pain relief and causes unnecessary suffering in patients, he says. While research shows that several opioid medications commonly used for post-operative pain relief are likely to be abused by opioid abusers, few studies have examined their abuse potential and subjective effects in people who don't abuse drugs.

"The majority of healthy non-drug-abusing volunteers do not report euphoria after being administered opioids in the lab either with or without pain."

For the last 7 years, Dr. Zacny has conducted a series of studies aimed at filling this critical gap in clinical knowledge. His research has examined the subjective and behavioral effects of powerful opioid medications, such as morphine and fentanyl, in non-drug-abusers. Dr. Zacny's research was recently recognized with a NIDA MERIT Award that will enable him to continue and expand his work.

"Most of what is known today about the mood-altering, psychomotor, and reinforcing aspects of opiates among people who don't abuse opioid drugs has come from Dr. Zacny's research," says Dr. Cora Lee Wetherington of NIDA's Division of Neuroscience and Behavioral Research. Generally, he has found that non-drug-abusing volunteers who are given these drugs do not report feeling the euphoria that opioid abusers do, she says. They also experience more drowsiness and impairment of psychomotor functions such as reaction time and eye-hand coordination from opioids than do opioid abusers, she adds.

Dr. Zacny's research also has shown that pain may modulate some of the subjective and behavioral effects produced by opioids in non-drug-abusers. In one study, non-opioid-abusing volunteers immersed their forearms either in ice-cold water, inducing constant pain, or lukewarm water, inducing no pain. When volunteers were given intravenous morphine while experiencing pain from the ice water, they reported feeling less euphoric, lightheaded, and sleepy than they felt following morphine administration when their arm was immersed in lukewarm water. However, regardless of whether or not they were experiencing pain, study participants did not feel the same amount of euphoria from morphine that drug abusers report, Dr. Zacny says.

"In our studies, we find the majority of healthy non-drug-abusing volunteers do not report euphoria after being administered opioids in the lab either with or without pain," Dr. Zacny stresses. "Since euphoria appears to be a factor in opioid abuse, it seems that the abuse potential of these opioid medications is generally low in such people," he says. Further clinical studies now are needed to assess the range of effects experienced by patients who receive opioid medications in hospitals, as opposed to laboratory settings, Dr. Zacny says. "Such studies could tell us if patients who have been given an opioid following an operation experience absolutely no euphoria or if some patients do experience such an effect."

Dr. James Zacny

Dr. James Zacny records a volunteer's report of the effects of intravenous morphine while she is experiencing pain from immersing her arm in ice water.

Currently, Dr. Zacny is studying other opioids with different mechanisms of action that are commonly given for pain relief following operations. This research is examining the extent to which different doses of meperidine, butorphanol, and nalbuphine administered in the presence of a painful stimulus produce such subjective effects as sedation, he says. "Our findings should give clinicians a better sense of how patients are feeling from these drugs."

Dr. Zacny also is studying the behavioral effects of oral opioids, such as oxycodone (Percodan) and hydrocodone (found in Vicodin), and propoxyphene (Darvon), that sometimes are given to people with pain that is expected to last for a few days to a week. None of these medications, which typically are given following such procedures as outpatient surgery or extraction of wisdom teeth, have been carefully scrutinized for their behavioral effects, he says. Characterizing these effects in people in pain without a history of drug dependence could aid in assessing these medications' abuse liability in this population and determining if they significantly impair performance, Dr. Zacny says.

In the future, Dr. Zacny would like to examine how opioid medications affect non-drug-abusing patients who receive them on a long-term basis for chronic pain. This research could have clinical implications for people suffering from such conditions as cancer, osteoarthritis, or even chronic lower back pain, he says. For example, research into long-term use of these medications could help determine if repeated use leads to euphoria in these patients, could provide information about possible cognitive and psychomotor impairments, and could establish whether and how tolerance to their effects develops over time.

Studies of the effects of opioids in chronic pain patients will be complex and will have to consider many other factors affecting chronic pain patients' reactions to these drugs. These factors include different disease states, coexisting conditions, such as depression, and other medications, Dr. Zacny says. "The MERIT Award will enable me to enter this realm of research where the potential for gaining important new information is very great," he says.


Conley, K.M.; Toledano, A.Y.; Apfelbaum, J.L.; and Zacny, J.P. The modulating effects of a cold water stimulus on opioid effects in volunteers. Psychopharmacology, 131:313-320, 1997. [Abstract]

About the MERIT Award

NIDA's MERIT-Method to Extend Research in Time-Award program gives outstanding NIDA researchers up to 10 years to focus on innovative research without the administrative burdens of preparing and submitting full grant applications for the MERIT extension. The 4- or 5-year extendable awards are granted to researchers who have received approval and outstanding priority scores for regular NIDA research projects. MERIT awardees are nominated by NIDA program staff, reviewed by a panel of staff and outside scientists convened by the NIDA Director, recommended by the National Advisory Council on Drug Abuse, and finally, selected by NIDA's Director.

NIDA NOTES - Volume 15, Number 1

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