Research Eases Concerns About Use
of Opioids To Relieve Pain
By Robert Mathias
Dec 2004 -
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
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 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
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]