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© 2001 American Academy of Pain Medicine, American Pain Society and American Society of Addiction Medicine
A consensus document from the American Academy of Pain Medicine, the American Pain Society,
and the American Society of Addiction Medicine.
BACKGROUND
Clear terminology is necessary for effective communication regarding medical issues. Scientists,
clinicians, regulators, and the lay public use disparate definitions of terms related to addiction. These
disparities contribute to a misunderstanding of the nature of addiction and the risk of addiction,
especially in situations in which opioids are used, or are being considered for use, to manage pain.
Confusion regarding the treatment of pain results in unnecessary suffering, economic burdens to society,
and inappropriate adverse actions against patients and professionals.
Many medications, including opioids, play important roles in the treatment of pain. Opioids, however,
often have their utilization limited by concerns regarding misuse, addiction, and possible diversion for
non-medical uses.
Many medications used in medical practice produce dependence, and some may lead to addiction in
vulnerable individuals. The latter medications appear to stimulate brain reward mechanisms; these
include opioids, sedatives, stimulants, anxiolytics, some muscle relaxants, and cannabinoids.
Physical dependence, tolerance, and addiction are discrete and different phenomena that are often
confused. Since their clinical implications and management differ markedly, it is important that uniform
definitions, based on current scientific and clinical understanding, be established in order to promote
better care of patients with pain and other conditions where the use of dependence-producing drugs is
appropriate, and to encourage appropriate regulatory policies and enforcement strategies.
Definitions Related to the
Use of Opioids for the Treatment of Pain
© 2001 American Academy of Pain Medicine, American Pain Society and American Society of Addiction Medicine
RECOMMENDATIONS
The American Academy of Pain Medicine, the American Pain Society, and the American Society of
Addiction Medicine recognize the following definitions and recommend their use.
I. Addiction
Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and
environmental factors influencing its development and manifestations. It is characterized
by behaviors that include one or more of the following: impaired control over drug use,
compulsive use, continued use despite harm, and craving.
II. Physical Dependence
Physical dependence is a state of adaptation that is manifested by a drug class specific
withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction,
decreasing blood level of the drug, and/or administration of an antagonist.
III. Tolerance
Tolerance is a state of adaptation in which exposure to a drug induces changes that result in
a diminution of one or more of the drug’s effects over time.
DISCUSSION
Most specialists in pain medicine and addiction medicine agree that patients treated with prolonged
opioid therapy usually do develop physical dependence and sometimes develop tolerance, but do not
usually develop addictive disorders. However, the actual risk is not known and probably varies with
genetic predisposition, among other factors. Addiction, unlike tolerance and physical dependence, is not
a predictable drug effect, but represents an idiosyncratic adverse reaction in biologically and
psychosocially vulnerable individuals. Most exposures to drugs that can stimulate the brain’s reward
center do not produce addiction. Addiction is a primary chronic disease and exposure to drugs is only
one of the etiologic factors in its development.
Addiction in the course of opioid therapy of pain can best be assessed after the pain has been brought
under adequate control, though this is not always possible. Addiction is recognized by the observation of
one or more of its characteristic features: impaired control, craving and compulsive use, and continued
use despite negative physical, mental, and/or social consequences. An individual’s behaviors that may
suggest addiction sometimes are simply a reflection of unrelieved pain or other problems unrelated to
addiction. Therefore, good clinical judgment must be used in determining whether the pattern of
behaviors signals the presence of addiction or reflects a different issue.
Behaviors suggestive of addiction may include: inability to take medications according to an agreed
upon schedule, taking multiple doses together, frequent reports of lost or stolen prescriptions, doctor
shopping, isolation from family and friends, and/or use of non-prescribed psychoactive drugs in addition
to prescribed medications. Other behaviors which may raise concern are the use of analgesic medications
for other than analgesic effects, such as sedation, an increase in energy, a decrease in anxiety, or
intoxication; non-compliance with recommended non-opioid treatments or evaluations; insistence on
rapid-onset formulations/routes of administration; or reports of no relief whatsoever by any non-opioid
treatments.
© 2001 American Academy of Pain Medicine, American Pain Society and American Society of Addiction Medicine
Adverse consequences of addictive use of medications may include persistent sedation or intoxication
due to overuse; increasing functional impairment and other medical complications; psychological
manifestations such as irritability, apathy, anxiety, or depression; or adverse legal, economic or social
consequences. Common and expected side effects of the medications, such as constipation or sedation
due to use of prescribed doses, are not viewed as adverse consequences in this context. It should be
emphasized that no single event is diagnostic of addictive disorder. Rather, the diagnosis is made in
response to a pattern of behavior that usually becomes obvious over time.
Pseudoaddiction is a term which has been used to describe patient behaviors that may occur when pain is
undertreated. Patients with unrelieved pain may become focused on obtaining medications, may “clock
watch,” and may otherwise seem inappropriately “drug seeking.” Even such behaviors as illicit drug use
and deception can occur in the patient's efforts to obtain relief. Pseudoaddiction can be distinguished
from true addiction in that the behaviors resolve when pain is effectively treated
Physical dependence on and tolerance to prescribed drugs do not constitute sufficient evidence of
psychoactive substance use disorder or addiction. They are normal responses that often occur with the
persistent use of certain medications. Physical dependence may develop with chronic use of many
classes of medications. These include beta blockers, alpha-2 adrenergic agents, corticosteroids,
antidepressants, and other medications that are not associated with addictive disorders. When drugs that
induce physical dependence are no longer needed, they should be carefully tapered while monitoring
clinical symptoms to avoid withdrawal phenomena and such effects as rebound hyperalgesia. Such
tapering, or withdrawal, of medication should not be termed detoxification. At times, anxiety and
sweating can be seen in patients who are dependent on sedative drugs, such as alcohol or
benzodiazepines, and who continue taking these drugs. This is usually an indication of development of
tolerance, though the symptoms may be due to a return of the symptoms of an underlying anxiety
disorder, due to the development of a new anxiety disorder related to drug use, or due to true withdrawal
symptoms.
A patient who is physically dependent on opioids may sometimes continue to use these despite
resolution of pain only to avoid withdrawal. Such use does not necessarily reflect addiction.
Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different
rates for different effects. For example, in the case of opioids, tolerance usually develops more slowly to
analgesia than to respiratory depression, and tolerance to the constipating effects may not occur at all.
Tolerance to the analgesic effects of opioids is variable in occurrence but is never absolute; thus, no
upper limit to dosage of pure opioid agonists can be established.
Universal agreement on definitions of addiction, physical dependence, and tolerance is critical to the
optimization of pain treatment and the management of addictive disorders. While the definitions offered
here do not constitute formal diagnostic criteria, it is hoped that they may serve as a basis for the future
development of more specific, universally accepted diagnostic guidelines. The definitions and concepts
that are offered here have been developed through a consensus process of the American Academy of
Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine
This document was prepared by the following committee members: Seddon Savage, MD (Chair) - APS;
Edward C. Covington, MD - AAPM; Howard A. Heit, MD - ASAM; John Hunt, MD - AAPM; David
Joranson, MSSW - APS; and Sidney H. Schnoll, MD, PhD - ASAM.
Approved by the AAPM Board of Directors on February 13, 2001
Approved by the APS Board of Directors on February 14, 2001
Approved by the ASAM Board of Directors on February 21, 2001

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