eMedicine Specialties > Psychiatry > Addiction

Opioid Abuse

Author: William J Meehan, MD, PhD, Staff Physician, Department of Psychiatry, University of Massachusetts Memorial Health Center
Coauthor(s): Steven A Adelman, MD, Director, Behavioral Health and Addiction Medicine, Harvard Vanguard Medical Associates; Ziaur Rehman, MD, Fellow in Pain Management, Department of Neurology, University of South Florida; Suzan Khoromi, MD, Fellow, Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Cranial Research, National Institutes of Health; James E Douglas, MD, Consulting Staff, Department of Psychiatry, Southwest Washington Medical Center; Consulting Staff, Department of Psychiatry, Tuality Center for Geriatric Psychiatry
Contributor Information and Disclosures

Updated: Apr 18, 2006

Introduction

Background

Opioids are the most powerful known pain relievers. Their use and abuse date back to antiquity. The pain relieving and euphoric effects of opioids were known to Sumerians (4000 BC) and Egyptians (2000 BC). International awareness of opioid abuse was stimulated early in the 20th century when President Theodore Roosevelt convened the Shanghai Opium Commission in 1909 to aid the Chinese empire in stamping out opioid addiction, especially opium smoking.

In 1913, President Woodrow Wilson's administration drafted legislation to limit the use of narcotics, requiring prescription in good faith; it became effective in 1915. Legitimate providers of narcotics and cocaine preparations were required to register with the Bureau of Internal Revenue and were mandated to keep records of most of the transactions. According to the act, legal possession by the consumer was dependent on the physician's or dentist's prescription. Legal actions were taken against the "dope doctors." However, only after many years of zealous campaign, the Harrison Act was fully enforced.

By 1918, the practice of maintaining opiate-dependent individuals on opiates was seriously questioned. The Treasury Department's special committee on Narcotic Traffic persuaded Congress to pass legislation against prescribing narcotics to people who were addicted and have no other problem.

The Narcotic Drug Import and Export Act of 1922 permitted import of crude narcotics to be manufactured into pure substances by American drug companies only.

Although opiate use dropped during World War II, the Federal Bureau of Narcotics, based on the reported post–World War I surge, anticipated resumption of opiate use and influenced Congress, which lead to legislation for mandatory minimum sentences. The death penalty also was allowed to be used at the discretion of the jury in dealing with certain drug sales.

The widespread use of methadone for opiate maintenance in the early 1960s was the major development that moderated the nation's narcotic control policy.

Opium is extracted from the plant Papaver somniferum. The main active ingredient is alkaloid morphine. Opioids, meaning opiate-like, are derivatives of opium. All opioids can produce euphoria and can be used as analgesics. Opioids can be classified as the following:

• Naturally occurring opium derivatives - Morphine
• Partially synthetic derivatives of morphine - Heroin, oxycodone, oxymorphone
• Synthetic compounds - Fentanyl, alfentanil, levorphanol, meperidine, methadone, codeine, propoxyphene

The term narcotic means drugs producing narcosis or sleep. Although narcotics do produce sleep, the term does not indicate their major therapeutic use today.

Pathophysiology

Opioid receptors in the mammalian CNS include mu, kappa, sigma, delta, and epsilon subtypes. These receptors are located in the brain (mostly in the periaqueductal grey), spinal cord, peripheral nerves, adrenal medulla, ganglia, and gut.

Stimulation of mu and sigma receptors produces intense feelings of well being and euphoria. Kappa-receptor stimulation produces dysphoria. Antagonism at these receptors may produce dysphoria, but not consistently. Antagonists block euphoria produced by opioids. Endogenous opioids, though not highly selective, have a preference for specific receptor types. Beta-endorphin is an endogenous ligand for the mu-receptor; enkephalins and dynorphins have an affinity for sigma- and kappa-receptors, respectively. The dopaminergic mesolimbic system, which originates in the ventral tegmental area (VTA) of the midbrain and projects to the nucleus accumbens, is crucial in (1) the reward effects of intracranial self-stimulation, (2) the natural rewards of water and food intake, and (3) the action of drugs of abuse, including opioids.

Basal activity of this system, expressed in dopamine release in the nucleus accumbens, is under the tonic control of 2 opposing opioid systems, activation of mu- and sigma-receptors increases, while kappa-receptor activation decreases the basal activity of the mesolimbic system. Experimental evidence with laboratory animals supports the idea that manipulation of these receptors with opioids and other substances of abuse (as well as electrical stimulation) affects self-administering behavior. These reward pathways are thought to have evolved for the natural rewards such as food and water intake (see Image 1).

Frequency

United States

A survey by the National Institutes of Health (NIH) demonstrates an upward trend in new heroin use since 1991. The prevalence of past 30-day heroin use (at least 1 instance of heroin use in the last 30 d) increased from 68,000 in 1993 to 216,000 in 1996; the lifetime prevalence of nonmedicinal use of narcotics is even higher. According to the National Comorbidity Survey performed in 1990-1992, 20-32% of people who are lifetime heroin users became dependent, while only 7.5 % of people who used analgesics became dependent.

According to the national, school-base Monitoring the Future Study, the percentage of 8th, 10th, and 12th graders who have used heroin has more than doubled since the late 1990s. This increase has largely been attributed to decreased price and increased purity in the last decade.

Epidemiologic data indicate that the nonmedical use and abuse of prescription opioids is increasing in the United States. Results from a surveillance program called the researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) system has determined that OxyContin, a sustained-release preparation of oxycodone hydrochloride, is the most commonly abused prescription opioid analgesic. Prevalence of abuse was rank ordered as follows:

1. OxyContin
2. Hydrocodone
3. Other oxycodone preparations
4. Methadone
5. Morphine
6. Hydromorphone
7. Fentanyl
8. Buprenorphine

Mortality/Morbidity

The death rate of people who use opioids is disproportionately high compared with that of people who use other IV drugs such as cocaine and phencyclidine (PCP). Heroin overdose comprises a substantial component of opioid-related mortality. Most deaths occur among IV heroin addicts in their late 20s or early 30s who have used heroin for 5-10 years. A recent period of abstinence may reduce tolerance and increase risk of overdose, and addicts have a 7-fold risk of overdosing in the first 2 weeks after leaving a residential treatment program.

Violence associated with buying or selling narcotics also causes mortalities. In some areas of the United States, death rates from drug-related violence are higher than death rates associated with overdose or HIV.

Screening tests for hepatitis A, B, and C are positive in up to 90% of IV heroin users. HIV infection is also very common in this population, with rates as high as 60% among heroin users in some areas of the United States.

Sex

Males abuse opioids more commonly than females, with the male-to-female ratio being approximately 3:1 for heroin and 1.5:1 for prescription opioids.

In a Polish study published in 1996, the direct mortality rate of people who use IV drugs was 25.7 deaths per 1000 person-years for men and 14.3 deaths per 1000 person-years for women. Compared with the general population, the risk of death was 11 times higher among males who used drugs and 20 times higher among females who used drugs.

Age

New heroin use has a negative association with age. Most people who are new users of heroin are younger than 26 years. Heroin use within the last 30 days was around 0.6 % in people aged 12-17 years, and the incidence of use decreases gradually in older age groups. The lifetime prevalence of opioid use in people aged 12-17 years is around 2.3%, and it is slightly higher in people aged 35-44 years because of peak heroin use in the 1960s and 1970s.

Clinical

History

• The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) defines opioid abuse as a maladaptive pattern of opioid use leading to clinically significant impairment or distress occurring in any of the following areas, within a 12-month period.
  • Failure to fulfill major job obligations at work, school, or home
  • Recurrent opioid use in hazardous situations, such as driving or operating heavy machines while impaired
  • Opioid-related legal problems
  • Social and interpersonal problems caused by or exacerbated by opioid use
• Most individuals who meet the criteria of opioid abuse and continue to use eventually meet the criteria of opioid dependence.
• The DSM-IV-TR defines opioid dependence as a syndrome characterized by a maladaptive pattern of opioid use, leading to clinically significant impairment or distress, as manifested by at least 3 of the following and occurring in a 12-month period.
  • Tolerance (see definition below)
  • Withdrawal (see definition below)
  • Opioids taken in larger amounts or for longer periods than intended
  • Persistent desire or unsuccessful efforts to cut down or control opioid use
  • A significant amount of time is spent in activities to obtain opioids
  • Important social, occupational, or recreational activities are given up or reduced
  • Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem
  Tolerance and withdrawal may or may not be associated with dependence.The World Health Organization (WHO) defines drug dependence as a syndrome in which the use of a drug or class of drugs takes much higher priority for a given person than behaviors that once had higher value. A decrease in volitional control over the use of opioid drugs is the central part of the behavioral symptoms observed in opioid dependence.
• Tolerance: Tolerance is the need for increasing doses of medication to achieve the initial effect of the drug. Tolerance to the analgesic and euphoriant effects and unwanted adverse effects, such as respiratory depression, sedation, and nausea, may develop. However, little tolerance develops to constipation and meiosis. Opioid tolerance usually does not develop in patients with cancer who are being treated for pain; the need for increasing doses in those patients typically is due to an increasing level of pain. No consistent relationship between intrinsic efficacy and tolerance exists.
• Withdrawal: Continuous administration of opioids leads to physical dependence, the emergence of withdrawal symptoms during abstinence. Physical dependence is expected after 2-10 days of continuous use when the drug is stopped abruptly. The onset and duration of withdrawal varies with the drug used. For example, meperidine withdrawal symptoms peak in 8-12 hours and last for 4-5 days. Heroin withdrawal symptoms usually peak within 36-72 hours and may last for 7-14 days. Symptoms of opioid withdrawal include the following:
  • Autonomic symptoms - Diarrhea, rhinorrhea, diaphoresis, lacrimation, shivering, nausea, emesis, piloerection (the phrase stopping "cold turkey" refers to piloerection, or "gooseflesh")
  • Central nervous system arousal - Sleeplessness, restlessness, tremors
  • Pain - Abdominal cramping, bone pains, and diffuse muscle aching
  • Craving - For the medication
• Addiction: The phenomenon of addiction is seen in a variable number of patients using drugs. Addiction is characterized as a psychological and behavioral syndrome in which the following features are observed:
  • Drug craving
  • Compulsive use
  • Strong tendency to relapse after withdrawal
  Addiction must be defined by the observation of maladaptive behaviors, such as adverse consequences due to drug use, loss of control over drug use, and preoccupation with obtaining opioids, rather than pharmacological phenomenon of physiologic dependence, tolerance, and dose escalation. Do not use the term addiction to describe patients who are merely physically dependent. Also, keep in mind that undertreatment in patients with pain may result in a pseudoaddiction, and opioid-seeking behavior may be mistaken for addiction.Long-acting medications, such as methadone and sustained-release morphine, tend to have slower onset of action, and the rush or high experienced with more rapid-onset medications is not as prominent. Thus, the longer-acting opioids are less likely to be abused.

Physical

• Dependence
  • Mental status effects include depression with any or all of its symptoms, such as sleep disturbances, lack of interest, selflessness, suicidal ideation, and poor coping skills.
  • Physiological effects: Because tolerance to many of the actions of the opioids develops, it is not likely for even a careful observer to notice the effects of opioids. Small-sized pupils may be the only observation because only very mild tolerance develops for miosis. Inflamed nasal mucosa may be seen if heroin is snorted.
• Withdrawal
  • Mental status effects include purposive behaviors, such as complaints and manipulations directed at getting more drug, and anxiety.
  • Physiologic effects
    • Autonomic signs - Tachycardia, high blood pressure, fever, piloerection (goose flesh), mydriasis, and lacrimation
    • Central nervous system arousal - Irritability
    • Yawning
  • In milder abstinence syndrome, clinical features may be limited to dysphoria, craving, yawning, lacrimation, rhinorrhea, and restlessness. In moderate-to-severe cases, piloerection, mydriasis, increased BP and pulse, and GI symptoms are seen as well.
• Intoxication
  • Mental status effects include euphoria, sedation, decreased anxiety, a sense of tranquility, and indifference to pain produced by mild-to-moderate intoxication. Severe intoxication can lead to delirium and coma.
  • Physiological effects
    • Respiratory depression (may occur while the patient maintains consciousness)
    • Alterations in temperature regulations
    • Hypovolemia (true as well as relative), leading to hypotension
    • Miosis
    • Needle marks or soft tissue infection
    • Increase sphincter tone (can lead to urinary retention)
• Addiction
  • The physical examination provides little information to add in the diagnosis of addiction. However, symptoms of opioid withdrawal and track marks are suggestive of addiction.
  • Constipation is a common occurrence due to almost continuous use of narcotics.

Causes

Opioid dependence is considered a biopsychosocial disorder. Pharmacological, social, genetic, and psychodynamic factors interact to influence abuse behaviors associated with drugs. However, pharmacological factors can be especially prominent, more so than in other types of drug use disorders.

• Pharmacological factors: Opioids are strongly reinforcing agents because of the euphoric effects and reported ability to reduce anxiety, increase self esteem, and help coping with daily problems. Most opioids associated with abuse and dependence are mu-agonists, such as heroin, morphine, hydrocodone, oxycodone, and meperidine. Some partial mu-agonists, such as buprenorphine, or some that have no mu-agonism, such as pentazocine, also can possess reinforcing properties. Rapid development of physical dependence and a protracted abstinence syndrome are unique to opioid use and can make abstinence difficult.
• Social factors: Easy drug availability and acceptable social attitudes make experimentation easy. A high rate of drug use is seen in areas of the city with poor parental functioning and higher crime and unemployment rates. Except for the association between higher exposure to the drug and higher rates of addiction, the precise role of social factors in creating dependent and addictive behaviors is uncertain. Of US service personnel in Vietnam between 1970 and 1972, 42% tried heroin; one half of those personnel became physically dependent, but very few continued to use heroin in their civilian life.
• Psychological factors: Ego defects in certain patients are postulated to form the basis of drug use. Opioids are theorized to help the ego in managing painful effects such as anxiety, guilt, and anger. Behavioral theory postulates that basic reward-punishment mechanisms perpetuate addictive behavior
• Genetic factors: Genetic epidemiologic studies suggest a high degree of heritable vulnerability for opioid dependence. Gene polymorphisms for dopamine receptors/transporters, opioid receptors, serotonin receptors/transporters, proenkephalin, and catechol-O-methyltransferase (COMT) all appear to be associated with vulnerability to opioid dependence. Future interventions for opioid dependence may include medications identified through genetic research.

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