eMedicine Specialties > Psychiatry > Addiction

Opioid Abuse

Author: William J Meehan, MD, Chief Resident in Clinical Research, Department of Psychiatry, University of Massachusetts Memorial Medical Center, University of Massachusetts Medical School
Coauthor(s): Steven A Adelman, MD, Director, Behavioral Health and Addiction Medicine, Harvard Vanguard Medical Associates
Contributor Information and Disclosures

Updated: Jan 22, 2010

Introduction

Background

Opioids are defined by their ability to bind to and influence opiate receptors on cell membranes. They can be divided into 3 classes:

• Naturally occurring opioids: The classic natural opioids are opium and morphine. Opium is extracted from the plant Papaver somniferum (the opium poppy), and morphine is the primary active component of opium. Endogenous neural polypeptides such and endorphins and enkephalins are also natural opioids.
• Semi-synthetic opioids: Semisynthesis is a type of chemical synthesis that uses compounds isolated from natural sources (eg, plants) as starting materials. Semi-synthetic opioids include heroin, oxycodone, oxymorphone, and hydrocodone.
• Synthetic opioids: Synthetic opioids are made using total synthesis, in which large molecules are synthesized from a stepwise combination of small and cheap (petrochemical) building blocks. Synthetic opioids include buprenorphine, methadone, fentanyl, alfentanil, levorphanol, meperidine, codeine, and propoxyphene.

In 1913, President Woodrow Wilson's administration drafted legislation to limit the use of narcotics, requiring prescription in good faith; this 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 transactions.

In 1917, the Harrison Narcotics Tax Act was interpreted by the courts in such a way that opioids could not be prescribed for the treatment of opioid addiction.

In the 1960s, Dole and Nyswander demonstrated that methadone was an effective treatment for opioid addiction.

In 1974, the Narcotic Addict Treatment Act allowed regulated methadone treatment for opioid addiction, but made off-label use of opioids illegal.

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 Media file 1).

Frequency

United States

Opioid use and abuse has increased markedly in the United States starting in the 1990s and continuing through at least 2006. This trend coincides with a controversial US campaign against undertreatment of pain that has caused an enormous increase in opioid prescriptions. Abuse of prescription opioids has grown particularly explosively during this time. A few statistics dramatically illustrate this problem:

• Americans constitute 4.6% of the world's population, but consume approximately 80% of the world's opioid supply.¹
• Americans consume 99% of the world's supply of hydrocodone (the opioid component of Vicodin).
• Americans consume roughly two-thirds of the world's illegal drugs.

The 2006 National Survey on Drug Use and Health (NSDUH), sponsored by the Substance Abuse and Mental health Services Administration (SAMHSA), provides data that graphically illustrate the increase in prescription opioid abuse in the last decade:²

• Between 1999 and 2006, the number of persons aged 12 and older illicitly using prescription pain relievers in the month prior to being surveyed increased from 2.6 million in 1999 to 5.2 million in 2006.
• In 2006, 5.2 million surveyed persons had used prescription pain relievers illicitly in the past month, compared with 0.3 million people who had used heroin.
• In 2006, 2.2 million persons aged 12 or older used prescription pain relievers illicitly for the first time. This is more than any other illicit drug, surpassing marijuana (2.1 million new users), and dwarfing heroin (91,000 new users). While past year initiates for prescription pain relievers have increased 63% from 1997-2006, past year initiates for heroin have decreased by 20% during that same period.
• Prescription opioids have been suggested to be an important gateway drug, and the fact that they are prescribed by doctors lulls users into believing they are safe.
• The great majority of illicitly used prescription opioids are obtained from 1 physician, not from drug dealers.
• In 2006, among persons aged 12 and older who have used prescription pain relievers nonmedically in the past 12 months, the following sources were reported:
• 55.7% reported they obtained drugs free of charge from a relative or friend.
• 14.8% reported they bought or stole drugs from a relative or friend.
• 19.1% reported they obtained drugs from 1 doctor.
• Only 1.6% reported getting drugs from more than 1 doctor.
• Only 3.9% reported buying drugs from a dealer or stranger.
• Only 0.1% reported purchasing drugs on the internet.
• In cases where nonmedical users of prescription pain relievers obtained their drugs from a friend or relative for free, 80.7% of individuals reported that their friend or relative had obtained the drug from just one doctor.

Strikingly, these data suggest that drug dealers are a relatively small source of illicitly used prescription opioids. Diversion through family and friends is now the greatest source of illicit opioids, and the majority of these opioids are obtained from 1 physician, not from "doctor shopping."

Mortality/Morbidity

Since 1990, data from numerous US jurisdictions have reported dramatic increases in mortality related to drug poisonings. This increase has been due primarily to unintentional drug poisonings attributed either to opioid pain relievers or unspecified drugs.

• From 1979-1990, unintentional drug poisonings increased on average 5.3% per year.
• From 1990-2002, unintentional drug poisonings increased on average 18.1% per year. This corresponded with increased prescription of opioids for pain management
• From 1999-2002, opioid analgesic poisonings on death certificates increased 91%. During the same period, fatal heroin and cocaine poisonings increased 12.4% and 22.8%, respectively.
• In 2002, 5,528 deaths were reported from prescription opioid analgesic poisonings, more than either heroin or cocaine. The increase in mortality generally corresponded to increase in sales for each prescribed opioid.

Increases in accidental heroin overdoses are postulated to stem in part from a combination of decreasing cost and increasing purity. According to the DEA, average heroin purity increased from 7% in 1980, to 48% in 2000, to 70% in 2003. This allows first-time users to get high by snorting heroin, and eventually advance to intravenous use when tolerance develops, making initial heroin use more palatable to some addicts. Increased purity also makes mistakes in dosing potentially more lethal.

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-TR³ 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 factors⁴ : 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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