CODEINE

OFFICIAL NAMES: Codeine, codeine phosphate, codeine sulfate, methylmorphine

STREET NAMES: T–threes, schoolboy, coties, dors and fours, cough syrup, barr (codeine cough syrup), down (codeine cough syrup), karo (codeine cough syrup), lean (codeine cough syrup), nods (codeine cough syrup)

DRUG CLASSIFICATIONS: Schedule II, III, or V, narcotic

OVERVIEW

Codeine is classified as an opiate analgesic. Analgesics are substances that, when ingested or injected, diminish or relieve pain; opiates are drugs that can be derived from opium. Opiates, along with opioids, the broader group to which opiates belong, are the most effective of all analgesics. All opioids are analgesics, but most analgesics are not opioids.

Many different drugs act as analgesics. One method of classifying these drugs is to separate them into two groups—those that require a doctor's prescription and those that do not. Medications that do not require a doctor's prescription are called over-the-counter (OTC) drugs. OTC analgesics include acetaminophen (Tylenol), aspirin, and ibuprofen. Codeine, a prescription analgesic, is one of the most frequently prescribed medications used worldwide to treat pain.

Pain is universal; everyone experiences different kinds of acute (short-term) pain during their life. However, too much pain for too long, (moderate to severe chronic pain), can be harmful, both physically and psychologically. Approximately one-third of all people in the United States experience moderate to severe chronic pain during their life. Half of all individuals who seek medical attention report pain as their primary complaint.

Codeine and other opioid medications are used medically because of their ability to relieve physical pain—in fact, it is the only reason for their medical use as a group. A broader view of opioids reveals that they also can have profound effects on emotional pain—which is perhaps a frequent, if unconscious, reason for their non-medical use/abuse. Physical and emotional pain often have an inseparable connection between them. Even something as simple as stubbing a toe usually elicits a short, but dramatic, emotional response. However, the primary medical use for codeine is only in the treatment of physical pain.

In considering the analgesic effects of opioids such as codeine, it is important to know that the body has two connected systems, one that signals pain and another that responds to it. Both systems have interacting physical and chemical components. The physical portion includes neurons of the central (brain and spinal cord) and peripheral nervous systems. The chemical portion includes substances that aid in the transmission of signals between nerve cells (neurotransmitters), along with chemicals and proteins that have specific roles in normal nerve cell function. The most important group of neurochemicals in the pain killing system is the endogenous opioids. An "endogenous" substance is something that is naturally produced by the body. Endogenous opioids function as the body's own analgesics.

The body's natural painkilling system, then, involves the interaction of endogenous opioids with neurons that transmit and process pain signals. Opioid medications such as codeine mimic the effects of certain endogenous opioids. However, ingested/injected opioids tend to produce much stronger effects than those of the endogenous variety.

Opioid receptors are the cell-surface proteins which all opioids interact with to produce their effects. An opioid, whether endogenous or in drug form, fits into a receptor somewhat like a key in a lock. Opioid attachment activates the receptor and initiates complex changes in the nerve cell. Activated opioid receptors produce chemical changes that reduce the ability of a nerve cell to transmit pain signals. They also decrease the "perception" of pain by neurons in the brain. In the absence of pain, those same chemical changes can produce euphoria. Loosely translated from Greek, euphoria means "good feeling."

Codeine is extracted from opium. Opium is a chemically complex drug derived from a flowering plant, the opium poppy. The scientific name for the opium poppy is Papaver somniferum, which translated from Greek means "poppy that causes sleep." Opium is produced by drying the thick liquid harvested from the unripe seed capsule of the flower. It contains several different medically important chemicals known as "alkaloids" (nonacidic chemicals), the most important being morphine and codeine.

Societies have used the medicinal properties of opium for several thousand years. Even up to the early part of the twentieth century, opium was used as a medicine to treat a large variety of conditions. For some of those conditions, particularly those involving pain and/or diarrhea, it was a highly effective treatment. However, by modern standards, most of opium's historical uses for illness would be considered medically useless or unsound because of the dangers of opium use.

Two of the most important effects of opium are its abilities to relieve pain and produce euphoria. Euphoria is best described as an exaggerated sense of well-being, possibly with mild elation or a sense of calmness. Opium's ability to produce euphoria may be what prompted its use by so many throughout history as a cure-all. After all, while it may not have had the curative effect on a person's illness that was suspected or promised, it usually made them feel better.

Achieving consistent results with opium has always been difficult. Different methods of production and naturally varying concentrations of morphine and codeine produce widely varying results from one batch to the next. Once the chemical methods became available, scientists were eager to isolate the active ingredient(s), hoping to produce a "pure" analgesic.

Morphine was isolated from opium in 1806, which was a significant step in scientific pharmacology. For the first time, a powerful, pain-relieving medicine was available whose effects were predictable. However, it eventually became clear that the addictive potential of morphine is equal to that of opium, with many of the same side effects. Undaunted, scientists began the quest, which is ongoing, for the "perfect" opioid—a drug with the analgesic power of morphine, but with much milder side effects and little or no addictive potential.

Codeine was extracted from opium in 1832, and was the first partial success in the attempt to discover a safer and less addictive drug. However, with fewer side effects came a less potent analgesic. About 100 mg of codeine are needed to produce the same effect as 10 mg of morphine. It was believed at the time (and it is still debated) that codeine's milder effects on a per weight basis actually result in fewer side effects when equally effective dosages are given (i.e., 100 mg of codeine produces fewer side effects than 10 mg of morphine). For the most part, standard medical practice has been to prescribe codeine for moderate pain, and reserve morphine for more severe pain.

Semi-synthetic and synthetic opioids (meperidine, hydrocodone, fentanyl, etc.) are the result of many attempts to produce effective yet safer analgesics. The fact that both morphine and codeine are still widely used indicates that the newer opioids have been only moderately successful. However, current knowledge of the opioid system makes the goal of producing the perfect (or near-perfect) opioid analgesic a more realistic possibility in the future.

Since the middle of the nineteenth century, most social attention to opium has focused on its use as an illicit drug. In fact, in many ways it has come to symbolize the worst aspects of illegal drugs. This negative social stigma has carried over to the derivatives of opium—the opioid drugs. While there is some basis for this perception, it has unfortunately generated undue fear, even within the medical professions, that anyone using an opioid drug, even someone in pain, is at great risk of becoming addicted.

CHEMICAL/ORGANIC COMPOSITION

Opium typically contains between 0.5% and 3.0% codeine by weight. Chemically, codeine is nearly identical in structure to morphine. The only difference between the two is that codeine contains an extra methyl group (two hydrogen atoms bound to a carbon atom) at one end of the molecule. In fact, once absorbed in the body, an enzyme removes the methyl group (demethylation) from codeine to produce morphine. Thus, codeine itself is not an analgesic.

The enzyme responsible for converting codeine to morphine is known as cytochrome P450 2D6, abbreviated CYP2D6. About 8% of people in the Caucasian population, 6% in the black population, and 1% of Asians have a genetic trait that results in a deficiency of CYP2D6. This means that codeine has little or no effect on them. A large number of other genetic variants of the CYP2D6 enzyme result in a wide variation in how well people metabolize codeine.

INGESTION METHODS

Codeine-containing medications are most often taken orally, either in tablet form or as syrup (also called "elixir"). Codeine may also be given by intramuscular (IM) injection. Intravenous codeine administration is not used because of the risk of causing dangerously low blood pressure (hypotension). Codeine suppositories are given rectally, but usually only in infants and children who have had surgery.

It is difficult, but possible, to extract the codeine from tablet and syrup preparations. This is usually done by people who wish to abuse codeine and need higher doses than could be safely taken when it is combined with other medications. Once extracted, the codeine powder is typically mixed with a liquid of some kind and drunk. Since OTC medicines with codeine contain very small amounts of the drug, large quantities must be purchased in order to be able to extract enough codeine to abuse. This can be expensive and cause suspicion in a single pharmacy.

Codeine is not routinely sold in the United States as an individual drug. It is combined instead with one or more other OTC analgesics or cough suppressants into a single compound medication. Codeine is familiar to most people as an ingredient in a series of analgesic preparations in combination with Tylenol-brand acetaminophen. The number after "Tylenol" designates the amount of codeine in each tablet:

• Tylenol #1 —8 mg codeine (not marketed in the United States)
• Tylenol #2 —15 mg codeine
• Tylenol #3 —30 mg codeine
• Tylenol #4 —60 mg codeine

All combinations contain 300 mg acetaminophen per tablet. Other pharmaceutical companies produce similar preparations that may have slightly different amounts of acetaminophen, but the number designation and codeine quantity stay constant across brands. Some preparations also include up to 30 mg of caffeine to help counteract drowsiness from the codeine.

THERAPEUTIC USE

Codeine is most often used in the treatment of mild to moderate pain that does not respond fully to OTC analgesics. A number of different cough-suppressant (antitussives) medications contain low concentrations of codeine. The effects of codeine on the nerves and muscles of the intestines make it an effective treatment for diarrhea. However, since equally effective OTC medications are available, codeine is now rarely used for this purpose.

For some time, the medical community has debated whether codeine is truly effective in relieving pain and suppressing coughs. Several studies have shown that codeine alone is not significantly more effective than maximum doses of nonprescription analgesics such as acetaminophen or ibuprofen. Most research has shown, however, that codeine added to nonprescription analgesics provides a small but significant benefit. Still, some studies have shown that certain cough medicines are equally effective with or without codeine. More research is needed to resolve this issue.

Even if the physical benefits from codeine were truly minimal, the classification of codeine as a narcotic (implication: "powerful") analgesic might provide a significant placebo effect in some individuals.

USAGE TRENDS

The United States imports about 70% of the world's opium. About 95% of that opium is consumed in the form of schedule III preparations, of which codeine is the most common. Until the mid-1970s, opium had been the main raw material used for the production of morphine and codeine. Since 1978, however, concentrate of poppy straw has been used with increasing frequency for that purpose. "Poppy straw" is a term used for the remainder of the poppy plant—but primarily refers to the seed capsule itself—once the seeds and opium-producing fluid have been removed. The majority of morphine and codeine production now comes from concentrate of poppy straw.

The concentrations of morphine and codeine in both raw opium and poppy straw vary greatly, but morphine concentrations as a percentage of total weight are typically about 10 times greater than are those of codeine. Therefore, processing of opium and poppy straw produces much more morphine than codeine. However, greater quantities of codeine than morphine are required for medical purposes. Based on the discrepancies between production and use of the two drugs, about 80% of morphine is converted into codeine.

The global manufacture of codeine underwent a 22% increase in the 1980s, from 162 tons (147,000 kg) in 1980, to 197 tons (180,000 kg) in 1989. The rate of production increased during the 1990s, with total codeine production reaching 280 tons (255,000 kg) in1999. Overall, a 65% increase in global codeine production occurred in the 20 years between 1980 and 1999. Most codeine goes directly into medications, but some is also used to produce other opioid medications such as dihydrocodeine and hydrocodone. Actual figures for the number of codeine prescriptions written in the United States in any particular year are difficult to obtain, since less than half of all states track these numbers. Of all prescriptions written for opioid analgesics, about 15% are for codeine.

Scope and severity

Just as the medical use of codeine has increased, its misuse and abuse have also increased, although not in proportion. The issue of drug abuse can be analyzed from many different perspectives and categorized in a number of ways. One method is to compare and contrast the abuse of illegal drugs (marijuana, cocaine, etc.) with that of legal drugs (OTC and prescription medications). The majority of national and international attention and resources go toward illegal drug abuse. However, prescription drug abuse is a large and growing proportion of the complete drug abuse picture.

Each year, the National Household Survey on Drug Abuse (NHSDA), conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA) of the United States Department of Health and Human Services, collects statistical data on five drug groups, including marijuana/hashish, psychotherapeutic drugs, cocaine/crack, hallucinogens, and inhalants. The medications included in the psychotherapeutic drug group are stimulants, sedatives, tranquilizers, and pain relievers. Codeine and other opioids constitute the majority of the pain relievers in the group.

In 2000, the NHSDA found 1.7% of all people 12 years and older reported nonmedical use of a psychotherapeutic medication during the previous month. More than 9 million Americans over age 12 reported use at any time during the year. Those in the 18-to 25-year-old age group have the highest rates of drug abuse. In 2000, 3.6% of individuals in that age group reported nonmedical use of prescription drugs in the month prior to when they were surveyed, but less than half that many, 1.6%, reported the same type of drug abuse in 1994. An estimated 1.6 million Americans used prescription pain relievers nonmedically for the first time in 1998. During the 1980s, there were generally fewer than 500,000 first-time users per year.

The Drug Abuse Warning Network (DAWN) is an ongoing program sponsored by SAMHSA. Approximately 500 hospital emergency rooms throughout the United States gather data from admitted patients on drugs of abuse (i.e., the number of times a specific drug is mentioned by ER patients). A study published in the Journal of the American Medical Association in 2000 compared the increase in legitimate medical use of opioids with one indicator of the increase in abuse of those same drugs. Specifically, five opioid drugs—morphine, fentanyl, oxycodone, hydromorphone, and meperidine—as a group showed a cumulative increase in medical use of nearly 250% from 1990 to 1996. Data collected from DAWN for the same time period showed a 7% increase in emergency room mentions of abuse of these drugs. As a proportion of all opioid drugs mentioned, the five drugs studied decreased from 23% in 1990 to 16% in1996. This means that mentions of other opioid analgesics, including codeine (although raw numbers for codeine were not analyzed), increased during that time period by 16%. By comparison, the reports of abuse of illicit drugs increased 110%. Admittedly, the data collected by DAWN evaluates only one facet of the drug abuse problem—drug abuse contributing to emergency room visits. However, from these data at least, it does not appear that a significant increase in medical use of opioid drugs resulted in a proportionate increase in abuse. More studies looking at a broader picture of opioid analgesic abuse are needed.

Age, ethnic, and gender trends

Between 1990 and 1998, abuse of some illegal drugs among teens and young adults leveled off or decreased slightly. However, increases in new users of prescription pain relievers were reported in young teens, age 12–17, as well as in young adults age 18–25. In 2000, the NHSDA found that the youngest teens, age 12–14, reported psychotherapeutic medications as the most frequent drugs of abuse, with that group alone making up 53% of the total of all drug abuse reports. Teens and young adults in the 18–25 age group reported prescription drug abuse at a rate of 36%, while 28% of those over age 26 reported that type of abuse. Most teenagers begin prescription drug abuse by taking someone else's medication, usually someone from their family. Teens are also more likely than adults to be acquainted with someone who sells prescription drugs like codeine illegally.

On the other end of the age spectrum, prescription drug abuse among older adults is also a growing concern. Persons 65 and older comprise 13% of the United States population, but consume about 33% of all prescription drugs. A study of 1,500 elderly patients found that 3% were abusing prescription drugs. Unlike people in younger age groups, however, the elderly are more likely to misuse prescription drugs than abuse them. If abuse does occur, it may begin with misuse due to inappropriate prescribing or the patient not following instructions correctly. Continued misuse may then progress to dependence and abuse, especially with medications such as codeine. Other factors may influence codeine misuse and abuse in older adults. There may be age-related physical changes that influence codeine metabolism, or confusion about the effects codeine can produce. The elderly also have a higher likelihood of other undiagnosed medical conditions, such as depression, that increase the risk for codeine abuse. Finally, a survey of elderly persons admitted to a treatment program found that 70% were female and of the various drugs of abuse in that group, 70% were opioids.

The NHSDA study showed that boys in the youngest age group (12–17) are more likely to experiment with illegal drugs, but girls of that age have a 20% higher rate of prescription drug abuse. In addition, for all teens of that age that abuse prescription drugs, girls are twice as likely to become addicted as boys are. Women are also more likely to abuse and become addicted to prescription drugs in the young- and middle- adult age groups. Part of this may be that women are prescribed potential drugs of abuse more often than men are.

At all age groups, whites are more likely than other racial or ethnic groups to abuse prescription drugs, and many people who abuse these drugs have psychiatric disorders. In 2000, the New England Journal of Medicine published a report on a survey of pharmacies in New York. The data showed that pharmacies in predominantly minority neighborhoods (greater than 60% non-white population) were three times less likely to stock enough opioid drugs to fill prescriptions on demand than were pharmacies in predominantly white neighborhoods. This may be due to financial constraints in trying to maintain inventories of drugs in those minority neighborhood pharmacies. However, it may also be from fear of crime. A number of pharmacies in the United States were burglarized for their opioid drugs, especially the drug OxyContin, in the late 1990s. The events made national headlines, and intensified the debate over the benefits and drawbacks of opioid drugs.

Health professionals (doctors, nurses, dentists, veterinarians, etc.) and their staff may be at risk for codeine abuse because of their ready access to the drug. On the other hand, one would expect health care workers to be at less risk due to their training and knowledge of the effects of drug abuse. In fact, health care workers do not appear to have rates of codeine or other opioid abuse much different from the rest of the population.

MENTAL EFFECTS

Most people describe the euphoria produced by codeine as a pronounced feeling of well-being and calmness. A few people may get a mild stimulant effect and a feeling of elation. Evidence indicates that the euphoria produced by codeine and other opioids is similar to, but stronger than, the perceived feeling from high levels of endogenous opioids in the body—the so-called endorphin rush experienced by some athletes after heavy exercise. Instead of euphoria after a codeine dose, some people report a feeling of dysphoria—a general feeling of discomfort and restlessness. Still other people may just feel drowsy, with no noticeable positive or negative effect on their mood.

It remains a misconception that opioids offer no true analgesic effect, but instead produce a type of euphoria that simply results in one not caring about their pain. With the discovery of opioid receptors in the central nervous system, along with an understanding of how opioids such as codeine affect nerve cells, no dispute remains that opioids are indeed potent pain relievers. Up to a certain limit (usually an amount great enough to produce serious side effects), the more codeine ingested in a single dose, the greater the analgesia and the more pronounced the mental effects would be.

People with moderate or severe pain who take prescribed doses of codeine usually obtain at least some relief from their pain, but generally do not report feelings of euphoria. Those with mild pain who take one of the higher doses of codeine (e.g., Tylenol #4) may experience pain relief along with some euphoria. People who abuse codeine are most likely to experience euphoric feelings, and are at the greatest risk of becoming addicted.

PHYSIOLOGICAL EFFECTS

Other than analgesia, the most common physiological effects produced by medicinal quantities of codeine are nausea, vomiting, constipation, and itching of the skin (pruritis). These symptoms would be considered relatively harmless (benign) side effects. They typically disappear in most people after taking the drug for several days, or by reducing the dosage. If someone has diarrhea prior to using codeine, the physiological side effect of constipation then becomes a medicinal effect for that symptom. For most people, the higher the codeine dose, the more likely side effects will be present or the more severe the side effects will be.

Harmful side effects

Overall, codeine's lower potency results in fewer side effects compared to other drugs in the class. The complication of greatest concern is respiratory depression. Opioids affect the area of the brain that controls breathing. A large enough single dose of any opioid, including codeine, can stop breathing completely, resulting in death. Combining codeine with another central nervous system depressant, such as alcohol or sedatives, is especially risky. Unfortunately, people who abuse codeine often abuse other drugs as well. While drowsiness itself is not a harmful side effect, it can be dangerous when driving or engaging in other activities that require concentration and alertness.

Since most codeine is dispensed as part of a compound preparation, potential side effects of the other drug(s) must also be considered. For instance, someone with stomach ulcers should not take codeine that is combined with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Another type of risk from a compound preparation relates to codeine abuse. For instance, a person who abuses codeine might routinely take a dose of 100–200 mg of codeine to produce noticeable euphoria. Using Tylenol #3 to obtain this dose would also mean ingesting 1,000–2,000 mg of acetaminophen. Taking that amount of acetaminophen for any extended period presents a risk for liver damage, especially in combination with alcohol.

Long-term health effects

There are very few adverse health effects as far as organ or tissue damage from long-term (years) use of codeine. This is in contrast to most other abused drugs, with alcohol and tobacco being the obvious examples.

The relative lack of any known serious organ or tissue damage produced by codeine use is counterbalanced, however, by its high risk for abuse and addiction. Even though codeine may be the least addictive of the group, opioids are arguably the most addictive drugs known. Drugs with a high risk of addiction also present a high risk for long-term use, which can include either years of continual use or a repeated cycle of use and abstinence. The latter can be especially difficult with codeine given the potentially serious withdrawal symptoms associated with stopping the drug suddenly. Most people with codeine addiction do not seek professional help, and self-treating an addiction usually involves stopping the drug suddenly.

A sudden withdrawal from codeine after a long period of use always results in some withdrawal symptoms. The longer and more serious the abuse, and the more suddenly the drug is stopped, the more difficult and painful the withdrawal symptoms will be. Chronic use of codeine can result in some tolerance to the drug so that higher doses must be taken to obtain the same initial effects. However, the level of tolerance seems to be less in people using codeine legitimately for pain. Long-term use also can lead to physical dependence, a process in which the body adapts to the presence of the drug, resulting in withdrawal symptoms if its use is abruptly stopped. Symptoms of withdrawal can include restlessness, muscle and bone pain, insomnia, diarrhea, runny nose, chills with goose bumps, and involuntary leg movements. The involuntary leg movements associated with opioid withdrawal are what originally lead to the phrase "kicking the habit." The phrase "quitting cold turkey" originated because the goose bumps on a person's skin that often occur during withdrawal resemble cold turkey skin.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Using alcohol while taking codeine poses a serious risk. Like codeine, alcohol is a CNS depressant, and the two drugs combined increase the risk of heavy sedation and respiratory depression. Other drugs that should be avoided or used only under a doctor's supervision while taking codeine include benzodiazepines (tranquilizers in the same class as Valium), most antihistamines, and sedatives/hypnotics (sleep medications). Certain types of antidepressants should be used with caution when taking codeine, especially monoamine oxidase (MAO) inhibitors and those in the selective serotonin reuptake inhibitor (SSRI) class. Some codeine abusers use glutethimide (Doriden), a potent tranquilizer, to produce effects similar to heroin increasing the risks for serious side effects and addiction.

TREATMENT AND REHABILITATION

Serious addiction to codeine is not as common as it once was, possibly due to the availability of greater numbers of competing, more potent opioids. The perception by some that addiction to a "weak" opioid like codeine is not serious results in fewer individuals seeking treatment for their codeine addiction. However, in those cases where treatment is needed, codeine addiction should be approached in the same manner as addiction to other opioids, such as heroin or morphine.

Codeine overdose can be treated with the opioid antagonist, Narcan (naloxone). The goal of treating codeine addiction is for the addicted person to stop taking the drug completely and permanently. Most people who overcome codeine addiction do so by themselves, but some may need professional assistance. In either case, it is invaluable for someone to have help and support from friends and family. For chronic addiction (addiction lasting more than one year), codeine may be replaced by methadone, another opioid medication. Methadone is provided to the patient either through a physician or through a qualified drug treatment program. In a structured setting, the patient and health care professionals have a much better chance of controlling drug use with methadone, and eventually may achieve complete abstinence. The benefits of methadone over codeine are that it only needs to be taken once a day, it reduces or eliminates withdrawal symptoms and the craving for codeine, and it has fewer side effects.

PERSONAL AND SOCIAL CONSEQUENCES

Illicit drug use provides little or no personal and social benefits, though codeine and other opioids do offer personal and social medical benefits. However these benefits must be weighed against the potential costs of abuse and addiction for individuals and society.

Most codeine prescriptions are written for Schedule III preparations. These medications provide an important middle ground between two drug groups—less effective OTC and nonnarcotic prescription analgesics on one side, and Schedule II analgesics on the other. Distribution and prescriptions are more tightly regulated for Schedule II than for Schedule III drugs. Consequently, for a patient whose pain level is not severe enough to require a Schedule II drug, yet is too severe for or does not respond well to OTC or other prescription analgesics, codeine can provide an effective compromise.

The social consequences of having a broad range of analgesics to treat chronic pain are significant. Conditions associated with chronic pain are the largest contributors to lost work time and productivity. In addition, home and family life may be disrupted for those whose pain is not effectively treated. Therefore, while a doctor must weigh the risks and benefits of treating with codeine on an individual basis, judicious use of codeine and other opioids would seem to present much greater social benefits than costs.

Personal costs—financial, physical, and emotional—can be significant for those individuals who abuse codeine and become addicted. An established addiction can be expensive to maintain, even with a relatively inexpensive medication (through legal purchase) such as codeine. Many people describe a serious opioid addiction as "all consuming"; everything in their life eventually revolves around obtaining more of the drug. With the drug as their focus, they lose friends, alienate family members, and they may be unable to hold a job. With a lower cost and greater availability compared to other opioids, codeine may serve as a starting point for a progression to more powerful, costly, and addictive Schedule II drugs, not to mention illicit drugs.

It might seem logical that anyone who goes to great lengths to obtain codeine is addicted, abusing it recreationally, or selling it for profit, but this is not always the case. While the situation is improving, many people with chronic pain still find it difficult to locate a doctor who will prescribe opioid analgesics. A person with chronic pain may show drug-seeking behavior if they find it difficult to obtain prescriptions for the medication. In fact, a doctor treating such a person might mistake the behavior for psychological addiction rather than somewhat desperate attempts to obtain relief for an ineffectively treated condition.

Codeine plays a relatively minor role in the overall picture of opioid prescription drug abuse. Evidence indicates that proper prescribing of codeine for legitimate medical concerns does not greatly increase the risk of addiction and abuse. Those in the medical community agree that more education is needed on both sides to help prevent the potential for abuse and addiction, so that patients truly in need are not denied access to codeine based on misperceptions and fear. The benefits for individuals and society are great when chronic pain is treated safely and effectively.

LEGAL CONSEQUENCES

Whether requiring a written order in a hospital chart (or other inpatient health care institution) or a prescription written on a special form, hospital and community pharmacies exercise special caution when dispensing codeine and other controlled substances. In some cases, a doctor may choose to telephone the patient's pharmacy with the prescription. However, for medication such as codeine, they must provide their DEA number and some relevant medical information. This helps to prevent someone from calling a pharmacy to obtain codeine by impersonating a physician. It is unlikely that anyone other than a physician or dentist would have access to both a valid DEA number and the medical knowledge necessary to sound credible to pharmacy staff when ordering such a medication.

It is illegal to write a prescription or an order for codeine without a valid medical license. Those professionals that may legally write prescriptions or orders for codeine include medical doctors (MD), doctors of osteopathy (DO), podiatrists (PO), dentists (DDS), and veterinarians (DVM). Physicians or dentists who knowingly write multiple prescriptions for patients without a valid medical reason are subject to possible disciplinary action and criminal prosecution. Writing and filling fake prescriptions for profit is a more serious offense. Likewise, it is illegal to obtain, or try to obtain, prescriptions for codeine under false pretenses (fabricated symptoms and scenarios). Nineteen states have a law (a felony in some) prohibiting a patient from obtaining the same controlled substance from multiple prescribers within a limited time period (doctor shopping). Unlike the illegal activities associated with most other drugs, the perpetrators of crimes involving prescription drugs are most often white, middle-class women. Their crimes usually involve doctor shopping and/or prescription forgery.

Many people in the government and medical community fear that increased production of opioid drugs correlates with increased rates of abuse and addiction. Pharmacies were increasingly burglarized for their opioid drugs, which seemed to bolster this argument. However, the newsworthiness of those crimes serves to overemphasize one side of the debate. Studies have consistently shown that patients with chronic pain who use opioids appropriately rarely become addicted. In 2001 and 2002, a number of groups advocating for effective pain management joined with government agencies, including the Drug Enforcement Administration (DEA), to begin a long-term effort to increase the availability of effective pain management drugs for patients, while decreasing the illegal use and abuse of these drugs.

Legal history

In the United States, the Harrison Narcotics Act of 1914 provided the first real regulation of the general sale of opiates. The exceptions were sales to licensed physicians for use on their own patients, and sales to those people who could provide a written prescription from a doctor. The adoption of laws controlling the production and distribution of all prescription medications occurred primarily because of morphine and codeine.

Codeine is a controlled substance in the United States. Its manufacture and distribution are controlled by the Food and Drug Administration (FDA) and the DEA. The majority of other countries have controls similar to those of the United States. International control is overseen by the International Narcotic Control Board (INCB).

Several foreign countries and some states continue to sell medications with small amounts of codeine over the counter. In the United States, though, even OTC codeine medications have restrictions. A person purchasing codeine must be at least 18 years of age and provide valid identification. In addition, their name may be entered in a special logbook maintained by the pharmacy.

Federal guidelines, regulations, and penalties

Injectable forms of codeine are classified under the Controlled Substances Act (CSA) as Schedule II, even though they do not typically contain more than 60 mg per dose. Analgesics containing 15–60 mg of codeine per single dose carry a Schedule III classification (although the upper single dose limit in many states is 90 mg). Schedule III drugs have a lower potential for abuse than drugs in Schedule II, and abuse of the drug may lead to moderate or low physical dependence and/or high psychological dependence.

Medications containing less than 15 mg of codeine per single dose (most contain either 8 mg or 12 mg) are classified as Schedule V. Cough suppressants with codeine make up the majority of this category. Drugs in Schedule V have a low potential for abuse, but abuse may lead to limited physical dependence and/or psychological dependence compared to drugs in Schedule IV.

See also Fentanyl; Heroin; Meperidine; Morphine; Opium; Oxycodone

RESOURCES

Books

American Cancer Society. American Cancer Society's Guide to Pain Control. Atlanta: American Cancer Society Health Content Products, 2001.

Andrews, Tom. Codeine Diary: A Memoir. Toronto: Little, Brown and Company Limited, 1998.

Booth, Martin. Opium: A History. New York: St. Martin's Press,1996.

Courtwright, David T. Forces of Habit: Drugs and the Making of the Modern World. Cambridge: Harvard University Press, 2001.

Kuhn, Cynthia, et al. Buzzed: The Straight Facts About the Most Used and Abused Drugs from Alcohol to Ecstasy. New York:W.W. Norton and Company, Inc., 1998.

Rudgley, Richard. Essential Substances: A Cultural History of Intoxicants in Society. New York: Kodansha America, Inc., 1994.

Periodicals

Brookoff, Daniel. "Chronic Pain: 1. A New Disease?" Hospital Practice 35 (July 15, 2000): 45-59.

Brookoff, Daniel. "Chronic Pain: 2. The Case for Opioids." Hospital Practice 35 (September 15, 2000): 69-84.

Demott, Kathryn. "Opioids Still Worthwhile Despite Street-drug Taint." Clinical Psychiatry News 29 (June 2001): 46.

Joranson, David E., et al. "Trends in Medical Use and Abuse of Opioid Analgesics." The Journal of the American Medical Association 282 (April 5, 2000): 1710-4.

Mitka, Mike. "Abuse of Prescription Drugs: Is a Patient Ailing or Addicted?" The Journal of the American Medical Association 283 (March 1, 2000): 1126.

Potter, Michael, et al. "Opioids for Chronic Nonmalignant Pain." Journal of Family Practice 50 (February 2001): 145.

Rich, Ben A. "Physicians' Legal Duty to Relieve Suffering." The Western Journal of Medicine 175 (September 2001): 151.

Walling, Anne D. "Codeine Plus Acetaminophen: Benefits and Side Effects." American Family Physician 54 (November 15,1996): 2302.

Weikel, Dan. "Rx for an Epidemic: Prescription Fraud—Abusing the System. Token Enforcement Allows Pill Peddlers to Flourish." Los Angeles Times (August 18, 1996): A1.

Other

Codeine Information. (March 29, 2002). <http://codeine.50g.com>.

Purdue Pharma L.P. "Painfully Obvious: The Effects of Abusing Prescription Drugs." (March 29, 2002). <http://www.painfullyobvious.com>.

United Nations Office for Drug Control and Crime Prevention. <http://www.undcp.org>.

"The Vaults of Erowid: Documenting the Complex Relationship between Humans and Psychoactives." (March 29, 2002). <http://www.erowid.org>.

Organizations

Drug Enforcement Administration (DEA), Information Services Section (CPI), 2401 Jefferson Davis Highway, Alexandria,, VA, USA, 22301, <http://www.usdoj.gov/dea>.

National Institute on Drug Abuse (NIDA), National Institutes of Health, 6001 Executive Boulevard, Room 5213, Bethesda, MD, USA, 20892-9561, (301) 443-1124, (888) 644-6432, [email protected], <http://www.drugabuse.gov/NIDAHome.html>.

Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services, 200 Independence Avenue SW., Room 738G, Washington, DC, USA, 20201, (202) 401-6295, <http://odphp.osophs.dhhs.gov>.

Office of FirstGov c/o GSA, 750 17th Street, NW, Suite 200, Washington, DC, USA, 20006-4634, <http://www.whitehousedrugpolicy.gov>.

SAMHSA-Center for Substance Abuse Prevention (CSAP),(301) 443-0365.

Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Dept. of Health and Human Services, 5600 Fishers Lane, Rockville,, MD, USA, 20857, (301) 443-6239, [email protected], <http://www.samhsa.gov>.

Substance Abuse and Mental Health Services Administration (SAMHSA)/Center for Substance Abuse Treatment (CSAT), 5600 Fishers Lane, Rockville, MD, USA, 20857, (301) 443-5700, [email protected], <http://www.samhsa.gov>.

U.S. Food and Drug Administration (FDA), 5600 Fishers Lane, Rockville, MD, USA, 20857-0001, (888) 463-6332, <http://www.fda.gov>.

Scott J. Polzin, MS