The opiates are derived from a naturally occurring substance, morphine, which comes from a specific variety of the poppy plant. There are naturally occurring opiates such as morphine and heroin and synthetically produced ones such as meperidine (Demerol) and propoxyphene (Darvon). As we’ve learned, there are also opiate-like substances called endorphins that are produced naturally in the brain. Opiates have a number of diverse actions in the body. In addition to pain relief, they provide a sense of euphoria and relaxation. This effect may be more pronounced in people who are addicted or who are at risk genetically for addiction.

There are also people who feel uncomfortable and uneasy when using opiates for pain relief. This constitutional difference is intriguing, and probably reflects differences in the genetic vulnerability to addiction to these drugs.

Opiates suppress the cough reflex and therefore are found in many cough preparations. They decrease the motility of the gastrointestinal tract and have a pharmaceutical use as a treatment for diarrhea. Opiates also cause the pupils to become constricted, provoke nausea, and are involved in the regulation of body temperature.

The pain-relieving effects of opiates have been appreciated for thousands of years; addiction to them has most likely been a problem for at least as long. When the brain is exposed to opiates such as morphine, physical tolerance and dependence develop, even at very low doses. It has been shown, for example, that hospital patients who are given even small doses of opiate medications for acute pain have a “mini” withdrawal syndrome even after the first dose. This does not mean that the patient has an addiction to opiates. It does mean that the brain reacts very quickly and strongly to the potentially addictive effects of these drugs. And, as with the benzodiazepines, a person can have a physiological dependence on an opiate drug because of medical use without becoming an addict. This is because there is more to addiction that just the body’s reaction to the drug; behavioral, psychological, and spiritual factors play a role as well. Supervised medical detoxification from long-term use of opiate analgesics for acutely painful conditions such as burns will correct any physiological dependence. Continuing someone on opiate analgesics when physiological dependence exists is appropriate if the pain cannot be managed in any other way, as, for example, with cancer.

I generally see two types of opiate addiction. The first is heroin addiction, which was widespread in the sixties and seventies, dropped off during the crack cocaine epidemic in the eighties, and is coming back at the turn of the century.

Heroin is a simple derivative of morphine which is not active when taken orally. In the past, it was typically injected intravenously (mainlined). We are now seeing people addicted to smoking or snorting heroin. They are able to avoid the risk of AIDS associated with dirty needles, but the addiction to the heroin is no less severe.

The second type is addiction to pharmaceutical opiate preparations. These include drugs such as meperidine (Demerol), pentazocine (Talwin), propoxyphene (Darvocet), and hydrocodone (Lorcet). This type of addiction usually starts when there is easy access to these medications and then progresses. Medical personnel, such as doctors and nurses, often become addicted to these drugs. People with chronic pain or headaches may begin to self-medicate emotional pain with prescription opiates. When addiction develops, these people frequently exaggerate their pain complaints, feign painful conditions such as kidney stones or migraines, and maintain multiple prescriptions from different doctors at various pharmacies. It can sometimes be difficult to tell the difference between someone with legitimate complaints of chronic pain and someone who uses these complaints to further an addiction, but careful evaluation and follow-up usually make it possible to handle a situation appropriately.

Several types of opiate receptors have different functions in the brain. Designing synthetic drugs that target only specific receptors may lead to effective pain medications that are less likely to cause addiction. One of these drugs is tramadol (Ultram), which is said to provide good pain relief without addiction potential. However, there are reports of people abusing or appearing to become dependent on tramadol, so the verdict is not yet in. It should be noted that meperidine (Demerol) was first thought to have this quality, but it turned out to be highly addictive. Tramadol should probably be used with caution until there is more experience with this drug, especially for people with a history of addiction. An intriguing development is the finding that tramadol may provide useful treatment for some psychiatric disorders, such as obsessive-compulsive disorder. It will be interesting to follow developments in the area of the opiate receptors and their differing functions.

The withdrawal syndrome associated with opiate addiction reflects the diverse actions of the opiates in the body. The term “cold turkey” was coined to describe what the withdrawing heroin addict looks like - shivering and covered with goose flesh.

The onset of withdrawal symptoms depends on how long it takes the drug or drugs to leave the system. Half-life is the measurement of the time it takes for one half of a drug to leave. Opiates with a short half-life, such as meperidine (Demerol) or heroin, leave the system within a matter of hours, and the onset of withdrawal symptoms follows soon after. Methadone, on the other hand, has a very long half-life, around one or two days.

Symptoms of opiate withdrawal include craving, muscle cramps, diarrhea, yawning, sweating, and runny nose, elevated temperature, and poor sleep. The condition has been compared to a case of the flu. Opiate withdrawal, unlike withdrawal from alcohol or the depressants, is more uncomfortable than it is medically dangerous.

Withdrawal can be treated by replacing the short half-life drug, such as heroin, with a longer half-life drug, such as methadone, and gradually tapering it off. It can also be treated symptomatically with drugs such as clonidine that block the specific symptoms of withdrawal. The acute symptoms, if not treated, last about a week for drugs with a short half-life and about two weeks for methadone. A protracted withdrawal syndrome that is often seen after the initial detoxification from opiates may last for months. It involves chronic, low-grade depression and a lack of stress tolerance, sometimes accompanied by drug cravings. It’s unclear whether this is a direct effect of the opiates or involves coexisting psychiatric problems.

The problem with treating opiate addiction has always been that there is a very high relapse rate. This may be due to the protracted withdrawal syndrome. One solution that is controversial is the use of methadone replacement for long-term treatment. A person in a methadone maintenance program remains physiologically dependent on opiates and participates in group and individual therapy to address the other aspects of the addiction. Since methadone has a long half-life, it can be administered under medical supervision at a clinic. The addict does not have to devote time and energy to locating and procuring the drug. Some people believe that abstinence is the only ideal road to recovery, but experience has shown that the quality of life of the street addict successfully maintained in a methadone program improves greatly. People are able to hold down jobs, take care of family responsibilities, and lead otherwise normal lives. There is a new drug with an even longer half-life called LAAM which may make maintenance programs more efficient since it needs to be given only weekly.

Opiates are not very toxic compared to other addictive substances like alcohol. The most common medical problem we see is overdose. This often happens when tolerance has developed to the mood-altering effects but not to the respiratory effects. The addict pushes the dose up to achieve a high, and respiratory arrest occurs accidentally. Obviously, street preparations of heroin are not standardized, and an unusually pure supply of heroin in the drug community often leads to an epidemic of overdose deaths.

Even though opiates themselves are relatively safe, opiate addicts are generally not well. The use of dirty needles leads to infections of all kinds, including AIDS. Drug supplies are “cut” with various substances, and these can cause serious organ damage when injected or smoked. Poor nutrition and poor hygiene also contribute to the development of infectious diseases. Pregnant addicts have many more complications with their pregnancies, and the infants are at risk for a variety of medical problems. There is some evidence that long-term exposure to opiates may permanently damage the endogenous opiate system of the addict’s brain, leading to chronic depression and anxiety.

Elizabeth Connell Henderson, M.D.

Glossary

Appendix A: Regulation of Addictive Substances

Appendix B: Sources of Additional Information