ADDICTION, TOLERANCE, AND DEPENDENCE

ADDICTION, TOLERANCE, AND DEPENDENCE

While the buzz from opiates might sound alluring, it comes at a cost. Opiate drugs stimulate all opioid systems simultaneously, so there are many unwanted effects that accompany the desirable ones. One of these is the cycles of withdrawal that opiate users experience. People who take opiates for a while (weeks) can develop significant dependence and addiction and undergo withdrawal when they stop. Most opiate addicts use heroin or other opiates several times a day. With this pattern of use, tolerance develops to many of the actions of opiates, but it develops to different effects at different rates. In experimental studies, tolerance develops quickly to the ability of opiates to suppress pain. However, patients experiencing intense, chronic pain like that associated with ter­minal cancer can actually show little tolerance to the analgesic effects of opiates. Tolerance also develops fairly well to the suppression of breath­ing (this is why opiate users can tolerate higher and higher doses). How­ever, the constipation remains, and the pinpoint pupils are slow to change. The latter is fortunate because it provides a useful sign of OD in a comatose patient and can help identify even a long-time user. While tolerance develops to opiate-induced euphoria, the drug keeps providing enough pleasure that users still get high.

Part of the tolerance results from chemical changes in how cells respond to opiates. The normal chain of events initiated by opiates adapts to the continuous presence of the drug. The adaptation becomes so thor­ough that cells function normally even though the drug is present. Another part of tolerance is purely a conditioned response. Pharmacolo­gists have learned from animal studies that if you give animals a dose of heroin every day in the same room, they tolerate higher and higher doses. However, if you move them to a strange environment, the dose that they usually tolerated kills them: we think that conditioned responses permit their bodies to anticipate and counter the effects of the drug. This condi­tioning effect probably does apply to humans. Frequently, very experi­enced opiate users who OD do so because they took the drug in an unfamiliar environment.

Opiate withdrawal is miserable but not life-threatening (unlike alcohol withdrawal). Again, in Junkie, William Burroughs provides a good description:

The last of the codeine was running out. My nose and eyes began to run, sweat soaked through my clothes. Hot and cold flashes hit me as though a furnace door was swinging open and shut. I lay down on the bunk, too weak to move. My legs ached and twitched so that any posi­tion was intolerable, and I moved from one side to the other, sloshing about in my sweaty clothes.... Almost worse than the sickness is the depression that goes with it. One afternoon I closed my eyes and saw New York in ruins. Huge centipedes and scorpions crawled in and out of empty bars and cafeterias and drugstores on Forty-second Street. Weeds were growing up through cracks and holes in the pavement. There was no one in sight. After five days I began to feel a little better.

The earliest signs of withdrawal are watery eyes, a runny nose, yawn­ing, and sweating. When people have been using opiates heavily, they experience mild withdrawal as soon as their most recent dose wears off. As withdrawal continues, the user feels restless and irritable and loses his appetite. Overall, it feels like the flu. As withdrawal peaks, the user suffers diarrhea, shivering, sweating, general malaise, abdominal cramps, muscle pains, and, generally, an increased sensitivity to pain. Yawning and diffi­culty sleeping gradually become more intense over the next few days. The worst of the physical symptoms abates after a few days.

If flu symptoms were all that happened when addicts stopped using, treating heroin addiction would be easy. Unfortunately, there is another symptom that is more intangible but much longer lasting. There is a dysphoria (the just-feeling-lousy feeling), which may be the reverse of opiate-induced euphoria. They experience a craving for the drug that can be so strong that it becomes the only thing they can think about. The craving for a fix can last for months, long after the physical symptoms have abated. This is the symptom that usually triggers relapse.

Most of these withdrawal signs are the opposite of acute drug effects For example, opiates cause constipation, and diarrhea occurs when people go through withdrawal. The body of the addict adapts to maintain a level of intestinal tract movement despite the presence of the opiate that is con­stipating. Remove the opiate, and the underlying processes that were counteracting it to keep things normal suddenly find themselves unhin­dered. The character in the movie Trainspotting experienced this effect, which necessitated his mad dash for the bathroom in one scene. This rep­resents the sort of yin-yang response the body has to any disruption. (If you shiver and feel cold when you are withdrawing from opiates, what do opiates usually do to body temperature?)

Many addiction researchers think that once people are established addicts, the desire to avoid withdrawal maintains addiction more than the pleasurable effects of the drug. Obviously, when people first get addicted, they haven't been taking the drug long enough to go through intense with­drawal if they stop. However, after several months or years, the withdrawal is stronger and may contribute more to an addict's continued drug taking. If you know taking the drug will solve the problem, it seems an easy solu­tion, doesn't it? In the end, it is a combination of changes in the brain that create the overwhelming compulsion to keep using narcotics (or any other highly addictive drug). Researchers think that the craving for a drug may result from chemical changes in two parts of the brain that unfortunately combine their efforts: the parts of the brain that seek reward are chemically changed to respond strongly to drug cues, and the parts of the brain that create anxiety and bad feelings start firing as soon as the drug wears off.