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.

POSITIVE HEALTH EFFECTS

POSITIVE HEALTH EFFECTS

Although we always urge caution when interpreting correlational studies, a recent large study based at the National Cancer Institute collected health data from more than 400,000 individuals in their fifties and sixties start¬ing in 1995 and following them for thirteen years. Across that time, men who drank two or three cups of coffee per day were 10 percent less likely to have died, and women were 13 percent less likely to have died. The study was not designed to answer the question of why coffee drinking was associated with better survival, but the findings are worth knowing about.

Two studies published in 2012 suggest that caffeine may also have bene¬fits for memory function when memory is challenged or in decline. In one study, individuals with "mild cognitive impairment"—a strong predictor of Alzheimer's disease—had their memory function evaluated and caf¬feine levels measured at the beginning of the study and again several years later. Those who had caffeine levels consistent with drinking about three cups of coffee were significantly less likely to have developed Alzheimer's disease than were those with no caffeine in their systems. This doesn't mean that caffeine prevents Alzheimer's disease. It could be that there was something else about the lifestyles of the people who had caffeine in their systems that helped forestall the onset of full Alzheimer's symptoms. For example, because caffeine in a stimulant it could simply have made the subjects more alert, making them more likely to engage in social or intellectual activities, both of which have been shown to promote cogni¬tive health in older people. The second recent study was a lab experiment with animals that had their memory function impaired when their brains were deprived of oxy­gen for a brief time. This condition, called "ischemia," often happens when people suffer a stroke and is known to result in memory and other cognitive deficits. Half of the mice received a dose of caffeine before the oxygen deprivation and the other half did not. Later, the mice that had received the caffeine regained their ability to form new memories 33 per­cent faster than the ones that had received no caffeine. It was as if the presence of caffeine at the time of the ischemia protected the animals' brains from suffering the full effect of the loss of oxygen. This could have been due to the caffeine disrupting the actions of adenosine in the brain. We wrote about how this action is part of why caffeine creates alertness. But when brain cells are injured or under stress, adenosine can reach dan­gerously high levels and actually damage the cells. Having the caffeine on board when the animals brains were stressed may have reduced the potential toxic effect of adenosine. Of course, this does not mean that everybody should walk around buzzed on caffeine all the time just in case they suffer a stroke or brain injury. But if it happens to be there, it might be protective.

CAFFEINE AND STRESS

CAFFEINE AND STRESS

Caffeine increases some of the normal stress responses because it increases the amount of adrenaline that is active in the body under stress­ful circumstances. Thus, it seems that caffeine users who find themselves under stress (or who use caffeine even more during stressful periods to work more effectively) may experience more of the effects that stress can produce. Adrenaline release increases blood pressure during stress, and the caffeine-induced rise adds to this. Thus, caffeine and stress together lead to greater bodily stress responses than either does alone.

CAFFEINE AND PANIC ATTACKS

In some people, caffeine can contribute to the experience of panic attacks, which generally come on suddenly and involve powerful feelings of threat and fear. The experience can be very debilitating for a brief period of time. It seems that caffeine is more likely to bring on panic attacks in people who have had them previously. However, relatively high doses of caffeine (greater than 700 milligrams) have been reported to lead to panic attacks in people who have never experienced them.

ENHANCEMENT OF PHYSICAL PERFORMANCE

Caffeine can slightly enhance physical endurance and delay fatigue asso­ciated with vigorous exercise in some people. One way that caffeine might accomplish this is by releasing fats into the blood for use as energy, enabling the body to conserve its other energy stores (in the form of stored sugars), thus allowing the athlete to sustain physical activity for a longer period of time. Caffeine may also help muscle performance during physical exercise, although the way this happens is not clear. What we do know is that caffeine dilates the bronchioles, making it easier for air to pass into the lungs. This would seem to have a beneficial effect on certain types of physical performance. Still, the most thorough studies of well-trained athletes are inconclusive. In some cases there appear to be performance-enhancing effects, and in others there are none. So the jury

remains out.

Two words of caution, though, for those who use caffeine for this pur­pose. Because caffeine causes an increased loss of water through urine production, a person exercising on caffeine may become dehydrated more rapidly during long periods of exercise such as distance running or cycling. This caution is particularly important for hot-weather exercisers. The other concern is the effects of caffeine on heart rate and heart rhythms. Strenuous exercise obviously stresses the heart, so a person with cardiovascular disease could experience problems while using caffeine to promote physical performance.

People who worry about their weight might be interested in the issue of fat metabolism. Products based on the supposed ability of caffeine and theophylline to "burn fat" include a theophylline cream placed on the market several years ago that was supposed to melt fat away. Just rub it on the offending fat pad! Unfortunately, the effectiveness of this treat­ment hasn't been established (one big problem is probably getting the theophylline through the skin and into the fat cells).

Likewise, there is tremendous interest in whether a combination of caf­feine and exercise can help to promote the burning of fat as fuel for weight loss. Fat cells really do have adenosine receptors, and xanthines really can cause a small release of stored fat, so some foods that include caffeine have been sold as fat burners. However, the scholarly research on these prod­ucts has demonstrated only small weight-loss effects. Coffee and its cous­ins may prove to be a useful part of weight-loss programs in the future, but at this point nothing "melts" fat except old-fashioned exercise and a healthy diet.