1995 LECTURE SERIES

Learning, Drug Anticipation and Drug Addiction

Dr. Shepard Siegel
McMaster University
March 28, 1995

People interested in drug addiction should become more interested in the processes of learning and memory. Numerous studies have shown that there exists a direct link between drug addiction and the learning and memory processes. Before discussing how learning and memory affect drug addiction it is important to define the term "drug addiction" and addictive drugs.

Addictive drugs have three defining characteristics. The first is tolerance. Tolerance is the condition where the effect of the drug decreases after repeated administrations. For example, the first time morphine is administered for pain relief it is very effective. However, after repeated dosages, the effectiveness of morphine gradually decreases. Tolerance, then, is the decreasing efficiency of a drug due to repeated administrations.

Physical dependence is another quality of drugs that produce addiction. A person who has taken a drug long enough to develop a tolerance will experience withdrawal symptoms when the drug is taken away. Withdrawal symptoms vary depending on the type of drug the person has been using, but these symptoms are all changes in physiology that can be measured.

The last characteristic of drugs that produce addiction is a craving for the substance. A craving is a compulsive desire for the drug even if there are no withdrawal symptoms. A long period of time may have passed since the person has had access to the drug, but in certain situations and under certain circumstances the person has an overwhelming desire to use the drug again.

Unfortunately, addiction is a fact of life. All living organisms are susceptible to addiction. Addiction is not limited to a certain culture, and both animals and humans can develop addictions.

It has become apparent that learning contributes to all aspects of addiction. Learning is the formation of associations between events. If two events happen closely in time, then we associate them. Both humans and animals have this reflex to associate events. We cannot experience two events linked by a short amount of time without them being associated. For example, humans were born with an innate response that causes the body to dilute an irritant, say acid, when it is introduced to the mouth. Hence, lemon juice in the mouth causes salivation. But because we associate events, the mere sight of a lemon causes many people to salivate.

Around the turn of the century Ivan Pavlov began studying the development of association and determined that previous experiences have a lot to do with the associations people make. For example, if a person has never eaten citrus fruit or seen a lemon, then the sight of a lemon would not cause the body to salivate. The idea that past experience plays a large role in associations is known as a conditional reflex because the association is contingent upon a person's previous experiences.

As a digestive physiologist, Pavlov realized that one cannot understand digestion without first considering conditional reflexes. Accordingly, Pavlov asserted that the digestive process begins as soon as food is seen or smelled. The body actually starts digesting the food even before it arrives. This is similar to the responses the body produces in anticipation of a drug.

Whether they are taken for medical reasons or pleasure, drugs are not presented in isolation. Just like lemon juice doesn't get into your mouth in isolation, drugs occur in certain circumstances. There are stimuli around that tell the body that lemon juice is going to be in the mouth soon. This causes salivation. Similarly, when drugs are administered in particular circumstances, at a particular time of day or in a particular ritual, the body reacts in anticipation of the introduction of the drug.

If a person has associated the environment where a drug is administered with the systemic effects of the drug, then simply being in that environment should elicit some change in behavior associated with the typical effects of that drug.

The body's conditional responses to drugs are both adaptive and preparatory. If the body thinks it will be presented with something that will decrease immune system activity then an increase in immune system activity is likely. When the body is presented with a type of insult similar to that provided by a drug, then the body reacts to lessen the effect of the insult.

Unlike conditional reflexes, tolerance is learned. If a person takes a drug they have had before, then their response to the drug depends on the previous effect of the drug. If the body's preparatory response is antagonistic to the effects of the drug, then the actual effect the drug has on the body will be lessened.

One line of evidence that supports learned tolerance is environmental specificity. If a person uses a drug in a usual room with all the usual drug administration cues, their bodies will imitate a learned response that will cancel the effects of the drug and produce a tolerance. However, if a person is administered a drug in a novel place, then the effect of the drug is greater because there are no associations, and the body will not prepare itself for the administration of the drug. The effect of a drug increases if a person gets the drug when and where they do not expect it.

The most dramatic demonstrations of environmental specificity is witnessed in cases of heroin overdose. Each year, approximately one percent of the North American population of heroin addicts dies from a so–called overdose. An overdose of heroin causes death because it suppresses the respiration center in the brain. However, evidence shows that the amount of heroin these addicts had in their bodies when they overdosed was not much when put in the context of their body's tolerance to the drug. Individuals often die from a dose of heroine equal to the dose they took the day before that produced only minor effects.

Investigators have interviewed heroin overdose survivors and found that most survivors reported that they took the drug under unusual circumstances, at a different time or in a different place than they usually take the drug. Amazingly, this demonstrates that people are at risk for heroin overdose if they take a "normal" dose of the drug where they haven't taken the drug before.

If a person takes the drug in a familiar setting, then the body makes preparatory responses that can save the person's life. If the drug is taken in an unfamiliar setting, then the body doesn't make these conditional responses and the person is at a greater risk of overdose.

Another type of evidence that shows how learning contributes to tolerance is called extinction of tolerance. Extinction of tolerance states that learned responses cannot only be established, but they can also be eliminated if the pairing is done away with. So, if you've learned to salivate at the sight of a lemon then you will no longer salivate at the sight of a lemon if you see the lemon over and over again without ever tasting it. This principle holds true for drugs.

The second defining characteristic of addictive drugs is withdrawal symptoms when a person stops using the drug. Withdrawal symptoms are learned drug responses –– the same responses responsible for tolerance. If the body is confronted with stimuli that in the past has signaled the drug, then the body will make responses that attenuate the effect of the drug.

If the body's response preparations are followed by the drug, then the user will not experience any symptoms –– but if the drug does not come then the body's preparations will manifest in the form of withdrawal symptoms. For example, when a person drinks decaffeinated coffee they are getting the taste without getting the caffeine. Because the signal for caffeine was present, the body began to slow itself down to combat the speeding up effect that caffeine creates. However, since the caffeine never followed, the person feels the effects of the body's preparation and experience fatigue.

There have been numerous experiments done with heroin addicts using a polygraph machine to monitor their heart rates, blood pressure and other physiological data. When addicts are shown a picture of a heroin related stimuli, such as a hypodermic syringe, the results conclusively show that the body does indeed make changes in preparation for the drug.

With this information in mind, one solution to treating drug addiction involves tolerance extinction. If the stimuli associated with drug use cause preparation symptoms, then exposure to these stimuli, without introduction of the drug, weakens the association. Clinicians using a form of therapy known as C–U–E exposure, which involves the presentation of drug–related stimuli followed by substance denial, have reported excellent results with this method.

Having a complete understanding of drug abuse requires an understanding of how our responses to a drug are modulated by learned compensations for the effect of the drug.

As we move forward towards a deeper understanding of drug tolerance and drug dependence and begin to develop new treatment strategies, our understanding of learning will continue to play a pivotal role.