Article summary of Drug Tolerance, Drug Addiction, and Drug Anticipation by Siegel - Chapter

How does Pavlovian conditioning work in the context of addiction? 

It has been known for decades that addicts experience symptoms of drug withdrawal when they encounter situations or environments that they associate with their drug use. Just the sight of drug paraphernalia or speaking about drugs to other people can elucidate these symptoms. This is due to Pavlovian (or classical) conditioning. In Pavlovian conditioning, there are unconditional and conditional stimuli, as well as unconditional and conditional responses. In the context of drug use, the unconditional stimulus is the pharmacological effect of the drug. The drug induces a compensatory response in the body. For example, alcohol has a temperature-lowering effect, so after ingestion, the body raises its temperature to compensate. The cues or environment accompanying the administration of the drug are the conditional stimuli, which need to be associated with the effects of the drug multiple times before being effective in elucidating withdrawal symptoms. Eventually, these cues (the conditional stimuli) will bring about conditional compensatory responses. These conditional compensatory responses also counteract the drug effect, even when no drug was administered.

What factors influence the strength of an addict’s tolerance? 

An addict’s tolerance to a certain drug increases when, due to repeated use, the drug’s effect on their body decreases. The more that the conditional compensatory response strengthens, and thus the drug’s effects are more highly counteracted, the higher someone’s tolerance will be. Situational specificity of tolerance is a concept that illustrates the effects of the specific environment (conditional stimuli) on drug tolerance levels. In experiments designed to demonstrate situational specificity of tolerance, people are administered drugs in the exact same environment multiple times in the tolerance-development phase. After, in a tolerance-test session, the participants are split up into two groups. One group is administered drugs in the same environment as before, and one group’s drug administration environment changes. Those in the unchanged environment will show heightened tolerance to the drug due to the conditional stimuli (the environmental cues). However, those in the changed environment will show lowered tolerance, and the effect of the drug on them is stronger than it was at the end of the tolerance-development phase. For example, college students have been shown to display less alcohol tolerance when they consume a familiar alcoholic beverage than when they consume an unfamiliar, peppermint-flavored blue beverage with the same alcohol content. This situational specificity of tolerance has also been shown to apply to potentially lethal doses of drugs.

What causes symptoms of withdrawal? 

Withdrawal symptoms are caused by conditional compensatory responses when there is no drug provided after the conditional stimuli. In other words, if a drug is not administered after the typical stimuli that precede drug use, withdrawal symptoms begin. The feeling of withdrawal is simply the compensatory response reaching its full expression because there is no drug effect to counteract it. It is important to note that the anticipation of drug use is what causes withdrawal, not the drug itself. In addition to drug compensatory responses, these withdrawal symptoms can also manifest as neurochemical responses which are felt as cravings. 

What are the different types of drug-related cues? 

There are two broad categories of cues when it comes to the Pavlovian conditioning of drugs: exteroceptive and interoceptive cues. Exteroceptive cues, which are more commonly used in experiments, are those that can be seen, heard, or smelled by both the experimenter and the subject. Interoceptive clues are those that only the subject is aware of which become associated with the administration of a drug. Within interoceptive cues, there are self-administration cues and drug-onset cues. Self-administration cues refer to the ritual that one participates in while administering themselves the drug, such as injecting themselves with a drug intravenously. This kind of cue will also function as a conditional stimulus, bringing about a conditional compensatory response. It has been shown that tolerance is higher after one goes through their typical self-administration procedure than when they are administered the same amount of the drug by an experimenter. Drug-onset cues describe the immediate effect of a drug before its full effect comes through. Drug-onset cues, such as the warm feeling that alcohol tends to immediately elicit, consistently precede the stronger effects of the drug. In rats, it has been shown that administering a small dose of a drug elicits symptoms of withdrawal when the full and expected dose is not then provided. The rats had associated the drug-onset cues with the eventual full drug effect. 

What are the implications of these findings for addiction treatment? 

Behavioral therapies for drug addiction can utilize Pavlovian conditioning. In these therapies, predrug conditional cues can be extinguished by presenting the addict with the conditional cue and denying them access to the drug. It would be helpful to incorporate interoceptive drug cues, including memories, emotions, and cognitions into the pool of conditional predrug cues. Accurate insight into the possible predrug cues for the addict, both exteroceptive and interoceptive, will allow for the most effective drug addiction treatment.