Psychological dependence and Classical conditioning:

Salvador Dalí said that everybody should try Hashish, but only once. This sentence summarizes society’s fear towards drugs. People are afraid of drugs, but mostly, we are afraid of ourselves. We are afraid of not being able to control our will and fall into a downward spiral of unlimited pleasure and self-destruction if we dare to do drugs just once.

Most people assume that frequent consumption of a drug can cause dependence, although most of us don’t really understand or even consider why, we just embrace the idea. That’s what we’ve been told by our parents and teachers, and they learnt it from their own parents and teachers without questioning it either, and so on. The perpetuation of this mantra, although very easy and comfortable, is not very smart. It is important to be informed in order to form our own opinions and not be manipulated.

Let’s start with the definition of “drug”. According to the FDA, a drug is:

“[…] (A) articles recognized in the official United States Pharmacopeia or formulary, (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals”.

Considering that in this article we are going to be talking about psychoactive drugs, we’ll take the last definition. Now, let’s review some of the symptoms of substance dependence. When someone is dependent to a drug:

  • He or she might experience tolerance towards that drug (the dependent individual has to consume higher doses to reach the same effects than before).
  • Withdrawal symptoms might occur if he or she stops using that substance.
  • The individual might be incapable of controlling his or her use of that particular substance.

These symptoms might have a physiological, pharmacological and/or a psychological origin. In the first two cases, the origin resides on the chemical interactions of the drug with the body, primarily the central nervous system. Psychological dependence is the big unknown though. However, according to some studies, psychological dependence might be the result of a form of learning process, similar to that of Classical conditioning.


How does Classical conditioning work?

Classical conditioning (also known as Pavlovian conditioning) is a learning process in which an innate response to a potent stimulus gets associated with a previously neutral stimulus.

A conditioned stimulus (or neutral stimulus) is the one that despite causing a certain response in the studied individual, is neutral to the response that we want to condition. Meanwhile, the innate or unconditioned stimulus is the one that causes the response that we want to condition.

To recap, so far we have:

Conditioned stimulus  – – ->  Neutral response

Unconditioned stimulus  – – ->  Unconditioned response

Now if we simultaneously and systematically present both stimuli (conditioned and unconditioned stimuli) in the presence of the unconditioned response, the conditioned stimulus will eventually trigger both neutral and unconditioned responses. This is phenomenon is called acquisition.

However, if the conditioned stimulus is presented repeatedly in the absence of the unconditioned stimulus, the latter will not trigger the appearance of the conditional response anymore. This phenomenon is known as extinction.

This whole mechanism is easier to understand by using Pavlov’s dog case as an example.

When a dog is presented with food (unconditioned stimulus), it would start salivating (unconditioned response). But if a bell is rang every time that food is presented to the dog (conditioned stimulus), the dog will associate the sound of the bell with the presence of food and every time that it heard the bell ringing, it would salivate, even in the absence of food.


Siegel’s experiment

The idea of tolerance and dependence as products of Classical conditioning was first proposed by Ivan Pavlov himself in 1927, although it was not empirically demonstrated until the late 70’s by Professor Shepard Siegel, from McMaster University, in Hamilton (Canada).

When a drug is used (unconditioned stimulus), it affects the structure or a function of a part of the body creating a compensatory response from it in order to restore equilibrium (unconditioned response). However, if that drug is systematically taken alongside the same environmental cues and under the same circumstances, these factors will begin to function as conditioned stimulus which produces the same unconditioned response in the body opposing the effects of the drug.

Most drugs generate a homeostatic disruption of the body in a physiological and psychological level. Siegel found that the body tends to maintain a homeostatic equilibrium in all of its systems, both physiologically and psychologically, by generating a response to the homeostatic disruption produced by the drug. For instance, ethanol has a vasodilator effect and therefore it causes a drop in body temperature. When this happens, the body reacts by trying to restore bodily functions to normal levels and thus it generates a compensatory response, which in the case of ethanol would be increasing body temperature.

This process was also hypothesized by Dr. Richard Solomon in his opponent-process theory (Solomon, 1978). Solomon proved that when an unconditional stimulus that triggers an unconditioned (pleasant or unpleasant) reaction is presented and removed, an opposite state would appear as a result of the compensatory response that the body generates to counteract the initial stimulus. He called this phenomenon ‘’hedonic contrast”. We can find examples of this process in our everyday lives; it’s the pleasure that comes after scratching an itch, the sadness that arises when our ice cream falls off the cone, or the relief that comes when landing safely after a parachute jump.

If the process is repeated systematically, the organism would trigger the compensatory response even in anticipation of the unconditioned stimulus.

This compensatory response can occur before ingestion of the drug. E.g., So when you are planning to go to the bar with friends you may experience a drop in body temp… or someone who has a problem with heroin may begin to go into physiological withdrawal by walking by the corner of their dealer.

According to Siegel’s compensatory response model, the direct effect of a drug on the individual serves as the unconditioned stimulus (UCS), whereas the individual homeostatic regulatory systems attempt to defend itself against the drugs effect and maintain homeostasis is the unconditioned response (UCR). Through repeated drug administration, a stimulus that is often paired with the UCS becomes a conditioned stimulus (CS) and serves as an early warning signal that the homeostatic regulatory system that a UCS is imminent. The regulatory system then prepares itself by eliciting a defensive conditioned response (CR). Through repeated drug administration episodes, the link between the UCS and the CS becomes stronger and eventually the CS can elicit a CR in the absence of the UCS. This CR may then influence the individual’s homeostatic state resulting in the onset of withdrawal symptoms, craving, and likely future drug use (in order to alleviate unwanted withdrawal symptoms).

So, in Pavlovian terms:

Drinking alcohol (unconditioned stimulus) – – -> Increase in body temperature (unconditioned response)


In Siegel’s experiment (Crowel, Hinson, & Siegel, 1981), the researchers administered ethanol injections to a group of rats while a particular stimulus was being presented to them (white noise). These injections were alternated with saline injections and a different environment. Rats’ body temperature was continuously monitored in order to check if a compensatory response was being generated.

The first time that rats received ethanol injections in the presence of white noise, a reduction in body temperature was observed. However, the intensity of that temperature drop decreased with subsequent trials despite receiving the same amount of ethanol. Rats were developing a tolerance to the injections of ethanol in the presence of white noise.

In order to determine if a compensatory response was being produced by the environmental cues, saline solution was injected in the presence of white noise, while a control group received saline solution injections in the absence of those environmental cues. The results showed that rats that received saline solution injections in the presence of white noise experienced an increase in body temperature while the rats in the control group did not experience such change. Additionally, Siegel found that the tolerance to ethanol that rats had acquired decreased if rats were injected with ethanol in a different environment. Meaning that if rats received a similar dose of ethanol to that they were used to, but in a different environment, they experienced a drop in body temperature again.

Siegel found that this same effect would occur with opiates, barbiturates and benzodiazepines (Hinson & Siegel, 1983), suggesting that this mechanism was not exclusive to alcohol.

The results of these experiments may seem meaningless, but the implications of Siegel’s discoveries are very important for the understanding and treatment of substance dependence. Siegel’s theories suggest that both dependence and tolerance could have a strong psychological component and therefore, operant drug treatment approaches should incorporate aspects of Classical conditioning in order to address the effect that environmental cues have in the process of acquisition of tolerance and dependence.


Siegel also found that tolerance would increase when the user was exposed to the usual drug associated environmental cues, but not when the user was exposed to different conditions. This process was termed “situational specificity of tolerance” (Siegel, Baptista, Kim, McDonald, & Weise-Kelly, 2000).

It is believed that this situational specificity of tolerance could be the cause of the high incidence of opioid overdose among long-term dependent heroin users. To prove his point, Siegel reported the case of a cancer patient who was receiving morphine injection by prescription at home and died of an overdose (Shepard & Ellsworth, 1986). The patient received morphine injections in his bedroom for four weeks, with a gradual increase in dosage level as the patient developed tolerance to the drug. One day, the patient received his scheduled morphine injection in the living room instead of in his bedroom and he suffered a fatal overdose of morphine. Siegel explanation suggested that the bedroom was acting as a form of conditioned stimulus generating a compensatory response on the patient to the effects of morphine. However, when that stimulus was removed, that compensatory response disappeared, producing the fatal overdose.


The applications of these theories reach further than just dependence to so called “hard drugs”. Having a coffee after lunch or a cigarette after having sex could become habits hard to change if done systematically under the same environment and under the same circumstances.

Like Aldous Huxley said, “Habit converts luxurious enjoyments into dull and daily necessities”.



Crowel, C., Hinson, R., & Siegel, S. (1981). The Role of Conditional Drug Responses in Tolerance to the Hypothermic Effects of Ethanol. Psychopharmacology, 51-54.

Hinson, R., & Siegel, S. (1983). Anticipatory Hyperexcitability and Tolerance to the Narcotizing Effect of Morphine in the Rat. Behavioral Neuroscience, 759-767.

Pavlov, I. P. (1927). Conditioned Reflexes. London: Oxford University Press.

Shepard, S., & Ellsworth, D. W. (1986). Pavlovian Conditioning and Death from Apparent Overdose of Medically Prescribed Morphine: A Case Report. Bulletin of the Psychonomic Society, 278-280.

Siegel, S., Baptista, M. A., Kim, J., McDonald, R. V., & Weise-Kelly, L. (2000). Pavlovian Psychopharmacology: The Association Basis of Tolerance. Experimental and Clinical Psychopharmacology, 276-293.

Solomon, R. L. (1978). The Opponent-Process Theory of Acquired Motivation: The Cost of Pleasure and the Beneficts of Pain. Eastern Psychological Association. American Psychologist.

Siegel, S., Krank, M.D. & Hinson, R. E.  (1987)  Anticipation of pharmacological and nonpharmacological events.  Journal of Drug Issues, 1:83-110. 0.38 Impact Factor

Siegel, S., Hinson, R. E., Krank, M.D. & McCully, J.  (1982) Heroin “overdose” death: The contribution of drug-associated environmental cues.  Science, 216:436-7.  31.48 Impact Factor


Michelle Theissen

Michelle Theissen


An Honours graduate with a Psychology B.A. from the University of British Columbia, Michelle will begin her Masters in Clinical Psychology in fall 2016, continuing her research examining the motivations and outcomes of recreational and therapeutic use of cannabis and psychedelics. Find out more.

Antonio Cillero

Antonio Cillero

A Queen's University graduate with a Master’s degree in Chemical Engineering, Antonio helped translate Alexander Shulgin’s PIHKAL and TIHKAL to Spanish and is head translator at Find out more.