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Indeed, the drug is so reinforcing that the organism self-administering it becomes totally preoccupied with drug acquisition. Fischman, , p. The four primary studies cited in support of these views were published between and The stark picture presented by these studies, however, contrasts sharply with most other laboratory animal research on cocaine. Such studies typically manipulate factors commonly shown to affect human drug taking in natural settings, including 1 drug dose, 2 access to the drug, 3 effort required to obtain the drug, and 4 the presence or absence of alternative nondrug reinforcers.

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The four toxicity studies are notable for eliminating most such environmental variation, thus establishing baseline conditions under which animals can be induced to self-administer fatal doses of cocaine. However, even a change in basic elements of the cocaine-toxicity procedures engenders a qualitatively different picture of cocaine self-administration.

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Having access to an unlimited, direct flow of high concentrations of cocaine at all times at little or no cost effort is an unusual situation. On the other hand, animals readily "manage" their cocaine use within daily routines when they are given only periodic opportunities to inject cocaine. Such results suggest that applying even modest environmental constraints to drug use, as opposed to uninterrupted access, dramatically affects cocaine self-administration.

Two studies of cocaine use following the unlimited-access studies have compared unlimited with somewhat limited-access conditions. Dworkin, Goeders, Grabowski, and Smith compared a group of rats that had unlimited access to cocaine and a group that were switched from unlimited access every hour to every other hour. Note that this second group of experienced cocaine-using rats still had considerable access to cocaine, which was fully available on alternating hours throughout the entire day.

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The former group of rats died within 28 days of being given unlimited access, while none of the rats in the limited-access condition died by the time the study was terminated days. Fitch and Roberts reported similar results in a study that varied both dose and schedule of cocaine self-administration. When varying amount of access to cocaine, they found cyclic as opposed to uncontrolled or lethal cocaine self-administration in a condition that scheduled up to four self-administrations per hour.

At the middle dose, animals self-administered cocaine reliably, but intermittently or cyclically. At the lowest dose, they even failed to reliably self-administer the drug. When dose and access are constrained, as they would be in any naturalistic context of drug use, animals show patterns of drug taking typical for those of other drugs. Cocaine self-administration has frequently been compared with patterns of use of other stimulants in the same studies.

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One of the four toxicity studies also offered rhesus monkeys unlimited self-administration of d-amphetamine Deneau et al. Another toxicity study Johanson et al. All six of these animals died.


Consideration of the conditions in which cocaine self administration takes place is also crucial to understanding cocaine's toxicity. Drug administration was in small cubicles 1. These harnesses require that the animals' mobility be curtailed, thus restricting other activities.

Such conditions are, of course, dictated by the research goal of allowing the animals to express urges for the drug via direct drug self-administration. Alternative research methods for studying drug reinforcement could offer a tradeoff between options for self-administering drugs versus conducting ordinary species activities.

Alexander and his colleagues Alexander, Peele, Hadaway et al. Rats exposed to the option of a sweetened morphine solution drank one-eighth as much morphine in a large cage they shared with other rats as did rats housed in small, socially-isolating cages. Further experiments by this group indicated that both the added space and companionship were critical factors affecting drug use.

As shown in the toxicity study comparing cocaine and heroin self-administration in rats by Bozarth and Wise , although cocaine was more often fatal, all animals reliably self-administered morphine, while only 83 percent self-administered cocaine. This pattern is typical in studies of unlimited access to cocaine and other psychomotor stimulants in laboratory animals Johanson et al.

Figure 1. Data are expressed as mean number of infusions per hour of testing, and error bars represent SEM. Figure derived from from Bozarth and Wise Cocaine creates cyclic patterns of intake marked by periods when the animal administers little or no drug even though cocaine is constantly available. This does not support the idea that cocaine is an especially reinforcing pharmacological compound that leads to compulsive drug use, but rather suggests that the erratic self-administration of cocaine is a direct behavioral effect of the drug.

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In other words, drug activation is channeled into furthered cocaine use when a cocaine is freely available and b this is the only significant response available to the animal. Canadian researchers Fitch and Roberts expressed a similar view:. Conversely, if extended drug access permits continued accumulation of drug levels, then the influence of the drug may be carried forward to sustain self-administration behavior and disrupt other functions.

The accepted, classical view is that animals self-administer the drug to maintain the highest possible levels of drug reinforcement. If compulsive usage patterns serve to achieve such ends, then animals which have experienced unlimited access should respond more frenetically as access becomes constrained. For example, in the study described above by Dworkin et al.

If maintaining high drug levels is the motivation, then animals in this condition should respond at about double the rate a response rate which they can easily manage. Instead, the animals which had cocaine available every other hour reduced their responding and cocaine intake fell, not to one-half, but to one-fourth the exposure animals received in the unlimited-access condition. This finding affirms the view that toxic levels of cocaine self-administration occur more as a function of the direct behavioral effects of the psychomotor stimulant including motivational effects on animal hunger than as a result of any unique reinforcing properties inherent to cocaine.

Addicts' descriptions of their harrowing drug habits are typical media fare and, along with repeated references to animal cocaine-toxicity studies, comprise the major source for claims of cocaine's addictiveness see DeGrandpre, In , WHO in conjunction with the United Nations Interregional Crime and Justice Research Institute published results from the "largest global study on cocaine use ever undertaken," conducted from to Among other findings, summarized in a WHO press release March 20, , the study reported that there is "an enormous variety in the types of people who use cocaine, the amount of drug used, the frequency of use, the duration and intensity of use, the reasons for using cocaine and any associated problems that users experience.

Such evidence on human reactions to cocaine includes the following sources:. Of current users those who have used the drug in the last year , a third used the drug 12 or more times a year, and 10 percent used cocaine once a week or more. These results replicate another, earlier study:. Cocaine use appears to be experimental in nature and to involve few experiences for a substantial portion of those who report any lifetime experience with the drug.

Indeed, only a small minority of long-term cocaine users actually progress to addiction i. Of the 50 regular users Siegel tracked for over a decade, only five became compulsive users at any point. Studies of ongoing cocaine users in Canada, Scotland, Australia, and Holland identify controlled use as the most common usage pattern Cohen, ; Ditton, Farrow, Forsyth et al. At the same time, as found in WHO's global study of cocaine, the level of use and appearance of problems vary with setting and lifephase.

However, what is most notable is that, in response to these problems, heavy users in these studies rarely seek treatment and typically quit or cut back on their own Erickson et al. Risk was lower for married subjects and diminished with age.

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Compared to the toxicity studies, human drug use in natural settings is less passive, constrained, and irreversible. As well as being more actor-determined, human drug use also takes place within a set of values and a cultural milieu for which animals have no equivalent. When people quit smoking or other drug addictions, they typically cite family, career, or existential motivations Peele, Cocaine elevates the mood of most human subjects in a way indistinguishable from amphetamines Fischman, Schuster, Resnekov et al.

This preference disappeared over several trials, however, despite the subjects' continued identification of positive mood changes from drug use. Over time, these subjects were less interested in savoring the mood enhancement of the drug than in conducting their ordinary lives. Viewing reinforcement as a drug property would predict that the subjects continued taking the drugs; their actual behavior shows that drug use was competing against other activities that maintained a higher priority for users see also Lamb et al.

Drugs which animals can be made to self-administer compulsively also have strong abuse potential for humans Johanson, Pharmacological properties may make certain drugs suitable for compulsive use by humans, but these properties alone are insufficient to predict or explain the variability inherent in human usage patterns. In fact, drug self-administration by animals alone does not predict the drugs most commonly abused by humans Hartnoll, Nor do animals respond compulsively to the substances to which Americans or Britons are most commonly addicted: caffeine Hughes et al.

Obviously, a range of legal, psychological, social, and economic factors influence patterns of use of drugs. But these factors counterbalance subjugation to drugs among humans for even the most dependence-producing drugs, such as nicotine:. Non-pharmacological factors such as availability, relative cost, social pressures, legal consequences of use, and marketing practices provided the best explanation for the greater number of deaths associated with nicotine and the greater incidence of progression to addictive levels of intake than occurs with other addicting drugs.

Drug use by humans in natural environments reflects inherent costs associated with drug use especially illicit use and the tradeoffs between drugs and other available activities. Along with drug dosage, this model also incorporates factors affecting demand, such as income, work cost to obtain the drug, and the availability and cost of alternative reinforcers.

This economic framework provides a method of quantifying the dynamic interaction between competing drug and nondrug activities, relationships that have been investigated in some detail since the time of earlier research examining cocaine's toxicity. To wit, how is drug consumption affected by cost? Is demand for cocaine inelastic, as proposed in some versions of the addiction model cf.

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Fischman, ? Does availability of important alternative rewards depreciate cocaine-taking responses in animals? Figure 2 displays five demand curves for drug and non-drug reinforcers tested under similar experimental conditions. In all cases, increasing the unit price of the reinforcer i. Figure 2. Each data point represents an individual experimental session. The evidence derived from the behavioral-economic analyses is inconsistent with the idea that "Cocaine Consider Figure 3, which shows response-rate functions i. In all five studies, as unit price increases, response rate first increases, reaches a maximum, and then decreases.

The top response-rate graph in Figure 3 corresponds to the top demand curve graph in Figure 2, indicating that the nonlinear demand function results from a bitonic response-rate function. While the animal may at first attempt partially to maintain consumption by increasing bar-pressing, it eventually decreases its responses and accepts drastically depleted cellular cocaine levels.