On the other hand, an addicted person will be motivated by the drug of abuse. "That is one of the basic changes that trigger the aberrant behavior that you see in a person who is addicted," Volkow said. Such behavior is "the compulsion to take the drug, despite the fact there are severe, adverse consequences," she added.
Confounding Variables
"If [psychotherapeutic] prescription medications have the potential for producing abuse and addiction, why don't they do it frequently?" Volkow asked. The answer lies in the fact that the drug's effects are not just a function of the drug itself but other factors such as dose, frequency of dosing, route of administration, expectations and context of administration.
Volkow cited the example of a patient being prescribed a stimulant for attention-deficit/hyperactivity disorder and being told to take three tablets a day or 10 mg of the drug every three hours. If the patient is addicted to cocaine or methylphenidate, the patient will likely take it every 30 minutes at 30 mg doses.
"When individuals abuse methylphenidate, they don't take it in a tablet, they inject or snort it. The route of administration determines the speed by which the drug gets into the brain," she said. If individuals inject intravenous methylphenidate, "they will feel a high, which cocaine abusers say is indistinguishable from that they get with intravenous cocaine. However, when you give them oral methylphenidate, they don't feel anything, even though you may be delivering as high a dose as when delivered intravenously."
The effects of expectation on brain responses to drugs of abuse also have been studied. In drug abusers, the subjective responses to a drug are more pleasurable when the person expects to receive the drug than when they do not. Volkow cited an imaging study she and colleagues conducted examining the response of brain glucose utilization to intravenous methylphenidate in cocaine abusers under distinct conditions of expectation and no expectation (Volkow et al., 2003).
Four conditions were tested: 1) individuals expected and received methylphenidate; 2) individuals expected methylphenidate but received placebo; 3) individuals expected placebo but received methylphenidate; and 4) individuals expected and received placebo.
The increases in metabolism were approximately 50% larger when methylphenidate was expected than when it was not, and these differences were significant in the cerebellum (vermis) and thalamus. Methylphenidate-induced increases in self-reports of "high" were also approximately 50% greater when subjects expected to receive it than when they did not.
