In Brief

Studies have shown that drug tolerance and craving can be set off by sights, sounds and smells previously associated with drug use. Now, a new study in the Journal of Experimental Psychology: Animal Behavior Processes (Vol. 28, No. 3) suggests that internal cues, including subtle changes in perception and emotion, can also act as triggers. The results could have important implications for drug addiction treatments and the administration of analgesic drugs.

The study's authors, Marta Sokolowska and Shepard Siegel, PhD, of McMaster University, and Joseph A. Kim, PhD, of the University of California, San Francisco, examined the effect of extremely small "probe" doses of morphine on pain sensitivity in morphine-tolerant rats. They found that a rat receiving a probe dose of about 0.5 mg/kg--an amount too small to have an analgesic effect but big enough to mimic the early stages of a larger dose--would remove its tail from hot water almost twice as fast as a rat receiving a saline injection. The rat's hypersensitivity to pain suggests that tolerance is an attempt to compensate for the expected effects of a drug, and that the compensatory response can be triggered by internal cues.

In previous attempts to explain drug tolerance, says Siegel, "most people have talked about environmental cues, the location or the time at which you take the drug. What this shows is that internal cues are important, specifically early drug onset cues."

One implication of the study is that drug addiction treatments might be more successful if they taught patients how to cope with cravings elicited by early drug onset cues.

"There are a lot of treatments of drug addiction that attempt to decrease the association between drug cues and the effect of the drug," says Siegel. "One way to increase the efficacy of these treatments is to include this very, very potent cue for the drug, these early onset cues, which [outside of the treatment setting] are almost inevitably followed by the full drug effect."

The study also has implications for the way analgesic drugs are administered. Although some clinicians are aware that changes in a patient's environment can affect drug tolerance, few know that changes in the route of administration--such as switching from an oral drip to a transdermal patch, which can alter internal drug cues--could have similar effects.