Objective-Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans.Method-Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions.Results-During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the nondrug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex).Conclusions-These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.Craving for a drug is a cardinal feature of addictive disorders and is clinically significant because of its potential to trigger drug use and relapse (1). The cocaine epidemic in the United States has prompted an intensive, largely unsuccessful search for medications to treat cocaine craving (2,3). This search has likely been complicated by a heterogeneous target: drug desire that emerges during cocaine cessation (4) may well have a different brain substrate than desire induced by cocaine itself (5) and the cues that signal it (6). Noninvasive brain imaging studies have recently begun to examine the brain substrates of both withdrawal-based craving (7,8) and cue-induced craving (9-11) in humans. We present here a hypothesis-guided imaging study of cue-induced cocaine craving in which we used evocative video cues from our prior work, which measured peripheral and subjective correlates of that state (6,(12)(13)(14).Human cocaine users often experience profound desire for the drug when they encounter cues (people, places, paraphernalia, etc.) associated with cocaine (6,15). Cue-induced cocaine craving is sometimes accompanied by a number of signs and symptoms similar to the effects Address reprint requests to Dr. Childress, Addiction Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, 3900 Chestnut St., Philadelphia, PA 19104; childress@research.trc.upenn.edu.. Data presented in part at meetings of the Society for Neurosciences, the College on Problems of Drug Dependence, the American Psychiatric Association, and the American College of Neuropsychopharmacology (1994Neuropsychopharmacology ( -1997 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript of cocaine itself, including generalized arousal, palpitations, light-head...
