Importance: A common trigger for relapse in drug addiction is the experience of craving via exposure to cues previously associated with drug use. Preclinical studies have consistently demonstrated incubation of cue-induced drug-seeking during the initial phase of abstinence, followed by a decline over time. In humans, the incubation effect has been shown for alcohol, nicotine, and methamphetamine addictions, but not for heroin or cocaine addiction. Understanding the trajectory of cue-induced craving during abstinence in humans is of importance for addiction medicine.
Objective: To assess cue-induced craving for cocaine in humans using both subjective and objective indices of cue-elicited responses.
Design, setting, and participants: Seventy-six individuals addicted to cocaine with varying durations of abstinence (ie, 2 days, 1 week, 1 month, 6 months, and 1 year) participated in this laboratory-based cross-sectional study from June 19, 2007, to November 26, 2012. The late positive potential component of electroencephalography, a recognized marker of incentive salience, was used to track motivated attention to drug cues across these self-selected groups. Participants also completed subjective ratings of craving for cocaine before presentation of a cue, and ratings of cocaine "liking" (hedonic feelings toward cocaine) and "wanting" (craving for cocaine) after presentation of cocaine-related pictures. Data analysis was conducted from June 5, 2015, to March 30, 2016.
Main outcomes and measures: The late positive potential amplitudes and ratings of liking and wanting cocaine in response to cocaine-related pictures were quantified and compared across groups.
Results: Among the 76 individuals addicted to cocaine, 19 (25%) were abstinent for 2 days, 20 (26%) were abstinent for 1 week, 15 (20%) were abstinent for 1 month, 12 (16%) were abstinent for 6 months, and 10 (13%) were abstinent for 1 year. In response to drug cues, the mean (SD) late positive potential amplitudes showed a parabolic trajectory that was higher at 1 (1.26 [1.36] µV) and 6 (1.17 [1.19] µV) months of abstinence and lower at 2 days (0.17 [1.09] µV), 1 week (0.36 [1.26] µV), and 1 year (-0.27 [1.74] µV) of abstinence (P = .02, partial η2 = 0.16). In contrast, the subjective assessment of baseline craving (mean [SD] rating: 2 days, 26.05 [9.85]; 1 week, 18.70 [11.01]; 1 month, 10.87 [10.70]; 6 months, 6.92 [8.47]; and 1 year, 3.00 [3.77]) and cue-induced liking (mean [SD] rating: 2 days, 3.06 [2.34]; 1 week, 2.33 [2.87]; 1 month, 1.15 [2.03]; 6 months, 1.00 [2.24]; and 1 year, 1.00 [1.26]) and wanting (mean [SD] rating: 2 days, 3.44 [2.62]; 1 week, 2.72 [2.87]; 1 month, 1.46 [2.33]; 6 months, 1.00 [2.16]; and 1 year, 1.00 [1.55]) of cocaine showed a linear decline from 2 days to 1 year of abstinence (P ≤ .001, partial η2 > 0.26).
Conclusions and relevance: The late positive potential responses to drug cues, indicative of motivated attention, showed a trajectory similar to that reported in animal models. In contrast, we did not detect incubation of subjective cue-induced craving. Thus, the objective electroencephalographic measure may possibly be a better indicator of vulnerability to cue-induced relapse than subjective reports of craving, although this hypothesis must be empirically tested. These results suggest the importance of deploying intervention between 1 month and 6 months of abstinence, when addicted individuals may be most vulnerable to, and perhaps least cognizant of, risk of relapse.