Incubation of Cue-Induced Craving in Adults Addicted to Cocaine Measured by Electroencephalography

Abstract

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.

Conflict of interest statement

Disclosures: None reported.

Figures

Figure 1. Grand Averages of Event-Related Potentials (ERPs) in Response to Drug-Related and Neutral Cues at the Centroparietal Electrode Site

Next to each waveform is the scalp topography (ie, a schematic map of the ERP amplitude at and around different electrode locations on the scalp, with the nose pointing north) of the drug cue reactivity (relative to neutral) in that group. The color intensity on the scalp topographies ranges from +3 µV (dark red) to −3 µV (dark blue), such that the red color intensity reflects increased amplitude in response to drug cues vs neutral cues and the blue color intensity reflects decreased amplitude in response to drug cues vs neutral cues.

Figure 2. Drug Cue Reactivity Measured With Late Positive Potential (LPP) Amplitude

A quadratic (solid), rather than linear (dotted), trajectory is seen from 2 days to 1 year of abstinence. Circles indicate observed LPP amplitude.

Figure 3. Self-reported Craving and Cue-Induced Liking and Wanting Cocaine

Ratings continue to decline during an extended duration of abstinence. Solid brackets indicate P < .05; dotted brackets, P < .10; and vertical lines within the bars, ±1 SEM.