EEG Indicates That Cocaine Relapse Vulnerability Peaks 1 to 6 Months Into Abstinence

This research:

  • Suggests that electroencephalography (EEG) may provide an objective measure of cocaine-addicted participants’ vulnerability to cue-induced relapse.
  • Indicates that the period from 1 to 6 months of abstinence is a time of increased vulnerability to cue-induced relapse to cocaine.

Studies have shown that people who cease taking some drugs experience “incubation” of cue-induced craving, whereby cues that they associate with the drug elicit craving that is mild at first, becomes stronger with longer abstinence, then fades. Incubation has been demonstrated following cessation of alcohol, nicotine, and methamphetamine, but not to the same degree with all of them, and not with all drugs—for example, not with heroin. However, some or all of this variability may stem from studies’ use of subjective measures of cue reactivity, such as self-reported craving, rather than objective measurements.

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Figure 1. Late Positive Potential (LPP) Measurements in Response to Photographic Cocaine Cues in Cocaine-Addicted Adults Abstinent for Various Lengths of Time The amplitude of LPP cue reactivity was higher in study participants who had been abstinent for 1 month or 6 months than in those who had been abstinent for 2 days, 1 week, or 1 year. These findings suggest the presence of an incubation effect for cue-induced relapse vulnerability. See full text description at end of article.

Dr. Muhammad A. Parvaz and colleagues from the Icahn School of Medicine at Mount Sinai, New York, recently demonstrated that a component of cocaine-dependent participants’ electroencephalography (EEG) signal follows an incubation-like trajectory in response to drug cues. Besides affirming other evidence indicating that cocaine-dependent participants’ craving incubates, the finding suggests that EEG can provide an objective measure of susceptibility to relapse cues. If borne out in future research, it may pave the way for relapse prevention treatments that fit participants’ vulnerability to cue-induced relapse at each point in the incubation trajectory.

The Mount Sinai team obtained EEG recordings of 76 people with cocaine dependence while exposing them to photographs of cocaine preparation and use. The study participants had been abstinent for 2 days (25 percent), 1 week (26 percent), 1 month (20 percent), 6 months (16 percent), or 1 year (13 percent).

The researchers compared the five participant groups’ EEGs, focusing on a component that they interpreted as an indicator of the intensity of cue-induced cocaine craving. Previous studies had linked the amplitude of this component, called the late positive potential (LPP), to participants’ self-reports of cocaine craving. More generally, studies have indicated that LPP amplitude reflects the strength of attentional and emotional responses to motivational cues, including drug cues.

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Figure 2. Subjective Craving in Response to Photographic Cocaine Cues in Cocaine-Addicted Adults Abstinent for Various Lengths of Time In contrast to the findings for EEG cue reactivity (Figure 1), subjective measures of craving (e.g., “liking cocaine,” “wanting to use cocaine”) decreased in a linear manner with increasing duration of abstinence. The horizontal lines above the bars indicate statistically significant differences between the groups (solid lines: P < 0.05; dotted lines: P < 0.10). See full text description at end of article.

The researchers’ comparison revealed a pattern consistent with incubation of cue-induced craving: The participants with 1 month or 6 months of abstinence exhibited higher LPP amplitude when viewing the photographs than the participants with shorter or longer abstinence (see Figure 1).

The parabolic trajectory traced by the study participants’ LPP amplitude parallels observations of animals’ willingness to work for cocaine after varying lengths of abstinence. In contrast, the participants’ ratings of how much they “liked” and “wanted to use” cocaine after viewing the photographs declined linearly with increasing length of abstinence (see Figure 2). Accordingly, the researchers propose that LPP amplitude is a better gauge of cocaine-dependent participants’ vulnerability to relapse than the participants’ ratings of their desire for the drug.

The Mount Sinai researchers’ findings indicate that cocaine-addicted adults may be most vulnerable to relapse after 1 to 6 months of abstinence (a timeframe in which most are discharged from treatment), but may not be aware of this vulnerability. If further studies replicate the findings, EEG assessment of cue-induced responsiveness may be useful in the clinical setting for assessing relapse risk and tailoring interventions to maintain abstinence among cocaine-addicted adults.

This research was supported by NIH grants DA033088, DA40046, DA023579, DA034954-01, and DA041528-01.

Text Description of Figure 1

The figure shows graphic representations of tissue sections from the prefrontal cortex of a control mouse (left) and an amphetamine-exposed mouse (right). The yellow lines entering the tissue sections from the bottom represent dopamine axons that split and form synapses in the prefrontal cortex. Green circles represent the normal synapses that are closely spaced in the prefrontal cortex of the control mouse. Some of these synapses can also be found in the prefrontal cortex of the amphetamine-exposed mouse (green circles), but at a lower density. Also, additional dopamine synapses are spread out beyond the normal area in the amphetamine-exposed mouse, indicated by red circles.

Text Description of Figure 2

The three bar charts show the differences in the levels of miR-218, Dcc mRNA, and DCC protein between control mice (lighter colors) and amphetamine-exposed mice (darker colors). In all three charts, the level of the variable measured is set as 1.0 for the control mouse and the level for the amphetamine-exposed mouse is shown as the fold change relative to the control mouse. The left chart (blue bars) illustrates the levels of miR-218. The level is 1.0 for the control mouse and approximately 1.9 for the amphetamine-exposed mouse. The middle chart (green bars) shows the levels of Dcc mRNA. The level is again 1.0 for the control mouse and approximately 0.4 for the amphetamine-exposed mouse. The right chart (purple bars) shows the levels of DCC protein. The level is again set at 1.0 for the control mouse and is approximately 0.6 for the amphetamine-exposed mouse.

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