A neuroeconomic signature of opioid craving: How fluctuations in craving bias drug-related and nondrug-related value

Abstract

How does craving bias decisions to pursue drugs over other valuable, and healthier, alternatives in addiction? To address this question, we measured the in-the-moment economic decisions of people with opioid use disorder as they experienced craving, shortly after receiving their scheduled opioid maintenance medication and ~24 h later. We found that higher cravers had higher drug-related valuation, and that moments of higher craving within-person also led to higher drug-related valuation. When experiencing increased opioid craving, participants were willing to pay more for personalized consumer items and foods more closely related to their drug use, but not for alternative "nondrug-related" but equally desirable options. This selective increase in value with craving was greater when the drug-related options were offered in higher quantities and was separable from the effects of other fluctuating psychological states like negative mood. These findings suggest that craving narrows and focuses economic motivation toward the object of craving by selectively and multiplicatively amplifying perceived value along a "drug relatedness" dimension.

Fig. 1. Hypothesized model of drug craving.

Drug craving in opioid use disorder, like food craving in healthy people, is hypothesized to act on normative valuation mechanisms: opioid craving should selectively amplify the value of options judged as more drug related, and more so when these options are available in higher quantities. This interaction between drug-relatedness, amount, and craving may explain how acute psychological craving biases decisions toward drug seeking and use.

Fig. 2. Experimental design.

A On Day 1, participants rated each of 40 common consumer items and snack foods on their subjective drug relatedness and general desirability, among other dimensions. For each participant, these ratings were used to sub-select a 12-item choice set that (1) provided maximal spread in drug relatedness (that was of main interest here), while (2) de-coupling this dimension from general desirability thus minimizing the possibility of a systematic bias in the desirability of the items chosen as drug-related or nondrug-related (see Supplementary Information for details on selection of the initial 40-item fixed set and the choice set personalization procedure). The final selected choice sets only partly overlapped across participants, revealing a high degree of subjectivity in drug relatedness judgements (Fig. S1). B Following screening and choice set selection on Day 1, participants completed two task sessions, one after taking their daily methadone dose and the other ~24 h since the last dose of methadone (Days 2 and 3, randomized crossover order). Each task session was composed of 4 blocks. Each block was composed of 101 trials. Trials were randomly presented and consisted of 48 willingness-to-pay bid trials for each of the 12 items in the personalized choice set presented in 4 different quantities (depicted in blue), 48 desire rating trials for each of the same 12 items × 4 quantities (gray), 3 mood rating trials for each of happiness, stress, and boredom (teal), and 2 craving rating trials for each of heroin and methadone (red). For purposes of analysis, the three mood state ratings were averaged for each block into a composite negative mood measure and the two craving ratings were averaged into a composite opioid craving measure. To incentivize participants to provide their “true” momentary value (i.e., bid) for each item and to report only on their current subjective experience in each block, the task was structured such that it could end with a fixed (2%) probability after each block in a session, ending regardless after the 4^th block. At the end of the session, one bid trial from the last completed block was randomly selected and played out to determine a participant’s bonus.

Fig. 3. Opioid craving dynamics.

A Momentary reported opioid craving (% of scale’s max) by study day (after 24 h from methadone dosing and shortly after dosing; randomized order) and task block (up to four) within a day. Craving was higher 24 h after methadone dosing and varied substantially both between- and within-person across the task blocks (intraclass correlation coefficient = 0.56). B Within-person variability in reported craving (range in opioid craving ratings; gray points show single-participant data) was comparable across blocks within a day to variability across days. ***P = 0.001, n.s. nonsignificant.

Fig. 4. Observed pattern of craving effects in valuation.

A Change in the subjective value (bid) for each of the task items on offer with opioid craving, ranked by the individually rated drug relatedness of each item across participants. B Subjective value (bids) for each quantity of the item with the lowest and highest drug relatedness in the choice set for each participant (shaded areas in A), at the lowest (peach), and highest (dark red) opioid craving task blocks for that participant. For visualization purposes, only data for each participant’s highest vs. lowest craving blocks (both panels) and highest vs. lowest drug-related items (B) are shown. The analyses reported in the text and tables used the full dataset. See Table 1 and Supplementary Information, Tables S3–S5.