Conditioned Salivary Response to Prescription Opioid Medication As a Physiological Marker of Opioid Misuse That Is Modifiable with Mindfulness Training

Background

Patients with chronic noncancer pain are commonly treated with long-term opioid therapy (LTOT) despite risks including opioid misuse, overdose, and development of opioid use disorder. Approximately 25% of people receiving LTOT for pain engage in opioid misusing behaviors such as unauthorized dose escalation or taking prescription opioids to induce euphoria. Addictive use of prescription opioids is theorized to arise and be and maintained, in part, through the same conditioning processes that undergird other substance use disorders: by virtue of dopaminergic activation in brain reward circuitry, repeated consumption of drugs comes to imbue drug-related cues (e.g., the sight of an opioid pill) with incentive salience, leading to physiological cue-reactivity, cue-elicited craving, and compulsive drug use. Opioid-treated chronic pain patients may be at elevated risk for developing conditioned opioid cue-reactivity as their prescribed LTOT dosing schedules simultaneously function as fixed reinforcement schedules.

Methods

In Study 1, participants (i.e., chronic pain patients receiving LTOT) completed an in vivo opioid exposure task. In Study 2, participants completed this same task and then were randomly assigned to receive 8 weeks of MORE or supportive group (SG) psychotherapy. The opioid medication reactivity task consisted of two, 3-minute blocked conditions (i.e., opioid and neutral). In the opioid cue block, participants placed dental cotton rolls in their mouths. while (i) holding a bottle of their most commonly used opioid medication, (ii) looking closely at the medication inside the bottle, and (iii) taking out one pill and hold it 12” from their face. After the three-minute opioid observation period, the three dental cotton rolls were removed and placed in a previously weighed plastic cup. In the neutral condition, Participants completed the same set of procedures, but rather than using their prescribed opioid, participants withdrew paperclips from a generic unmarked bottle.

Results

In study 1, RM-ANOVA and RM-ANCOVA revealed that opioid medication task block had a significant effect on opioid treated chronic pain patients’ self-reported craving and salivation. Craving and salivation during the opioid medication block was significantly higher than craving during the neutral object block. In study 2, Linear mixed modeling revealed MORE patients reported decreased opioid cue-elicited craving and salivation from pre- to post-treatment whereas SG patients reported an increase in opioid cue-elicited craving and salivation.

Conclusions and Implications

In this investigation, we observed that chronic pain patients treated with LTOT exhibited salivary reactivity and cue-elicited craving during in vivo exposure to their prescribed opioid, and that this physiological and subjective reactivity was malleable to mindfulness-based intervention. Specifically, we found that exposure to the patient’s own prescribed opioid resulted in significantly greater increases in salivation and craving than exposure to a neutral cue. We then found that participants who received 8 weeks of treatment with MORE evidenced significantly greater decreases in opioid cue-reactivity than participants in an active control condition, as evidenced by reduced salivation and craving ratings. Thus, salivation may serve as a useful, objective index of opioid cue-reactivity.