Endogenous theta stimulation during meditation predicts reduced opioid dosing following treatment with Mindfulness-Oriented Recovery Enhancement

Chronic pain is prevalent among veterans, and long-term opioid therapy (LTOT) is often prescribed, leading to maladaptive neuroplastic changes that reduce self-regulatory capacity and exacerbate opioid dose escalation. Mindfulness-based interventions (MBIs), such as MORE, have shown promise in mitigating opioid misuse. MBIs involve focused attention and open monitoring meditation techniques that modulate frontal midline theta (FMT) and alpha oscillations, impacting self-referential processing. This study aimed to investigate whether MORE, compared to a supportive psychotherapy control, would alter alpha and theta power and FMT coherence during meditation, and whether these changes would correlate with reduced opioid dosing and altered self-referential processing. The researchers hypothesized that increased theta power, specifically in the frontal regions, would mediate the effect of MORE on reducing opioid dosage. The high prevalence of chronic pain and opioid use among veterans, coupled with the potential for MBIs to positively influence brain activity associated with self-regulation and pain management, provides a strong rationale for this research. The study's success in demonstrating a mechanism for the effectiveness of MORE in reducing opioid use could have important implications for pain management and addiction treatment strategies within the veteran population and beyond.

The literature review extensively covers the high prevalence of chronic pain and opioid use among veterans, the negative consequences of LTOT including maladaptive neuroplasticity and reduced self-regulatory capacity, and the potential benefits of MBIs in addressing these issues. Studies on the neural mechanisms of meditation, particularly the role of alpha and theta oscillations in mindfulness, are reviewed. Previous research demonstrates that mindfulness meditation modulates alpha and theta brainwave activity, which are associated with self-referential processing and self-regulation. The introduction also cites prior research supporting the use of MBIs in treating substance use disorders and chronic pain. This establishes a foundation for the study's hypothesis that MORE, by influencing brain oscillations associated with self-regulation, would reduce opioid use in veterans.

Sixty-two veterans receiving LTOT were randomly assigned to either an 8-week MORE program or a supportive group psychotherapy control. EEG data were recorded during 10-minute mindfulness meditation sessions (5 minutes eyes open, 5 minutes eyes closed) before and after the intervention. EEG data were analyzed to assess changes in alpha and theta power and FMT coherence. Opioid dosage was tracked using the Timeline Followback method. Changes in self-referential processing were assessed using the Nondual Awareness Dimensional Assessment (NADA) and the Perceived Body Boundaries Scale (PBSS). Repeated-measures ANOVAs were used to analyze EEG data, and a linear mixed-effects model examined changes in opioid dosage. Path analysis was conducted to assess mediation of opioid dose reduction by changes in frontal theta power. The study employed rigorous methodology, including blinding of assessors to group assignment and control for confounding variables such as pre-treatment opioid dose, benzodiazepine, and THC use. Detailed EEG data processing steps are described, ensuring data quality and validity. The study was adequately powered to detect changes in EEG spectra. The use of a manualized active control group (supportive group psychotherapy) helps to isolate the specific effects of mindfulness training.

Veterans in the MORE group demonstrated significantly increased alpha and theta power (with larger effect sizes for theta) and increased FMT coherence compared to the control group. These neural changes were associated with altered self-referential processing, as measured by the NADA and PBSS. Crucially, MORE significantly reduced opioid dosage over time, and this reduction was partially mediated by increases in frontal theta power. The increase in frontal theta power correlated with decreases in opioid dose. Path analysis confirmed that the effect of MORE on reducing opioid dose was statistically mediated by increases in frontal theta power during mindfulness meditation. Additional analyses showed a positive correlation between mindfulness practice duration and changes in theta coherence, frontal theta power, and central alpha power. These findings provide strong support for the hypothesis that increased frontal theta power, induced by mindfulness meditation, plays a role in reducing opioid use. Effect sizes for the increase in theta power were moderate to large. The statistical significance of the findings is consistently highlighted throughout the results section.

The findings suggest that mindfulness meditation, specifically as delivered through the MORE program, can increase frontal theta power, potentially enhancing inhibitory control over opioid dose escalation behaviors. This increase in theta power may mediate the reduction in opioid use observed in the MORE group. The observed changes in self-referential processing further support the idea that the mechanism of action involves alterations in brain activity related to self-awareness and self-regulation. The study's results provide further evidence for the efficacy of MBIs in treating opioid misuse. The association between increased meditation practice duration and EEG changes suggests a dose-response relationship, supporting the potential for enhancing therapeutic benefits with increased practice. Future studies could investigate whether combining exogenous (neurostimulation) and endogenous (mindfulness meditation) theta stimulation may further enhance therapeutic effects. The limitations of the current study (discussed below) are considered in the context of these findings.

This study demonstrates that the MORE intervention increases frontal theta power during mindfulness meditation, which is associated with a reduction in opioid use among veterans with chronic pain. The findings suggest a novel neurocognitive mechanism by which mindfulness meditation may reduce opioid dependence. Future research should explore the potential of combining exogenous and endogenous theta stimulation and examine the long-term effects of MORE on opioid use and other clinical outcomes in larger, more diverse samples. The use of higher-density EEG and more detailed investigation into other potentially influential factors could further refine our understanding of the relationships between mindfulness practice and opioid use.

The study used a limited number of EEG electrodes, which may have constrained the ability to perform detailed source localization analysis. The influence of acute opioid effects on the day of EEG recording is also a limitation, although sensitivity analyses controlled for this to an extent. The sample size was modest, limiting the generalizability of the findings. Future studies should employ higher-density EEG, larger sample sizes, and longer follow-up periods to address these limitations. Furthermore, the possibility that reduced opioid dosing could have influenced EEG changes, rather than the other way around, needs further investigation through multiple follow-up assessments of EEG and opioid usage.