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

Veterans experience chronic pain at greater rates than the rest of society and are more likely to receive long-term opioid therapy (LTOT), which, at high doses, is theorized to induce maladaptive neuroplastic changes that attenuate self-regulatory capacity and exacerbate opioid dose escalation. Mindfulness meditation has been shown to modulate frontal midline theta (FMT) and alpha oscillations that are linked with marked alterations in self-referential processing. These adaptive neural oscillatory changes may promote reduced opioid use and remediate the neural dysfunction occasioned by LTOT. In this study, we used electroencephalography (EEG) to assess the effects of a mindfulness-based, cognitive training intervention for opioid misuse, Mindfulness-Oriented Recovery Enhancement (MORE), on alpha and theta power and FMT coherence during meditation. We then examined whether these neural effects were associated with reduced opioid dosing and changes in self-referential processing. Before and after 8 weeks of MORE or a supportive psychotherapy control, veterans receiving LTOT (N = 62) practiced mindfulness meditation while EEG was recorded. Participants treated with MORE demonstrated significantly increased alpha and theta power (with larger theta power effect sizes) as well as increased FMT coherence relative to those in the control condition—neural changes that were associated with altered self-referential processing. Crucially, MORE significantly reduced opioid dose over time, and this dose reduction was partially statistically mediated by changes in frontal theta power. Study results suggest that mindfulness meditation practice may produce endogenous theta stimulation in the prefrontal cortex, thereby enhancing inhibitory control over opioid dose escalation behaviors.Subject terms: Human behaviour, Addiction     

The physiology and toxicology of acute inhalation phosphine poisoning in conscious male rats

Phosphine (PH₃) is a toxidrome-spanning chemical that is widely used as an insecticide and rodenticide. Exposure to PH₃ causes a host of target organ and systemic effects, including oxidative stress, cardiopulmonary toxicity, seizure-like activity and overall metabolic disturbance. A custom dynamic inhalation gas exposure system was designed for the whole-body exposure of conscious male Sprague-Dawley rats (250–350?g) to PH₃. An integrated plethysmography system was used to collect respiratory parameters in real-time before, during and after PH₃ exposure. At several time points post-exposure, rats were euthanized, and various organs were removed and analyzed to assess organ and systemic effects. The 24?h post-exposure LCt₅₀, determined by probit analysis, was 23,270?ppm?×?min (32,345?mg?×?min/m³). PH₃ exposure affects both pulmonary and cardiac function. Unlike typical pulmonary toxicants, PH₃ induced net increases in respiration during exposure. Gross observations of the heart and lungs of exposed rats suggested pulmonary and cardiac tissue damage, but histopathological examination showed little to no observable pathologic changes in those organs. Gene expression studies indicated alterations in inflammatory processes, metabolic function and cell signaling, with particular focus in cardiac tissue. Transmission electron microscopy examination of cardiac tissue revealed ultrastructural damage to both tissue and mitochondria. Altogether, these data reveal that in untreated, un-anesthetized rats, PH₃ inhalation induces acute cardiorespiratory toxicity and injury, leading to death and that it is characterized by a steep dose-response curve. Continued use of our interdisciplinary approach will permit more effective identification of therapeutic windows and development of rational medical countermeasures and countermeasure strategies.