Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide

<p>Abstract</p> <p>Background</p> <p>Respiratory depression, a potentially fatal side-effect of opioid-overdose, may be reversed by timely administration of an opioid antagonist, such as naloxone or naltrexone. Tampering with a formulation of morphine sulfate and sequestered naltrexone hydrochloride extended release capsules (MS-sNT) releases both the opioid morphine and the antagonist naltrexone. A study in recreational opioid-users indicated that morphine and naltrexone injected in the 25:1 ratio (duplicating the ratio of the formulation) found MS-sNT reduced morphine-induced euphoric effects vs intravenous (IV) morphine alone. In the same study, the effects of morphine + naltrexone on end-tidal carbon dioxide (EtCO₂), a measure of respiratory-depression, were evaluated and these data are reported here.</p> <p>Methods</p> <p>Single-center, placebo-controlled, double-blind crossover study. Non-dependent male opioid users were randomized to receive single IV doses of placebo, 30 mg morphine alone, and 30 mg morphine + 1.2 mg naltrexone. EtCO₂was measured by noninvasive capnography.</p> <p>Results</p> <p>Significant differences in EtCO₂least-squares means across all treatments for maximal effect (E_max) and area under the effect curve (AUE_0-2, AUE_0-8, AUE_0-24) were detected (all p ≤ 0.0011). EtCO₂E_maxvalues for morphine + naltrexone were significantly reduced vs morphine alone (42.9 mm Hg vs 47.1 mm Hg, p < 0.0001) and were not significantly different vs placebo (41.9 mm Hg). Median time to reach maximal effect (TE_max) was delayed for morphine + naltrexone vs morphine alone (5.0 h vs 1.0 h).</p> <p>Conclusions</p> <p>Results provide preliminary evidence that the naltrexone:morphine ratio within MS-sNT is sufficient to significantly reduce EtCO₂when administered intravenously to non-dependent male recreational opioid-users. Further studies with multiple measures of respiratory-function are warranted to determine if risk of respiratory depression is also reduced by naltrexone in the tampered formulation.</p

Emotional Reactions to Pain Predict Psychological Distress in Adult Patients with Sickle Cell Disease (SCD)

Differentiating somatic from emotional influences on the experience of chronic pain has been of interest to clinicians and researchers for many years. Although prior research has not well specified these pathways at the anatomical level, some evidence, both theoretical and empirical, suggest that emotional reactions influence the experience of disease and non-disease-related pains. Other studies suggest that treatments directed at negative emotional responses reduce suffering associated with pain. The current study was conducted to explore the influence of emotional reactions to pain as a predictor of psychological distress in a sample of adult Blacks with Sickle Cell Disease (SCD). Using cross-sectional survey data, we evaluated whether negative emotional reactions to the experience of pain were predictive of psychological distress after controlling for the somatic dimension of pain and age in n = 67 Black patients with Sickle Cell Disease (SCD). Results showed that greater negative emotion associated with pain predicted Somatization (p < .01), Anxiety (p < .05), Phobic Anxiety (p < .05), and Psychoticism (p < .05). Increased negative emotion associated with pain was also predictive of the General Symptoms Index (p < .05) and the Positive Symptoms Total from the SCL-90-R (p < .01). We believe the current study demonstrates that negative emotional reactions to the experience of pain in adults with SCD are predictive of psychological distress above and beyond the influences of age and the direct nociceptive experience. We also believe these data to be valuable in conceptualizing the allocation of treatment resources toward a proactive approach with early identification of patients who are responding poorly for the purpose of potentially reducing later psychopathology. A deeper understanding of the ways that subpopulations cope with chronic disease-related pain may produce models that can be ultimately generalized to the consumers of the majority of healthcare resources

Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended-Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users

OBJECTIVE: To evaluate the pharmacodynamic (PD) effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN) capsules compared with controlled-release morphine sulfate (MS) and placebo when crushed and administered intranasally

Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended-Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users

OBJECTIVE: To evaluate the pharmacodynamic (PD) effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN) capsules compared with controlled-release morphine sulfate (MS) and placebo when crushed and administered intranasally.METHODS: The present study was a randomized, double-blinded, placebo-controlled, single-dose (30 mg), three-way crossover study in healthy, nondependent recreational opioid users. PD measures included assessment of subjective drug effects using visual analogue scales (VAS) ranging from 0 to 100 and assessments of pupil diameter. Blood samples were collected for pharmacokinetic analyses.RESULTS: Both MS and MSN showed significantly higher PD values compared with placebo. MSN showed significantly lower scores for drug liking and high VAS scores on both mean peak effect (Emax) (69.6 and 55.2, respectively) and in area under the effect curve over 2 h (86.3 and 66.7, respectively) following dosing compared with MS (Emax 87.6 and 86.6, respectively; area under the curve over 2 h 120.6 and 132.9, respectively; Pud_less_than0.001). MSN showed significantly lower Emax for all other positive subjective effects (good drug effects, overall drug liking, and take drug again VAS scores) compared with MS (Pud_less_than0.001). Peak minimum pupil diameter was significantly larger for MSN than MS (P=0.002). Mean peak plasma concentration (Cmax) and median time to Cmax for morphine following administration of MSN and MS were similar (27.3 ng/mL and 0.57 h versus 27.7 ng/mL and 0.6 h, respectively). Naltrexone mean Cmax was 1497 pg/mL after MSN and median time to Cmax was 0.55 h.CONCLUSIONS: When crushed and administered intranasally, MSN was associated with significantly lower ratings of drug liking and other positive subjective effects compared with MS.Peer Reviewe

Loving-kindness meditation for chronic low back pain: Results from a pilot trial

Purpose: Loving-kindness meditation has been used for centuries in the Buddhist tradition to develop love and transform anger into compassion. This pilot study tested an 8-week loving-kindness program for chronic low back pain patients. Method: Patients (N = 43) were randomly assigned to the intervention or standard care. Standardized measures assessed patients’ pain, anger, and psychological distress. Findings: Post and follow-up analyses showed significant improvements in pain and psychological distress in the loving-kindness group, but no changes in the usual care group. Multilevel analyses of daily data showed that more loving-kindness practice on a given day was related to lower pain that day and lower anger the next day. Conclusions: Preliminary results suggest that the loving-kindness program can be beneficial in reducing pain, anger, and psychological distress in patients with persistent low back pain. Implications: Clinicians may find loving-kindness meditation helpful in the treatment of patients with persistent pain. <br/

Forgiveness and chronic low back pain: A preliminary study examining the relationship of forgiveness to pain, anger, and psychological distress

Clinical observations suggest that many patients with chronic pain have difficulty forgiving persons they perceive as having unjustly offended them in some way. By using a sample of 61 patients with chronic low back pain, this study sought to determine the reliability and variability of forgiveness assessments in patients and to examine the relationship of forgiveness to pain, anger, and psychological distress. Standardized measures were used to assess patients’ current levels of forgiveness, forgiveness self-efficacy, pain, anger, and psychological distress. Results showed that forgiveness-related constructs can be reliably assessed in patients with persistent pain, and that patients vary considerably along dimensions of forgiveness. Furthermore, correlational analyses showed that patients who had higher scores on forgiveness-related variables reported lower levels of pain, anger, and psychological distress. Additional analyses indicated that state anger largely mediated the association between forgiveness and psychological distress, as well as some of the associations between forgiveness and pain. These findings indicate that forgiveness can be reliably assessed in patients with persistent pain, and that a relationship appears to exist between forgiveness and important aspects of living with persistent pain.<br/