Comparison of self-reported substance use with biological testing among treatment-seeking patients with opioid use disorder.

BACKGROUND: Several factors may influence the validity of self-report. In this study, we aimed to assess the validity of self-reported drug use compared to urine testing among treatment-seeking patients with opioid use disorder (OUD). METHODS: This cross-sectional study recruited 293 patients with OUD, referred to the Iranian National Center for Addiction Studies (INCAS) clinic, from November 2015 to June 2017. The study compared self-reported opioid use in the past 72 h with the results of urinalysis, using immunoassay technique. We estimated sensitivity, negative predictive value, percent agreement, positive percent agreement, and Cohen's kappa statistics for those with OUD. RESULTS: The sensitivity of self-reported opioid use was 85.9%. Percent agreement, positive percent agreement, and Cohen's Kappa statistics between self-reported opioid use and urine testing for morphine in the first month were 88.5%, 78.1%, and 77.0, respectively. Multilevel logistic regression showed that longer treatment duration (OR = 1.21, 95%CI: 1.07-1.37, p-value = 0.002) was significantly associated with the agreement of self-reported opioid use with urine testing. CONCLUSION: Self-report can be used as a reliable method for monitoring treatment adherence combined with random urine tests.

Evaluation of dynorphin and kappa-opioid receptor level in the human blood lymphocytes and plasma: Possible role as a biomarker in severe opioid use disorder.

BACKGROUND: The dynorphin (DYN)/kappa opioid receptor (KOR) system plays an important role in the development of addiction, and dysregulation of this system could lead to abnormal activity in the reward pathway. It has been reported that the expression state of the neurotransmitters and their receptors in the brain is reflected in peripheral blood lymphocytes (PBLs). METHODS: We have evaluated the PBLs and plasma samples of four groups: 1) subjects with severe opioid use disorder (SOD), 2) methadone-maintenance treated (MMT) individuals, 3) long-term abstinent subjects having former SOD, and 4) healthy control subjects (n = 20 in each group). The mRNA expression level of preprodynorphin (pPDYN) and KOR in PBLs has been evaluated by real-time PCR. Peptide expression of PDYN in PBLs has been studied by western blot, and DYN concentration in plasma has been measured by ELISA. RESULTS: The relative expression level of the pPDYN mRNA and PDYN peptide in PBLs were significantly up-regulated in SOD, MMT, and abstinent groups compared to control subjects. No significant difference was found in the plasma DYN concentration between study groups. The expression level of the KOR mRNA in PBLs was significantly decreased in all three study groups compared to the control subjects. CONCLUSION: the expression changes in the DYN/KOR system after chronic exposure to opioids, including methadone, seems to be stable and does not return to normal levels even after 12 months abstinence. These long-time and permanent changes in PBLs may serve as a biomarker and footprint of SOD development in the periphery.

Morphine exposure before conception affects anxiety-like behavior and CRF level (in the CSF and plasma) in the adult male offspring.

It has been proven that exposure to some drugs even before gestation had transgenerational effects. To investigate the changes which induced by parental morphine exposure before gestation; mainly the anxiety-like behavior, Corticotropin Releasing Factor (CRF) level in the CSF and plasma, CRF Receptor 1 (CRFR1), and the level of protein kinase C (PKC-α) were evaluated in the male offspring. Male and female Wistar rats were exposed to morphine for 21 following days. Ten days after last drug exposure, animals were prepared for mating in 4 distinct groups as follow: drug-naïve female and male (used as control), drug-naïve female and morphine-abstinent male, drug-naïve male and morphine-abstinent female, and morphine abstinent male and female. Offspring were subjected to assess anxiety-like behavior (using elevated plus maze test). CSF and plasma were gathered, and the CRF level was evaluated by ELISA. Using real-time PCR, the CRFR1 level in the brain was evaluated. Results showed that anxiety-like behavior increased in the offspring of morphine-abstinent parent(s) compared with the control group. CRF level in the plasma and CSF also increased in the litter of morphine-abstinent parent(s). CRFR1 mRNA level was upregulated in the brain of offspring with one and/or two morphine-abstinent parent(s). Furthermore, the level of PKC-α was decreased in the brain of offspring which had one and/or two morphine-abstinent parent(s). Taken together, our findings indicated that morphine exposure even before gestation induced transgenerational effects via dysregulation of HPA axis which results in anxiety in the adult male offspring.