Maintenance therapy with buprenorphine and methadone is the gold standard pharmacological treatment for opioid use disorder (OUD). Despite these compounds demonstrating substantial efficacy, a ...significant number of patients do not show optimal therapeutic responses. The abuse liability of these medications is also a concern. Here we used rats to explore the therapeutic potential of the new long-acting pan-opioid agonist Cebranopadol in OUD. We tested the effect of cebranopadol on heroin self-administration and yohimbine-induced reinstatement of heroin seeking. In addition, we evaluated the abuse liability potential of cebranopadol in comparison to that of heroin under fixed ratio 1 (FR1) and progressive ratio (PR) operant self-administration contingencies. Oral administration of cebranopadol (0, 25, 50 μg/kg) significantly attenuated drug self-administration independent of heroin dose (1, 7, 20, 60μg/inf). Cebranopadol also reduced the break point for heroin (20 μg/inf). Finally, pretreatment with cebranopadol significantly attenuated yohimbine-induced reinstatement of drug seeking. In abuse liability experiments under FR1 contingency, rats maintained responding for heroin (1, 7, 20, 60μg/inf) to a larger extent than cebranopadol (0.03, 0.1, 0.3, 1.0, 6.0μg/inf). Under PR contingency, heroin maintained responding at high levels at all except the lowest dose, while the break point (BP) for cebranopadol did not differ from that of saline. Together, these data indicate that cebranopadol is highly efficacious in attenuating opioid self-administration and stress-induced reinstatement, while having limited abuse liability properties. Overall, the data suggest clinical potential of this compound for OUD treatment.
•Methadone and buprenorphine are the goldstandard therapies in OUD. Their abuse liability is a concern.•Cebranopadol, a first-in-class opioid agonist that also activates the NOP receptor, is in phase-III for pain.•Cebranopadol reduces the motivation for heroin self-administration and heroin seeking.•Results demonstrate a low abuse liability of cebranopadol in rat self-administration experiments.•Cebranopadol is candidate for immediate clinical investigation in OUD disorder patients.
Chronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This imbalance includes changes in GABA receptors – importantly in GABAA subtypes – ...and glutamate receptors, especially in NMDA subtypes. A better comprehension of the different roles of GABAAR and NMDAR subunits could be helpful to define new strategies to counteract the deleterious effects observed during alcohol withdrawal. Taurine, a sulfonated amino acid, has been proposed to attenuate alcohol withdrawal symptoms due to its neuromodulatory properties. In this study, we evaluated the correlations between GABAAR and NMDAR subunits in the hippocampus of rats chronically treated with alcohol or in alcohol withdrawal, and the effects of taurine treatment on these parameters. Male Wistar rats received alcohol (2 g/kg) or water by oral gavage (control), 2 × /day, for 28 days. From day 29 to day 33, withdrawal rats received water instead of alcohol and all groups were reallocated to receive 100 mg/kg taurine or saline intraperitoneally (i.p.), once a day. On day 34, rats were euthanized and the hippocampus was dissected for GABAAR α1, α4, δ, and γ2 and NMDAR GluN2A and GluN2B subunits mRNA expression determination by RT qPCR. There were no differences between groups in the studied GABAAR and NMDA subunits. However, we observed a correlation of α1 and γ2 subunits induced by taurine, while in the alcohol group there was a correlation between α4 and GluN2A. In the group treated with alcohol and taurine, we observed an extra correlation, between α1 and GluN2A. After 5 days of withdrawal, a correlation observed in the control group, between δ and GluN2A, was reestablished. The correlation found between subunits suggests a neuroadaptation of GABAergic and glutamatergic systems in withdrawal rats. Results from this study contribute to the elucidation of the mechanisms beyond neuroadaptations observed in alcohol use and withdrawal.
•Chronic alcohol and withdrawal disrupt GluN2A/2B subunits co-expression.•Chronic alcohol increases GABAAR α4 and NMDAR GluN2A subunits co-expression.•Taurine increases α1 and γ2 mRNA GABAAR expression in alcohol and control rats.•Five days of withdrawal restores some correlations between GABAAR and NMDAR subunits.
Aims: Drugs today are one of the urgent and complex problems. One of the interventions that can be done to motivate quitting drug addiction is counselling This study aims to map evidence related to ...the strategies of counselling in victims of drug abuse and strategies in conducting counselling. Methods: Search databases for this study were PubMed, CINAHL, Science Direct and Google Scholar. Article identification was carried out based on the criteria for the year of publication (2013-2022), RCT / A Cross Section Study/Cross-Sectional Study, English and Indonesian Language, Fulltext, Teenagers to the elderly. Using the PRISMA flowchart, data extraction and scoping with the keywords (English): “Drug Dependence OR Subtance Abuse AND Counselling AND Drug Abuser” and keywords in Indonesian language “Ketergantungan Narkoba OR Penyalahgunaan Zat AND Konseling AND Pengguna Narkoba”. Results: The results of the study found that of the 9 articles that met the criteria. The main findings reveal that there are strategies in counselling, namely by means of drug counselling (drug handling controlled and monitored by doctors and nurses as psychoeducation providers) and telephone. counselling that can be used in screening and planning action. Conclusion: The conclusion of this study is that in counselling drug users there are several types, methods, and approaches included in the provision of counselling that are more effective in increasing motivation to recover or drug dependence in patients who are prescribed drugs by doctors compared to those who do not have prescription drugs. It is expected to contribute to the field of nursing as a strategy in counselling victims of drug abuse or people with drug addiction.
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