Effects of repeated binge intake of the pyrovalerone cathinone derivative 3,4-methylenedioxypyrovalerone on prefrontal cytokine levels in rats - a preliminary study.

Drugs of abuse activate neuroimmune signaling in addiction-related regions of the brain, including the prefrontal cortex (PFC) which mediates executive control, attention, and behavioral inhibition. Traditional psychostimulants including methamphetamine and cocaine are known to induce PFC inflammation, yet the effects of synthetic cathinone derivatives are largely unexplored. In this study, we examined the ability of repeated binge-like intake of the pyrovalerone cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) to alter cytokine profiles in the PFC. Male and female rats were allowed to intravenously self-administer MDPV (0.05 mg/kg/infusion) or saline as a control under conditions of prolonged binge-like access, consisting of three 96 h periods of drug access interspersed with 72 h of forced abstinence. Three weeks following cessation of drug availability, PFC cytokine levels were assessed using antibody arrays. Employing the unsupervised clustering and regression analysis tool CytoMod, a single module of co-signaling cytokines associated with MDPV intake regardless of sex was identified. With regards to specific cytokines, MDPV intake was positively associated with PFC levels of VCAM-1/CD106 and negatively associated with levels of Flt-3 ligand. These findings indicate that prolonged MDPV intake causes changes in PFC cytokine levels that persist into abstinence; however, the functional ramifications of these changes remain to be fully elucidated.

Current and emerging pharmacotherapies for opioid dependence treatments in adults: a comprehensive update.

INTRODUCTION: Opioid use disorder (OUD) is characterized by compulsive opioid seeking and taking, intense drug craving, and intake of opioids despite negative consequences. The prevalence of OUDs has now reached an all-time high, in parallel with peak rates of fatal opioid-related overdoses, where 15 million individuals worldwide meet the criteria for OUD. Further, in 2020, 120,000 opioid-related deaths were reported worldwide with over 75,000 of those deaths occurring within the United States. AREAS COVERED: In this review, we highlight pharmacotherapies utilized in patients with OUDs, including opioid replacement therapies, and opioid antagonists utilized for opioid overdoses and deterrent of opioid use. We also highlight newer treatments, such as those targeting the neuroimmune system, which are potential new directions for research given the recently established role of opioids in activating neuroinflammatory pathways, as well as over the counter remedies, including kratom, that may mitigate withdrawal. EXPERT OPINION: To effectively treat OUDs, a deeper understanding of the current therapeutics being utilized, their additive effects, and the added involvement of the neuroimmune system are essential. Additionally, a complete understanding of opioid-induced neuronal alterations and therapeutics that target these abnormalities - including the neuroimmune system - is required to develop effective treatments for OUDs.