Circadian disruptions and their role in the development of hypertension.

Circadian fluctuations in physiological setpoints are determined by the suprachiasmatic nucleus (SCN) which exerts control over many target structures within and beyond the hypothalamus via projections. The SCN, or central pacemaker, orchestrates synchrony between the external environment and the internal circadian mechanism. The resulting cycles in hormone levels and autonomic nervous system (ANS) activity provide precise messages to specific organs, adjusting, for example, their sensitivity to approaching hormones or metabolites. The SCN responds to both photic (light) and non-photic input. Circadian patterns are found in both heart rate and blood pressure, which are linked to daily variations in activity and autonomic nervous system activity. Variations in blood pressure are of great interest as several cardiovascular diseases such as stroke, arrhythmias, and hypertension are linked to circadian rhythm dysregulation. The disruption of normal day-night cycles, such as in shift work, social jetlag, or eating outside of normal hours leads to desynchronization of the central and peripheral clocks. This desynchronization leads to disorganization of the cellular processes that are normally driven by the interactions of the SCN and photic input. Here, we review autonomic system function and dysfunction due to regulation and interaction between different cardiorespiratory brain centers and the SCN, as well as social, lifestyle, and external factors that may impact the circadian control of blood pressure.

Pharmacology and Therapeutic Potential of Benzothiazole Analogues for Cocaine Use Disorder.

Pharmacological targeting of the dopamine D4 receptor (D4R)─expressed in brain regions that control cognition, attention, and decision-making─could be useful for several neuropsychiatric disorders including substance use disorders (SUDs). This study focused on the synthesis and evaluation of a novel series of benzothiazole analogues designed to target D4R. We identified several compounds with high D4R binding affinity (Ki ≤ 6.9 nM) and >91-fold selectivity over other D2-like receptors (D2R, D3R) with diverse partial agonist and antagonist profiles. Novel analogue 16f is a potent low-efficacy D4R partial agonist, metabolically stable in rat and human liver microsomes, and has excellent brain penetration in rats (AUCbrain/plasma > 3). 16f (5-30 mg/kg, i.p.) dose-dependently decreased iv cocaine self-administration in rats, consistent with previous results produced by D4R-selective antagonists. Off-target antagonism of 5-HT2A or 5-HT2B may also contribute to these effects. Results with 16f support further efforts to target D4R in SUD treatment.

Impact of an osteopathic peer recovery coaching model on treatment outcomes in high-risk men entering residential treatment for substance use disorders.

CONTEXT: The United States has witnessed a disproportionate rise in substance use disorders (SUD) and co-occurring mental health disorders, paired with housing instability, especially among racially minoritized communities. Traditional in-patient residential treatment programs for SUD have proven inconsistent in their effectiveness in preventing relapse and maintaining attrition among these patient populations. There is evidence showing that peer recovery programs led by individuals who have lived experience with SUD can increase social support and foster intrinsic motivation within participants to bolster their recovery. These peer recovery programs, when coupled with a standardized training program for peer recovery coaches, may be very efficacious at improving patient health outcomes, boosting performance on Substance Abuse and Mental Health Services Administration (SAMHSA) national outcome measures (NOMs), and helping participants build an overall better quality of life. OBJECTIVES: The goal of this study is to highlight the efficacy of a peer recovery program, the Minority Aids Initiative, in improving health outcomes and associated NOMs in men with SUD and/or co-occurring mental health disorder. METHODS: Participants received six months of peer recovery coaching from trained staff. Sessions were guided by the Manual for Recovery Coaching and focused on 10 different domains of recovery. Participants and coaches set long-term goals and created weekly action plans to work toward them. Standardized assessments (SAMHSA's Government Performance and Results Act [GPRA] tool, Addiction Severity Index [ASI]) were administered by recovery coaches at intake and at the 6-month time point to evaluate participant progress. Analyses of participant recovery were carried out according to SAMHSA's six NOMs and assessed the outcomes of the intervention and their significance. RESULTS: A total of 115 participants enrolled in the program over a 2-year period. Among them, 53 were eligible for 6-month follow-up interviews. In total, 321 sessions were held, with an average of three sessions per participant. Participants showed marked improvement across five of the six NOMs at the end of the 6-month course and across all ASI outcomes, with the exception of three in which participants reported an absence or few symptoms at intake. CONCLUSIONS: Our study shows that participants receive benefits across nearly all NOM categories when paired with recovery coaches who are well trained in medication-assisted treatment (MAT) and medications for opioid use disorder (MOUD) over a 6-month period. We see the following: a higher rate of abstinence; increased housing stability; lower health, behavioral, and social consequences; lower depression and anxiety; longer participant-recovery coach exposure time; and higher follow-up rates. We hope that our results can contribute to advancements and greater acceptance in the implementation of peer recovery coaching as well as an improvement in the lives of the communities affected by substance use.