Prescription psychostimulants for cocaine use disorder: A review from molecular basis to clinical approach.

Cocaine use is a public health concern in many countries worldwide, particularly in the Americas and Oceania. Overdose deaths involving stimulants, such as cocaine, have been increasing markedly in North America, especially with concurrent opioid involvement. To date, no pharmacological treatment is available to treat stimulant (including cocaine) use disorders. Prescription psychostimulants (PPs) could be useful to treat cocaine use disorder (CUD) as they share the pharmacological effects with cocaine, as evidenced by a recent meta-analysis that assessed 38 randomized clinical trials (RCTs). PPs were found to promote sustained abstinence and reduce drug use in patients with CUD. The aim of this paper is to provide a narrative review of the clinical pharmacology of PPs and comment on the current stage of evidence supporting PPs to treat CUD. We also propose a model of care that integrates PPs with evidence-based psychosocial interventions (such as cognitive-behavioural therapy [CBT] and contingency management [CM]), a harm reduction approach and case management with social support.

Violent Behaviours among Adolescents and Young Adults: Association with Psychoactive Substance Use and Parenting Styles.

This study extends existing research on the relationship between psychoactive substance use among young people and violent behaviour, by evaluating the possible effect of the modification of parenting in a nationally representative sample of 14,685 Italian students drawn from the 2019 wave of the ESPAD Italia survey (51% male; mean age about 17 years). Parental dimensions considered in the study were rule-setting, monitoring, and emotional support, as well as the possible absence of a parent. Relative risk ratios and binary logistic regressions were used to estimate the associations separately for adolescents (15-17) and young adults (18-19). Overall, parental rule-setting, perceived parental monitoring, and emotional support were protective factors for substance use, and the strength of this relationship increased with the frequency of use. Among adolescents, the absence of a parent represented a risk factor. In both age groups, the odds of engaging in violent behaviour was increased among those reporting alcohol intoxication and substance use and the greater the frequency of use, the greater the increase in the odds. As parental monitoring and emotional support decreased, the odds of engaging in violent behaviour increased (except in the case of lower parental support among young adults), while the opposite applies to parental rule-setting. The odds of engaging in violent behaviour were increased among those reporting the absence of a parent only in the adolescent age group. Parental rule-setting was found to have an effect only among adolescents, increasing the odds of violent behaviour among frequent drinkers. Our results might be helpful to signal adolescents who would be more prone to adopt violent behaviour in order to target prevention policies.

Early parent-child interactions and substance use disorder: An attachment perspective on a biopsychosocial entanglement.

This review aims to elucidate environmental and genetic factors, as well as their epigenetic and neuroendocrine moderators, that may underlie the association between early childhood experiences and Substance Use Disorders (SUD), through the lens of parental attachment. Here we review those attachment-related studies that examined the monoaminergic systems, the hypothalamic pituitary adrenal stress response system, the oxytoninergic system, and the endogenous opioid system from a genetic, epigenetic, and neuroendocrine perspective. Overall, the selected studies point to a moderating effect of insecure attachment between genetic vulnerability and SUD, reasonably through epigenetic modifications. Preliminary evidence suggests that vulnerability to SUDs is related with hypo-methylation (e.g. hyper-expression) of high-risk polymorphisms on the monoaminergic and hypothalamic pituitary adrenal system and hyper-methylation (e.g. hypo-expressions) of protective polymorphisms on the opioid and oxytocin system. These epigenetic modifications may induce a cascade of neuroendocrine changes contributing to the subclinical and behavioural manifestations that precede the clinical onset of SUD. Protective and supportive parenting could hence represent a key therapeutic target to prevent addiction and moderate insecure attachment.

Suicide mortality risk in a cohort of individuals treated for alcohol, heroin or cocaine abuse: Results of a follow-up study.

Cohort study. This follow-up study (from 1975 to 2016) was aimed to estimate the mortality risk for suicide in a cohort of patients presenting to a public treatment centre for addiction (SERD) with Alcohol Use Disorder (AUD), Heroin Use Disorder - HUD or Cocaine Use Disorder (CUD), also relating to their access to a Mental Heath Service. Crude Mortality Rates for suicide were higher for patients with AUDs, for men and subjects 45-64 years old. Hanging was the main cause of suicide death. We highlight an increase in mortality in the period 2009-2012, which coincides with the economic recession, and in the year of first contact with a SERD. The Standardized Mortality Ratios (SMRs) were 4.9, higher among females than males. From the multivariate analysis, a higher risk for patients that were separated or divorced was observed. The results of our study provide some guidance on the features of subjects at greatest risk of death from suicide, which may be useful in reducing and preventing suicide and gaining a better clinical management of patients with SUDs.

Mortality Risk among Cocaine Users before and after the Economic Recession: Results of a Longitudinal Study.

BACKGROUND: Studies have highlighted 2 different groups of cocaine users (CUs): "socially integrated" (stable living conditions, regular employment, use cocaine alone or in combination with other psychoactive substances) and "socially marginalized" (socioeconomic and health problems, former or current heroin users, many injecting cocaine). These differences are also found in the elevated mortality risk for CUs, higher among subjects with cocaine and heroin use. This study targeted residents in Northern Italy who turned to a public treatment center for drug addiction following problems caused by primary cocaine use between 1982 and 2016. OBJECTIVES: To estimate mortality risk for subjects who have never used heroin (CUs) compared to that of subjects who have used heroin (HCUs). METHOD: Retrospective cohort study. We selected 1,993 subjects; 18,015 Person Years (PY). RESULTS: Over time, the quota of subjects injecting cocaine and using heroin decreased, while patients not using heroin increased. Both new patients and crude mortality rates (CMR) decreased during the years 2009-2012 and increased in the following period. CMRs were 5.55 per 1,000 PY, higher for HCUs, men and subjects aged over 44 years. Standardized mortality rates were 3.49, higher for women, injecting cocaine and HCUS. Among CUs, most of the deaths were from injury excluding drug related and tumors; among HCUs, from drug-related causes and diseases of the cardiovascular system. CONCLUSION: The study results show a change in the characteristics of SERD clients being treated for primary cocaine use, which are reflected both in mortality risk and causes of death. After a long period of a decrease, mortality risk increased in the period after the economic recession. Aspects concerning the effects of the economic recession on the problematic consumption of cocaine and on the risk of death are discussed.

Mortality Risk among Heroin Users Accessing Treatment: Natives and Non-Natives Patients Results of a Longitudinal Study.

The aim of this study was to examine mortality risk and causes of death for natives and non-natives in a cohort of heroin population of treated in Northern Italy. Crude Mortality Rates (CMRs) were 12.78 per 1,000 Person Years (PY), Standardized Mortality Rate (SMR) was 9.93. Mortality has been decreasing over time, was higher for patients who accessed the treatment services before 2001 and has been increasing with age. CMRs and SMRs were higher among natives, while non-natives were distinguished by higher CMRs and SMRs for suicide. The natives were at greater risk of death than non-natives both injecting and non-injecting, but the mortality risk was not statistically significant in the different periods of first admission. Among non-native patients, older on average, there was a lower proportion of injecting, and a higher quota of people unemployed than among Italian natives. We highlight differences between the various areas of origin concerning consumption patterns and risk of death. The results of the study highlight a particular sub-population of heroin users, the non-natives, who as compared with the Italians, have less invasive consumption styles, reach the health services later but benefit from fewer medical controls.