Most individuals with schizophrenia suffer some cognitive dysfunction: such deficits are predictive of longer-term functioning; and current dopamine-blocking antipsychotics have made little impact on this domain. There is a pressing need to develop novel pharmacological agents to tackle this insidious but most disabling of problems. The acetylcholinergic system is involved in cognitive and attentional processing, and its metabotropic and nicotinic receptors are widespread throughout the brain. Deficits in acetylcholinergic functioning occur in schizophrenia, and high rates of tobacco smoking have been posited to represent a form of self-medication. The nicotinic acetylcholine receptor (nAChR) has emerged as a putative target to improve cognitive deficits in schizophrenia, and this study systematically reviewed the emerging data. Nineteen studies were identified, covering three compound classes: agonists at the α7 and α 4β2 nAChRs, and positive allosteric modulators. Overall data are underwhelming: some studies showed significant improvements in cognition but as many studies had negative findings. It remains unclear if this represents drug limitations or nascent study methodology problems. The literature is particularly hindered by variability in inclusion of smokers, generally small sample sizes, and a lack of consensus on cognitive test batteries. Future work should evaluate longer-term outcomes, and, particularly, the effects of concomitant cognitive training.

BackgroundCharge-free heroin use disorder treatment in Italy follows two main approaches, i.e., harm reduction treatment (HRT) strategy in community low-threshold facilities for drug addiction and opioid agonist treatment (OAT) in high-threshold facilities for opioid addiction, focusing on pharmacological maintenance according to the Dole and Nyswander strategy. We aimed to compare the impact of HRT and OAT on patient outcome, as assessed through negativity for drugs on about 1-year urinalyses.MethodsWe examined retrospectively the urinalyses of HRT and OAT patients for which at least four randomly sampled urinalyses per month were available for about 1 year, during which patients were undergoing methadone or buprenorphine maintenance; urinalyses focused on heroin, cocaine, cannabinoids, and their metabolites.ResultsIncluded were 189 HRT and 58 OAT patients. The latter were observed for a significantly longer period. There was a higher proportion of heroin- and cocaine-clean urinalyses in OAT patients, with cocaine-clean urinalyses discriminating best between the two groups. OAT patients were older, with longer dependence duration, more severe addiction history, and received lower methadone doses. Buprenorphine maintenance was more often associated with heroin-clean urinalyses. The higher the methadone doses, the lower were the percentage of heroin-clean urinalyses in HRT patients (negative correlation).ConclusionsThe OAT approach was related to higher recovery and polyabuse abstinence rates compared to the HRT approach, despite greater severity of substance use, psychiatric and physical comorbidities. Our results are consistent with the possibility to use lower maintenance opiate doses (after induction and stabilization in methadone treatment according to Dole and Nyswander methodology) in treating heroin addiction. This seemed to be impossible adopting the currently accepted HRT model.

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