Cristiano Chiamulera’s research while affiliated with University of Verona and other places

Introduction Benzodiazepines (BDZs) are among the most abused substances worldwide, and high-dose BDZ abuse is considered a specific type of addiction. Cue reactivity (CR) is a hypersensitivity to motivational stimuli and, in substance use disorders, it increases craving and facilitates relapse, especially in chronic users. Virtual reality (VR) may be a viable technology to implement in CR paradigms. The general objective of this study is the implementation of a VR protocol to identify the causal relationship between the environmental features of a specific setting and craving responses in BDZ abusers. Methods Moreover, we investigated the correlation between the degree of BDZ craving and measures of mood, affect, attention, sense of presence, and cybersickness in the subjects, and evaluated the effectiveness that different VR environments have in discriminating between BDZ abusers and controls by comparing the degree of BDZ craving and all of the aforementioned variables in the two groups. Results Our data suggest that cues can indeed become conditioned to elicit craving responses in high-dose BDZ abusers, but more studies are necessary to confirm this hypothesis. Conclusion Moreover, the use of VR can be a good choice to observe environmental craving for BDZs since it presents a realistic simulation of real-world settings.

Tobacco addiction is the primary preventable factor contributing to global mortality, and nicotine is one of the substances with the greatest potential for addiction. With a strong affinity for the α4β2 subtype receptor, cytisine (CYT) functions as a partial agonist of the acetylcholine nicotinic cholinergic receptor. It counteracts the effects of nicotine without causing any withdrawal symptoms. These features, combined with its limited mild adverse effects and minimal drug–drug interactions, make cytisine a cost-effective treatment for smoking cessation. The current protocol describes a prospective observational study on the safety and efficacy of CYT administered to inpatient smokers of the Integrated University Hospital of Verona (IUHVR), Veneto (Italy). This is a monocentric, observational, and prospective study on both sex smokers over the age of 18 years admitted to the IUHVR who meet the criteria for recruitment and have given their consent. Eligible participants will be assigned to the CYT intervention based on the West dosing schedule and will be followed up for 12 months from treatment initiation. Evaluation of safety, efficacy, and compliance will be assessed at 7 and 25 days, with follow-up at 3, 6, and 12 months from the start of the treatment (quit day). During each visit, any adverse events or adverse reactions reported by patients following the intake of CYT will be evaluated. This study will contribute, for the first time, to the knowledge about the use of CYT for smoking cessation in a hospital setting.

The incidence of neurodegenerative disorders like Alzheimer’s or Parkinson’s Disease, characterized by a progressive cognitive decline, is rising worldwide. Despite the considerable efforts to unveil the neuropsychological bases of these diseases, there is still an unmet medical need for effective therapies against cognitive deficits. In recent years, increasing laboratory evidence indicates the potential of phytotherapy as an integrative aid to improve cognitive functions. In this review, we describe the data of plant whole extracts or single compounds’ efficacy on validated preclinical models and neuropsychological tests, aiming to correlate brain mechanisms underlying rodent behavioral responses to human findings. After a search of the literature, the overview was limited to the following plants: Dioscorea batatas, Ginkgo biloba, Melissa officinalis, Nigella sativa, Olea europaea, Panax ginseng, Punica granatum, and Vitis vinifera. Results showed significant improvements in different cognitive functions, such as learning and memory or visuospatial abilities, in both humans and rodents. However, despite promising laboratory evidence, clinical translation has been dampened by a limited pharmacological characterization of the single bioactive components of the herbal products. Depicting the contribution of the single phytochemicals to the phytocomplex’s pharmacological efficacy could enable the comprehension of their potential synergistic activity, leading to phytotherapy inclusion in the existing therapeutic package against cognitive decline.

Background: Preclinical studies suggested the exposure to environmental enrichment (EE) as an intervention able to prevent or reduce nicotine-taking and nicotine-seeking behaviors. Virtual reality (VR) may help to test the effects of EE in smokers in a reproducible and feasible manner. Materials and Methods: In the present study, 31 smokers (14 women) were divided into two groups: (1) exposure to a virtual EE (VR-EE) and (2) exposure to a virtual neutral environment (VR-NoEE). Cigarette craving was assessed as basal and evoked, at different timepoints during the session. Behavior activity during VR exposure, mood, and subjective measures were also collected. Results: EE exposure in VR significantly reduced craving scores from basal timepoint. This was not observed in the VR-NoEE group, which significantly increased craving compared with values at neutral scenario. When both groups were exposed to smoking-related VR scenario, the VR-EE group showed an increased craving compared with previous timepoint up to score values not different from those in the VR-NoEE group. A significant positive correlation between basal craving scores and interactive behavior with virtual smoking cues was observed in the VR-NoEE but not in the VR-EE group. Conclusion: These findings suggest that virtual EE might have an inhibitory effect in smokers on basal, but not on evoked cigarette craving. Noteworthily, the interactive activity correlation to craving scores in the VR-NoEE participants was not observed in the VR-EE group, adding further evidence that the enrichment simulation was nonetheless able to modify behavior in the smoking-related scenario.

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and, in turn, modulate reward‐seeking behaviours: here, we have investigated such a possibility following a brief EE exposure. Adult male Sprague–Dawley rats were exposed to EE for 22 h and the expression of critical elements of the glutamate synapse was measured 2 h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT‐1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes in glutamatergic mPFC, NAc and Hipp. Such changes are area‐specific and involve postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins, thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to dynamically modulate the glutamatergic synapses in mPFC‐NAc‐Hipp circuits, which may modulate rewarding and memory processes.

Rationale Environmental enrichment (EE) is a non-pharmacological approach that has been shown to be effective in reducing food-taking in rats. Studies in human volunteers are still in their infancy, given the difficulty to translate the complexity of EE in clinical practice. Virtual reality (VR) is a promising methodological approach, but no study has yet applied it to model and test EE in humans. Objectives The present study is the first to assess the effects of virtual EE on craving for palatable food. Methods Eighty-one healthy volunteers (43 women) were divided into three groups: (i) exposure to a virtual EE (VR-EE), (ii) exposure to a virtual neutral environment (VR-NoEE), and (iii) without exposure to VR (No VR). Craving for palatable food at basal level and evoked by neutral and palatable food images was assessed before and after the VR simulation. Behavior during VR exposure and subjective measures related to the experience were also collected. Results VR-EE group showed a significantly greater decrease in pre-post craving difference compared to No VR for all assessments and at basal level compared to VR-NoEE. Interestingly, an inverse correlation between craving and deambulation in the VR simulation emerged in VR-EE group only. Conclusions The study highlighted the feasibility of exposing human subjects to an EE as a virtual simulation. Virtual EE induced effects on basal craving for food that suggest the potential for further improvements of the protocol to extend its efficacy to palatable food cues.

Background The “Eye Movement Desensitisation and Reprocessing” (EMDR) is a therapy targeting traumatic memories. Although memories from their substance use memory may increase the risk of relapse, only a few studies investigated the effects of EMDR in addiction. Methods Individuals with substance use disorders (SUD) receiving TAU in a residential setting were randomized for EMDR in conjunction with TAU (EMDR + TAU) and TAU groups. Craving for the substance, substance target memory features, relapse rates and other measures of EMDR efficacy were assessed after intervention at 6 weeks (T1) and 6-month follow-up (T2). Results EMDR + TAU significantly suppressed substance craving, pleasantness, and target memory vividness at T1, but increased substance unpleasant scores. EMDR effects were also significantly observed at T2 for pleasantness and vividness. EMDR + TAU group showed high scores and reported benefits from EMDR, but not significant differences in relapse rate, vs. TAU group. Conclusion Our study suggests that EMDR + TAU in SUD inpatient in a residential setting may reduce substance craving, and in the meantime, provides proof-of-concept on targeting substance memory.

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its complexity, the underling mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and in turn, modulate reward-seeking behaviors. Here, we explore the hypothetical metaplastic effects induced by brief EE exposure on glutamatergic transmission in brain areas involved in rewarding and memory processes. Adult male Sprague-Dawley rats were exposed to EE for 22h and the expression of critical elements of the glutamate synapse were measured 2h after the end of EE in medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp). We focused our attention on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT-1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes on glutamatergic mPFC-NAc-Hipp brain areas, which are critical for reward and learning processes. Such changes were area-specific and involved a rearrangement of postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to cause metaplastic activity at glutamatergic synapses in mPFC-NAc-Hipp circuits, which may modulate several mental processes such as rewarding, learning and memory processes.