Nature-based experience in Venetian lagoon: Effects on craving and wellbeing in addict residential inpatients.

Introduction: It is known that exposure to the natural environment may positively modulate mental processes and behaviors; in particular, it can reduce stress, anxiety, and depressive symptoms. This suggests a potential integration of "nature experience" into the treatment for substance use disorder (SUD) since various types of addiction are associated with anxiety and depression. Considering that only one study has been reported to date in patients with alcohol use disorder, the effect of nature experience in SUD patients' needs to be further investigated. This study aimed to test the effects of exposure to a natural lagoon environment on craving and measures of wellbeing in SUD patients in comparison to exposure to an urban environment. Methods: Twenty-four SUD patients were divided into three groups of eight participants and exposed to two walking sessions (interspersed with a 1-week wash-out period) in a natural environment typical of the Venetian lagoon, an Urban walk, or staying at the residential center based on a Latin-square design. Before and after each session, drug craving, mood, wellbeing, agency, openness to the future, and restorativeness were assessed. Results: The Nature walk significantly decreased craving in participants compared to their pre-walk values, and compared to craving after the Urban walk, with the latter significantly increased vs. pre-walk values. The Nature walk significantly decreased negative mood and increased wellbeing and agency. Openness to the future and restorativeness measures showed significant improvement after the Nature walk compared to the Urban walk. On the other hand, craving scores after the Urban Walk positively correlated with negative mood and a Sense of Negative Agency values and negatively correlated with wellbeing scores. Discussion: Our results confirm that "nature experience" may improve mood, wellbeing, attention, stress relief, openness, and sense of being active in SUD patients. Moreover, we also showed a specific effect on drug craving-a key symptom of SUD.

Impulsivity and alexithymia predict early versus subsequent relapse in patients with alcohol use disorder: A 1-year longitudinal study.

INTRODUCTION: Longitudinal psychopathological predictors of relapse in alcohol use disorder are unclear. METHODS: Relapses, sociodemographic and psychopathological risk factors were assessed in 171 alcohol use disorder outpatients within a 1-year follow up. Impulsivity and alexithymia were evaluated using the Barratt Impulsiveness Scale and the Toronto Alexithymia Scale, respectively. RESULTS: At endpoint, 39% of patients maintained abstinence, 30.9% relapsed at ≤1 month from detoxification (early), 30.1% at >1 month (subsequent). Baseline Barratt Impulsiveness Scale score was predictive of early versus subsequent relapse (odds ratio 1.12, p = 0.005) and versus abstinence (odds ratio 1.17, p < 0.001). Toronto Alexithymia Scale score was a risk factor for subsequent versus early relapse (odds ratio 1.13, p = 0.003) and versus abstinence (odds ratio 1.21, p < 0.001). DISCUSSION AND CONCLUSIONS: Impulsivity predicted relapse within the first 4-weeks; alexithymia showed delayed effects. Time-varying effects of specific relapse factors emphasise the need for preliminary careful assessment and personalised interventions to promote long-term abstinence.

The recognition and management of protracted alcohol withdrawal may improve and modulate the pharmacological treatment of alcohol use disorder.

About 50% of persons with an alcohol use disorder may have symptoms of alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption. Protracted alcohol withdrawal (PAW), an underestimated and not yet clearly defined clinical condition that follows the acute stage of AWS, is characterized by the presence of substance-specific signs and symptoms (i.e. anxiety, irritability, mood instability, insomnia, craving) common to acute AWS, but persisting beyond the generally expected acute AWS time frames. Considering that PAW symptoms are mainly related to the neuro-adaptive changes of gamma-aminobutyric acid (GABA) and N-methyl-d-aspartate (NMDA) systems, naltrexone, nalmefene, and disulfiram may not be able to suppress the symptoms of PAW. After treatment of the acute phase of AWS, a more specifically pharmacological therapy able to suppress PAW symptoms could perhaps be used earlier and may be more helpful in preventing the risk of alcohol relapse, which remains higher during the first months of treatment. In light of this, medications acting on GABA and NMDA neurotransmitter systems to counterbalance the up-regulation of NMDA and the down-regulation of GABA could be employed in combination and started as soon as possible.

Association between Adult Attention Deficit/Hyperactivity Disorder and Intravenous Misuse of Opioid and Benzodiazepine in Patients under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study.

BACKGROUND: Intravenous misuse and attention-deficit/hyperactivity disorder (ADHD) are common in patients under opioid maintenance treatment (OMT), who often misuse benzodiazepine (BZD). OBJECTIVES: To explore the rate of adult ADHD among patients under OMT in Italy and whether screening positive for adult ADHD is associated with OMT and BZD misuse and emergency room (ER) admission because of misuse. METHODS: We recruited 1,649 patients from 27 addiction units (AUs) in Italy and collected data on the self-reported rate of OMT intravenous misuse (prevalence, repeated misuse, main reason, temporal pattern in relation to AU access, experience), concurrent intravenous and intranasal BZD misuse (prevalence, type of misused BZD), ADHD and ER admissions because of misuse complications. RESULTS: Screening positive for adult ADHD was found in 11.2% patients (ADHD+), with a significant gender difference (women: 15.3%, men: 10.3%). OMT misuse was reported by 24.4 and 18.5% patients during lifetime and in the previous 6 months respectively. BZD misuse was reported by 20.0 and 8.6% patients for intravenous and intranasal route respectively. Misuse was significantly more common in ADHD+ (OMT 27.4-33.1%, BZD 14.5-31.5%) than ADHD- group (OMT 17.4-23.3%, BZD 7.9-18.3%). The multivariate logistic regression model showed positive screening for ADHD to be significantly associated with intravenous OMT misuse in the previous 6 months, and intravenous/intranasal BZD misuse, independently of age, gender and route of previous heroin administration. CONCLUSIONS: Screening positive for adult ADHD was associated with OMT and BZD misuse. AU physicians and medical personnel should focus on OMT patient's features that are associated with a higher likelihood of misuse, in particular ADHD.

Intravenous Misuse of Methadone, Buprenorphine and Buprenorphine-Naloxone in Patients Under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study.

BACKGROUND: The act of intravenous misuse is common in patients under opioid maintenance treatment (OMT), but information on associated factors is still limited. OBJECTIVES: To explore factors associated with (a) intravenous OMT misuse, (b) repeated misuse, (c) emergency room (ER) admission, (d) misuse of different OMT types and (e) concurrent benzodiazepine misuse. METHODS: We recruited 3,620 patients in 27 addiction units in Italy and collected data on the self-reported rate of intravenous injection of methadone (MET), buprenorphine (BUP), BUP-naloxone (NLX), OMT dosage and type, experience of and reason for misuse, concurrent intravenous benzodiazepine misuse, pattern of -misuse in relation to admission to the addiction unit and ER -admissions because of misuse. According to inclusion/exclusion criteria, 2,585 patients were included. RESULTS: Intravenous misuse of OMT substances was found in 28% of patients with no difference between OMT types and was associated with gender, age, type of previous opioid abuse and intravenous benzodiazepine misuse. Repeated OMT misuse was reported by 20% (i.e., 71% of misusers) of patients and was associated with positive OMT misuse experience and intravenous benzodiazepine misuse. Admission to the ER because of misuse complications was reported by 34% of patients, this outcome being associated with gender, employment, type of previous opioid abuse and intravenous benzodiazepine misuse. OMT dosage was lower than the recommended maintenance dosage. CONCLUSIONS: We offered new information on factors associated with intravenous OMT misuse, repeated misuse and ER admission in Italian patients under OMT. Our data indicate that BUP-NLX misuse is not different from that of BUP or MET. Choosing the more expensive BUP-NLX over MET will likely not lead to the expected reduction of the risk of injection misuse of the OMT. Instead of prescribing new and expensive OMT formulations, addiction unit physicians and medical personnel should better focus on patient's features that are associated with a higher likelihood of misuse. Care should be paid to concurrent benzodiazepine and OMT misuse.

Gender-related psychopathology in opioid use disorder: Results from a representative sample of Italian addiction services.

AIMS: Gender and psychiatric comorbidity seem to influence patients' inter-individual response to Opioid Substitution Treatments (OST) in Opioid Use Disorder (OUD) management. The aim of the study was to assess psychopathological dimensions in an Italian sample of OUD individuals entering a methadone/buprenorphine maintenance program; secondary, we evaluated the possible gender-specific differences within the psychopathological profiles. METHODS: In a cross-sectional study, we recruited 1052 (792 male; 260 female) OUD subjects receiving OST. All patients underwent a clinical and psychometric evaluation assessing demographics, psychiatric history, psychopathological features via the Symptom Checklist-90-Revised (SCL-90-R), and were prescribed psychopharmacological treatments. RESULTS: Our results reveal gender-specific differences in a real-world sample of opioid-maintained OUD individuals attending public addiction services in Italy. Compared to men, women reported higher scores in both General Symptomatic Index (GSI) and in all the SCL-90-R sub-scales. No impact of pharmacological treatment was detected. Finally, regression analysis revealed that being in methadone-maintenance group was significantly associated with high GSI scores in the male, but not female, group. CONCLUSIONS: Increasing the knowledge of psychopathological dimensions in patients with OST, with relevance to gender differences, is important for a better understanding of factors that influence the outcome and for further development in gender-tailored strategies.

Alcohol use disorder and GABAB receptor gene polymorphisms in an Italian sample: haplotype frequencies, linkage disequilibrium and association studies.

BACKGROUND: Alcohol use disorder (AUD) is a complex trait with genetic and environmental influences. Several gene variants have been associated with the risk for AUD, including genes encoding the sub-units of the γ-aminobutyric acid (GABA) receptors. AIM: This study evaluated whether specific single nucleotide polymorphisms (SNPs) in genes encoding GABAB receptor sub-units can be considered as candidates for the risk of AUD. SUBJECTS AND METHODS: Seventy-four AUD subjects and 128 Italian controls were genotyped for 10 SNPs in genes encoding GABA-B1 and GABA-B2 sub-units (GABBR1 and GABBR2). Allele, genotype, and haplotype frequencies were tested for the association with the AUD trait. RESULTS: A significant difference between AUD individuals and controls was observed at genotype level for rs2900512 of GABBR2 gene. The homozygous T/T genotype was not found in the controls, whereas it was over-represented in the AUD individuals. Under the recessive model (T/T vs C/T + C/C) this result was statistically significant, as well as the Odds Ratio for the association with the AUD trait. CONCLUSIONS: The results provide preliminary data on the association between GABAB receptor gene variation and risk of AUD. To confirm this finding, studies with larger samples and additional characterisation of the phenotypic AUD trait are required.

Harm Reduction as "Continuum Care" in Alcohol Abuse Disorder.

Alcohol abuse is one of the most important risk factors for health and is a major cause of death and morbidity. Despite this, only about one-tenth of individuals with alcohol abuse disorders receive therapeutic intervention and specific rehabilitation. Among the various dichotomies that limit an effective approach to the problem of alcohol use disorder treatment, one of the most prominent is integrated treatment versus harm reduction. For years, these two divergent strategies have been considered to be opposite poles of different philosophies of intervention. One is bound to the search for methods that aim to lead the subject to complete abstinence; the other prioritizes a progressive decline in substance use, with maximum reduction in the damage that is correlated with curtailing that use. Reduction of alcohol intake does not require any particular setting, but does require close collaboration between the general practitioner, specialized services for addiction, alcohology services and psychiatry. In patients who reach that target, significant savings in terms of health and social costs can be achieved. Harm reduction is a desirable target, even from an economic point of view. At the present state of neuroscientific knowledge, it is possible to go one step further in the logic that led to the integration of psychosocial and pharmacological approaches, by attempting to remove the shadows of social judgment that, at present, are aiming for a course of treatment that is directed towards absolute abstention.

Pharmacological management of alcohol dependence: from mono-therapy to pharmacogenetics and beyond.

Almost 10% of the world's population is affected by alcohol use disorders, and the treatment of alcohol dependence (AD) still remains a challenge. Patients with AD can differ in many traits. Three drugs (disulfiram, naltrexone, and acamprosate) have been approved by the FDA for the treatment of AD, and in some European countries sodium oxybate is also approved for this purpose. Combined pharmacological therapy has not provided such convincing results. Considering the fact that the "ideal" and effective drug for all types of alcoholic patients does not exists, the future challenge will be to identify a personalized approach. Recent data has shown that this objective can be achieved by investigating the genetic variability of the patient. Moreover, the use of replacement molecules can probably be considered an advantageous therapeutic opportunity (i.e. sodium oxybate). In addition, reduction of alcohol consumption is increasingly accepted as a viable treatment goal, and the use of nalmefene "as-needed" (a pharmacological approach similar to naltrexone, but, possibly, with lower hepatotoxicity) may help in the treatment of AD. Thus, it is important to stress that a pharmacological approach to treat AD should be preceded by the definition of patient characteristics; this may help in the choice of the most appropriate drug and it can be done more easily when more pharmacological options approved for the treatment of AD are also available.

Sodium oxybate in maintaining alcohol abstinence in alcoholic patients according to Lesch typologies: a pilot study.

Sodium oxybate (SO) is a γ-amino-butyric acid (GABA)-ergic drug currently used for the treatment of alcohol dependence (AD) in some European countries. The aim of this study was to describe the effect of SO administration in alcoholics classified according to Lesch alcoholism typology (LAT). Forty-eight patients were enrolled and classified into four groups according to LAT. All patients were treated with oral SO (50 mg/kg of body weight t.i.d.) for 12 weeks. All patients significantly reduced their alcohol intake (p<0.001). Alcohol abstinence during the 12 weeks of treatment did not differ between the four groups at the end of treatment. Craving for SO did not significantly differ amongst groups; cases of SO abuse were very limited and were observed in almost 10% of patients. In conclusion, our study showed an overall efficacy of SO in the treatment of AD irrespective of LAT categories. However, our results confirm that alcoholics with psychiatric co-morbidity, particularly with a borderline personality disorder of Axis II, are at a greater risk of developing craving for and abuse of the drug: until craving for alcohol and craving for SO are characterized in depth, SO should be used with caution in these patients.

New frontiers in alcoholism and addiction treatment.

Drug addiction and alcoholism are behavioural disorders characterized by a profound alteration of several brain circuits induced by chronic drug use. Their treatment is yet based on empiricism and today only few pharmacological strategies are fully effective to control both drug use and relapse. The present paper reviews the most updated pharmacotherapies able to contrast both alcoholism and drug addiction including the new patented drugs and the future therapeutic trends.