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Purpose of review: Substance use disorders (SUD) affect differentially women and men. Although the prevalence has been reported higher in men, those women with addictive disorders present a more vulnerable profile and are less likely to enter treatment than men. The aim of this paper is to present an overview of how sex and gender may influence epidemiology, clinical manifestations, social impact, and the neurobiological basis of these differences of women with SUD, based on human research. Recent findings: The differences in prevalence rates between genders are getting narrower; also, women tend to increase the amount of consumption more rapidly than men, showing an accelerated onset of the SUD (telescoping effect). In respect to clinical features, the most important differences are related to the risk of experience psychiatric comorbidity, the exposure to intimate partner violence, and the associated high risks in sexual and reproductive health; and those who are mothers and addicted to substances are at risk of losing the custody of children accumulating more adverse life events. Some of these differences can be based on neurobiological differences: pharmacokinetic response to substances, sensitivity to gonadal hormones, differences in neurobiological systems as glutamate, endocannabinoids, and genetic differences. Summary: Specific research in women who use drugs is very scarce and treatments are not gender-sensitive oriented. For these reasons, it is important to guarantee access to the appropriate treatment of women who use drugs and a need for a gender perspective in the treatment and research of substance use disorders.

People who inject drugs (PWID) experience more gaps at each stage of the HIV care continuum than others living with HIV. The study aimed to describe the effectiveness of an integrated care model to reach the UNAIDS 90–90–90 target. This cross-sectional study included PWID who met the criteria for DSM-5 substance use disorder. They received a multidisciplinary comprehensive program, including medical HIV care, substance use treatment, and psychosocial support, at a drug-use treatment outpatient facility during 2019. The percentage of patients reaching the 90–90–90 UNAIDS target was the main study variable. Two hundred and twenty-one PWID were monitored at the facility during a median follow-up of 98 months (IQR: 61–143). Current HIV status was established in all PWID, of whom 84/221 (38.0%) tested HIV-positive. All the 84 patients (100%) received antiretroviral therapy, and 76(90.5%) had RNA HIV-1

HIV-infected people with substance use disorders (HIV-SUDs) are at increased risk of leaving hospital against medical advice (LHAMA). The aim of this study was to evaluate the incidence of LHAMA in HIV-SUDs admitted to a patient-centered hospital where they receive integrated care, including healthcare, substance use treatment, and social support. Observational study was conducted at an urban acute-care university teaching hospital. Integrated care included a specialist in addiction medicine and a social worker incorporated into the medical staff. LHAMA was defined as participants leaving the hospital without the physician's permission and not returning within 6 h. Two hundred and ninety-nine HIV-SUDs were hospitalized, and 79 (26.4%) patients were readmitted, generating a total of 517 admissions during 2010-2016. Over the study period, 45 LHAMA were registered, yielding an incidence of 8.7%. On multiple logistic regression analysis, admission for malignancies (OR:4.2

Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100&ndash, 200 mg, mean 150 mg) or intranasally (n = 5, 50&ndash, 100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.

Background: Non-medical use (NMU) of prescription GABA analogs (pregabalin and gabapentin) has been reported especially in opiate dependent persons. However, by now the prevalence of NMU of gabapentinoids in the general population has not been sufficiently evaluated. The aim of this research paper is to determine the prevalence of prescription GABA analog NMU and associated demographics in five European countries with special detail of Spain.Methods: The RADARS Survey of Non-Medical Use of Prescription Drugs Program (NMURx) is a harmonized series of contemporaneous cross-sectional surveys of adults conducted in multiple countries. NMURx collects data from the general population in each participating country about NMU of prescription drugs, illicit drugs, and associated demographics. NMU was defined as “using a medication without a doctor's prescription or for any reason other than what was recommended by their doctor.” Responses from Spain (4Q2017, n=10,062) were analyzed in detail. Comparative data were available from France, Germany, Italy, and UK. Responses were collected using non-probability quota sampling and post-stratification population weighting was applied to reflect the national distributions of adults, based on age, gender, and census region. Rates of NMU and associated demographics were reported as rate of past 90-day NMU per 100,000 adult population with 95% confidence intervals.Results: Germany (1,197 per 100,000 adult population [95% CI: 1,004.3–1,379.1]) and United Kingdom (1,067 per 100,000 adult population [95% CI: 851.3–1,283.2]) presented the highest prevalence of gabapentinoids NMU. In Spain the prevalence of past 90 days GABA analog NMU was: 344.4, 95% (CI 204.8–484.0), with male predominance. Those who non-medically use GABA analogs had a higher prevalence of lifetime chronic pain, lifetime illicit drug use, and previous substance abuse treatment. In Spain, 20% of respondents who ever have used gabapentinoids, reported a lifetime NMU; the prevalence was higher for pregabalin 624 (6.2%) than for gabapentin 444 (4.4%). The main reasons for use were to self-treat pain and other medical conditions.Conclusions: The risk of NMU of gabapentinoids should not be neglected. Subjects with a history of chronic pain and lifetime substance use disorders had an increased risk of NMU of gabapentinoids.

Background Energy drinks (EDs) reduce sleepiness and fatigue and improve driving performance whereas alcohol does just the opposite. Although it is a trendy combination among young people, the effects of alcohol mixed with EDs on driving performance have been poorly studied. The aim was to assess if there is an interaction between the effects of both drinks on driving-related skills as well as perceptions about driving ability. Methods We conducted a randomized, double-blind, and placebo-controlled 4-way crossover clinical trial. Participants were 16 healthy volunteers. Interventions of 60 g of ethanol and 750 mL of Red Bull (RB) were administered in 2 separated doses. Conditions were alcohol + RB placebo, alcohol + RB, alcohol placebo + RB, and both placebos. Objective performance was assessed using a tracking test and simple reaction time, N-Back, and movement estimation tasks. Additionally, willingness to drive, other subjective effects, and ethanol and caffeine blood concentrations were also measured. Results Alcohol increased the time outside the road in the tracking test and increased simple reaction time, but the addition of RB had no main or interaction effects on performance. Nonetheless, driving-related skills after alcohol + RB were better than after alcohol alone. Willingness to drive increased with the combination of drinks. RB also reduced alcohol-induced sedation whereas drunkenness did not change. These effects were seen even though alcohol + RB increased alcohol (14.8%) and caffeine plasma concentrations (17.6%). Conclusions Mixing EDs with alcohol predisposes consumers to drive under alcohol influence, perhaps in part because EDs counteract its detrimental effects on driving-related skills. Clinicaltrials.gov: NCT02771587.

Dual disorders (DD) and gender differences comprise an area of considerable concern in patients with substance use disorder (SUD). This study aims to describe the presence of DD among patients with SUD admitted to a general hospital and attended by a consultation liaison addiction service (CLAS), in addition to assessing its association with addiction severity and quality of life from a gender perspective, between 1 January and 30 September 2020. The dual diagnosis screening interview (DDSI), the severity of dependence scale (SDS), and the WHO well-being index were used to evaluate the patients. In the overall sample, DD prevalence was 36.8%, (women: 53.8% vs. men: 32.7%, NS). In both genders the most prevalent DD was depression (33.8%, women: 46.2% vs. men: 30.9%, p = 0.296). Women presented more panic disorders (46.2% vs. 12.7%, p = 0.019) and generalized anxiety (38.5% vs. 10.9%, p = 0.049) than men. When DD was present, women had worse quality of life than men (21.7 vs. 50 points, p = 0.02). During lockdown period 77 patients were attended to and 13 had COVID-19 infection, with no differences in relation to sociodemographic and consumption history variables. The study confirms a high prevalence of DD among patients with SUD admitted to a general hospital for any pathology, and its being associated with worse quality of life, particularly in women.

Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).

Antecedentes: El consumo de cocaína es un creciente problema de salud en todo el mundo. Además, los pacientes con trastorno por consumo de cocaína (TCC) presentan una alta comorbilidad con el trastorno depresivo mayor (TDM). Estos pacientes pueden presentar dos tipos de TDM: trastorno depresivo mayor primario (TDM-P) y trastorno depresivo mayor inducido por cocaína (TDM-IC). El objetivo de este estudio es evaluar las diferencias en la sintomatología depresiva (TDM-P vs. TDM- IC) en los pacientes con TCC para mejorar su tratamiento. Métodos: Se llevó a cabo un análisis secundario en una muestra transversal de 160 pacientes que presentaban TCC y algún TDM. La evaluación clínica, así como el diagnóstico diferencial entre TDM-P y TDM-IC, se realizó utilizando la entrevista PRISM. Resultados: Los hombres representaron el 80% de la muestra con una edad media de 38,61 años y el 64,5% sólo tenía estudios primarios. El diagnóstico de TDM-IC (61,3%) fue más frecuente que el de TDM-P (38,7%). Los pacientes con TDM-IC mostraron una edad de aparición más temprana para el TCC. El 79,4% de los pacientes cumplían criterios para otro trastorno por consumo de sustancias. Únicamente el criterio “Cambios en el peso o en el apetito” fue estadísticamente más prevalente (57,1%) en los pacientes con TDM-P. Conclusiones: Existen diferencias en el criterio “Cambios en el peso o en el apetito” entre TDM-P y TDM-IC. Se necesita más investigación a fin de obtener un diagnóstico diferencial entre los dos tipos de depresión y proporcionar un mejor tratamiento para los pacientes con TCC.

Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72-1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach. This work was supported by grants from the Instituto de Salud Carlos III–ISCIII Red de Trastornos Adictivos 2016 (RD16/0017/0010, RD16/0017/0003; Fondo de Investigación Sanitaria (FIS) (PI09/02121, PI12/01838, PI14/00178, PI16/00603); National R + D+I and funded by the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (FEDER) grant Juan Rodes (JR 16/00020); Ministerio de Sanidad, Política Social e Igualdad, Plan Nacional Sobre Drogas (PNSD) (2012I054); Suport Grups de Recerca AGAUR-Gencat (2017 SGR 316, 2017 SGR 530); Acció instrumental d’Intensificació de Professionals de la Salut - Facultatius especialistes (PERIS) (SLT006/17/00014); and Ministerio de Economía y Competitividad (MTM2015-64465-C2-1-R). The funding agencies had no role in study design, data collection, interpretation, or had influence on the writing.

Opioid use disorder continues to be an important public health concern, reaching epidemic ranges in some countries as well as the consequences associated with consumption. A review of the pharmacology of different opioid drugs available is presented. Also, a current state of the art in the treatment of opioid-related disorders is reviewed. Opioid overdose is a potentially fatal medical emergency that can be reversed with naloxone, an antagonist of opioid receptors, in different doses and routes depending on the opioid that caused the intoxication. For opioid use disorders, the main pharmacological approach is substitution treatment (methadone, buprenorphine, slow-release oral morphine) with the objective of neurochemical stabilization, avoiding the reinforcing effect, and decreasing withdrawal symptoms and craving; there is also a naltrexone depot formulation approved for relapse prevention, associated with psychosocial interventions that seek to restore functionality and prevent relapse. In this chapter, the authors review the current state of knowledge in the field focused on clinical practice.

Hallucinogenic drugs have as their primary effect the production of disturbances of perception. Hallucinogens can be classified according to their chemical structure as indoleamines (similar to serotonin), phenethylamines (similar to catecholamines), dissociatives (phencyclidines) and others (including salvinorin, dextromethorphan, muscarinic antagonists and cannabinoids). The hallucinogenic effects appear to be related to the agonistic action on 5-HT2A receptors in the cortex. These actions seem to cause a functional imbalance at various levels (cortical areas, limbic system, which is a group of brain structures involved in emotional regulation), contributing to distort the integrative action. Hallucinogens produce substance use disorder, induce acute tolerance to its effects and do not present withdrawal syndrome. The novel psychoactive substances (NPS) can induce substance use disorder, intoxication and in some cases withdrawal syndrome (for those with psychostimulant properties). Depending on the substance and pharmacological effects, the DSM-5 diagnostic criteria for hallucinogens or stimulants can be applied. The therapeutic aim in these cases is to reduce consumption and achieve the abstinence. There are no specific drugs for treating the addiction caused by these substances. Some hallucinogens are under evaluation for its therapeutic use in different mental disorders.

Background People with substance use disorders are considered at increased risk of COVID-19 and its more serious complications, however data on the impact of COVID-19 are lacking. The study aimed to describe the clinical characteristics and outcomes of COVID-19 on people with substance use disorders. Methods an observational study was carried out including patients aged ≥ years with COVID-19 pneumonia admitted to an urban hospital during March 12 to June 21,2020. Results Among 2078 patients admitted, 27 (1.3%) were people with substance use disorders: 23(85.2%) were men with a median age of 56.1 + 10.3 years and. The main SUD were alcohol in 18(66.7%) patients, heroine in 6(22.2%) and cocaine in 3(11.1%) and 24(88.8%) patients were on ongoing substance use disorder treatment. One or more comorbidities associated to COVID-19 risk were observed in 18(66.6%) of patients. During a median length of stay of 10 days (IQR:7-19), severe pneumonia developed in 7(25.9%) patients, acute respiratory distress syndrome in 5 (18.5%) and none died. Conclusion Larger sample sizes and sero-epidemiological studies are needed to confirm the low incidence of severe COVID-19 on patients with SUD.

Background: In clinical practice, there is the need to have clinical and biological markers to identify induced depression. The objective was to investigate clinical, biological and genetic differences between Primary Major Depression (Primary MD) and Alcohol Induced MD (AI-MD). Methods: Patients, of both genders, were recruited from psychiatric hospitalisation units. The PRISM instrument was used to establish the diagnoses. Data on socio-demographic/family history, clinical scales for depression, anxiety, personality and stressful life events were recorded. A blood test was performed analysing biochemical parameters and a Genome Wide Association Study (GWAS) to identify genetic markers associated with AI-MD. Results: A total of 80 patients were included (47 Primary MD and 33 AI-MD). The AI-MD group presented more medical comorbidities and less family history of depression. There were differences in traumatic life events, with higher scores in the AI-MD (14.21 ± 11.35 vs. 9.30 ± 7.38; p = 0.021). DSM-5 criteria were different between groups with higher prevalence of weight changes and less anhedonia, difficulties in concentration and suicidal thoughts in the AI-MD. None of the genetic variants reached significance beyond multiple testing thresholds; however, some suggestive variants were observed. Conclusions: This study has found clinical and biological features that may help physicians to identify AI-MD and improve its therapeutic approach. This project has received funding from the European Union’s Horizon 2020 research and innovation programme 2014–2020 under Grant Agreement No. 634143 (MedBioinformatics) and ISCIII-Red de Trastornos Adictivos-RTA-FEDER (RD12/0028/0009 and RD16/0017/0010). Acció instrumental d’Intensificació de Professionals de la Salut—Facultatius especialistes (PERIS: SLT006/17/00014).

Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of new psychoactive substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in humans. Eleven male volunteers participated as outpatients in four experimental sessions in a double-blind, randomized, cross-over, and placebo-controlled clinical trial. Participants received a single oral dose of 200 mg of mephedrone plus 0.8 g/kg of alcohol (combination condition); 200 mg of mephedrone plus placebo alcohol (mephedrone condition); placebo mephedrone plus 0.8 g/kg of ethanol (alcohol condition); and placebo mephedrone plus placebo alcohol (placebo condition). Outcome variables included physiological (blood pressure, heart rate, temperature, and pupil diameter), psychomotor (Maddox wing), subjective (visual analogue scales, Addiction Research Center Inventory 49 item short form, and Valoración de los Efectos Subjetivos de Sustancias con Potencial de Abuso questionnaire), and pharmacokinetic parameters (mephedrone and ethanol concentrations). The study was registered in ClinicalTrials.gov, number NCT02294266. The mephedrone and alcohol combination produced an increase in the cardiovascular effects of mephedrone and induced a more intense feeling of euphoria and well-being in comparison to the two drugs alone. Mephedrone reduced the sedative effects produced by alcohol. These results are similar to those obtained when other psychostimulants such as amphetamines and 3,4-methylenedioxymethamphetamine are combined simultaneously with alcohol. The abuse liability of mephedrone combined with alcohol is greater than that induced by mephedrone alone.

Lysergic acid diethylamide (LSD) was studied from the 1950s to the 1970s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders. LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry. The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry. PRISMA guidelines for systematic review were followed. A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies (MAPS) databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included. Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias. A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to 567 patients in a dose ranging from 20 to 800 mcg. Despite the design heterogeneity of clinical trials, positive results were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe significant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up. Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus anxiety symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Clinical trials are only available for posttraumatic stress disorder (PTSD) and for social anxiety. Concerning the comorbid substance use, all the studies have included patients with alcohol use, none of them have dealt with cocaine, cannabis or nicotine use. Although some treatments have shown benefit for anxiety symptoms without benefits for alcohol or other substance use, only limited pharmacological approaches have been assayed (sertraline, desipramine, paroxetine, buspirone, naltrexone and disulfiram). Our results suggest that 1) we can (weakly) recommend the use of desipramine over paroxetine to alleviate symptoms of anxiety in patients with a PTSD and alcohol use; 2) In these patients, the use of naltrexone to reduce symptoms of anxiety is also recommended (weak strength); and 3) SSRI antidepressants vs placebo can be recommended to reduce alcohol use (weak recommendation). Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-alpha, IL-1 beta, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [ CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to "Diagnostic and Statistical Manual of Mental Disorders, 4 th edition, text revision" (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-alpha (p

Altres ajuts: This work was supported by grants from Ministerio de Sanidad, Política Social e Igualdad (Plan Nacional Sobre Drogas, PNSD 2015I054 and 2016I024). Soy beans contain isoflavones, including daidzein and genistein, with biological activities related to therapeutic effects in reducing osteoporosis, decreasing adverse menopausal manifestations, providing protection from cardiovascular diseases, and reducing hormone-dependent cancers and age-related cognitive-decline. Daidzein has been described as inhibiting the aldehyde-dehydrogenase-2 enzyme (ALDH2), and reducing alcohol use in clinical pilot studies. Our aim was to evaluate the possible interactions between a soy extract product and alcohol in a crossover, single blind, randomized study. Ten healthy male volunteers participated in two experimental sessions: one with a single dose of alcohol (0.5 g/kg, Vodka Absolut, Sweden), and the other with four capsules of a soy extract product (Super-Absorbable Soy Isoflavones, Life-Extension, United States) and, 2 h later, the same dose of alcohol. Results showed no differences in vital signs except a slightly higher significative reduction in diastolic blood pressure at 2, 3, 4, and 8 h after administration with alcohol alone in comparison with soy extract+alcohol. Ethanol-induced subjective and adverse effects were similar for both conditions with the exception of headache (higher at 8 h after alcohol alone). Our results demonstrate that a single dose of a soy isoflavone extract did not influence alcohol pharmacokinetics and pharmacological effects and did not induce any disulfiram-reaction symptoms. Soy extract and alcohol did not interact and can be administered safely.

Fentanyl, fentanyl analogs, and other new synthetic opioids (NSO) have burst onto the illegal drug market as new psychoactive substances (NPS). They are often sold as heroin to unsuspecting users and produce euphoria through their agonist action on μ- opioid receptors. Their high consumption, often combined with other substances, has led to multiple intoxications during recent years. In some countries, such as the United States, the consumption of opioids, whether for medical or recreational purposes, has become epidemic and is considered a public health problem. Fentanyl analogs are more potent than fentanyl which in turn is 50 times more potent than morphine. Furthermore, some fentanyl analogs have longer duration of action and therefore interactions with other substances and medicines can be more serious. This review is focused on the potentially most frequent interactions of opioid NPS taking into account the drugs present in the reported cases of poly-intoxication, including other illegal drugs of abuse and medication. Substances involved are mainly antidepressants, antihistamines, antipsychotics, benzodiazepines, analgesics, anesthetics, psychostimulants, other opioids, alcohol, and illegal drugs of abuse. The interactions can be produced due to pharmacokinetic and pharmacodynamic mechanisms. Naloxone can be used as an antidote, although required doses might be higher than for traditional opioid intoxications. It is crucial that doctors who habitually prescribe opioids, which are often misused by patients and NPS users, be aware of designer opioids’ potentially life-threatening drug-drug interactions in order to prevent new cases of intoxication.

La concurrencia de depresión y un trastorno por uso de sustancias (TUS) en pacientes que presentan patología dual ha sido reconocida desde hace mucho tiempo como una consideración importante en la práctica clínica. Esta revisión sintetiza la evidencia de intervenciones farmacológicas y psicosociales para trastornos comórbidos de depresión y uso de sustancias y además proporciona recomendaciones clínicas respecto de las mejores intervenciones para tratar a estos pacientes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Nuestros resultados sugieren que: 1) en pacientes con depresión y consumo de alcohol, se recomienda la administración de antidepresivos inhibidores de la recaptación de serotonina (ISRS) no selectivos en lugar de los ISRS para mejorar los síntomas depresivos (recomendación fuerte). No se recomiendan antidepresivos ISRS (recomendación fuerte) ni antidepresivos no ISRS (recomendación débil) para reducir el consumo de alcohol; 2) en pacientes con depresión y consumo de cannabis, no se recomienda el uso de venlafaxina (recomendación débil); 3) en pacientes con depresión y consumo de cocaína, no se recomienda el uso de antidepresivos ISRS para mejorar los síntomas depresivos (recomendación débil) o para reducir el consumo de cocaína (recomendación fuerte). El uso de antidepresivos no ISRS solo se recomienda para mejorar los síntomas depresivos (recomendación fuerte); 4) no se recomienda la administración de bupropión para reducir el consumo de nicotina (recomendación fuerte), y 5) en cuanto al tratamiento psicológico, en pacientes con depresión y trastorno de alcohol concurrente, tanto la farmacoterapia como la terapia cognitivo-conductual tienen efectos positivos en la internalización de los síntomas y en la reducción del consumo de alcohol (recomendación débil). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multisitio y más grandes para proporcionar más evidencia definitiva. Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence.

Cannabis is the most commonly used illicit drug among adolescents and young adults, including pregnant women. There is substantial evidence for a significant association between prenatal cannabis exposure and lower birth weight in offspring, and mixed results regarding later behavioural outcomes in the offspring. Adolescent cannabis use, especially heavy use, has been associated with altered executive function, depression, psychosis and use of other drugs later in life. Human studies have limitations due to several confounding factors and have provided scarce information about sex differences. In general, animal studies support behavioural alterations reported in humans and have revealed diverse sex differences and potential underlying mechanisms (altered mesolimbic dopaminergic and hippocampal glutamatergic systems and interference with prefrontal cortex maturation). More studies are needed that analyse sex and gender influences on cannabis-induced effects with great clinical relevance such as psychosis, cannabis use disorder and associated comorbidities, to achieve more personalized and accurate treatments.

PURPOSE OF REVIEW Cannabis is globally the most commonly cultivated, trafficked and consumed illicit drug of abuse. The current article provides an updated overview of existing comprehensive interventions for preventing and reducing cannabis use. RECENT FINDINGS The PubMed database was searched for evidence regarding comprehensive interventions for preventing and reducing cannabis use from June 2016 to January 2018. The search resulted in 274 articles. Twenty-one studies were selected for assessment and 13 fulfilled the inclusion criteria. Six systematic reviews regarding preventive, psychosocial, pharmacological and risk reduction interventions were identified. Psychosocial interventions included therapist-assisted and computerized interventions. Four therapist-assisted, one computerized and two pharmacological clinical trials were published over the review period. Overall, considering the three different approaches (preventive, psychosocial or pharmacological) promising results have been found in certain interventions in reducing cannabis use among different types of users. In addition, recommendations to reduce adverse health outcomes related to cannabis use have also been reviewed. SUMMARY Although relevant findings have been found so far, further research with adequately powered trials assessing comprehensive interventions for reducing cannabis use remains a need before definitive treatment recommendations can be established.

The efficacy of methadone maintenance treatment (MMT) in opioid use disorder is well established but responses vary. The influence of methadone pharmacodynamics and pharmacokinetics on dose requirements and program outcomes remains controversial despite the increasing number of studies evaluating genetic influences on response to methadone treatment. Furthermore, patients require different doses (usually between 60 and 100 mg/day), and there are no clear data on a plasma concentration associated with treatment success. We review the evidence regarding the influence of genetics on pharmacokinetic and pharmacodynamic factors in terms of MMT outcome. We also analyse the influence of genetics on the occurrence of severe adverse events such as respiratory depression and ventricular arrhythmia in methadone treatment. The outcomes of MMT may be influenced by a combination of environmental, drug-induced, and genetic factors. The influence of pharmacokinetic genetic variability can be clinically managed by modifying the posology. A better understanding of pharmacodynamic factors could help in selecting the best opioid for substitution treatment, but patient phenotype must still be considered when establishing a maintenance treatment. Pharmacogenetic studies represent a promising field that aims to individualize treatments according to genetic backgrounds, adapting medication and doses according to possible outcomes and the risk of adverse events.

New psychoactive tryptamines may be a public health risk since they intend to mimic the hallucinogenic effects of regulated psychoactive drugs. Few studies describe uses and clinical effects of unregulated new psychoactive tryptamines. This study aims (1) to explore the presence of tryptamines classified as NPS among the substances delivered for analysis to a harm-reduction organization; (2) to describe the substances found in the samples after analysis; and (3) to compare analytical results of regulated vs. non-regulated tryptamines. Samples delivered and analyzed by gas chromatography-mass spectrometry from 2006 to 2015 were included. A descriptive study of results was conducted. From 25,296 samples that were delivered, 436 were tryptamines; from these 232 (53.21%) were non-regulated. The most delivered non-regulated tryptamine was 4-AcO-DMT. A search of the PubMed database in July 2016 revealed that no studies in humans have ever been carried out with 4-AcO-DMT. Unregulated tryptamines likely contained one unadulterated substance (p ≤ 0.001). The number of samples submitted which contained tryptamines increased during the course of the study, with significant differences in client expectations vs. analysis results between the controlled and uncontrolled groups. There is a need for further research in order to prevent the potential health risks associated with their use.

Since its introduction in the 1960s by Dole and Nywswander [1], methadone maintenance treatment (MMT) is the most widely used therapy to treat opioid dependence and is considered its first-line treatment. Its efficacy has been proven in terms of decrease of heroin use and retaining patients in treatment; also, it reduces the risk behaviors associated with HIV infection, decreases criminal behavior related with drug use, reduces the risk of fatal overdose and improves health-related quality of life [2]. However, between 30 and 80% of treated patients relapse in heroin use or drop out from MMT [3]. Besides moral concepts and prejudices that hinder legislation and interfere with the implementation of MMT programs based in the scientific evidence to improve their effectiveness [4], in the last decade there has been an increasing interest in the study of the influence of pharmacogenetics in order to develop individualized therapies in response to interindividual variability in MMT response.

Background Concern regarding the QTc interval in human immunodeficiency virus (HIV)-infected patients has been growing in recent years, and cases of prolonged QTc interval and torsades de pointes have been described in HIV-infected patients on methadone therapy. This study aimed to determine the prevalence and factors associated with long QTc interval in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. Methods A cross-sectional study was conducted in opioid-dependent HIV-infected patients on methadone maintenance therapy at a drug abuse outpatient center. Patients with any cardiac disease, drug-positive urine test, electrolyte abnormalities, and changes in their antiretroviral therapy (ART) or methadone doses in the last 2 months were excluded. Heart rate and QT interval in lead II were measured using the Bazett formula. Results Ninety-one patients were included: 58 (63.7%) were men with a median age of 44.5 years and 68 of 91 (74.7%) were on ART. Median methadone dose was 70 mg/day (range 15-250 mg/day) and mean QTc interval was 438 ± 34 ms. Prolonged QTc interval (>450 ms) was documented in 33 of 91(36.3%) patients, and 3 of 91 (3.2%) had QTc >500 ms. On multiple linear regression analysis, methadone doses (P = .005), chronic hepatitis C-induced cirrhosis (P = .008), and being ART-naive (P = .036) were predictive of prolonged QTc. Conclusions The prevalence of prolonged QTc interval in opioid-dependent HIV-infected patients on methadone maintenance therapy is high. Risk factors for prolongation of the QTc interval are chronic hepatitis C-induced cirrhosis, higher methadone doses, and being ART-naive. Thus, electrocardiographic monitoring is required to minimize cardiovascular morbidity and mortality in this specific HIV group.

PurposeImprovement in Access to Treatment for People with Alcohol and Drug Related Problems (IATPAD) was a European study that detected barriers and facilitators to accessing treatment for patients with alcohol and drug‐related problems. This article seeks to compare the findings from a qualitative study with patients and staff in Catalunya (Spain).Design/methodology/approachThe paper describes a multi‐centre, qualitative study. A purposive sample of 47 staff, from a randomly selected sample of the three main entrance points to treatment for patients with alcohol and drug problems in Catalunya, were recruited from: Out‐patient General Psychiatry Centres (CSMA); Out‐patient Addiction Centres (CAS); and Primary Care Centres (CAP). In addition, open‐ended responses were collated from 142 additional staff on barriers and facilitators to accessing treatment for patients with alcohol and drug problems and how these barriers could be improved. A total of 25 patients from two CAS were interviewed in‐depth. The framework approach was used to interpret qualitative interviews.FindingsThe main barriers and facilitators to accessing treatment identified by staff and patients were patients' motivation, centres' opening hours, staff attitudes, the provision of information about services, and the co‐ordination and integration of different services – mainly the mental health and addiction sectors.Originality/valueThis paper describes and compares the main barriers and facilitators to accessing treatment from both staff and patients' point of view. Recommendations are made in order to improve service accessibility for patients with addiction problems and those with a dual diagnosis.

Antidepressants are commonly used in substance abusers due to the potential effect on some underlying mechanisms involved in drug use disorders and to treat comorbid depression. A systematic review of the literature of the efficacy of antidepressant drugs in subjects with drug abuse disorders, including alcohol, cocaine, nicotine and opioid, with and without comorbid depression was performed. Only randomised, double-blind, controlled trials have been evaluated. A meta-analysis was done with the included studies that used common evaluation procedures in alcohol, cocaine and opioid dependence. Based on the present review some recommendations may be proposed. The prescription of antidepressants for drug abuse seems only clear for nicotine dependence with or without previous comorbid depression (bupropion and nortryptiline). In alcohol dependence without comorbid depression, the use of any antidepressant seems not justified, while in cocaine dependence has to be clarified. The use of antidepressants in alcohol, cocaine or opioid dependence with comorbid depression needs more studies in well-defined samples, adequate doses and duration of treatment to be really conclusive. Interestingly, SSRIs do not seem to offer significant advantages compared with tricyclic drugs in substance abuse disorders. Differences both related to individual characteristics and specific antidepressant drugs need to be clarified in future studies.

IntroductionShabu is a crystal methamphetamine whose consumption is common among the community of Philippine immigrants in Spain.ObjectivesTo describe the sociodemographic, healthcare and clinical characteristics of patients using shabu who have been treated by the psychiatry and addiction department of a tertiary hospital.MethodsWe describe the cases of patients treated in the psychiatry and addiction department of the hospital del Mar in Barcelona, Spain with methamphetamine use disorder. We collected sociodemographic variables, monitoring features and psychiatric comorbidity from the review of medical records.ResultsTen cases of patients with severe use disorder of shabu were identified. Eight patients are from the Philippines. Nine are men (90%). At the beginning of the medical follow-up the average age was 30 years (21–41 years). All of them reported being unemployed. Four patients were referred urgently to the hospital from an ambulatory care center, two belonged to a specific program for children and adolescents, two were treated at the emergency department and two were assessed during their admissions in other departments. Regarding clinical characteristics, six had associated psychiatric disorders: two have paranoid schizophrenia, two had induced psychotic episode, one had unspecified psychosis and other had conduct disorder.ConclusionsShabu is a drug that the Philippine community in Spain consumes in their daily life in a social context. However, consumption of this drug could be linked to the onset of psychotic symptoms. Registration is necessary to standardize the consumption pattern in order to establish a relationship between consumption and the appearance of psychotic and organic symptoms.Disclosure of interestThe authors have not supplied their declaration of competing interest.

This study investigates differences in terms of clinical and treatment management in psychiatric hospitalization associated to smoking ban. We collected data regarding medication, socio-demographic and admission characteristics from all patients admitted to an acute psychiatric hospital before and after a smoking ban was in force. We also assessed a limited sample of patients before and after the ban regarding nicotine dependence, motivation to quit smoking and attitudes towards the ban. More number of leaves of absence and movement restrictions during the ban period occurred in comparison to the pre-ban period. On the contrary a lack of significant differences in terms of hospital stay (duration, rate of voluntary admissions and voluntary discharges), use of sedatives and doses of antipsychotics was found. A period of adjustment regarding the deal with leave of access and facilitate nicotine replacement treatment may help future psychiatric facilities planning smoking free policies.

Mortality of alcohol and drug abusers is much higher than the general population. We aimed to characterize the role of the primary substance of abuse on the survival of patients admitted to treatment and to analyze changes in mortality over time.Longitudinal study analyzing demographic, drug use, and biological data of 5023 patients admitted to three hospital-based treatment units in Barcelona, Spain, between 1985 and 2006. Vital status and causes of death were ascertained from clinical charts and the mortality register. Piecewise regression models were used to analyze changes in mortality.The primary substances of dependence were heroin, cocaine, and alcohol in 3388 (67.5%), 945 (18.8%), and 690 patients (13.7%), respectively. The median follow-up after admission to treatment was 11.6 years (IQR: 6.6-16.1), 6.5 years (IQR: 3.9-10.6), and 4.8 years (IQR: 3.1-7.8) for the heroin-, cocaine-, and alcohol-dependent patients, respectively. For heroin-dependent patients, mortality rate decreased from 7.3×100person-years (p-y) in 1985 to 1.8×100p-y in 2008. For cocaine-dependent patients, mortality rate decreased from 10.7×100p-y in 1985 to2.5×100p-y after 2004. The annual average decrease was 2% for alcohol-dependent patients, with the lowest mortality rate (3.3×100p-y) in 2008.Significant reductions in mortality of alcohol and drug dependent patients are observed in recent years in Spain. Preventive interventions, treatment of substance dependence and antiretroviral therapy may have contributed to improve survival in this population.

During the 1980s, Spain had very strict laws limiting access to opioid agonist maintenance treatment (OAMT). Because of this, mortality among people who used illicit opioids and other illicit drugs was high. Spain was also the European country with the highest number of cases of acquired immunodeficiency syndrome transmitted through illicit drug injection.The rapid spread of human immunodeficiency virus (HIV) infection among people using heroin led to a shift from a drug-free approach to the treatment of opioid dependence to one focused on harm reduction. A substantial change in legislation made it possible to meet public health needs and offer OAMT as part of harm reduction programmes in the public health system, including prisons.Legislative changes were made throughout the country, although at a different pace in different regions.Legal changes facilitated the expansion of OAMT, which has achieved a coverage of 60%. A parallel reduction in the annual incidence of HIV infection has been reported. Reductions in morbidity and mortality and improved health-related quality of life have been described in patients undergoing OAMT.The treatment of opioid dependence has been more heavily influenced by moral concepts and prejudices that hinder legislation and interfere with the implementation of OAMT than by scientific evidence. To fulfil public health needs, OAMT should be integrated in harm reduction programmes offered primarily in public facilities, including prisons. Longitudinal studies are needed to detect unmet needs and evaluate programme impact and suitability.Dans les années 1980, l'Espagne avait des lois très strictes limitant l'accès au traitement de maintien par agoniste des opioïdes (TMAO). Pour cette raison, la mortalité parmi les utilisateurs d'opioïdes illicites et autres drogues illégales était élevée. L'Espagne était également le pays européen présentant le plus grand nombre de cas de syndrome d'immunodéficience acquise transmis par injection de drogues illicites.La propagation rapide du virus de l'immunodéficience humaine (VIH) chez les personnes consommant de l'héroïne a mené au basculement d'une approche non médicalisée du traitement de la dépendance aux opiacés à une position axée sur la réduction des risques. Un changement important de la législation a permis de répondre aux besoins de santé publique et d'offrir un traitement de maintien par agoniste des opioïdes dans le cadre des programmes de réduction des risques dans les organismes de santé publique, y compris les prisons.Des modifications législatives ont été apportées dans tout le pays, bien qu'à un rythme différent selon les régions.Les adaptations juridiques ont facilité le développement du traitement de maintien par agoniste des opioïdes, qui a atteint une couverture de 60%. Une réduction parallèle de l'incidence annuelle de l'infection par le VIH a été observée. Des réductions de morbidité et de mortalité ainsi qu'une amélioration de la qualité de vie liée à la santé ont été décrites chez les patients suivant un tel programme.Le traitement de la dépendance aux opiacés a été plus fortement influencé par des concepts moraux et les préjudices qui entravent la législation et interfèrent avec la mise en place de programmes de traitement que par des preuves scientifiques. Afin de répondre aux besoins de santé publique, des traitements de maintien par agoniste des opioïdes devraient être intégrés dans les programmes de réduction des risques, majoritairement proposés dans les lieux publics, y compris les prisons. Des études longitudinales sont nécessaires pour détecter les besoins non satisfaits et pour évaluer l'impact et la pertinence du programme.Durante la década de los años 80, las estrictas leyes en España limitaban en acceso al tratamiento de mantenimiento con opioides agonistas, por lo que la mortalidad entre los consumidores de opiáceos y otras drogas ilegales era elevada. España era el país europeo con el mayor número de casos de síndrome de la inmunodeficiencia adquirida transmitidos por la inyección de drogas ilegales.La rápida propagación de la infección por el virus de la inmunodeficiencia humana (VIH) entre personas que consumían heroína ocasionó un cambio de un enfoque sin fármacos para el tratamiento de la dependencia de opiáceos a otro dirigido a la reducción de daños. Un cambio importante en la legislación permitió satisfacer las necesidades de salud pública y ofrecer el tratamiento de mantenimiento con opioides agonistas como parte de los programas de reducción de daños en el sistema de salud pública, incluidas las prisiones.Se realizaron cambios legislativos en todo el país, aunque a un ritmo distinto en las diferentes regiones.Los cambios legales facilitaron la expansión del tratamiento de mantenimiento con opioides agonistas, que alcanzó una cobertura del 60 %. Se ha constatado una reducción paralela de la incidencia de la infección por el VIH, y se ha evidenciado una disminución de la morbilidad y la mortalidad, así como una mejora en la calidad de vida entre los pacientes que se someten al tratamiento de mantenimiento con opioides agonistas.El tratamiento de la dependencia de opiáceos ha estado más influido por conceptos y prejuicios morales que dificultan la legislación e interfieren en la puesta en marcha del tratamiento de mantenimiento con opioides agonistas que por las pruebas científicas. A fin de cumplir con las necesidades de salud pública, se debería integrar el tratamiento de mantenimiento con opioides agonistas en los programas de reducción de daños ofrecidos en centros públicos, incluidas las prisiones. Es necesario realizar estudios longitudinales para detectar las necesidades insatisfechas y evaluar el impacto e idoneidad del programa.خلال ثمانينيات القرن العشرين، وضعت إسبانيا قوانين بالغة الصرامة تحد من إتاحة العلاج الصياني بناهض المواد الأفيونية المفعول (OAMT). ونظراً لهذا، كان معدل الوفيات بين الأشخاص الذين استخدموا المواد الأفيونية المفعول غير المشروعة وغيرها من الأدوية غير المشروعة مرتفعاً. وكانت إسبانيا أيضاً البلد الأوروبي الذي يوجد به أعلى عدد من حالات الإصابة بمتلازمة العوز المناعي المكتسب التي يتم نقلها من خلال حقن الأدوية غير المشروعة.أدى الانتشار السريع لعدوى فيروس العوز المناعي البشري (HIV) بين الأشخاص الذين يستخدمون الهيروين إلى التحول من أسلوب خال من الأدوية للعلاج المعتمد على المواد الأفيونية المفعول إلى أسلوب يركز على الحد من الأضرار. وبفضل تغيير كبير في التشريعات، تحققت تلبية احتياجات الصحة العمومية وتقديم العلاج الصياني بناهض المواد الأفيونية المفعول كجزء من برامج الحد من الأضرار في نظام الصحة العمومية، بما في ذلك السجون.تم إدخال تغييرات تشريعية في أنحاء البلد، على الرغم من اختلاف وتيرتها في الأقاليم المختلفة.يسّرت التغييرات القانونية توسيع العلاج الصياني بناهض المواد الأفيونية المفعول، الذي حقق تغطية بنسبة 60 %. وتم الإبلاغ عن انخفاض مواز في الحدوث السنوي لعدوى فيروس العوز المناعي البشري. وتم وصف الانخفاضات في معدلات المراضة والوفيات وتحسين نوعية الحياة المرتبطة بالصحة لدى المرضى الذين يخضعون للعلاج الصياني بناهض المواد الأفيونية المفعول.تأثر العلاج بالاعتماد على المواد الأفيونية المفعول بشدة بالمفاهيم الأخلاقية وأوجه الإجحاف التي تعوق التشريعات وتتعارض مع تنفيذ العلاج الصياني بناهض المواد الأفيونية المفعول مقارنة بتأثره بالبيّنات العلمية. ولتلبية احتياجات الصحة العمومية، ينبغي دمج العلاج الصياني بناهض المواد الأفيونية المفعول في برامج الحد من الأضرار المقدمة بشكل رئيسي في المرافق العمومية، بما في ذلك السجون. ولابد من إجراء دراسات طولية لكشف الاحتياجات غير الملباة وتقييم أثر البرامج ومدى ملاءمتها.在20 世纪80 年代，西班牙的法律非常严格地限制使用阿片受体激动剂维持治疗（OAMT）。因此，使用非法阿片类药物和其他非法毒品的人的死亡率很高。西班牙也是通过非法毒品注射感染艾滋病的病例数量最多的欧洲国家。艾滋病毒（HIV）感染在使用海洛因的人群中迅速蔓延，导致阿片类药物依赖无毒治疗方法转变为以减少伤害为主的治疗。立法上的重大变革使我们能够满足公共健康需求，并在包括监狱在内的公共卫生系统中提供OAMT作为减少伤害方案的一部分。尽管各地步调不一，但是在全国各地都有立法的变革。法律变革促进OAMT的推广，实现了60%的覆盖率。据报告，HIV感染的年发病率也发同步降低。在接受OAMT治疗的患者中也有发病率和死亡率减少以及健康相关生活质量改善的报告。道德观念和偏见对阿片类药物依赖治疗的严重影响比科学证据更大，它们阻碍了立法并干扰了OAMT的实施。要满足公众的卫生需求，应将OAMT纳入主要由公共设施（包括监狱）提供的减少伤害方案中。需要进行纵向研究以发现未满足的需求，并评估方案的影响和适用性。В 1980-е годы в Испании действовали очень строгие законы, ограничивавшие доступ к поддерживающей терапии агонистами опиоидов (ПТАО). По этой причине смертность среди людей, которые потребляли запрещенные опиоиды и другие запрещенные наркотики, была высока. Испания также относилась к числу европейских государств с наибольшим числом случаев синдрома приобретенного иммунодефицита, передаваемого через внутривенное введение запрещенных наркотиков.Стремительное распространение инфекции вируса иммунодефицита человека (ВИЧ) среди людей, потребляющих героин, привело к замене немедикаментозного подхода к лечению опиоидной зависимости методом, ориентированным на снижение вреда. Существенное изменение законодательства позволило удовлетворить требования общественного здравоохранения и предложить ПТАО в рамках программ сокращения вреда в системе общественного здравоохранения включая тюрьмы.Изменение законодательства было проведено по всей стране хоть и с разными темпами в разных регионах.Изменение законодательства упростило распространение ПТАО, охват которого достиг 60%. Одновременно отмечалось снижение числа новых случаев ВИЧ-инфекции в год. Сокращения заболеваемости и смертности, а также улучшение качества жизни, обусловленное здоровьем, отмечены у пациентов, получавших ПТАО.На лечение опиоидной зависимости наибольшее влияние оказывают не научные доказательства, а моральная концепция и предубеждения, которые затрудняют изменение законодательства и препятствуют внедрению ПТАО. Для удовлетворения требований общественного здравоохранения требуется внедрение ПТАО в программы сокращения вреда, предлагаемые преимущественно в государственных учреждениях включая тюрьмы. Длительные повторные исследования необходимы для определения неудовлетворенных потребностей, а также оценки влияния программы и ее пригодности.

Background: There is increasing interest in the pharmacogenetic basis for explaining differences between patients in treatment outcome among methadone-treated subjects. Most studies have focused on genetic polymorphisms related to methadone pharmacokinetics and, to a lesser extent, those genes implicated in the pharmacodynamics of methadone. Objective: This study aimed to investigate the associations between response to methadone maintenance treatment (MMT) and polymorphisms in genes coding for the OPRM1 opioid receptor, the metabotropic glutamate receptors GRM6 and GRM8, the nuclear receptor NR4A2, the photolyase enzyme cryptochrome 1 (CRY1), and the transcription factor myocardin (MYOCD), which have previously been associated with the risk of opioid dependence disorder. Methods: The study used an association, case-control design, conducted in the setting of an MMT program in a drug abuse outpatient center in Barcelona, Spain. We recruited 169 opioid-dependent patients (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders [4th Edition] criteria) receiving MMT. The inclusion criteria included Caucasian ethnicity, being enrolled in MMT for at least 6 months, and receiving a stable methadone dose for the previous 2 months. The exclusion criteria included language-related barriers, severe cognitive impairment, or any medical disorder that would interfere with the research assessments. Single nucleotide polymorphism (SNP) variants in several candidate genes and regions were genotyped: MYOCD (rs1714984), GRM8 (rs1034576), CRY1 (rs1861591), GRM6 (rs953741), OPRM1 (rs1074287), NR4A2 (rs1405735), and the intergenic variants rs965972 (1q31.2) and rs1867898 (2q21.2). MMT response status was assessed by the number of opioid-positive controls detected by random urinalysis in the previous 2 months. We used the chi-squared test and p-value for the allele frequencies of the eight SNPs in responders versus nonresponders, and multivariate logistic regression analyses to examine associations between genotypes in the responder and ronresponder groups under codominant, dominant, and recessive models of inheritance. Results: A final sample of 116 opioid-dependent patients were included and classified as methadone responders (n = 83) and nonresponders (n = 33), according to illicit opioid use detection in random urinalysis. The responders and nonresponders showed similar demographic and clinical characteristics. All SNPs were in Hardy-Weinberg equilibrium. Subjects carrying the AA genotype at rs1861591 CRY1; Chr 12: 105941056 G>A) had a higher risk of being nonresponders (odds ratio [OR] = 2.99; 95% CI 1.14, 7.85; = 0.035), although this difference disappeared with multiple testing corrections. Patients carrying the A allele at rs1714984 MYOCD; Chr 17: 12558425 G>A) had an increased risk of being nonresponders only if they were also carriers of the AG genotype at rs953741 GRM6; Chr5: 178262451 A>G) [OR= 10.83; 95% CI 2.52, 46.66; p = 0.006]. Conclusions: A positive association was observed between response to methadone and two variants in the genes MYOCD and GRM6. A pharmacogenetic epistatic effect between SNPs in MYOCD and GRM6 appears to modulate inter-individual variations in MMT response.

A systematic review and meta-analysis according to the methodology developed by the Cochrane Collaboration and the Quality of Reporting of Meta-Analyses statement based on randomized controlled trials to evaluate the efficacy of anticonvulsants in subjects with cocaine dependence were performed. Fifteen randomized, double-blind, placebo-controlled clinical trials involving 1,236 patients were included. Two outcome measures were evaluated: retention in the anticonvulsant treatment (compared to the placebo treatment) and the subsequent cocaine use, measured by urinalysis results. The efficacy of the seven anticonvulsant drugs analyzed was not homogenous. On average, 50% of the enrolled participants were lost to follow-up. Treatments did not show an improvement in subject retention compared to placebo. Overall, the number of cocaine-positive urine samples was close to statistical significance (95% confidence interval = 0.85-1.06) compared to placebo. Available clinical trials indicate that there is insufficient evidence to justify the use of anticonvulsant drugs in treating cocaine dependence.

Background There is a concern about cardiac rhythm disorders related to QTc interval prolongation induced by methadone. A cross-sectional study was designed to evaluate the prevalence of long QTc (LQTc) interval in patients in methadone maintenance treatment (MMT) and risk factors for LQTc. Methods The study population included 109 subjects (74 males, median age 43 years). Socio-demographic and toxicological variables were recorded, as well as concomitant use of drugs related with QT prolongation, history of heart diseases, and corrected QT interval by heart rate (QTc) in the ECG. Plasma concentrations of ( R )-methadone and ( S )-methadone enantiomers were determined in 69 subjects. Results Ten patients (9.2%) presented a QTc above 440 ms but a QTc above 500 ms was observed in only 2 (1.8%). Patients with QTc above 440 ms compared with the remaining subjects were older (median [25th–75th percentile range]: 49 [39–56] years vs. 37 [33–43]; Wilcoxon's W = 217.5, p = 0.002) and took a higher daily dose of methadone (median [25th–75th percentile range]: 120 [66–228] mg/day vs. 60 [40–110] mg/day; W = 298.5, p = 0.037). Methadone dose correlated with QTc interval (Pearson's r 2 = 0.291, p = 0.002). Patients with and without long QTc showed no differences in plasma concentrations of ( R )-methadone and ( S )-methadone enantiomers. Conclusions The prevalence of LQTc was 9.2%. An association between LQTc and methadone doses was observed but the relationship with plasma concentrations of methadone enantiomers is unclear.