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The focus here was on the pharmacological and clinical pharmacological issues pertaining to the vast range of drugs (e.g. synthetic cannabimimetics, synthetic opioids, novel stimulants, novel psychedelics, PCP/ketamine-like compounds, prescribed medicinal compounds and popular psychotropic herbs/plants) discussed by Internet-based enthusiasts of new/novel psychoactive substances (NPS), ‘e-psychonauts’. Currently ongoing related in silico studies, followed by further in vitro and in vivo/preclinical studies, will hopefully provide important findings in terms of which molecules within each given NPS class may present with higher levels of receptor affinities, and hence clinical potency. Understanding the pharmacological characteristics/potency of those novel recreational molecules will hopefully help in predicting related NPS diffusion, morbidity and possible lethality data.

The dissociative subtype of posttraumatic stress disorder (PTSD) was officially introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In accordance with this new classification, prior studies using Latent Class Analysis (LCA) empirically identified a subgroup of patients that were characterized by a high severity of dissociative symptoms. Despite the high prevalence of PTSD in patients with substance use disorders (SUD), however, no LCA studies on the dissociative subtype of PTSD exist in this population so far. Therefore, the current study aimed to identify subgroups of patients with different symptom and exposure profiles in patients with SUD and PTSD. It was assumed that one symptom and exposure profile could be identified that would be characterized by higher dissociative symptoms, higher additional psychopathology and a higher burden of childhood trauma, as compared to other subgroups. In N = 258 female patients with SUD and PTSD, clinical characteristics of dissociative symptoms, PTSD severity, borderline personality disorder (BPD), depression, childhood trauma and substance abuse were assessed. To identify symptom and exposure profiles, Latent Class Analysis was applied. A three-class solution indicated the best model fit to our data. One class was characterized by a high probability of dissociative symptoms (D-PTSD class), whereas the other two classes were characterized by lower probabilities of dissociative symptoms. The D-PTSD class encompassed 18.7% of the patients. In accordance with our hypothesis, the D-PTSD class showed higher probabilities of PTSD severity, borderline personality disorder symptoms, depressive symptoms, childhood emotional and sexual abuse, childhood emotional neglect, and drug abuse. Our results indicate that the dissociative subtype of PTSD could also be identified in a sample of female patients with SUD. Patients with SUD and PTSD characterized by the dissociative subtype showed more severe psychopathological symptoms than the remaining patients, indicating enhanced clinical needs for this vulnerable group.

The use of several new psychoactive substances (NPS) has become very popular and is posing global health risks. Chemically and pharmacologically diverse molecules are constantly emerging and are presenting with a wide range of clinical implications. Serotonin toxicity, and specifically Serotonin Syndrome (SS), might develop as a result of an over-activation of the serotoninergic system caused by several mechanisms resulting in a classic triad of altered mental status, neuromuscular effects, and autonomic hyperactivity. In the present systematic review, we have investigated and summarized the available evidence related to the association between SS and NPS intake. Three retrospective studies, two case series and five case reports were included in this systematic review; several NPS were found to be implicated in SS occurrence These include psychedelic phenethylamines, e.g. 2, 5-dimethoxy-4-iodophenethylamine (2C-I); 2-(4-Iodo-2,5-dimethoxyphenyl)- N-I[(2-methyoxyphenyl)methyl]ethanamine (25I-NBOMe); and 5-(2-aminopropyl)indole (5-IT); and synthetic cathinones, e.g. mephedrone; 3,4-methylenedioxypyrovalerone (MDPV); methylone; butylone; NRG3; alpha-methyltryptamine (AMT); methoxphenidine (MXP); and the antidepressant bupropion. Bupropion was here misused at high dosages and/or in combination with other licit/illicit serotonergic drugs. Whilst most substances were ingested orally, nasal insufflation (with both 5-IT and 2C-I) and sublingual administration of blotter paper (with 25I-NBOMe) were reported as well. Interestingly, the psychiatric history was negative for most subjects, apart from two cases. Clinicians should be aware of NPS potential risks and the severe consequences of their recreational use, including SS. Also, due to their undetectability in routine and common drug screenings, the diagnostic challenges posed by NPS should not be underestimated during the treatment of such patients.

Mismatch negativity (MMN) is an electrophysiological index of prediction error processing and recently has been considered an endophenotype marker in schizophrenia. While the prediction error is a core concept in the MMN generation, predictability of deviance occurrence has rarely been assessed in MMN research and in schizophrenia patients. We investigated the MMN to 12% temporally predictable or unpredictable duration decrement deviant stimuli in two runs in 29 healthy controls and 31 schizophrenia patients. We analyzed MMN amplitudes and latencies and its associations with clinical symptoms at electrode Fz. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4s while it varied randomly in the unpredictable condition. In the random condition we found diminished MMN amplitudes in patients which normalized in the regular deviance condition, resulting in an analysis of variance main effect of predictability and a predictability x group interaction. Deviance predictability did not affect the MMN of control subjects and we found no relevant results with regard to MMN latencies. Our results indicate that MMN amplitudes in patients normalize to the level of the control subjects in the case of a temporally fixed regular deviant. In schizophrenia patients the detection of deviance is basically intact. However, the temporal uncertainty of deviance occurrence may be of substantial relevance to the highly replicated MMN deficit in schizophrenia patients.

Background and aims Individuals with heroin addiction are prone to dysfunctional decision-making. They frequently choose the short-term rewarding option of drug intake despite experiencing long-term negative consequences. Opioid maintenance treatment (OMT) is the most common treatment of heroin addiction. Methods In this study, 38 individuals in an early stage of abstinence from heroin addiction (ESA-HA individuals) at the end of inpatient detoxification treatment and 41 individuals in long-term OMT were examined. Decision-making was assessed by (I) a modified version of the Iowa Gambling Task (IGT) with drug-related stimuli focusing on decision-making under ambiguity and (II) the Game of Dice Task (GDT) assessing decision-making under objective risk. Results OMT-individuals showed significantly better performance in the IGT than the ESA-HA-individuals. They also showed significantly less craving under exposure of drug-related pictures. In the GDT, OMT-individuals showed significantly less risky decision-making than ESA-HA-individuals. Conclusion The results suggest that patients receiving OMT show better functional decision-making and lower craving reactions. It could be assumed that the effectiveness of OMT in preventing relapse is linked to better decision-making and lower craving among these patients.

Background People who inject drugs (PWID) are the most important risk group for incident Hepatitis C virus (HCV) infection. In PWID in Europe HCV genotype 3a is highly prevalent. Unfortunately, many of the recently developed directly acting antiviral drugs against HCV (DAAs) are suboptimal for treatment of this genotype. Detection of resistance-associated variants (RAV) in genotype 3a may help to optimize treatment decisions, however, robust protocols for amplification and sequencing of HCV NS5A as an important target for treatment of genotype 3a are currently lacking. Objectives The aim of this study was to establish a protocol for sequencing of HCV NS5A in genotype 3a and to determine the frequency of RAVs in treatment-naive PWID living in Germany. Study design The full NS5A region was amplified and sequenced from 110 HCV genotype 3a infected PWID using an in-house PCR protocol. Results With the established protocol the complete NS5A region was successfully amplified and sequenced from 110 out of 112 (98.2%) genotype 3a infected PWID. Phylogenetic analysis of sequences from PWID together with unrelated genotype 3a sequences from a public database showed a scattered distribution without geographic clustering. Viral polymorphisms A30K and Y93H known to confer resistance in a GT3a replication model were present in 8 subjects (7.2%). Conclusions A protocol for amplification of nearly all GT3a samples was successfully established. Substitutions conferring resistance to NS5A inhibitors were detected in a few treatment-naive PWID.

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT.

Aims The aim of this randomized, controlled, multisite trial was to evaluate the efficacy of combined treatment with integrative behaviour therapy (IBT) and acamprosate on drinking behaviour in detoxified alcohol-dependent patients. Methods A total of 371 patients were randomized to one of the three treatment conditions: IBT plus acamprosate, IBT plus placebo, or supportive counselling (‘treatment as usual’, TAU) plus acamprosate. The main outcome was success rate, i.e., rate of abstinence plus improvement according to the criteria of Feuerlein and Kufner (1989) , at the end of the six-month treatment phase and at the subsequent six-month follow-up. Drinking status was validated by blood parameters (CDT, GGT, and MCV). Data were analyzed by an intent-to-treat model and missing data were classified as relapse. Results The success rates at the end of treatment under both TAU plus acamprosate (37.7%) and IBT plus placebo (48%) almost reached the levels derived from the literature. However, adding acamprosate to IBT did not result in the expected increase in success rate (IBT plus acamprosate: 47.6%), and success rates did not differ significantly between groups. Similarly, there was no significant difference between treatment success rates at follow-up. Conclusion The results suggest that the combination of acamprosate and IBT is not more effective than treatment with either IBT or acamprosate alone. However, the two acamprosate conditions differed in success rate by about 10%, which might constitute a clinically relevant though statistically non-significant effect.

The intensity of withdrawal in opiate dependence shows a high inter-individual variability. The 825CT polymorphism (rs5443) of the G-protein beta 3 (GNB3) subunit gene has a strong influence on clinical signs of sympathetic activity in cardiac research. This study was carried out in order to test the hypothesis that carriers of the T allele have an increased sympathetic activity in opiate withdrawal.Thirty-nine monovalent opiate addicted patients consecutively admitted to a detoxification ward were investigated. The main parameter for sympathetic activity was the pulse rate in the first 3 days after the regular end of gradual methadone reduction.Thirty-three out of 39 patients achieved a drug-free state: 22 carried a T allele (TT, CT), 11 belonged to the CC genotype group. The pulse rate was significantly (p0.05) raised in the T allele group compared to the CC genotype group on the first 2 days after stopping methadone administration. In addition, about a third of the T allele carriers needed clonidine treatment on the respective days, but only one patient among the 11 CC homozygotes. There was no significant difference between groups in systolic and diastolic blood pressures as well as in subjective withdrawal ratings.A group difference regarding pulse rate could be observed in a small sample and despite a higher degree of concomitant clonidine medication in T allele carriers. The failure to detect group differences in blood pressure and self-rated withdrawal symptoms may be attributed to the more complex regulation of blood pressure and the known weak correlation between objective and subjective withdrawal symptoms.

Purpose Only a few formal assessments of websites with drug-related contents have been carried out. We aimed here at fostering collection and analysis of data from web pages related to information on consumption, manufacture and sales of psychoactive substances. General methods An 8-language, two-engine, assessment of the information available in a purposeful sample of 1633 unique websites was carried out. Findings A pro-drug and a harm reduction approach were evident, respectively, in 18% and 10% of websites accessed. About 1 in 10 websites offered either psychoactive compounds for sale or detailed data on drugs' synthesis/extraction procedures. Information on a number of psychoactive substances and on unusual drugs' combinations not found in the Medline was elicited. Conclusions This represents the first review which is both comprehensive and multilingual of the online available information on psychoactive compounds. Health professionals may need to be aware of the web being a new drug resource for information and possibly purchase.

The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and substance use disorders has received considerable attention in recent clinical and scientific investigations. These two disorders are linked to one another in a variety of ways. The core symptoms of ADHD may be mimicked by the effects of psychoactive substance use, making it difficult to diagnose one disorder in the presence of the other. Individuals with ADHD may demonstrate earlier onset of the substance abuse and a pattern of more frequent or intense use. ADHD symptoms were explored as possible antecedents of opioid dependence. A total of 109 adult opioid-dependent, treatment-seeking male and female outpatients were investigated with an extended clinical semistructured interview to collect sociodemographic, drug-related, and clinical data. The results indicate that ADHD alone does not predispose the development of opioid dependence in our sample. Childhood ADHD symptoms may nevertheless be found more frequently related to school performance problems and difficulties in social adaptation, which was identified in more than half of our population. Patients with ADHD history seemed to experience a drug abuse career with more complications which need to be recognized with focused attention in order to start earlier treatment strategies.

Background To investigate whether users of a drug consumption facility (DCF) established as part of a health care centre for problem drug users fulfilled entry criteria, especially public drug consumption, risky drug-application and housing problems. We also investigated whether the drug consumption facility attracted hard-to-reach opiate users who usually do not use the health care system. Methods Structured interviews were carried out with 129 problem drug users beginning attendance at a drug consumption facility. Results Median length of the current episode of regular heroin use was 3 weeks. Sixty-seven per cent of clients had been in addiction specific treatment or had left prison during the previous 3 months. Regarding behaviour in the last month, 53% reported drug use in public, 53% use of non-sterile equipment or water, 22% needle sharing, 8% reported an emergency admission to hospital, and 43% were living in unstable accommodation. Only 10% of clients had never received treatment for their drug use and 87% were currently in contact with psychosocial services. Conclusions The majority of clients were chronic opiate users with high rates of risk behaviour. However, they did have recent contact with the drug treatment system. DCFs may be particularly important for opiate users after prison or treatment and/or for those with unstable accommodation.

Poster-Abstract