First German-speaking harm reduction conference in Vienna.

The first Harm Reduction DACH Conference [DACH = D (Germany), A (Austria), CH (Switzerland)] took place in Vienna on June 23rd, 2023, and focused on tobacco harm reduction. It is the first conference bringing together various experts of all three German-speaking countries to shed light on the subject of destigmatization and tobacco harm reduction and to share their experiences with the audience. All in all, the first German-speaking harm reduction conference has the goal to discuss and expand harm reduction in the German-speaking countries. This meeting report gives a brief overview of the conference.

Safety and feasibility of intranasal heroin-assisted treatment: 4-week preliminary findings from a Swiss multicentre observational study.

BACKGROUND: Heroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM. METHODS: This is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated. RESULTS: Participants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported. CONCLUSIONS: After four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM.

The suitability of oral diacetylmorphine in treatment-refractory patients with heroin dependence: A scoping review.

OBJECTIVE: To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. METHODS: The PubMed, Embase, Web of Science and PsycINFO databases were searched. Eleven published studies were identified and selected based on defined eligibility and exclusion criteria. RESULTS: Four pharmacokinetic studies reported negligible plasma concentrations of diacetylmorphine and its active metabolite 6-monacetylmorphine. Among six pharmacodynamic studies, three trials showed that oral diacetylmorphine reduced opioid withdrawal symptoms, one open-label pilot study reported that two patients experienced a modest 'rush' after oral diacetylmorphine and two studies found that patients could not distinguish between oral diacetylmorphine, methadone, or morphine. Regarding the clinical studies, a Swiss prospective cohort study in patients with heroin dependence showed high retention rates of oral diacetylmorphine treatment with few serious adverse events, whereas in the Canadian SALOME trial, oral diacetylmorphine treatment was prematurely discontinued because treatment retention of oral diacetylmorphine was lower than injectable diacetylmorphine maintenance treatment. Finally, two case studies illustrate the limitations and potential problems of oral diacetylmorphine in the treatment of treatment-refractory heroin dependent patients. CONCLUSIONS: Based on all published data, it is unlikely that oral diacetylmorphine produces a substantial 'rush'. Prescription of oral diacetylmorphine might therefore be effective only for treatment-refractory patients with heroin dependence (i) as maintenance treatment for those who never injected or inhaled opioids; (ii) as maintenance treatment for those who want to switch from injection to oral administration of diacetylmorphine; and/or (iii) to reduce opioid withdrawal symptoms.

One size does not fit all-evolution of opioid agonist treatments in a naturalistic setting over 23 years.

BACKGROUND AND AIMS: Opioid agonist treatment (OAT) is currently the most effective treatment for people with opioid dependence. In most countries, however, access to the whole range of effective medications is restricted. This study aims to model the distribution of different OAT medications within a naturalistic and relatively unrestricted treatment setting (Zurich, Switzerland) over time, and to identify patient characteristics associated with each medication. METHODS: We used generalized estimating equation analysis with data from the OAT register of Zurich and the Swiss register for heroin-assisted treatment (HAT) to model and forecast the annual proportion of opioids applying exponential distributions until 2018 and patient characteristics between 1992 and 2015. RESULTS: Data from 11 895 patients were included in the analysis. Methadone remains the mainstay of OAT, being prescribed to two-thirds of patients. Following its approval, the proportion of HAT increased rapidly and is now constant at 12.16% [95% confidence interval (CI) = 11.15-13.17]. The initial increase of proportions of buprenorphine or slow-release oral morphine (SROM) following their approval for OAT was slower. While in 2014 both medications had a proportion of 10.2% and 10.3%, respectively, our model predicts a further increase of SROM to 19.9% in 2018, with a ceiling level of 25.19% (21.40-28.98%) thereafter. SROM patients display characteristics similar to those treated with methadone; buprenorphine patients show the highest social integration; and HAT patients are the most homogeneous group, with highest mean age, most widespread injecting experience and lowest social integration. CONCLUSIONS: Based on data from Zurich, Switzerland from 1992 to 2015, there is no evidence for an excessive demand for a single medication in a naturalistic and liberal opioid agonist treatment setting. Rather, the specific patient characteristics associated with each medication underline the need for diversified treatment options for opioid dependence.

A Web-Based Self-Help Intervention With and Without Chat Counseling to Reduce Cannabis Use in Problematic Cannabis Users: Three-Arm Randomized Controlled Trial.

BACKGROUND: After alcohol and tobacco, cannabis is the most widely used psychoactive substance in many countries worldwide. Although approximately one in ten users develops serious problems of dependency, only a minority attend outpatient addiction counseling centers. A Web-based intervention could potentially reach those users who hesitate to approach such treatment centers. OBJECTIVE: To test the efficacy of a Web-based self-help intervention with and without chat counseling-Can Reduce-in reducing the cannabis use of problematic cannabis users as an alternative to outpatient treatment services. METHODS: Altogether, 436 participants were recruited by various online and offline media for the Web-based trial. A total of 308 of these were eligible for study participation and were randomly allocated in an unblinded manner to either self-help with chat (n=114), self-help without chat (n=101), or a waiting list control group (n=93). The fully automated self-help intervention consisted of eight modules designed to reduce cannabis use, and was based on the principles of motivational interviewing, self-control practices, and methods of cognitive behavioral therapy. Additional individual chat counseling sessions were based on the same therapeutic principles. The sessions were conducted by trained counselors and addressed participants' personal problems. The main outcomes were the frequency (number of days) and quantity of cannabis use (number of standardized joints) per week, as entered into the consumption diary at baseline and at the 3-month follow-up. Secondary outcomes included self-reported symptoms of cannabis use disorder, severity of cannabis dependence, risky alcohol use, and mental health symptoms. Intervention participation and retention were extracted from the user progress data and the consumption diary, respectively. RESULTS: Can Reduce participants were older (U=2.296, P=.02) and reported a greater number of cannabis use days at baseline than patients who entered outpatient treatment with cannabis as their main problem substance (data from the Swiss treatment demand monitoring statistics were used; chi-square [df 2]=4.0, P=.046). Participants in the self-help with chat study arm completed a mean of 3.2 modules and 27 out of 114 (23.7%) of the participants received at least one chat session. Participants in the self-help without chat study arm completed similar numbers of self-help modules. A total of 117 of 308 participants (38.0%) completed the 3-month follow-up assessment. The change in the mean number of cannabis use days per week at 3 months differed between self-help without chat (mean change 0.7, SD -0.2) and self-help with chat (mean change 1.4, SD -0.5; beta=-0.75, SE=0.32, t=-2.39, P=.02, d=0.34, 95% CI 0.07-0.61), as well as between self-help with chat and waiting list (mean change 1.0, SD -0.8; beta=0.70, SE=0.32, t=2.16, P=.03, d=0.20, 95% CI -0.07 to 0.47). However, there were no differences between self-help without chat and waiting list (beta=-0.05, SE=0.33, t=-0.16, P=.87, d=-0.14, 95% CI -0.43 to 0.14). Self-reported abstinence was significantly different in the self-help without chat study arm (2.0%) than in the self-help with chat study arm (8.8%; beta=-1.56, SE=0.79, P=.05, odds ratio [OR]=0.21, 95% CI 0.02-2.33). There were no significant differences between the study arms with respect to the secondary outcomes. CONCLUSIONS: Web-based self-help interventions supplemented by brief chat counseling are an effective alternative to face-to-face treatment and can reach a group of cannabis users who differ in their use and sociodemographic characteristics from those who enter outpatient addiction treatment. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 59948178; http://www.isrctn.com/ISRCTN59948178 (Archived by WebCite at http://www.webcitation.org/6bt01gfIr).

Evaluating the efficacy of a web-based self-help intervention with and without chat counseling in reducing the cocaine use of problematic cocaine users: the study protocol of a pragmatic three-arm randomized controlled trial.

BACKGROUND: Web-based self-help interventions that aim to reduce problematic substance use are able to reach "hidden" consumer groups in the general population who often fear stigmatization and thus avoid institutional addiction treatment. In Western European countries, including Switzerland, cocaine is the most widely used psychoactive substance after alcohol, tobacco, and cannabis. Although approximately one in six users develop serious problems of dependency, only a minority seeks help from psychiatrists or in outpatient counseling centers or psychiatric hospitals. Offering web-based therapy treatment may potentially reach users who hesitate to approach institutional treatment services and help them reduce their cocaine use before they get into more serious trouble. METHODS/DESIGN: The study will use a three-arm randomized controlled trial (RCT) design to test the efficacy of a web-based self-help intervention with or without guided chat counseling compared with that of a waiting list control condition in reducing or stopping cocaine use. The primary outcome measure will be the weekly quantity of cocaine used. Secondary outcome measures will include the number of cocaine use days in the past 30 days, the severity of cocaine dependence, the use of alcohol, tobacco, and/or other illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of eight modules that are designed to reduce cocaine use and depression symptoms. These modules are based on the principles of Motivational Enhancement Therapy and Cognitive Behavioral Therapy, such as Behavioral Self-Management. The three individual chat therapy sessions will be based on the same therapy approaches and will be tailored to participants' self-help data and aim to assist the reinstatement of social rewards and the improvement of social support and relationships. DISCUSSION: This study will be the first RCT to test the effectiveness of a web-based self-help intervention in combination with or without chat counseling in reducing cocaine use. The expected findings will contribute substantial knowledge that may help design effective guided and unguided web-based treatment for cocaine users. Moreover, the study will elucidate to what extent a therapeutic alliance with cocaine users can be established in a guided Internet-delivered setting. Additionally, the present study will investigate changes in social support with specific guided therapy interventions that aim to ameliorate social support and social perceptions and compare these changes with those in an unguided self-help intervention TRIAL REGISTRATION: Current Controlled Trials ISRCTN12205466 . Registered 24 February 2015.

Self-reported cravings for heroin and cocaine during maintenance treatment with slow-release oral morphine compared with methadone: a randomized, crossover clinical trial.

OBJECTIVE: Craving, an urge or increased desire to take a drug, is part of a cluster of behavioral, cognitive, and physiological phenomena that can develop after substance use. Self-reported cravings for heroin and cocaine are compared in opioid dependent patients while receiving maintenance treatment with slow-release oral morphine (SROM) or methadone. METHODS: Data from a 22-week open-label, randomized, crossover trial (per protocol sample n = 157) were examined by analysis of variance (ANOVA). Cravings for heroin and cocaine during the past 7 days were assessed at baseline and thrice during each 11-week treatment period using a Visual Analog Scale (heroin, VAS-H; cocaine, VAS-C), German versions of the brief Heroin Craving Questionnaire (HCQ), and the brief Cocaine Craving Questionnaire (CCQ). RESULTS: Mean (SD) heroin craving scores under methadone were 3.3 (2.4) (VAS-H) and 2.9 (1.4) (HCQ). Heroin craving scores under SROM were significantly lower, at 2.5 (2.2) (VAS-H) and 2.6 (1.2) (HCQ) (ANOVA: VAS-H P < 0.0001, HCQ P = 0.010). Cocaine craving scores were not significantly different (methadone: 1.6 (2.0) (VAS-C) and 2.1 (1.2) (CCQ) vs SROM: 1.4 (1.9) (VAS-C) and 2.1 (1.2) (CCQ); ANOVA: VAS-C P = 0.175, CCQ P = 0.536). No significant carry-over effects were detected. CONCLUSIONS: This study demonstrates that SROM is clinically more effective than methadone in reducing general craving for heroin during opioid maintenance treatment while not affecting cocaine craving.

Mental symptoms and drug use in maintenance treatment with slow-release oral morphine compared to methadone: results of a randomized crossover study.

BACKGROUND: Opioid maintenance treatment is the option of choice to stabilize opioid-dependent patients. Whilst efficacy of methadone and buprenorphine has been studied extensively, fewer data on slow-release oral morphine are available. AIMS: This study analyzes the effects of slow-release oral morphine compared to methadone with regard to self-reported mental symptoms, drug use and satisfaction with treatment. METHODS: The study was carried out as an open-label randomized crossover trial in 14 treatment sites in Switzerland and Germany. It comprised 2 crossover periods of 11 weeks each. For measuring mental symptoms, the Symptom Checklist-27 (SCL-27) was used. Drug and alcohol use was assessed by the number of consumption days, and treatment satisfaction by a visual analogue scale. RESULTS: A total of 157 patients were included for the analyses (per-protocol sample). Statistically significantly better outcomes for morphine as compared to methadone treatment were found for overall severity of mental symptoms (SCL-27 Global Severity Index), as well as 5 of the 6 syndrome groups of the SCL-27, and for treatment satisfaction. There were no statistically significant differences with regard to drug or alcohol use between groups. CONCLUSIONS: This study supports positive effects of slow-release oral morphine compared to methadone on patient-reported outcomes such as mental symptoms and treatment satisfaction with comparable effects on concomitant drug use. Slow-release oral morphine represents a meaningful alternative to methadone for treatment of opioid dependence.

Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone.

AIMS: To compare the efficacy of slow-release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone. DESIGN: Prospective, multiple-dose, open label, randomized, non-inferiority, cross-over study over two 11-week periods. Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment. SETTING: Fourteen out-patient addiction treatment centres in Switzerland and Germany. PARTICIPANTS: Adults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks. MEASUREMENTS: The efficacy end-point was the proportion of heroin-positive urine samples per patient and period of treatment. Each week, two urine samples were collected, randomly selected and analysed for 6-monoacetyl-morphine and 6-acetylcodeine. Non-inferiority was concluded if the two-sided 95% confidence interval (CI) in the difference of proportions of positive urine samples was below the predefined boundary of 10%. FINDINGS: One hundred and fifty-seven patients fulfilled criteria to form the per protocol population. The proportion of heroin-positive urine samples under SROM treatment (0.20) was non-inferior to the proportion under methadone treatment (0.15) (least-squares mean difference 0.05; 95% CI = 0.02, 0.08; P > 0.01). The 95% CI fell within the 10% non-inferiority margin, confirming the non-inferiority of SROM to methadone. A dose-dependent effect was shown for SROM (i.e. decreasing proportions of heroin-positive urine samples with increasing SROM doses). Retention in treatment showed no significant differences between treatments (period 1/period 2: SROM: 88.7%/82.1%, methadone: 91.1%/88.0%; period 1: P = 0.50, period 2: P = 0.19). Overall, safety outcomes were similar between the two groups. CONCLUSIONS: Slow-release oral morphine appears to be at least as effective as methadone in treating people with opioid use disorder.

Can reduce--the effects of chat-counseling and web-based self-help, web-based self-help alone and a waiting list control program on cannabis use in problematic cannabis users: a randomized controlled trial.

BACKGROUND: In European countries, including Switzerland, as well as in many states worldwide, cannabis is the most widely used psychoactive substance after alcohol and tobacco. Although approximately one in ten users develop serious problems of dependency, only a minority attends outpatient addiction counseling centers. The offer of a combined web-based self-help and chat counseling treatment could potentially also reach those users who hesitate to approach such treatment centers and help them to reduce their cannabis use. METHODS/DESIGN: This paper presents the protocol for a three-armed randomized controlled trial that will test the effectiveness of a web-based self-help intervention in combination with, or independent of, tailored chat counseling compared to a waiting list in reducing or enabling the abstention from cannabis use in problematic users. The primary outcome will be the weekly quantity of cannabis used. Secondary outcome measures will include the number of days per week on which cannabis is used, the severity of cannabis use disorder, the severity of cannabis dependence, cannabis withdrawal symptoms, cannabis craving, the use of alcohol, tobacco, and other non-cannabis illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of 8 modules designed to reduce cannabis use based on the principles of motivational interviewing, self-control practices, and methods of cognitive behavioral therapy. The two additional individual chat-counseling sessions in the additional chat condition will be based on the same therapy approaches and tailored to participants' self-help information data and personal problems. The predictive validity of participants' baseline characteristics on treatment retention and outcomes will be explored. DISCUSSION: To the best of our knowledge, this will be the first randomized controlled trial to test the effectiveness of online self-help therapy in combination or without chat counseling in reducing or enabling the abstention from cannabis use. It will also investigate predictors of outcome and retention for these interventions. This trial is registered at Current Controlled Trials and is traceable as ISRCTN59948178.

Sensorimotor gating and attentional set-shifting are improved by the mu-opioid receptor agonist morphine in healthy human volunteers.

Prepulse inhibition (PPI) of the acoustic startle response (ASR) has been established as an operational measure of sensorimotor gating. Animal and human studies have shown that PPI can be modulated by dopaminergic, serotonergic, and glutamatergic drugs and consequently it was proposed that impaired sensorimotor gating in schizophrenia parallels a central abnormality within the corresponding neurotransmitter systems. Recent animal studies suggest that the opioid system may also play a role in the modulation of sensorimotor gating. Thus, the present study investigated the influence of the mu-opioid receptor agonist morphine on PPI in healthy human volunteers. Eighteen male, non-smoking healthy volunteers each received placebo or 10 mg morphine sulphate (p.o.) at a 2-wk interval in a double-blind, randomized, and counterbalanced order. PPI was measured 75 min after drug/placebo intake. The effects of morphine on mood were measured by the Adjective Mood Rating Scale and side-effects were assessed by the List of Complaints. Additionally, we administered a comprehensive neuropsychological test battery consisting of tests of the Cambridge Neuropsychological Test Automated Battery and the Rey Auditory Verbal Learning Test. Morphine significantly increased PPI without affecting startle reactivity or habituation. Furthermore, morphine selectively improved the error rate in an attentional set-shifting task but did not influence vigilance, memory, or executive functions. These results imply that the opioid system is involved in the modulation of PPI and attentional set-shifting in humans and they raise the question whether the opioid system plays a crucial role also in the regulation of PPI and attentional set-shifting in schizophrenia.

Patterns of heroin, cocaine, and alcohol abuse during long-term methadone maintenance treatment.

Individuals' use of heroin, cocaine, and alcohol during long-term methadone maintenance treatment (MMT) was studied. Prospectively collected data from 103 heroin-addicted individuals who were consecutively admitted for MMT and remained 2 years in treatment were evaluated. The patients were assessed every 6 months with a standardized interview. Three longitudinal patterns of drug abuse were identified. A proportion of patients abstained fully from their particular drug use (26% from heroin, 39% from cocaine, and 19% from alcohol); a proportion (39%, 32%, and 47%, respectively) switched between periods of abuse and nonuse of these drugs; and chronic drug users (34%, 28%, and 33%, respectively) continued use, including periods of daily abuse throughout MMT. Different therapeutic interventions may be needed in patients with different longitudinal patterns of additional substance use during MMT.