Search

Abstract Background Cannabinoids have been of increasing interest mainly due to their putative efficacy in a wide array of psychiatric, psychosomatic, and neurological conditions. Aims This systematic review aims to synthesize results from randomized placebo-controlled trials regarding the efficacy and the dosage of cannabinoids as therapeutics in psychiatric disorders in children, adolescents, and young adults. Methods All publications up to June 30th, 2024, were included from PubMed and Embase. Eligibility criteria in accordance with the PRISMA-guidelines was applied. RCTs providing pre- and post-treatment parameters on cannabinoid therapies for mental disorders in comparison to controls in an age range from 0 to 25 years were included. Effect sizes were calculated as Hedges’ g for primary outcomes, and a multilevel random-effects meta-analysis was conducted to account for dependent outcomes from same study populations. Results We identified 7603 records, of which 8 independent clinical trials (reported in 9 publications) met the pre-established eligibility criteria, comprising 474 unique participants (245 treatment, 229 control). Analysis of 13 primary outcomes (of 7 clinical trials) revealed a modest positive overall effect for symptom improvement or normalization of brain physiology (Hedges’ g = 0.308, 95% CI: 0.167, 0.448). Autism spectrum disorder studies showed the most consistent evidence (g = 0.264, 95% CI: 0.107, 0.421), while other conditions showed wider confidence intervals. Age-stratified analysis showed that adult populations (mean age 23.3 years, n = 5 outcomes) demonstrated higher effect sizes (g = 0.463, SD = 0.402) compared to pediatric populations (mean age 11.8 years, n = 8 outcomes; g = 0.318, SD = 0.212). Whole plant preparations (g = 0.328, 95% CI: 0.083, 0.573) and pharmaceutical cannabinoids (g = 0.292, 95% CI: 0.069, 0.515) showed comparable effects. CBD dosages ranged from 17.5 mg to 600 mg per day, with no significant correlation between dosage and effect size (ρ = -0.014, p = 0.963). Mild to moderate side effects were reported, but no serious adverse events. Risk of bias assessment ranged from low (n = 3) to high (n = 5). Conclusion While meta-analysis of effect sizes for primary outcomes revealed modest positive effects, particularly for autism spectrum disorders, the current evidence remains insufficient to broadly recommend cannabinoids for treating mental disorders in youth populations. Larger, controlled studies with standardized outcomes are needed to establish definitive clinical recommendations.

Abstract Background Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a significant treatment barrier. Case Presentation We report on two cases of hospitalized patients with severe, active opioid use disorder, in which we initiated treatment with transdermal buprenorphine over 48 h, followed by the administration of a single dose of sublingual buprenorphine/naloxone and then extended-release subcutaneous buprenorphine. The patients did not experience precipitated withdrawal and only had mild withdrawal symptoms. Conclusions This provides preliminary evidence for a rapid induction strategy that may improve tolerability, caregiver burden, and treatment retention as compared to previous induction strategies.

Abstract Understanding drug market dynamics and their underlying driving factors is paramount to developing effective responses to the overdose crisis in North America. This paper summarises the distinct drug market trends observed locally and internationally over the past decade to extrapolate future drug market trajectories. The emergence of fentanyl on North American street markets from 2014 onwards led to a shift of street drug use patterns. Previously perceived as contaminants, novel synthetic opioids became the drugs of choice and a trend towards higher potency was observed across various substance classes. The diversification of distribution strategies as well as the regionalisation and industrialisation of production followed basic economic principles that were heavily influenced by prosecution and policy makers. Particularly, the trend towards higher potency is likely most indicative of what to expect from future illicit drug market developments. Nitazenes and fentanyl-analogues, several times more potent than fentanyl itself, are increasingly detected in toxicological testing and have the potential of becoming the drugs of choice in the future. The dynamic of drug import and local production is less clear and influenced by a multitude of factors like precursor availability, know-how, infrastructure, and the success of local drug enforcement strategies. Drug market dynamics and the current trajectory towards ultrapotent opioids need to be recognised by legislation, enforcement, and the health care system to prepare effective responses. Without significant improvements in treatment access, the implementation of preventative approaches and early warning systems, the mortality rate will continue to increase. Furthermore, there is no mechanism in place preventing the currently North American focused overdose crisis to spread to other parts of the globe, particularly Europe. A system of oversight, research, and treatment is needed to address mortality rates of historic proportions and prevent further harm.

Abstract Background Use of benzodiazepines (BZD) in patients receiving opioid agonist treatment (OAT) is common and associated with a variety of negative health and social outcomes. This cross-sectional study investigates the impact of BZD use in OAT patients on their quality of life (QoL). Methods A convenience sample of patients receiving oral OAT or heroin-assisted treatment in two outpatient centres in Basel, Switzerland was investigated. Participants (n = 141) completed self-report questionnaires on psychiatric symptoms and psychological distress (The Symptom Checklist 27, SCL-27), depressive state (German version of the Center for Epidemiological Studies Depression Scale), quality of life (Lancashire Quality of Life Profile, LQOLP) and use of BZD and other drugs (self-report questionnaire). Substance use was assessed by urine toxicology testing. Results In bivariate analysis, total QoL scores were significantly lower for lifetime, current, and prolonged BZD users compared to participants without the respective use patterns. There was no significant relationship between BZD dose and QoL. In multivariable linear regression models controlling for psychiatric symptom load and depressive state, only lifetime use predicted lower QoL, whereas other BZD use patterns were not significantly associated. Conclusions The association of lower QoL and BZD use in OAT patients is strongly confounded by co-occurring depressive state and psychiatric symptoms. Careful diagnosis and treatment of co-occurring mental disorders in OAT is paramount to improve QoL in this patient population and may also help reduce BZD use.

Abstract Background Heroin-assisted treatment (HAT) is a proven effective treatment option for individuals with severe opioid use disorder (OUD). In Switzerland, pharmaceutical heroin (diacetylmorphine, DAM) is available in tablet form or as injectable liquid. This creates a large barrier for individuals who require the rapid onset of effect but are either unable or do not want to inject, or who primarily snort opioids. Early experimental data has demonstrated that intranasal DAM administration can be a viable alternative to the intravenous or intramuscular route of administration. The purpose of this study is to assess the feasibility, safety, and acceptability of intranasal HAT. Methods This study will assess intranasal DAM using a prospective multicentre observational cohort study design in HAT clinics across Switzerland. Patients will be offered to switch from oral or injectable DAM to intranasal DAM. Participants will be followed-up over 3 years, with assessments at baseline, and after 4, 52, 104 and 156 weeks. The primary outcome measure (POM) is retention in treatment. Secondary outcomes (SOM) include prescriptions and routes of administration of other opioid agonists, illicit substance use, risk behaviour, delinquency, health and social functioning, treatment adherence, opioid craving, satisfaction, subjective effects, quality of life, physical health, and mental health. Conclusions The results derived from this study will generate the first major body of clinical evidence on the safety, acceptability, and feasibility of intranasal HAT. If proven to be safe, feasible and acceptable, this study would increase the accessibility of intranasal OAT for individuals with OUD globally as a critical improvement in risk reduction.

Abstract 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.

Abstract Background Traditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset (“rush”) but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts. Case presentation A 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff. Conclusions Nasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.

Abstract Background Heroin-assisted treatment has proven effective in reducing criminal offenses in opioid dependent individuals. Few studies attempted to explain the observed crime reduction and the reasons why these patients keep offending and getting incarcerated have to date not been explored. Methods Patients with a history of incarcerations during the time of participating in heroin-assisted treatment (n = 22) were invited to a semi-structured, narrative interview. Findings were evaluated with Mayring’s qualitative content analysis framework. Additionally, the Montreal Cognitive Assessment test and the multiple-choice vocabulary intelligence test used to assess cognitive impairment and premorbid intelligence levels. Results Three main categories emerged in patients’ narratives on their incarcerations: cocaine use, impaired functioning, and financial constraints. Lifetime prevalence of cocaine use disorder was 95.5% and their cocaine use often led to patients getting incarcerated. Impaired functioning mainly constituted the inability to receive and open mail. Financial constraints led to incarcerations in lieu of payment in 16 participants (72.7%). Categories overlapped notably and often occurred in close temporal proximity. A fourth category on the likelihood of getting incarcerated again in the future was inhomogeneous and ranged from the strong conviction to complete rejection of the scenario. Average premorbid intelligence levels were found, whereas the cognitive assessment suggested severe cognitive impairment in our sample. Conclusion Participants mainly reported to have committed minor offenses and not being able to pay for resulting fines. The resulting prison sentences are an unconvincing practice from a medical and economic perspective alike. Public expenditure and the interruptions of the continuum of care could be reduced by legislatively protecting these marginalised patients.

Abstract Background Intramuscular (IM) injection of drugs is associated with high rates of injecting-related injuries and diseases. However, little is known about the role of this route of administration in heroin-assisted treatment. The aim of this study was to determine the prevalence of IM diacetylmorphine administration and associated complications as well as to explore patients’ views and opinions on the topic and the underlying reasons for this practice. Methods The research site was a Swiss outpatient treatment centre specialised in heroin-assisted treatment. We conducted in-depth interviews with two patients who intramuscularly inject diacetylmorphine. Interviews were analysed qualitatively, and emerging themes were used to develop a 38-item questionnaire on IM injections. We then offered this questionnaire to all patients in the treatment centre. Results Five main themes emerged from the in-depth interviews: poor venous access, side effects, subjective effects, procedure for IM injection, and consideration of alternatives to IM. These themes covered the rationale for using this route of administration, complications, subjective effects of IM diacetylmorphine, hygiene and safety measures as well as alternative routes of administration. Fifty-three patients filled in the questionnaire. The lifetime prevalence of IM injections was 60.4% (n = 32) and 34.4% (n = 11) of the patients stated that IM injection was their primary route of administration. No participant reported using the IM route for street drugs. The main reason for IM injections was poor vein access. Other reasons given were time saving and less risk of injuries. Complications included induration of muscle tissue and pain, whereas more severe complications like thrombosis and infections of the injection site were reported much less often. Conclusion As the population of opioid-dependent individuals is aging and the deterioration of access veins is likely to increase, the frequency of IM injecting will equally increase. Even though our data show that the IM injection of diacetylmorphine in a clinical setting is a common practice and appears to be relatively safe, research on alternative routes of administration is needed to provide potentially less harmful alternative routes of administration in heroin-assisted treatment.