Background: Psychedelics such as lysergic acid diethylamide (LSD) and psilocybin have shown a beneficial effect on substance use disorder (SUD) symptoms. In this systematic review, we aimed to assess the efficacy and safety of psychoactive tryptamines in patients with an SUD or non-substance-related disorder (i.e., gambling disorder) in order to provide a comprehensive overview of the available evidence and identify potential research gaps.Methods: A systematic literature search was performed in eight different databases up to February 2024. Clinical trials were included that assessed the efficacy and safety of psychoactive tryptamines other than psilocybin and ibogaine. A quality assessment of the included trials was done based on the revised Cochrane risk-of-bias tools.Results: A total of four clinical trials (three randomized controlled trials and one single-arm clinical trial; n = 176 patients) were included, all in patients with alcohol use disorder. Dipropyltryptamine and diethyltryptamine were the two investigated psychoactive tryptamines. Abstinence ranged from 10% (duration of follow-up unknown) to 38% at 26 weeks of follow-up, and severity of alcohol use did not differ between the psychoactive tryptamine group and the control groups. Adverse effects were not well reported in the trials.Conclusion: Studies assessing the efficacy of psychoactive tryptamines other than psilocybin and ibogaine in addiction are scarce and show limited evidence for effectiveness in the treatment of addictive disorders.

BACKGROUND:Quetiapine, an antipsychotic, is registered for schizophrenia, bipolar disorder, and as an add-on therapy for major depressive disorder. Its anxiolytic and sedative effects make it attractive for off-label uses like insomnia, despite cardiovascular and metabolic side effects. The global increase in quetiapine use over the past decade warrants an examination of its prescribing patterns, especially off-label. AIM:This study investigated quetiapine prescribing trends in Dutch primary care, with a focus on off-label use. DESIGN & SETTING:A retrospective database study using national and regional prescribing data from the Netherlands. METHOD:National prescribing trends from 2003-2022 were analysed using data from the Drug Information Project database, focusing on the top 10 antipsychotics. Regional data from the Radboud University Medical Centre (UMC) Technology Centre Health Database provided detailed quetiapine prescribing patterns from 2012-2021, categorised by daily dose. Indications for quetiapine prescriptions from 2020-2022 were derived from the detailed Radboud UMC Technology Centre patient records, including free-text portions, with specific attention for use in sleep problems. RESULTS:Antipsychotic use increased from 1510 to 2061 per 100 000 population from 2003-2022, largely due to a 13-fold increase in quetiapine (66 to 870 per 100 000 population). Detailed regional data revealed a 3.3-fold increase in quetiapine use from 2012-2021, particularly at doses <100 mg/day. Among new quetiapine users in 2020-2022 from a subset of practices, 76.6% were for off-label indications, and sleep problems were the primary reason for starting quetiapine in 46.9% of cases. CONCLUSION:Off-label quetiapine prescribing, particulary for sleep problems, is rising in the Netherlands, despite guideline warnings. Further research on the drivers and long-term effects of this practice is needed.

OBJECTIVES:Opioids are commonly prescribed in the Emergency Department (ED) for acute pain management. However, their use carries significant risks, including dependence and misuse. This study aims to gain insight into the perspectives of ED physicians and physician assistants (PAs) concerning the multifaceted role of the ED in problematic opioid use. This is crucial for reducing opioid-related harms. DESIGN:A qualitative study, using semi-structured interviews. SETTING AND PARTICIPANTS:Interviews were conducted with twenty-five ED physicians and PAs from four hospitals in the Netherlands. A diverse group participated in the study, representing different hospital settings and levels of working experience. OUTCOME MEASURES AND ANALYSIS:Reflexive thematic analysis was performed to develop key themes reflecting participants' perspectives and attitudes towards the role of the ED in opioid related harms. RESULTS:Two key themes were developed from the analysis. The first theme 'Preventing opioid-related harms from an ED perspective' underscores the careful approach emergency physicians take when prescribing opioids. This involves restricting opioid prescriptions to specific indications, considering alternative pain management options, limiting prescription durations, and involving patients in shared decision-making. Beyond their own prescribing practices, emergency care providers also collaborate with general practitioners, navigate patient expectations, and operate within a broader societal landscape where pain is increasingly viewed as intolerable. The second theme 'Managing problematic opioid use at the ED' highlights the difficulties faced by emergency care providers in treating individuals who are already using or dependent on opioids. This includes recognizing, intervening, referring, and managing cases of problematic opioid use. This theme also considers the involvement of other healthcare professionals, such as pain specialists and psychiatrists, as well as the roles and responsibilities of patients. Additionally, it considers the broader societal context, particularly the extent of opioid-related harms in the Netherlands. CONCLUSIONS:This study sheds light on the complexities surrounding opioid use and emergency care providers' approach to mitigating opioid related harms while navigating patient needs and systemic challenges. EDs play a critical role in addressing opioid-related harms but face significant challenges. Strengthening provider education, integrating patient records, and enhancing partnerships with addiction services are key steps toward refining healthcare responses and policies for this ongoing public health crisis.

Introduction The Dutch National Pharmacotherapy Assessment (DNPA) was introduced in 2013 to improve clinical pharmacology and therapeutics (CPT) education. This study investigated final-year medical students’ perceived motivation and level of preparation for the DNPA in different scenarios: mandatory vs. non-mandatory, and traditional high-stakes assessment programme vs. programmatic assessment programme. Methods In this survey study, students from four Dutch medical schools participated. In two medical schools the DNPA is a mandatory assessment in a programmatic assessment programme, and in two schools it is a mandatory, high-stakes assessment in a traditional assessment programme. The questionnaire included six 5-point Likert-type questions, and one open-ended question. Results A total of 142 final-year medical students completed the survey. Their overall satisfaction with and current preparation for the DNPA was good (both median scores were 4 out of 5), without differences between students with a traditional or programmatic assessment programme. The majority of the students said they would be more (or much more) motivated (62.7%) and prepared (59.2%) if the DNPA were a high-stakes assessment rather than a programmatic assessment; the non-mandatory or mandatory nature of the assessment would only modestly affect their motivation and preparation (62.7% of the students would be less or similar motivated, 74.6% less or similar prepared). Students opined that the DNPA should be given earlier in the curriculum, together with more dedicated CPT education. Conclusion While students expressed a greater motivation and preparation when having a high-stakes assessment, and almost a similar motivation and preparation for mandatory and non-mandatory assessments, there were no notable differences in their current perceived motivation and preparation across medical schools with different assessment programmes. This suggests that students appreciate the importance of the DNPA assessment, being almost similarly motivated to prepare for the assessment regardless of whether it is mandatory or non-mandatory or a programmatic or high-stakes assessment.

Polypharmacy is increasingly recognized as a relevant issue in diabetes care, but its prevalence and clinical relevance in individuals with type 1 diabetes remain underexplored. This study aimed to determine the prevalence of polypharmacy and to identify associated clinical and psychological factors. Participants were recruited from a tertiary diabetes outpatient clinic between February 2020 and April 2021. Polypharmacy was defined as the concurrent use of five or more medications, including insulin. Clinical, sensor‐based, and psychosocial data were collected. Logistic regression was used to identify variables independently associated with polypharmacy. A total of 484 individuals with type 1 diabetes were included (mean age 51.3 ± 15.9 years; 51.2% male; median diabetes duration 30 [IQR 16–40] years; mean HbA 1c 60.3 ± 11.6 mmol/mol). Polypharmacy was present in 175 (36.2%) participants. Individuals with polypharmacy were more often female, were older, and had longer diabetes duration, higher BMI, higher HbA 1c , more complications, and higher rates of hospital admission. They also were more likely to have impaired awareness of hypoglycemia and reported higher levels of fear of hypoglycemia with no differences in hyperglycemia‐related worry or behavior or diabetes‐related emotional distress. Polypharmacy affects over one‐third of individuals with type 1 diabetes and is associated with poorer health status and a greater hypoglycemia‐related burden. Future studies should investigate whether targeted medication review and psychological interventions may alleviate some of the burden in this high‐risk group.

BACKGROUND:The Dutch National Pharmacotherapy Assessment (DNPA), which focuses on assessing medication safety and essential drug knowledge, was introduced to improve clinical pharmacology and therapeutics education in the Netherlands. This study investigated how the performance of final-year medical students on the DPNA was affected by the assessment programme (traditional with summative or formative assessment, and programmatic assessment). METHODS:This multicentre retrospective longitudinal observation study (2019-2023) involved final-year medical students from four medical schools in the Netherlands. The DNPA was used in different ways - either as a summative or formative assessment in a traditional assessment programme or as a non-high-stakes assessment in a programmatic assessment programme. Three medical schools changed from assessment programme over time. RESULTS:This study involved 1894 students. Summative assessment resulted in significantly higher scores and pass rates than formative assessment in a traditional assessment programme (mean score of 84.3% vs. 67.5%, and pass rate of 60.4% vs. 5.9%). In contrast, slightly lower scores were obtained when the assessment was non-high-stakes as part of a programmatic assessment programme rather than a summative assessment in a traditional assessment programme (mean score of 81.% vs. 84.3%, pass rate of 51.8% vs. 60.4%). In curricula where the assessment became summative instead of formative, scores and pass rates significantly improved (mean increase of +14.4% and 42.3%, respectively), when the assessment programme changed from traditional with summative assessment to programmatic with non-high-stakes assessment, scores and pass rates modestly decreased (decrease of 3.3% and 14.2%, respectively). CONCLUSION:Integrating the DNPA within a traditional assessment programme is most effective when assessed summatively, as it results in significantly higher scores compared to formative assessment. In the context of a programmatic assessment programme, the scores may be slightly lower. Changing assessment programmes within a medical school influences DNPA scores. Scores increase when the assessment is summative rather than formative within a traditional assessment programme. Conversely, scores mildly decrease when the assessment programme shifts from traditional with summative assessment to non-high-stakes programmatic assessment.

BACKGROUND:Quetiapine, an antipsychotic, is registered for schizophrenia, bipolar disorder, and as an add-on therapy for major depressive disorder. Its anxiolytic and sedative effects make it attractive for off-label uses like insomnia, despite cardiovascular and metabolic side effects. The global increase in quetiapine use over the past decade warrants an examination of its prescribing patterns, especially off-label. AIM:This study investigates quetiapine prescribing trends in Dutch primary care, with a focus on off-label use. DESIGN & SETTING:A retrospective database study using national and regional prescribing data from the Netherlands. METHOD:National prescribing trends from 2003-2022 were analysed using data from the Drug Information Project database, focusing on the top 10 antipsychotics. Regional data from the Radboudumc Technology Centre Health Database provided detailed quetiapine prescribing patterns from 2012-2021, categorized by daily dose. Indications for quetiapine prescriptions between 2020-2022 were derived from the detailed RTC patient records, including free-text portions, with specific attention for use in sleep problems. RESULTS:Antipsychotic use increased from 1510 to 2061 per 100 000 between 2003-2022, largely due to a 13-fold increase in quetiapine (66 to 870 per 100000). Detailed regional data revealed a 3.3-fold increase in quetiapine use from 2012-2021, particularly at doses<100 mg/day. Among new quetiapine users in 2020-2022 from a subset of practices, 76.6% were for off-label indications, and sleep problems were the primary reason for starting quetiapine in 46.9% of cases. CONCLUSION:Off-label quetiapine prescribing, particulary for sleep problems, is rising in the Netherlands, despite guideline warnings. Further research on the drivers and long-term effects of this practice is needed.

To harmonize and modernize clinical pharmacology and therapeutics (CPT) education across Europe, we developed the European Prescribing Exam. Before its introduction into medical degree programs, it is crucial to understand the potential barriers to its implementation and ways to overcome them. Therefore, the aim of this study was to identify barriers and potential solutions to the implementation of the European Prescribing Exam. This qualitative World Café (WC) study involved CPT teachers who participated in a 2-day event focused on the European Prescribing Exam. There were five tables in the WC, each dedicated to a different topic of implementation: (1) organization, (2) technical aspects, (3) content, (4) rollout logistics, and (5) politics. Participants rotated randomly between the tables every 20 min. During each round, they were encouraged to identify barriers and solutions, which were then discussed. The rounds continued until data saturation was reached. Findings were summarized at the end of the WC. We used inductive thematic analysis using a semantic approach to analyze the data. In total, 26 CPT teachers (female: n = 14) from 19 medical schools in 15 European countries participated. After four rounds, 86 potential barriers and 86 solutions were identified. Most barriers were related to the topics “Content” (n = 22), “Organization” (n = 20), and “Technical aspects” (n = 18). Thematic analysis identified 11 themes, three of which were overarching, meaning they applied to multiple topics. The most significant themes included barriers related to curricula, motivation, information technology, and relevance. This study shows that organizing and implementing the European Prescribing Exam will be challenging. However, participants proposed potential solutions for nearly all barriers, which suggest that the implementation of the European Prescribing Exam is feasible.

Polypharmacy is associated with negative health outcomes including drug-related hospital admissions, particularly in older patients. Approximately half of drug-related (re)admissions are potentially preventable, and are therefore a target for healthcare interventions. Several studies have investigated the effects of in-hospital medication reviews on clinically relevant outcome measures, such as drug-related readmissions (DRAs). The identified factors for success of the intervention were multicomponent interventions, multidisciplinary approaches, attention to transitional care and the selection of high-risk patients. In the present study, the impact of transitional multidisciplinary pharmacotherapeutic care (TMPC) on DRAs in a high-risk population is assessed. Less Is More: Optimized pharmacotherapy with improved coNtinuity of CarE in hospitaLized oLder peOple (LIMONCELLO) is a cluster randomized controlled trial. A cluster is defined at the hospital level, and each cluster is randomly allocated (1:1) to the intervention or control group stratified by university or general hospitals. Patients aged 70 years and older with polypharmacy, a current non-elective hospital admission, completed medication reconciliation, and an increased risk of a DRA, as determined by the use of a DRA prediction model, are selected. TMPC consists of four elements: a pharmacotherapeutic analysis, a transitional multidisciplinary discussion, a pharmacotherapeutic care interview including shared decision-making with the patient, and a discharge letter with the pharmacotherapeutic plan sent to the general practitioner and community pharmacist. The comparator is usual care provided in the participating control hospitals. The primary outcome is the proportion of patients with DRA in the first 30 days after discharge. The secondary outcomes include cost-effectiveness, quality of life, and mortality. The novelty of this study lies in the selection of a patient group expected to be at high risk for DRAs, on the basis of an evidence-based prediction model, as well as in the combination of components used in the intervention. By selecting high-risk patients and applying a multicomponent approach, this study is expected to increase current knowledge on the effects of TMPC on clinically relevant outcomes and cost-effectiveness in hospitalized older patients. Clinicaltrials.gov: NCT05899114, prospective submission, registration June 02 2023 (first inclusion June 5 2023).

The WHO Global Patient Safety Challenge "Medication Without Harm" emphasizes the need to improve doctors' prescribing competence. Junior doctors are particularly at risk of prescribing errors due to inadequate training. To address this, the European Prescribing Exam was developed to standardize and improve clinical pharmacology and therapeutics (CPT) education across Europe. This study describes the development and quality analysis of the first two pilot examinations. Based on European consensus studies and the Dutch National Pharmacotherapy Assessment, an assessment blueprint was developed. Two pilot examinations, each with 36 knowledge-based and 11 skills-based questions, were administered between 2020 and 2023 at 16 medical schools in 11 countries. We assessed exam quality through reliability (standard error of measurement, Cronbach's alpha, item-rest correlations (Rir-value), difficulty index (DI)), and content validity (content validity ratio's (CVR)). Questions with a negative Rir or CVR, or DI < 0.44 were flagged as potential lower quality. In addition, students' scores (% of maximum) and differences between schools and curricula were evaluated. A total of 3109 students participated (Examination 1: 1371; Examination 2: 1745). Most questions were of high quality; 20/94 (21.3%) were flagged. Median scores on the examinations were 66.2% (IQR 55.4-74.3) and 58.9% (IQR 52.1-65.8) for pilot 1 and 2, respectively. Students from schools with problem-based learning or a national prescribing examination scored significantly higher (P < 0.001). In conclusion, this study demonstrates the feasibility of a standardized European Prescribing Exam. However, the wide variation and generally low median scores highlight the need to improve and harmonize CPT education across Europe.

OBJECTIVE:This qualitative study explores the experiences and needs of older patients with polypharmacy regarding transitional pharmacotherapeutic care during hospital admission and following discharge, identifying areas for improvement. METHODS:A qualitative study was conducted using semi-structured interviews with patients discharged from two Dutch hospitals (academic and non-academic). Patients were asked about their experiences and needs related to medication management, information provision, attitude towards medication changes, decision-making, interactions with healthcare providers and involvement of professional and non-professional support networks. Interviews were transcribed verbatim and analyzed thematically using the Framework approach. RESULTS:Thirteen interviews were conducted. Patients reported diverse experiences and needs regarding transitional pharmacotherapeutic care. Three key themes emerged: patient context, trust in the healthcare system and collaborative decision-making. Participants showed a high level of trust in the organization of healthcare and varying awareness of the benefits of extensive collaboration between healthcare professionals across healthcare settings. CONCLUSIONS:Patients' experiences with pharmacotherapeutic care during hospital admission and following discharge were partly influenced by a high level of trust in the healthcare system. However, shortcomings were noted in adapting care to individual informational needs, patient contexts, and involvement in decision-making about medication changes. PRACTICE IMPLICATIONS:To optimize patients' experiences in pharmacotherapeutic transitional care, it is essential to balance patient autonomy with professional guidance in the development of new patient-centered medication optimization interventions. Healthcare professionals should ask and document patient preferences in communication and support regarding medication decisions. Clear communication about the role of each healthcare professional may enhance patient awareness of potential medication errors, as some patients now put their trust in the organization of healthcare.

ObjectivesThe COVID-19 pandemic and related lockdown measures disrupted global healthcare provision, including opioid prescribing. In North America, opioid sales declined while opioid-related deaths increased. In Europe, the effect of the pandemic on prescribing is not yet known. Given the ongoing increase in opioid-related harm and mortality, it is crucial to analyse the impact of the COVID-19 crisis and lockdown measures on opioid prescribing. Therefore, the objective of this study was to characterise opioid prescribing in the Netherlands during the COVID-19 pandemic.DesignA nationwide register-based study characterising opioid prescribing using aggregated insurance reimbursement data.SettingDutch healthcare during the first 2 years of the COVID lockdown.ParticipantsThe whole Dutch population.Primary and secondary outcome measuresComparing the number of opioid prescriptions during the pandemic with a prepandemic period using a risk ratio (RR), with separate analysis on the prescription type (first-time or repeat prescription), patients’ sex, age and socioeconomic status. We also explored lockdown effects.ResultsDuring the first lockdown, the total number of new opioid prescriptions and prescriptions to young patients (briefly) decreased (RR 0.88, 95% CI 0.88 to 0.89 and RR 0.73, 95% CI 0.70 to 0.75, respectively), but the overall number of opioid prescriptions remained stable throughout the pandemic compared with prepandemic. Women, older patients and patients living in lower socioeconomic areas received more opioids per capita, but the pandemic did not amplify these differences.ConclusionsThe pandemic appears to have had a limited impact on opioid prescribing in the Netherlands. Yet, chronic use of opioids remains an important public health issue.

IntroductionJunior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education.Methods and analysisThis modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in ≥80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision.Ethics and disseminationThe study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO‐ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.

ObjectivesWe determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia.MethodsIn this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.3% Δ9-tetrahydrocannabinol and 8% cannabidiol (max. times inhalation sessions/day), or a combination of both for 6 weeks. The primary endpoint was treatment-related adverse events, assessed using a 10-point composite adverse event (cAE) score; additionally, we recorded daily reported pain relief and daily tablet and cannabis consumption.ResultsIn total, 23 patients were treated with oxycodone, 29 with cannabis, and 29 with the oxycodone/cannabis combination. Three patients from the oxycodone group (13%) and 18 patients from the cannabis groups (31%, 9 in each group) withdrew from the trial within 2–3 weeks because of the severity of AEs. There were no differences in treatment-related cAE scores among the three groups that completed the study (p = 0.70). The analgesic responder rate showed a ≥1- point reduction in pain in 50% and a ≥2-point reduction in 20% of patients, while 50% of patients experienced no treatment benefit. The combination treatment reduced oxycodone tablet consumption by 35% (p = 0.02), but it did not affect the number of cannabis inhalation sessions.ConclusionsCannabis combined with oxycodone offered no advantage over either treatment alone, except for a reduction in opioid tablet intake; however, the overall drug load was the highest in the combination group. Moreover, cannabis was poorly tolerated and led to treatment discontinuation in one-third of participants treated with cannabis.Clinical Trial RegistrationThe trial was registered at the WHO International Clinical Trials Registry Platform (trialsearch.who.int) on July 26, 2019, identifier NL7902.

Drug-induced QT prolongation increases the risk of Torsade de Pointes (TdP). Drug-induced QT prolongation is a complex and unpredictable system due to many uncertainties. Risk factors such as electrolyte disturbances, heart failure and genetics play an important role in estimating the effect on QT prolongation. Moreover, the degree of QT prolongation is not always directly related to the risk of TdP and the assessment of the QT-interval is variable depending on the type and timing of QT measurement. Therefore, the variation in QT measurement may be larger than the effect of certain drugs on the QT interval. Because of the potentially lethal risk, several measures are undertaken to reduce the risk of QT prolongation and TdP, while their effect and proportionality are unclear. We suggest we should be less stringent in certain settings when risk of TdP is extremely low given the limited availability of our resources.

Corticosteroids are often administered locally to prevent systemic exposure and side effects. It is not well known that all forms of locally administered corticosteroids can have systemic side effects. Because doctors are less aware of systemic side effects when using locally administered corticosteroids, these side effects are not always recognized and treated as such. In addition, this means that good incidence figures for systemic side effects of local corticosteroid therapy are lacking. The individual risk of developing systemic side effects varies greatly because it depends on a large number of factors. Knowledge of these risk factors can help to estimate which patients are at risk of systemic side effects. Certain agents, such as fluticasone inhaler or budesonide nasal spray, have an increased risk of systemic side effects. By switching to an alternative, if the case permits it, the risk of systemic side effects can be reduced.

OBJECTIVE:Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine. METHODS:The study was performed in 14 subjects with OUD. They received a single dose of 10mg/kg ibogaine hydrochloride. Plasma PKs of ibogaine, noribogaine, and noribogaine glucuronide were obtained during 24 h. Cytochrome P450 isoenzyme 2D6 (CYP2D6) genotyping was performed. The PKs were analyzed by means of nonlinear mixed effects modeling and related with corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity. RESULTS:The PK of ibogaine were highly variable and significantly correlated to CYP2D6 genotype (p < 0.001). The basic clearance of ibogaine (at a CYP2D6 activity score (AS) of 0) was 0.82 L/h. This increased with 30.7 L/h for every point of AS. The relation between ibogaine plasma concentrations and QTc was best described by a sigmoid Emax model. Spearman correlations were significant (p < 0.03) for ibogaine but not noribogaine with QTc (p = 0.109) and cerebellar effects (p = 0.668); neither correlated with the severity of opioid withdrawal symptoms. CONCLUSIONS:The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and/or applying individualized dosing based on CYP2D6 genotype.

In this narrative review, we discuss evidence for psilocybin- and LSD-assisted treatment of alcohol use disorder (AUD) and major depressive disorder (MDD). We describe limitations of psychedelic research and posit methodological considerations when designing a trial in patients with both disorders. In AUD, a growing evidence base for psilocybin treatment shows a promising beneficial and sustained effect on measures of drinking frequency. In MDD, a recent meta-analysis has demonstrated that psilocybin therapy provides a large and consistent reduction in depressive symptoms compared to no treatment. Co-occurrence of MDD and AUD is quite prevalent, and this comorbidity exacerbates symptomatology of the two individual disorders and complicates their treatment. Theoretically, patients presenting with both AUD and MDD would benefit from an integrated therapy that could treat MDD and AUD simultaneously. We believe that more research into the efficacy of psilocybin in patients with both AUD and MDD is warranted and justified.