A systematic literature review of clinical trials and therapeutic applications of ibogaine

BACKGROUND Iboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating substance use disorders (SUDs). For many SUDs, still no effective pharmacotherapies exist. Distinct psychoactive and somatic effects of the iboga alkaloids set them apart from classic hallucinogens like LSD, mescaline, and psilocybin. AIMS The study team performed this systematic review focusing on clinical data and therapeutic interventions involving ibogaine and noribogaine. METHODS The team conducted a search for all publications up to December 7, 2020, using PubMed and Embase following PRISMA guidelines. RESULTS In total, we identified 743 records. In this review, we consider 24 studies, which included 705 individuals receiving ibogaine or noribogaine. This review includes two randomized, double-blind, controlled clinical trials, one double-blind controlled clinical trial, 17 open-label studies or case series (including observational or retrospective studies), three case reports, and one retrospective survey. The published data suggest that ibogaine is an effective therapeutic intervention within the context of SUDs, reducing withdrawal symptoms and craving. Data also point toward a beneficial impact on depressive and trauma-related psychological symptoms. However, studies have reported severe medical complications and deaths, which seem to be associated with neuro- and cardiotoxic effects of ibogaine. Two of these fatalities were described in the 24 studies included in this review. CONCLUSION Treatment of SUDs and persisting comorbidities requires innovative treatment approaches. Rapid-onset therapies such as the application of ibogaine may offer novel treatment opportunities for specific individuals. Rigorous study designs within medical settings are necessary to warrant safe application, monitoring, and, possibly, medical intervention

Co-occurring Mental Disorders in Transitional Aged Youth With Substance Use Disorders – A Narrative Review

Adolescence and emerging adulthood are often referred to as youth. Transitional psychiatry addresses this target group, which considers patients between 15 and 25 years of age. Substance use usually begins and peaks at this stage of life. Psychiatric disorders, foremost attention-deficit/hyperactivity disorder, and affective disorders, conduct disorders, and first-episodes psychosis frequently appear in early life stages. This review aims to provide a broad overview of transitional-aged youth's most common psychiatric comorbidities with substance use disorders. A literature search was conducted in Embase and Pubmed, and the main findings are described narratively. We present main findings for the following comorbidities: attention-deficit/hyperactivity disorder, conduct disorder, personality disorders, affective disorders, psychotic disorders, and the phenomena of overdose and suicidality. In conclusion, co-occurring mental health disorders are common and appear to facilitate the development of substance use disorders and exacerbate their overall course. Substance use also affects the severity and course of comorbid psychiatric disorders. Overall, data on transition-age youth with substance use disorders are highly inconsistent. Universal screening and treatment guidelines do not yet exist but should be aimed for in the future

Experiences with take-home dosing in heroin-assisted treatment in Switzerland during the COVID-19 pandemic–Is an update of legal restrictions warranted?

Heroin-assisted treatment comprises the use of diacetylmorphine (pharmaceutical heroin) for individuals with severe opioid use disorder. In Switzerland, take-home doses in heroin-assisted treatment are more strictly regulated as compared to conventional opioid agonist treatment. In light of the COVID-19 pandemic, the Swiss Federal Council provisionally adapted its policy, allowing for longer prescriptions of take-home diacetylmorphine. Before the beginning of the pandemic, take-home doses only occurred in exceptional circumstances and under strict criteria for patient eligibility. Following the legislative adaptations, we critically revised our internal centre policies as well. We report our experiences with oral take-home diacetylmorphine from a Swiss outpatient university centre specialising in heroin-assisted treatment. An additional 45 patients received take-home doses following the first lockdown. While some patients wished to return to their previous treatment regimen, most patients managed their medication well and showed good adherence. We also noticed an increase of treatment admissions that are likely related to the relaxed regulations. Previously, the strict therapeutic framework of visiting a HAT centre twice a day for supervised dispensing seemed to have discouraged these individuals from seeking medical treatment. From a medical point of view, the politically driven restrictions on take-home doses in heroin-assisted treatment are questionable and do not support the goal of harm reduction

Case report: Psychosis and catatonia in an adolescent patient with adipsic hypernatremia and autoantibodies against the subfornical organ.

This is the first description of a patient in which adipsic hypernatremia, a rare autoimmune encephalitis, presented in combination with complex psychiatric symptomatology, including psychosis and catatonia. Adipsic hypernatremia is characterized by autoantibodies against the thirst center of the brain. These autoantibodies cause inflammation and apoptosis in key regions of water homeostasis, leading to lack of thirst and highly increased serum sodium. To date, the symptoms of weakness, fatigue and drowsiness have been associated with adipsic hypernatremia, but no psychiatric symptomatology. Here, we showcase the first description of an adolescent patient, in which severe and complex psychiatric symptoms presented along with adipsic hypernatremia. The patient experienced delusion, hallucinations, restlessness and pronounced depression. Further, he showed ritualized, aggressive, disinhibited and sexualized behavior, as well as self-harm and psychomotor symptoms. Due to his severe condition, he was hospitalized on the emergency unit of the child and adolescent psychiatry for 8 months. Key symptoms of the presented clinical picture are: childhood-onset complex and treatment-resistant psychosis/catatonia, pronounced behavioral problems, fatigue, absent thirst perception, hypernatremia and elevated prolactin levels. This case report renders first evidence speaking for a causal link between the autoimmune adipsic hypernatremia and the psychotic disorder. Moreover, it sheds light on a new form of autoimmune psychosis

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system’s response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform

Antimicrobial Natural Products

Although the first antibiotic, penicillin, was discovered in 1928 from a microbial natural source (a mould, Penicillium notatum), there is earlier evidence of using natural materials including moulds and herbs for the treatment of infections. Following the serendipitous discovery of penicillin by Alexander Fleming, there have been hundreds of antibiotics (natural, semisynthetic and synthetic) discovered for clinical uses. However, the pathogenic organisms have developed resistances to existing antibiotics though various mechanisms. Such antibiotic resistance or antimicrobial resistance (AMR) is a critical problem of today’s healthcare system urging the development of new antibiotics. This chapter has primarily focused into antimicrobial compounds developed through natural routes that are currently available as antibiotics for clinical uses and/or are at various developmental stages within the drug development pipeline for potential treatment of minor and life threatening infections. The chapter also provides an overview on the catastrophic problem of antimicrobial resistance, its causes, how it spreads as well as modes of developing antimicrobial resistance (AMR)

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

Chronic High-Dose Buprenorphine Does Not Block Subjective High from Diacetylmorphine in a Patient in Heroin-Assisted Treatment

We present the case of a 35-year-old woman in heroin-assisted treatment (HAT) expressing the wish for the transition to oral opioid agonist treatment. After failed attempts to change to oral diacetylmorphine and slow-release oral morphine, respectively, she was induced on overlapping buprenorphine (BUP) treatment with the Bernese method. Gradual dose increases to BUP 48 mg per day did not result in attenuation of subjective effects of IV diacetylmorphine (DAM) 190 mg. Instead, the patient showed increased sedation. BUP was then reduced to 32 mg per day. After the gradual reduction of IV DAM, she reinitiated illicit substance use. IV DAM was again raised to an effective dose leading to stabilization and reduction of illicit substance use. BUP was subsequently reduced to 8 mg per day. This combination was continued as the patient felt comfortable and reported less early morning withdrawal than with exclusive DAM treatment. We discuss possible underlying mechanisms and explanations as well as clinical implications

Co-occurring mental disorders in transitional aged youth with substance use disorders - a narrative review.

Adolescence and emerging adulthood are often referred to as youth. Transitional psychiatry addresses this target group, which considers patients between 15 and 25 years of age. Substance use usually begins and peaks at this stage of life. Psychiatric disorders, foremost attention-deficit/hyperactivity disorder, and affective disorders, conduct disorders, and first-episodes psychosis frequently appear in early life stages. This review aims to provide a broad overview of transitional-aged youth's most common psychiatric comorbidities with substance use disorders. A literature search was conducted in Embase and Pubmed, and the main findings are described narratively. We present main findings for the following comorbidities: attention-deficit/hyperactivity disorder, conduct disorder, personality disorders, affective disorders, psychotic disorders, and the phenomena of overdose and suicidality. In conclusion, co-occurring mental health disorders are common and appear to facilitate the development of substance use disorders and exacerbate their overall course. Substance use also affects the severity and course of comorbid psychiatric disorders. Overall, data on transition-age youth with substance use disorders are highly inconsistent. Universal screening and treatment guidelines do not yet exist but should be aimed for in the future

Herausforderungen der Opioid-Agonistentherapie aus der Perspektive der Mitarbeitenden in Behandlungszentren : Ergebnisse einer Online-Umfrage

Dank verbesserter Behandlungsmöglichkeiten opioidabhängiger Menschen ist ein Anstieg der Zahl älterer Patienten in Opioid-Agonistentherapie (OAT) zu verzeichnen. Insgesamt verbesserte sich die Lebenserwartung dieser Patienten in den letzten Jahren deutlich und das Durchschnittsalter der Patienten in OAT nahm zu. Bei den über 50-jährigen OAT-Patienten fiel auf, dass sich diese Population im Vergleich zur gleichaltrigen Normalbevölkerung in schlechterem Gesundheitszustand sowie auf niedrigerem sozialen Funktionsniveau befindet. Die Entstehung eines neuen Patientenkollektives stellt komplexe Ansprüche an das Gesundheitssystem. Insbesondere betrifft dies die somatische, psychiatrische und psychosoziale Versorgung dieser Patientengruppe. Diese Herausforderungen wurden kaum untersucht. Mittels einer Online-Umfrage wurde eine Analyse der Situation aus Sicht der Behandlungsanbieter in der deutschsprachigen Schweiz durchgeführt. Dabei wurden aus Sicht der Mitarbeitenden Bedarf an verbesserter altersgerechter Infrastruktur, ausgearbeitete Konzepte im Umgang mit älteren Patienten sowie Fortbildungen im Bereich „Palliative Care“ festgestellt. Einigkeit bestand darüber, dass die OAT auch für ältere Patienten weiterhin ermöglicht werden sollte. = The number of elderly patients that receive an opioid agonist treatment (OAT) increased, partly due to improved treatment options for people with opioid dependency. The life expectancy of these patients improved significantly and the mean age of OAT-patients increased. Generally, OAT-patients older than 50 years suffer from worse overall health and a lower level of social functioning than the normal population. The development of this new collective of elderly patients challenges the health system due to the complexity of adequate somatic, psychiatric and psychosocial care. These challenges have rarely been studied. We designed an online-survey for the staff of German-speaking OAT-treatment centres in Switzerland to analyse the current situation. We found that members of staff demanded improved infrastructure for elderly patients, clear concepts of treating elderly OAT-patients and further education in palliative care. The survey indicated consensus among staff members of the different treatment centres that OAT should be available and facilitated for elderly patients