A case of severe and prolonged γ-hydroxybutyrate (GHB) withdrawal syndrome successfully managed with a slow benzodiazepine and baclofen taper.

INTRODUCTION: γ-hydroxybutyrate (GHB) is a GABA-B agonist that rapidly produces effects that are likened to both alcohol and MDMA/ecstasy. GHB use can lead to neuroadaptation with a characteristic withdrawal syndrome. There is currently a paucity of data on the progression of GHB withdrawal, however, due to the drug's short half-life it is generally considered to be typically 5-7 days, although some cases can be severe and complicated by life threatening delirium. Here, we present a case of severe GHB withdrawal, which recurred on multiple occasions over 56 days, despite initial clinical stabilisation on each occasion and toxicological evidence of abstinence from GHB between episodes. CASE PRESENTATION: A male patient in his 30s presented with agitated delirium on a background of severe GHB use disorder with a 15-year history of daily high dose GHB use. Following 3 hospital admissions over 8 weeks, all requiring intravenous sedation and tracheal intubation, the patient's withdrawal delirium was successfully treated with a slow benzodiazepine and baclofen wean over a period of 6 months. Relapse to GHB use between hospitalisations was excluded toxicologically via blood analysis performed at an institute of forensic pathology. DISCUSSION AND CONCLUSIONS: This case highlights that GHB withdrawal can be more prolonged than previously reported in the literature and in some cases may require slow and prolonged tapering of treatment to prevent re-emergence of delirium. Similar to previous case reports, benzodiazepines and GABA-B receptor agonists appear to be appropriate drug classes to manage GHB withdrawal.

Overview of global monitoring systems for the side effects and adverse events associated with medicinal cannabis use: a scoping review using a systematic approach.

OBJECTIVES: The use of cannabis-based medicine (CBM) as a therapeutic has surged in Australia over the past 5 years. Historically, the United Nations Single Convention on Narcotic Drugs (1961) prohibited cannabis use in Europe, the USA, the UK and Australia, leading to legislative resistance and limited preclinical data on CBM. Existing safety monitoring systems for CBM are poorly structured and do not integrate well into the workflows of busy health professionals. As a result, postmarketing surveillance is inconsistent. This review aims to evaluate international systems for monitoring CBM side effects and adverse events. DESIGN: To undertake a scoping review with a systematic approach, we used the Population, Intervention, Comparison, Outcome (PICO) framework to develop keyword elements, and two search queries to maximise search sensitivity and specificity. DATA SOURCES: Search queries were entered into Embase and Scopus for peer-reviewed literature, and additional searches for grey literature were conducted on 23 June 2023. ELIGIBILITY CRITERIA: We included 54 full-text articles in the review: 39 from peer-reviewed searches, 8 from grey literature and 7 from citations of relevant texts. DATA EXTRACTION AND SYNTHESIS: Our search yielded two main forms of monitoring systems: databases and registries. Out of the 24 monitoring systems identified, there were 10 databases and 14 registries, with databases often created by regulatory authorities. Systems differed in methods of causality assessment, level of detail collected, terminology and affiliations. RESULTS: Within the monitoring systems with enough published data for analysis, all except one remain active at the time of this review. VigiBase is the largest centralised monitoring system, receiving international case reports, however data heterogeneity persists. CONCLUSIONS: Our study emphasises the need for a centralised, consistent and accessible system for the postmarketing surveillance of side effects and adverse events associated with medicinal cannabis use.

The dual orexin receptor antagonist suvorexant in alcohol use disorder and comorbid insomnia: A case report.

Key Clinical Message: This case suggests using dual orexin receptor antagonists to treat alcohol use disorder and comorbid sleep disorders may be effective, commencing treatment in withdrawal and continuing it to prevent relapse. Abstract: Effective medications for the treatment of alcohol use disorder are limited. This is partially due to the heterogenous nature of the symptomatology associated with alcohol use disorder and the abundance of presenting comorbidities. One common, and often overlooked, symptom that occurs during withdrawal of alcohol use is sleep disruption. Here, we report a case study of a participant with comorbid alcohol use disorder and insomnia. This participant was treated with a dual orexin receptor antagonist, suvorexant (Belsomra®), currently approved to treat insomnia. We demonstrate improvements in alcohol cravings, physical and psychological health, and sleep outcomes with treatment. These data support abundant preclinical and emerging clinical data in this space. The findings from this case report highlight the potential for suvorexant to treat comorbid alcohol use disorder and insomnia with fully powered, randomized controlled trials moving forward.

Priorities for research promoting mental health in the south and east of Asia.

Progress in promoting mental health, preventing mental illness, and improving care for people affected by mental illness is unlikely to occur if efforts remain separated from existing public health programs and the principles of public health action. Experts met recently to discuss integrating public health and mental health strategies in the south and east of Asia, especially in low- and middle-income countries. Areas of research identified as high priority were: 1) integrating mental health into perinatal care; 2) providing culturally-adjusted support for carers of people with mental and physical disorders; 3) using digital health technologies for mental health care in areas with limited resources and 4) building local research capacity. Selection of these areas was informed by their relative novelty in the region, ease of implementation, likely widespread benefit, and potential low costs. In this article, we summarise available evidence, highlight gaps and call for collaborations with research centres, leaders and persons with lived experience within and beyond the region.

Tobacco treatment incorporating contingency management, nicotine replacement therapy, and behavioral counseling for pregnant women who use substances: a feasibility trial.

Introduction: Most pregnant women with substance use problems smoke, and few will quit during their pregnancy. Tobacco treatment is often overlooked, with the focus usually placed on other substance use. Additionally, few targeted effective treatments for this group exist. To address this, the feasibility of an intensive tobacco treatment incorporating contingency management (CM) that featured non-face-to-face delivery was examined. Methods: A single-arm pre-post design feasibility trial was conducted in three antenatal services that support women who use substances in metropolitan Australia. Participants were over the age of 15, had <33-week gestation, and smoked tobacco daily. They received financial incentives for daily carbon monoxide-verified smoking abstinence or reduction through an internet-based CM programme, nicotine replacement therapy (NRT) posted to women and partners or household members who smoked and telephone-delivered behavioral counseling from study enrolment to birth. Results: Of the 101 referrals, 46 women (46%) consented. The mean (SD) age was 31(±6) years, and the gestation period was 22(±6) weeks. Nineteen (41%) of those enrolled were retained for 12-week postpartum. Of 46 women, 32 (70%) utilized CM; 32 (70%) used NRT for ≥2 weeks; 23 (50%) attended ≥1 counseling session; and 15 (22%) received NRT for partners/household members. Fifteen (33%) were verified abstinent from tobacco at delivery after a median (IQR) period of abstinence of 65(36-128) days. All non-smokers at birth utilized NRT and financial incentives, and 9/15 (60%) utilized counseling. Four (9%) were abstinent at 12-week postpartum. Median cigarettes smoked/day reduced from baseline to delivery (10(6-20) to 1(0-6) p =< 0.001). Women who quit smoking had more education (72% vs. 33% p =< 0.02), completed more CO samples (median (IQR) 101(59-157) vs. 2(0-20) p =< 0.001), and received more incentives (median (IQR) $909($225-$1980) vs. $34($3-$64) p =< 0.001). Intervention acceptability was rated favorably by participants (9 items rated 0-10 with scores >5 considered favorable). Discussion: This study demonstrated the feasibility and acceptability of a consumer-informed, non-face-to-face intensive tobacco treatment, highlighting the potential of remotely delivered technology-based CM to reduce the health impact of tobacco smoking in high-priority populations. The intervention demonstrates scale-up potential. Future studies should extend treatment into the postpartum period, utilizing new technologies to enhance CM delivery and improve counseling provision and partner support. Clinical trial registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374196, ACTRN1261800056224.

Evidence from Human Studies for Utilising Cannabinoids for the Treatment of Substance-Use Disorders: A Scoping Review with a Systematic Approach.

Substance-use disorders are pervasive, comorbid with a plethora of disease and possess limited treatment options. Medicinal cannabinoids have been proposed as a novel potential treatment based on preclinical/animal trials. The objective of this study was to examine the efficacy and safety of potential therapeutics targeting the endocannabinoid system in the treatment of substance-use disorders. We performed a scoping review using a systematic approach of systematic reviews, narrative reviews, and randomised control trials that utilised cannabinoids as treatment for substance-use disorders. For this scoping review we used the PRISMA guidelines, a framework for systematic reviews and meta-analyses, to inform our methodology. We conducted a manual search of Medline, Embase, and Scopus databases in July 2022. Of the 253 results returned by the databases, 25 studies including reviews were identified as relevant, from which 29 randomised controlled trials were derived and analysed via a primary study decomposition. This review captured a small volume of highly heterogenous primary literature investing the therapeutic effect of cannabinoids for substance-use disorders. The most promising findings appeared to be for cannabis-use disorder. Cannabidiol appeared to be the cannabinoid showing the most promise for the treatment of multiple-substance-use disorders.

Using Social Media Data to Investigate Public Perceptions of Cannabis as a Medicine: Narrative Review.

BACKGROUND: The use and acceptance of medicinal cannabis is on the rise across the globe. To support the interests of public health, evidence relating to its use, effects, and safety is required to match this community demand. Web-based user-generated data are often used by researchers and public health organizations for the investigation of consumer perceptions, market forces, population behaviors, and for pharmacoepidemiology. OBJECTIVE: In this review, we aimed to summarize the findings of studies that have used user-generated text as a data source to study medicinal cannabis or the use of cannabis as medicine. Our objectives were to categorize the insights provided by social media research on cannabis as medicine and describe the role of social media for consumers using medicinal cannabis. METHODS: The inclusion criteria for this review were primary research studies and reviews that reported on the analysis of web-based user-generated content on cannabis as medicine. The MEDLINE, Scopus, Web of Science, and Embase databases were searched from January 1974 to April 2022. RESULTS: We examined 42 studies published in English and found that consumers value their ability to exchange experiences on the web and tend to rely on web-based information sources. Cannabis discussions have portrayed the substance as a safe and natural medicine to help with many health conditions including cancer, sleep disorders, chronic pain, opioid use disorders, headaches, asthma, bowel disease, anxiety, depression, and posttraumatic stress disorder. These discussions provide a rich resource for researchers to investigate medicinal cannabis-related consumer sentiment and experiences, including the opportunity to monitor cannabis effects and adverse events, given the anecdotal and often biased nature of the information is properly accounted for. CONCLUSIONS: The extensive web-based presence of the cannabis industry coupled with the conversational nature of social media discourse results in rich but potentially biased information that is often not well-supported by scientific evidence. This review summarizes what social media is saying about the medicinal use of cannabis and discusses the challenges faced by health governance agencies and professionals to make use of web-based resources to both learn from medicinal cannabis users and provide factual, timely, and reliable evidence-based health information to consumers.

Corrigendum to: Use of electronic medical records to monitor the safe and effective prescribing of medicinal cannabis: is it feasible?

BACKGROUND: General practitioners are well positioned to contribute to the pharmacovigilance of medical cannabis via the general practice electronic medical record (EMR). The aim of this research is to interrogate de-identified patient data from the Patron primary care data repository for reports of medicinal cannabis to ascertain the feasibility of using EMRs to monitor medicinal cannabis prescribing in Australia. METHODS: EMR rule-based digital phenotyping of 1 164 846 active patients from 109 practices was undertaken to investigate reports of medicinal cannabis use from September 2017 to September 2020. RESULTS: Eighty patients with 170 prescriptions of medicinal cannabis were identified in the Patron repository. Reasons for prescription included anxiety, multiple sclerosis, cancer, nausea, and Crohn's disease. Nine patients showed symptoms of a possible adverse event, including depression, motor vehicle accident, gastrointestinal symptoms, and anxiety. CONCLUSIONS: The recording of medicinal cannabis effects in the patient EMR provides potential for medicinal cannabis monitoring in the community. This is especially feasible if monitoring were to be embedded into general practitioner workflow.