The Role of Medicinal Cannabis as an Emerging Therapy for Opioid Use Disorder.

This narrative review explores current insights into the potential use of medicinal cannabis-related products as an emerging therapy for opioid use disorder in the landscape of increasing knowledge about medicinal cannabis-based products, commercialisation and global legalisation. Preclinical studies have provided preliminary insight into the putative neurobiological mechanisms that underpin the potential for medicinal cannabis to be considered a therapeutic in opioid use disorder and addiction. With the progressive legalisation of cannabis in many jurisdictions worldwide, contemporary research has highlighted further evidence that medicinal cannabis may have efficacy in reducing cravings and withdrawal effects, and therefore may be considered as an adjunct or standalone to current medications for opioid use disorder. Despite this potential, the landscape of research in this space draws from a large number of observational studies, with a paucity of rigorous randomised controlled trials to ascertain a true understanding of effect size and safety profile. With current challenges in implementation that arise from political and legal qualms about adopting medicinal cannabis on the background of associated social stigma, significant hurdles remain to be addressed by government, policy-makers, healthcare providers and researchers before medical cannabis can be introduced globally for the treatment of opioid use disorder.

The aim of this review was to synthesise current evidence to understand how medicinal cannabis products may be able to tackle the signs, symptoms and outcomes related to opioid dependence. At the present time, opioid dependence is associated with a significant burden of disease and death in the community. Current treatment for opioid dependence includes supplying controlled-release opioids in a regulated (and often observed) manner in the community. However, despite the implementation of this strategy, the outcomes related to opioid use and dependence remain relatively unchanged, indicating that the current gold standard treatment is not as effective as it should be. Following the legalisation and commercialisation of medicinal cannabis, there has been increased research into the ways these products can be leveraged for different conditions and indications, including in opioid dependence. Given this context, in this narrative we explore this preliminary evidence and evaluate the steps required in further research and policy changes before more widespread implementation of medical cannabis can be considered.

Intravenous methadone in the management of acute postoperative pain in a chronic cancer pain patient: A case report and review of the literature.

Key Clinical Message: The current landscape of literature highlights that there is insufficient well-powered and robust evidence to support the integration of intravenous methadone into current guidelines and frameworks in supporting the pain management of cancer patient with complex pain syndromes. However, there is preliminary evidence, both from the literature as well as this case study that highlights intravenous methadone may be efficaciously and safety used for the management of postoperative pain in cancer patients with chronic pain undergoing operative management. Further research is required to fully elucidate key considerations of integrating this medication into clinical practice including consideration into dosing, opioid conversion, tolerance, and safety. Abstract: Methadone is a broad-spectrum analgesic with long duration of effect. Its multimodal mechanism of action, such as through effects on mu-opioid receptor and presynaptic N-methyl-D-aspartate receptors, has led to its current use in the management of opioid dependence in the community and in palliative care. These properties however make methadone appealing in the management of postoperative pain, particularly for patients with complex analgesic requirements. We report on an interesting case whereby intravenous methadone was effectively used for postoperative analgesia in a 56-year-old female with complex chronic pain secondary to a mucinous pelvic neoplasm of unclear primary who underwent palliative resection. Further, we review the literature surrounding usage of methadone in this setting to understand current challenges and barriers to implementation of methadone as an analgesia option for chronic pain patients following surgery. To do this, a case report and literature review was conducted in accordance to the CARE case report guidelines. The patient provided written consent for the de-identification and use of their medical information and data for the generation and publication of this case report. Our case report and literature review demonstrate there remains significant heterogeneity, unfamiliarity, and scarce use of intravenous methadone in the perioperative and postoperative space in the management of patients with complex pain regimens such as chronic cancer pain patients. Despite this, our case report and literature review highlight as a broad analgesic, intravenous methadone warrants consideration following more rigorous research and development of safe use guidelines into its use for this purpose.

The Therapeutic Potential of Cannabidiol in Revolutionising Opioid Use Disorder Management.

Opioid use disorder (OUD) is a significant cause of morbidity and mortality worldwide and is linked to a complex interplay of biopsychosocial factors as well as the increasing overprescription and availability of opioid medications. Current OUD management relies on the controlled provision of opioid medications, such as methadone or buprenorphine, known as opioid replacement therapy. There is variable evidence regarding the long-term efficacy of these medications in improving the management of OUD, thereby necessitating an exploration into innovative approaches to complement, or even take the place of, existing treatment paradigms. Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has garnered attention for its diverse pharmacological properties, including anti-inflammatory, analgesic, and anxiolytic effects. Preliminary studies suggest that CBD may target opioid withdrawal pathways that make CBD a potential therapeutic option for OUD. This narrative review synthesises current literature surrounding OUD and offers a nuanced review of the current and future role of CBD in managing this condition. In doing so, we highlight the potential avenues to explore with respect to CBD research for the guidance and development of further research opportunities, framework and policy development, and clinical considerations before medicinal CBD can be integrated into evidence-based clinical guidelines.

Colecalciferol Initiation Post Minimal Trauma Fracture.

Purpose: The purpose of this study was to determine the proportion of patients admitted to a major tertiary teaching hospital in Australia aged 50 years and older with a confirmed neck of femur or vertebral minimal trauma fracture, who are commenced on colecalciferol supplementation by discharge, and to describe the doses prescribed. Methods: A subanalysis of a retrospective audit of electronic medical files for patients admitted with a minimal trauma fracture of the hip or vertebra between January 1, 2016, and June 30, 2016, was conducted. Results: A total of 406 patients were screened and 64 patients were included in the audit. In this subanalysis of these 64 patients eligible for inclusion, 38 were not on any vitamin or mineral supplementation at admission. Of these, 26 patients (68.4%) had their serum colecalciferol levels measured, and 21 patients (55.2%) overall were initiated on colecalciferol. Conclusion: Over half of patients with a minimal trauma fracture were commenced on colecalciferol therapy, but a noteworthy proportion of patients remain untreated. Patients with colecalciferol levels are more likely to be initiated on therapy compared with those of whom levels were not taken during admission. This is a missed opportunity for intervention that may place patients at a higher risk of subsequent fracture; therefore, effective strategies should be implemented to address this treatment gap in the future.

Modeling allosteric regulation of de novo pyrimidine biosynthesis in Escherichia coli.

With the emergence of multifaceted bioinformatics-derived data, it is becoming possible to merge biochemical and physiological information to develop a new level of understanding of the metabolic complexity of the cell. The biosynthetic pathway of de novo pyrimidine nucleotide metabolism is an essential capability of all free-living cells, and it occupies a pivotal position relative to metabolic processes that are involved in the macromolecular synthesis of DNA, RNA and proteins, as well as energy production and cell division. This regulatory network in all enteric bacteria involves genetic, allosteric, and physiological control systems that need to be integrated into a coordinated set of metabolic checks and balances. Allosterically regulated pathways constitute an exciting and challenging biosynthetic system to be approached from a mathematical perspective. However, to date, a mathematical model quantifying the contribution of allostery in controlling the dynamics of metabolic pathways has not been proposed. In this study, a direct, rigorous mathematical model of the de novo biosynthesis of pyrimidine nucleotides is presented. We corroborate the simulations with experimental data available in the literature and validate it with derepression experiments done in our laboratory. The model is able to faithfully represent the dynamic changes in the intracellular nucleotide pools that occur during metabolic transitions of the de novo pyrimidine biosynthetic pathway and represents a step forward in understanding the role of allosteric regulation in metabolic control.